Suitability of machine learning models for prediction of clinically defined Stage III/IV periodontitis from questionnaires and demographic data in Danish cohorts.

AIM: To evaluate if, and to what extent, machine learning models can capture clinically defined Stage III/IV periodontitis from self-report questionnaires and demographic data. MATERIALS AND METHODS: Self-reported measures of periodontitis, demographic data and clinically established Stage III/IV periodontitis status were extracted from two Danish population-based cohorts (The Copenhagen Aging and Midlife Biobank [CAMB] and The Danish Health Examination Survey [DANHES]) and used to develop cross-validated machine learning models for the prediction of clinically established Stage III/IV periodontitis. Models were trained using 10-fold cross-validations repeated three times on the CAMB dataset (n = 1476), and the resulting models were validated in the DANHES dataset (n = 3585). RESULTS: The prevalence of Stage III/IV periodontitis was 23.2% (n = 342) in the CAMB dataset and 9.3% (n = 335) in the DANHES dataset. For the prediction of clinically established Stage III/IV periodontitis in the CAMB cohort, models reached area under the receiver operating characteristics (AUROCs) of 0.67-0.69, sensitivities of 0.58-0.64 and specificities of 0.71-0.80. In the DANHES cohort, models derived from the CAMB cohort achieved AUROCs of 0.64-0.70, sensitivities of 0.44-0.63 and specificities of 0.75-0.84. CONCLUSIONS: Applying cross-validated machine learning algorithms to demographic data and self-reported measures of periodontitis resulted in models with modest capabilities for the prediction of Stage III/IV periodontitis in two Danish cohorts.

Development of video tutorials to help parents manage children with acute illnesses using a modified Delphi method.

AIM: Children often fall sick, which causes concern among parents. Online health information can be confusing and difficult to understand. We aimed to produce simple, informative video tutorials on the symptoms ill children present. METHODS: We used a modified Delphi method to produce video tutorials on the symptoms of fever, vomiting and diarrhoea, abdominal pain, breathing difficulties, sore throat, red eyes, earache and rash. We identified the most common symptoms in acutely ill children. During the first consensus round, experts rated statements on out-of-hospital management from existing health information. Video tutorials were produced from statements rated to be included. The second consensus round involved video showings and editing. Two videos were evaluated in focus groups by parents. RESULTS: During the first round, experts rated a median of 79 (40-154) statements for each symptom. Panels consisted of a median of seven (6-11) experts, primarily. Panels reached a consensus on inclusion, neutrality or exclusion in 83% of statements. The second round led to adjustments to the videos and final approval by experts. Most parents evaluated the videos as 'informative, easy to understand and calming'. CONCLUSION: We produced video tutorials on the common symptoms ill children present using a modified Delphi method. Feedback from parents in focus groups was positive.

Social inequality in tooth loss: separate and joint effects of household income and dental visits.

OBJECTIVE: The aim of the study was to investigate the separate and joint effects of household income and dental visits on tooth loss. BASIC RESEARCH DESIGN: Participants from the Social Inequality in Cancer Cohort (SIC) were followed in registers for household income (2000), dental visits (2002-2009) and tooth loss (2010-2016). Logistic regression was used to assess the effect of household income and dental visits on tooth loss, and linear models were applied to assess the separate and joint effects of household income and dental visits. RESULTS: In total, 10.8% of the participants had tooth loss (⟨15 teeth present). Low household income and irregular dental visits showed significantly higher odds ratios for tooth loss. Compared to regular dental visits, irregular dental visits accounted for 923 (95% CI 840 - 1,005) extra cases of tooth loss per 10,000 persons, and compared to high household income, low household income accounted for 1,294 (95% CI 1,124 - 1,464) additional cases of tooth loss per 10,000 persons. Further, due to household income-dental visit interaction, we observed 581 (95% CI 233 - 928) extra cases of tooth loss per 10,000 persons. CONCLUSION: Low household income and irregular dental visits are important in relation to social inequality in tooth loss. Irregular dental visits are associated with higher risk of tooth loss among persons with low household income compared to persons with high household income. Such interaction may be explained by differences in susceptibility to tooth loss across household income groups.

Effect of metformin and insulin vs. placebo and insulin on whole body composition in overweight patients with type 2 diabetes: a randomized placebo-controlled trial.

Some studies indicate potential beneficial effects of metformin on body composition and bone. This trial compared metformin + insulin vs placebo + insulin. Metformin treatment had a small but positive effect on bone quality in the peripheral skeleton, reduced weight gain, and resulted in a more beneficial body composition compared with placebo in insulin-treated patients with type 2 diabetes. INTRODUCTION: Glucose-lowering medications affect body composition. We assessed the long-term effects of metformin compared with placebo on whole body bone and body composition measures in patients with type 2 diabetes mellitus. METHODS: This was a sub-study of the Copenhagen Insulin and Metformin Therapy trial, which was a double-blinded randomized placebo-controlled trial assessing 18-month treatment with metformin compared with placebo, in combination with different insulin regimens in patients with type 2 diabetes mellitus (T2DM). The sub-study evaluates the effects on bone mineral content (BMC), density (BMD), and body composition from whole body dual-energy X-ray absorptiometry (DXA) scans which were assessed at baseline and after 18 months. RESULTS: Metformin had a small, but positive, (p < 0.05) effect on subtotal, appendicular, and legs BMC and BMD compared with placebo. After adjustment for sex, age, vitamin D, smoking, BMI, T2DM duration, HbA1c, and insulin dose, the effects on appendicular BMC and BMD persisted (p < 0.05 for both). The changes in appendicular BMC and BMD corresponded approximately to a 0.7% and 0.5% increase in the metformin group and 0.4% and 0.4% decrease in the placebo group, respectively. These effects were mostly driven by an increase in BMC and BMD in the legs and a loss of BMC and BMD in the arms. During 18 months, all participants increased in weight, fat mass (FM), FM%, and lean mass (LM), but decreased in LM%. The metformin group increased less in weight (subtotal weight (weight-head) - 2.4 [- 3.5, - 1.4] kg, p value < 0.001) and FM (- 1.5 [- 2.3, - 0.8] kg, p value < 0.001) and decreased less in LM% (0.6 [0.2, 1.1] %, p value < 0.001) compared with the placebo group. CONCLUSION: Metformin treatment had a small positive effect on BMC and BMD in the peripheral skeleton and reduced weight gain compared with placebo in insulin-treated patients with T2DM.

Synergies of THESEUS with the large facilities of the 2030s and guest observer opportunities.

The proposed THESEUS mission will vastly expand the capabilities to monitor the high-energy sky. It will specifically exploit large samples of gamma-ray bursts to probe the early universe back to the first generation of stars, and to advance multi-messenger astrophysics by detecting and localizing the counterparts of gravitational waves and cosmic neutrino sources. The combination and coordination of these activities with multi-wavelength, multi-messenger facilities expected to be operating in the 2030s will open new avenues of exploration in many areas of astrophysics, cosmology and fundamental physics, thus adding considerable strength to the overall scientific impact of THESEUS and these facilities. We discuss here a number of these powerful synergies and guest observer opportunities.

Inequality, Familial Aggregation, and Risk Prediction of Caries in Siblings.

INTRODUCTION: Social and family conditions are likely of great importance to dental health; however, limited evidence of familial aggregation of caries among adolescent siblings exists. Moreover, social and family-level factors have never been evaluated as isolated caries predictors at the individual level. OBJECTIVES: The objectives were to evaluate socioeconomic patterning of caries among siblings, assess sibling-specific aggregation of caries within families, and examine if such aggregation differed by parental socioeconomic position (SEP). We also evaluated the discriminant ability of sibling caries, SEP, and other social and familial factors in predicting caries in cosiblings. METHODS: This nationwide register-based study included all 15-y-olds in Denmark in 2003 (index siblings) and their biological siblings born within ±3 y (cosiblings). Clinical and sociodemographic data for each subject were compiled from Danish national dental, social, and population registers. Caries was measured by the decayed, missing, and filled tooth surfaces (DMFS) index. Predictors included SEP (parental education, income, and occupational social class), gender, birth order, immigration status, and household type. Adjusted SEP-caries associations were estimated using negative binomial regression. Familial aggregation was evaluated using adjusted pairwise odds ratios from alternating logistic regressions. Caries prediction was based on classification and regression tree (CART) analyses. RESULTS: The study included 23,847 sibling pairs (n = 47,694). Socioeconomic patterning of caries was similar among the index and cosiblings with significant graded SEP-caries associations. Significant sibling-specific aggregation of caries was observed; cosiblings of caries-affected index siblings had odds of having caries 3.9 times (95% confidence interval: 3.65-4.18) as high as that of cosiblings with caries-free index siblings. This sibling similarity was stronger in socioeconomically disadvantaged families (adjusted pairwise odds ratios: 3.08-5.47). CART revealed index sibling caries as the single most important caries predictor, with caries predicted in ≥84% of cosiblings of adolescents with ≥3 carious tooth surfaces. CONCLUSIONS: Caries in a sibling should prompt preventive family-based approaches targeting cosiblings. KNOWLEDGE TRANSFER STATEMENT: This study revealed significant socioeconomic patterning of caries in adolescent siblings. Prediction modeling indicated that the single most important caries predictor among cosiblings was index sibling caries. Information on sibling caries level should be routinely combined with clinical evaluation to identify children at risk. Moreover, information on social and family conditions should be used to target prevention and health promotion at the school or municipal level. These approaches could possibly contribute to reducing the existing caries inequalities.

Characterisation of footpad lesions in organic and conventional broilers.

Recent data suggest that organic broilers often score worse on footpad lesions than conventional broilers but also that the current scoring of organic broiler feet may be misleading. In order to characterise footpad lesions in organic broilers, this study assessed and compared footpad lesions in a sample of 2987 conventional and 3578 organic broiler feet obtained from a large Danish abattoir during summer and winter. The feet were scored according to two scoring systems: the modified Danish surveillance scoring system and a histopathology-based new scoring system specifically developed to target the ability to differentiate between broiler feet with hyperkeratosis and ulcers. For both systems, all broiler feet with visible lesions were cross-sectionally incised. Significant differences between the two production systems were found for both scoring systems (χ2 = 710; P < 0.001 and χ2 = 247; P < 0.001 for the new and the surveillance systems, respectively), showing that a larger proportion of the organic feet compared to conventional feet - summer and winter - exhibited signs of hyperkeratosis. In addition, a smaller fraction of the organic feet than of the conventional feet were given the outermost scores, that is, normal or ulcerated; 13.4% v. 25.3% broiler feet were given score 0 for organic v. conventional production systems, respectively (χ2 = 152; P < 0.001), and 18.4% v. 23.8% feet were given score 4 for organic v. conventional production systems, respectively (χ2 = 308; P < 0.001). Thus, the results suggest that surveillance scoring systems such as the one used in Denmark are useful for the examination of footpad lesions in broilers from both types of production systems. However, the results have also raised attention to a typical characteristic of the feet of organic broilers, that is, profound hyperkeratosis, which may underlie potential misclassifications in surveillance scoring systems like the one used in Denmark. Among the possible solutions to this challenge to the correctness and fairness of the scoring system are improved procedures (such as mandatory incision), training of technicians and calibration of results (especially for the organic footpads).

Barriers and facilitators for prevention in Danish dental care.

Objective: To explore barriers and facilitators to oral disease prevention in Danish dental care from a multi-stakeholder perspective. Methods: Eleven semi-structured focus groups and interviews about Danish oral healthcare were conducted with 27 stakeholders (general public, dental teams, dental policy makers) in Copenhagen. Transcripts were analyzed using deductive thematic analysis independently by KR and HL, supervised by JC and KVC. Results: Seven broad themes were identified, including both barriers and facilitators: Knowledge and attitudes, Education and training, Regulation, Incentivization, Multidisciplinary approach, Access to care and the Dental professional-patient relationship. Whilst all themes were relevant to each group of stakeholders, the salient driver within each theme was different for each group. Conclusions: Stakeholder perspectives on the Danish Oral health care system suggest the following are important features for a preventively focused system: (a) Involving all stakeholders in oral healthcare planning. (b) Securing sufficient and ongoing briefing regarding disease prevention for all stakeholders. (c) Regulatory support and creation of incentives to promote and facilitate implementation of disease prevention. (d) Appropriate prevention for disadvantaged groups within society which may be possible to a higher degree by means of multidisciplinary collaboration. (e) Personal relations between the patient and the professional based on mutual trust.

A program review of a community-based oral health care program for socially vulnerable and underserved citizens in Denmark.

OBJECTIVES: To describe the oral health and oral health-related quality of life among social vulnerable adults enrolled in a special oral care program, and to evaluate the effect of oral care on their oral health-related quality of life. METHOD: Social workers identified social vulnerable persons in social centres and referred them to the program. Dental clinics were arranged including a well-motivated staff to be special responsive to these clients. The participants, (n = 235, mean age 43.5 years) with drug abuse, being homeless, permanently unemployed, or with mental problems were offered low-cost treatment services. Data collection was made by clinical registration and questionnaires. Oral health-related quality of life was measured by means of the Oral Health Impact Profile-14 index (OHIP-14). RESULTS: 94% of the participants had actual decayed teeth (mean 9.5). Forty-four per cent had not visited a dentist within 5 years and less than one-third reported tooth brushing twice a day, 17% even less frequent. One hundred and forty-six completed the dental program within the program period. Mean OHIP-14 score was 28.6 at baseline. Among those who fulfilled the program, the OHIP-14 score was reduced to 9.9 (p < .001). CONCLUSION: Oral health among the study population was very poor. However, oral problems in this group can be solved, and their oral health-related quality of life can be increased although it requires special arrangements and special clinical environment.

The effect of metformin versus placebo in combination with insulin analogues on bone mineral density and trabecular bone score in patients with type 2 diabetes mellitus: a randomized placebo-controlled trial.

Some antihyperglycemic medications have been found to affect bone metabolism. We assessed the long-term effects of metformin compared with placebo on bone mineral density (BMD) and trabecular bone score (TBS) in patients with type 2 diabetes. Metformin had no significant effect on BMD in the spine and hip or TBS compared with a placebo. INTRODUCTION: Patients with type 2 diabetes mellitus (T2DM) have an increased risk of fractures despite a high bone mass. Some antihyperglycemic medications have been found to affect bone metabolism. We assessed the long-term effects of metformin compared with placebo on bone mineral density (BMD) and trabecular bone score (TBS). METHODS: This was a sub-study of a multicenter, randomized, 18-month placebo-controlled, double-blinded trial with metformin vs. placebo in combination with different insulin regimens (the Copenhagen Insulin and Metformin Therapy trial) in patients with T2DM. BMD in the spine and hip and TBS in the spine were assessed by dual-energy X-ray absorptiometry at baseline and after 18 months follow-up. RESULTS: Four hundred seven patients were included in this sub-study. There were no between-group differences in BMD or TBS. From baseline to 18 months, TBS decreased significantly in both groups (metformin group, - 0.041 [- 0.055, - 0.027]; placebo group - 0.046 [- 0.058, - 0.034]; both p < 0.001). BMD in the spine and total hip did not change significantly from baseline to 18 months. After adjustments for gender, age, vitamin D, smoking, BMI, duration of T2DM, HbA1c, and insulin dose, the TBS between-group differences increased but remained non-significant. HbA1c was negatively associated with TBS (p = 0.009) as was longer duration of diabetes, with the femoral neck BMD (p = 0.003). Body mass index had a positive effect on the hip and femoral neck BMD (p < 0.001, p = 0.045, respectively). CONCLUSIONS: Eighteen months of treatment with metformin had no significant effect on BMD in the spine and hip or TBS in patients with T2DM compared with a placebo. TBS decreased significantly in both groups. TRIAL REGISTRATION: ClinicalTrials.gov (NCT00657943).

Mitochondria, glycogen, and lipid droplets in skeletal muscle during testosterone treatment and strength training: a randomized, double-blinded, placebo-controlled trial.

Low testosterone levels in aging men are associated with insulin resistance. Mitochondrial dysfunction, changes in glycogen metabolism, and lipid accumulation are linked to insulin resistance in skeletal muscle. In this randomized, double-blinded, placebo-controlled study, we investigated the effects of six-month testosterone replacement therapy (TRT) and strength training (ST) on mitochondrial, glycogen, and lipid droplet (LD) content in skeletal muscle of aging men with subnormal bioavailable testosterone (BioT) levels. Mitochondrial, glycogen, and LD volume fractions in muscle biopsies were estimated by transmission electron microscopy. Insulin sensitivity (insulin-stimulated Rd) and body composition were assessed by euglycemic-hyperinsulinemic clamp and dual X-ray absorptiometry, respectively. TRT significantly increased total testosterone levels, BioT, and lean body mass (LBM) (p < 0.05), whereas percent body fat decreased (p < 0.05), and insulin sensitivity was unchanged. Baseline mitochondrial volume fraction correlated inversely with percent body fat (ρ = -0.43; p = 0.003). Δ-mitochondrial fraction correlated positively with Δ-total testosterone (ρ = 0.70; p = 0.02), and Δ-glycogen fraction correlated inversely with Δ-LBM (ρ = -0.83; p = 0.002) during six-month TRT, but no significant changes were observed in mitochondrial, glycogen, and LD volume fractions during TRT and ST. In conclusion, in this exploratory small-scale study, the beneficial effects of six-month TRT on total testosterone, LBM, and percent body fat were not followed by significant changes in fractions of mitochondria, glycogen, or lipid in skeletal muscle of aging men with lowered testosterone levels. Six-month ST or combined three-month ST+TRT did not change intramyocellular mitochondria, glycogen, and LD fractions compared to placebo. However, further studies with a larger sample size are needed.

Genetic predisposition to adiposity is associated with increased objectively assessed sedentary time in young children.

Increased sedentariness has been linked to the growing prevalence of obesity in children, but some longitudinal studies suggest that sedentariness may be a consequence rather than a cause of increased adiposity. We used Mendelian randomization to examine the causal relations between body mass index (BMI) and objectively assessed sedentary time and physical activity in 3-8 year-old children from one Finnish and two Danish cohorts [NTOTAL=679]. A genetic risk score (GRS) comprised of 15 independent genetic variants associated with childhood BMI was used as the instrumental variable to test causal effects of BMI on sedentary time, total physical activity, and moderate-to-vigorous physical activity (MVPA). In fixed effects meta-analyses, the GRS was associated with 0.05 SD/allele increase in sedentary time (P=0.019), but there was no significant association with total physical activity (beta=0.011 SD/allele, P=0.58) or MVPA (beta=0.001 SD/allele, P=0.96), adjusting for age, sex, monitor wear-time and first three genome-wide principal components. In two-stage least squares regression analyses, each genetically instrumented one unit increase in BMI z-score increased sedentary time by 0.47 SD (P=0.072). Childhood BMI may have a causal influence on sedentary time but not on total physical activity or MVPA in young children. Our results provide important insights into the regulation of movement behaviour in childhood.

Sow level risk factors for early piglet mortality and crushing in organic outdoor production.

Piglet mortality is a major problem in organic pig production affecting both farm economy and animal welfare. Knowledge is scarce on the risk factors of piglet mortality in Danish commercial organic pig production. The objectives of this study were to evaluate season, litter size, parity, sow body condition and stillborn littermates as risk factors for early piglet mortality and crushing of liveborn piglets from parturition until castration at day 3 to 5 postpartum (pp). The study was conducted over a 1-year period in nine commercial Danish organic pig herds practicing outdoor farrowing all year round. Data included recordings on 3393 farrowings with 50 284 liveborn piglets of which 14.8% died before castration. A subset of the dead piglets were collected and necropsied to identify crushed piglets. The average number of liveborn piglets per litter was 14.8 (SD=3.7) and the average time from parturition until castration was 4.1 (SD=1.7) days. A negative binomial regression analysis was used to model the effect of the predictive variables on the early piglet mortality accounting for different time periods from parturition to castration. An increase in maternal body condition score (BCS) and parity significantly increased the risk of dying between parturition and castration. Early mortality was found to be lowest during spring (March to May) and highest during summer (June to August). Being born into a litter with one or more stillborn littermates increased the risk of early mortality. The risk factors for crushing of piglets were evaluated using a logistic analysis. A significant effect of parity and litter size was found where the odds of at least one piglet in a litter with mortality was diagnosed as crushed increased with increasing parity and litter size. In conclusion, being born during summer (June to August), high parity and maternal BCS and stillborn littermates were found to be risk factors for piglet mortality between parturition and castration. In addition, parity and increasing litter size were found to be risk factors for crushing of piglets in litters with mortality.

Pregnancy outcome in four women with inflammatory bowel disease treated with budesonide MMX.

BACKGROUND: Maintaining disease remission throughout pregnancy in women with inflammatory bowel disease is of the utmost importance to decrease the risk of adverse outcome. In general, corticosteroids are safe to use during pregnancy, but no data exist in the specific use of budesonide MMX. We report four cases of budesonide MMX in pregnancy and pregnancy outcome. METHODS: Four women with inflammatory bowel disease experienced disease activity during pregnancy. They were treated with budesonide MMX in an attempt to obtain clinical remission. Disease activity was assessed through physician's global assessment as well as lower endoscopy. RESULTS: Budesonide MMX proved effective in achieving remission in three out of four women. One woman had an uncomplicated colectomy in the second trimester. All children were born normal for gestational age, with no congenital abnormalities and have reached all their developmental milestones. The four children have received vaccines according to the national immunization program without complications. CONCLUSION: No adverse pregnancy outcomes were reported after the use of budesonide MMX. To our knowledge, this is the first report on the safety of budesonide MMX treatment in pregnant women with inflammatory bowel disease.

Strong and frequent T-cell responses to the minor allergen Phl p 12 in Spanish patients IgE-sensitized to Profilins.

BACKGROUND: Profilins are dominant pan-allergens known to cause cross-sensitization, leading to clinical symptoms such as pollen-food syndrome. This study aimed to determine the T-cell response to Phl p 12 in profilin-sensitized patients, by measuring the prevalence, strength and cross-reactivity to clinically relevant profilins. METHODS: The release of Phl p allergens from pollen was determined by mass spectrometry and immunochemistry. T-cell responses, epitope mapping and cross-reactivity to profilins (Phl p 12, Ole e 2, Bet v 2 and Mal d 4) were measured in vitro using PBMCs from 26 Spanish grass-allergic donors IgE-sensitized to profilin. Cross-reactivity was addressed in vivo using 2 different mouse strains (BALB/c and C3H). RESULTS: Phl p 12 and Phl p 1 are released from pollen simultaneously and in similar amounts. Both T-cell response frequency (17/26 donors) and strength were comparable between Phl p 12 and Phl p 1. T-cell cross-reactivity to other profilins correlated with overall sequence homology, and 2 immunodominant epitope regions of Phl p 12 were identified. Data from mice immunized with Phl p 12 showed that cross-reactivity to Bet v 2 was mediated by conserved epitopes and further influenced by additional genetic factors, likely to be MHC II. CONCLUSION: The strength, prevalence and cross-reactivity of T-cell responses towards Phl p 12 are comparable to the major allergen Phl p 1, which supports the hypothesis that T cells to Phl p 12 can play an important role in development of allergic symptoms, such as those associated with pollen-food syndrome.

The effect of poly (lactic-co-glycolic) acid composition on the mechanical properties of electrospun fibrous mats.

The aim of this study was to investigate the influence of polymer molecular structure on the electrospinnability and mechanical properties of electrospun fibrous mats (EFMs). Polymers with similar molecular weight but different composition ratios (lactic acid (LA) and glycolic acid (GA)) were dissolved in binary mixtures of N,N-dimethylformamide (DMF) and tetrahydrofuran (THF). The intrinsic viscosity and rheological properties of polymer solutions were investigated prior to electrospinning. The morphology and mechanical properties of the resulting EFMs were characterized by scanning electron microscope (SEM) and dynamic mechanical analysis (DMA). Sufficiently high inter-molecular interactions were found to be a prerequisite to ensure the formation of fibers in the electrospinning process, regardless the polymer composition. The higher the amount of GA in the polymer composition, the more ordered and entangled molecules were formed after electrospinning from the solution in THF-DMF, which resulted in higher Young's modulus and tensile strength of the EFMs. In conclusion, this study shows that the mechanical properties of EFMs, which depend on the polymer molecule-solvent affinity, can be predicted by the inter-molecular interactions in the starting polymer solutions and over the drying process of electrospinning.

Effects of fluid restriction on measures of circulatory efficacy in adults with septic shock.

BACKGROUND: The haemodynamic consequences of fluid resuscitation in septic shock have not been fully elucidated. Therefore, we assessed circulatory effects in the first 24 h of restriction of resuscitation fluid as compared to standard care in intensive care unit (ICU) patients with septic shock. METHODS: This was a post-hoc analysis of the multicentre CLASSIC randomised trial in which patients with septic shock, who had received the initial fluid resuscitation, were randomised to a protocol restricting resuscitation fluid or a standard care protocol in nine ICUs. The highest plasma lactate, highest dose of noradrenaline, and the urinary output were recorded in five time frames in the first 24 h after randomisation. We used multiple linear mixed effects models to compare the two groups. RESULTS: We included all 151 randomised patients; the cumulated fluid resuscitation volume in the first 24 h after randomisation was median 500 ml (Interquartile range (IQR) 0-1500) and 1250 ml (500-2500) in the fluid restriction group and standard care group, respectively. The estimated differences in the fluid restriction group vs. the standard care group were 0.1 mM (95% confidence interval -0.7 to 0.9; P = 0.86) for lactate, 0.01 µg/kg/min (-0.02 to 0.05; P = 0.48) for dose of noradrenaline, and -0.1 ml/kg/h (-0.3 to 0.2; P = 0.70) for urinary output during the first 24 h after randomisation. CONCLUSIONS: We observed no indications of worsening of measures of circulatory efficacy in the first 24 h of restriction of resuscitation fluid as compared with standard care in adults with septic shock who had received initial resuscitation.

Reduction of calprotectin and phosphate during testosterone therapy in aging men: a randomized controlled trial.

OBJECTIVES: To investigate the effect of testosterone treatment on biomarkers calprotectin, fibroblast growth factor 23 (FGF23), soluble Klotho, phosphate, calcium, parathyroid hormone, creatinine and estimated glomerular filtration rate. DESIGN: Randomized, double-blinded, placebo-controlled study. SETTING: Odense Androgen Study-the effect of Testim and training in hypogonadal men. PARTICIPANTS: Men aged 60-78 years old with a low normal concentration of free of bioavailable testosterone <7.3 nmol/L and waist circumference >94 cm recruited from 2008 to 2009 (N = 48) by advertisement. INTERVENTION: Participants were randomized to receive 5-10 g gel/50-100 mg testosterone (Testim®, Ipsen, France) or 5-10 g gel/placebo. RESULTS: The plasma levels of calprotectin and phosphate were significantly reduced in the group receiving testosterone therapy (gel) compared to the placebo group (p < 0.05). Testosterone treatment did not have any significant effect on plasma levels of FGF23 or soluble Klotho. The reduction in phosphate levels was inversely associated with bioavailable testosterone. CONCLUSION: Compared to the placebo group, 6 months of testosterone therapy (gel) reduced calprotectin and phosphate levels suggesting decreased inflammation and decreased cardiovascular risk.

Sow-level risk factors for stillbirth of piglets in organic sow herds.

In Danish organic pig production, one-third of total born piglets die before weaning, and stillbirth has previously crudely been estimated to account for 27% of the total preweaning mortality. The objective of this study was to evaluate season, litter size, parity and body condition of the sow as risk factors for stillbirth in nine commercial Danish organic pig herds. The study was conducted over a 1-year period, and the data included registrations on 5170 farrowings with 82 906 total born piglets. The average number of total born piglets per litter was 16.0, and the number of stillborn piglets per litter was 1.1. A significant effect of season was seen with an odds ratio for stillbirth of 1.15 during summer (May to August) compared with the remaining part of the year. A non-linear effect of litter size was seen where an increase in litter size from 11 to 16 resulted in an odds ratio of stillbirth of 1.11. An increase in litter size from 16 to 21 resulted in an odds ratio of stillbirth of 1.45. A significant interaction between body condition and parity was present. In first parity sows, an increase in body condition score from 2 (thin) to 3 (moderate) and from 3 to 4 (fat) increased the probability of stillbirth with an odds ratio of 1.23 and 1.36, respectively. In sows with parity above 4, an increase in body condition score from 2 to 3 and from 3 to 4 decreases the probability of stillbirth with an odds ratio of 0.68 and 0.79, respectively. In conclusion, increasing litter size and being born during the summer months of May to August were found to be risk factors for stillbirth. Furthermore, an interaction between body condition and parity showed that thin sows with parity above 4 had a substantially increased risk of stillbirth compared with normal and fat sows with parity above 4. In contrast, for parity 1 sows risk of stillbirth was increased in fat sows.