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Background Following resuscitated out-of-hospital cardiac arrest (OHCA), inflammatory markers are significantly elevated and associated with hemodynamic instability and organ dysfunction. Vasopressor support is recommended to maintain a mean arterial pressure (MAP) above 65 mmHg. Glucocorticoids have anti-inflammatory effects and may lower the need for vasopressors. This study aimed to assess the hemodynamic effects of prehospital high-dose glucocorticoid treatment in resuscitated comatose OHCA patients. Methods The STEROHCA trial was a randomized, placebo-controlled, phase 2 trial comparing one prehospital injection of methylprednisolone 250 mg with placebo immediately after resuscitated OHCA. In this sub-study, we included patients who remained comatose at admission and survived until intensive care unit (ICU) admission. The primary outcome was cumulated norepinephrine use from ICU admission until 48 h reported as mcg/kg/min. Secondary outcomes included hemodynamic status characterized by MAP, heart rate, vasoactive-inotropic score (VIS), and the VIS/MAP-ratio as well as cardiac function assessed by pulmonary artery catheter measurements. Linear mixed-model analyses were performed to evaluate mean differences between treatment groups at all follow-up times. Results A total of 114 comatose OHCA patients were included (glucocorticoid: n = 56, placebo: n = 58) in the sub-study. There were no differences in outcomes at ICU admission. From the time of ICU admission up to 48 h post-admission, patients in the glucocorticoid group cumulated a lower norepinephrine use (mean difference − 0.04 mcg/kg/min, 95% CI − 0.07 to − 0.01, p = 0.02). Moreover, after 12–24 h post-admission, the glucocorticoid group demonstrated a higher MAP with mean differences ranging from 6 to 7 mmHg (95% CIs from 1 to 12), a lower VIS (mean differences from − 4.2 to − 3.8, 95% CIs from − 8.1 to 0.3), and a lower VIS/MAP ratio (mean differences from − 0.10 to − 0.07, 95, BACKGROUND: Following resuscitated out-of-hospital cardiac arrest (OHCA), inflammatory markers are significantly elevated and associated with hemodynamic instability and organ dysfunction. Vasopressor support is recommended to maintain a mean arterial pressure (MAP) above 65 mmHg. Glucocorticoids have anti-inflammatory effects and may lower the need for vasopressors. This study aimed to assess the hemodynamic effects of prehospital high-dose glucocorticoid treatment in resuscitated comatose OHCA patients.METHODS: The STEROHCA trial was a randomized, placebo-controlled, phase 2 trial comparing one prehospital injection of methylprednisolone 250 mg with placebo immediately after resuscitated OHCA. In this sub-study, we included patients who remained comatose at admission and survived until intensive care unit (ICU) admission. The primary outcome was cumulated norepinephrine use from ICU admission until 48 h reported as mcg/kg/min. Secondary outcomes included hemodynamic status characterized by MAP, heart rate, vasoactive-inotropic score (VIS), and the VIS/MAP-ratio as well as cardiac function assessed by pulmonary artery catheter measurements. Linear mixed-model analyses were performed to evaluate mean differences between treatment groups at all follow-up times.RESULTS: A total of 114 comatose OHCA patients were included (glucocorticoid: n = 56, placebo: n = 58) in the sub-study. There were no differences in outcomes at ICU admission. From the time of ICU admission up to 48 h post-admission, patients in the glucocorticoid group cumulated a lower norepinephrine use (mean difference - 0.04 mcg/kg/min, 95% CI - 0.07 to - 0.01, p = 0.02). Moreover, after 12-24 h post-admission, the glucocorticoid group demonstrated a higher MAP with mean differences ranging from 6 to 7 mmHg (95% CIs from 1 to 12), a lower VIS (mean differences from - 4.2 to - 3.8, 95% CIs from - 8.1 to 0.3), and a lower VIS/MAP ratio (mean differences from - 0.10 to - 0.07, 95% CIs from

OBJECTIVES: Preclinically, curcumin has been shown to protect against glucocorticoid-induced insulin resistance. We evaluated the effect of curcumin administered with prednisolone in healthy overweight or obese men.METHODS: In a double-blind, parallel-group trial, 24 overweight/obese non-diabetic men were randomised to one of three intervention groups A) prednisolone placebo+curcumin placebo, B) prednisolone (50 mg/day)+curcumin placebo or C) prednisolone and curcumin (400 mg/day). Curcumin or curcumin placebo treatment started one day prior to 10-day prednisolone or prednisolone placebo treatment. The primary endpoint was change in prednisolone-induced insulin resistance assessed by homeostatic model assessment of insulin resistance (HOMA2-IR). Other endpoints included anthropometric measurements, magnetic resonance spectroscopy-assessed hepatic fat content, blood pressure, circulating metabolic markers and continuous glucose monitoring measures.RESULTS: Baseline characteristics (mean ± SD): age 44.2 ± 13.7 years, body mass index 30.1 ± 3.5 kg/m2, glycated haemoglobin A1c 33.3 ± 3.2 mmol/mol, HOMA2-IR 1.10 ± 0.45 and fasting plasma glucose 5.2 ± 0.4 mmol/L. Prednisolone significantly increased HOMA2-IR (estimated treatment difference 0.36 [95% CI 0.16; 0.57]). Co-treatment with curcumin had no effect on HOMA2-IR (estimated treatment difference 0.08 [95% CI -0.13; 0.39]). Prednisolone increased glycated haemoglobin A1c, insulin, C-peptide, glucagon, blood pressure, mean interstitial glucose, time spent in hyperglycaemia and glucose variability, but no protective effect of curcumin on any of these measures was observed.CONCLUSIONS: In this double-blind, placebo-controlled parallel-group study involving 24 overweight or obese men randomised to one of three treatment arms, curcumin treatment had no protective effect on prednisolone-induced insulin resistance or other gluco-metabolic perturbations.

This was an exploratory, prospective, longitudinal, cohort study that aimed to establish “healthy” reference levels related to growth parameters and glucose metabolites in preterm infants. This was conducted to further investigate growth and metabolic disturbances potentially related to neonatal illness. The study sample consisted of 108 preterm infants born before 32 weeks in 2018–2019 in the Capital Region of Denmark. Repetitive blood samples were acquired at the neonatal wards, while clinical data were obtained from the regional hospital medical record system. Thirty-four “healthy” preterm infants (31%) were identified. The “ill” infants were divided into four subgroups dependent on gestational age and small for gestational age. Reference levels for the growth parameters and metabolic biomarkers glucose, albumin, and adiponectin, and two glucose control indicators, glycated albumin and fructosamine, were determined for the “healthy” and “ill” subgroups. The “ill” extremely preterm infants had increased glucose levels (mean difference 0.71 mmol/L, 95% CI 0.23; 1.18 mmol/L) and glycated albumin (corrected; %) (mean difference 0.92 mmol/L, 95% CI 0.38 mmol/L;1.47 mmol/L) compared to the “healthy” infants. In “ill” extremely preterm infants and “ill” very preterm infants born small for gestational age, levels of biomarkers containing proteins were decreased. In the “Ill” extremely preterm infants and infants born small for gestational age, postnatal growth was continuously decreased throughout the postconceptional period. The short-term glucose-control indicator, glycated albumin (corrected; %), reflected well the high glucose levels due to its correction for the depleted plasma-protein pool. Keywords: preterm infants; blood biomarkers; glucose; metabolism; plasma-protein depletion; healthy reference levels, This was an exploratory, prospective, longitudinal, cohort study that aimed to establish “healthy” reference levels related to growth parameters and glucose metabolites in preterm infants. This was conducted to further investigate growth and metabolic disturbances potentially related to neonatal illness. The study sample consisted of 108 preterm infants born before 32 weeks in 2018–2019 in the Capital Region of Denmark. Repetitive blood samples were acquired at the neonatal wards, while clinical data were obtained from the regional hospital medical record system. Thirty-four “healthy” preterm infants (31%) were identified. The “ill” infants were divided into four subgroups dependent on gestational age and small for gestational age. Reference levels for the growth parameters and metabolic biomarkers glucose, albumin, and adiponectin, and two glucose control indicators, glycated albumin and fructosamine, were determined for the “healthy” and “ill” subgroups. The “ill” extremely preterm infants had increased glucose levels (mean difference 0.71 mmol/L, 95% CI 0.23; 1.18 mmol/L) and glycated albumin (corrected; %) (mean difference 0.92 mmol/L, 95% CI 0.38 mmol/L;1.47 mmol/L) compared to the “healthy” infants. In “ill” extremely preterm infants and “ill” very preterm infants born small for gestational age, levels of biomarkers containing proteins were decreased. In the “Ill” extremely preterm infants and infants born small for gestational age, postnatal growth was continuously decreased throughout the postconceptional period. The short-term glucose-control indicator, glycated albumin (corrected; %), reflected well the high glucose levels due to its correction for the depleted plasma-protein pool.

Aim: To investigate the impact of hypoglycaemia, hyperglycaemia and glycaemic variability on arrhythmia susceptibility in people with type 1 diabetes. Materials and Methods: Thirty adults with type 1 diabetes were included in a 12-month observational exploratory study. Daytime and night-time incident rate ratios (IRRs) of arrhythmias were determined for hypoglycaemia (interstitial glucose [IG] <3.9 mmol/L), hyperglycaemia (IG >10.0 mmol/L) and glycaemic variability (standard deviation and coefficient of variation). Results: Hypoglycaemia was not associated with an increased risk of arrhythmias compared with euglycaemia and hyperglycaemia combined (IG ≥ 3.9 mmol/L). However, during daytime, a trend of increased risk of arrhythmias was observed when comparing time spent in hypoglycaemia with euglycaemia (IRR 1.08 [95% CI: 0.99-1.18] per 5 minutes). Furthermore, during daytime, both the occurrence and time spent in hyperglycaemia were associated with an increased risk of arrhythmias compared with euglycaemia (IRR 2.03 [95% CI: 1.21-3.40] and IRR 1.07 [95% CI: 1.02-1.13] per 5 minutes, respectively). Night-time hypoglycaemia and hyperglycaemia were not associated with the risk of arrhythmias. Increased glycaemic variability was not associated with an increased risk of arrhythmias during daytime, whereas a reduced risk was observed during night-time. Conclusions: Acute hypoglycaemia and hyperglycaemia during daytime may increase the risk of arrhythmias in individuals with type 1 diabetes. However, no such associations were found during night-time, indicating diurnal differences in arrhythmia susceptibility.

Introduction Due to reports of severely reduced insulinotropic effect of the incretin hormone glucose-dependent insulinotropic polypeptide (GIP) in type 2 diabetes (T2D), GIP has not been considered therapeutically viable. Recently, however, tirzepatide, a novel dual incretin receptor agonist (activating the GIP receptor and the glucagon-like peptide 1 (GLP-1) receptor) has demonstrated greater glucose and body weight-lowering properties as compared to GLP-1 receptor agonist therapy. The contribution of GIP receptor activation to effects of tirzepatide remains unknown. We will evaluate the glucose-lowering effect of exogenous GIP in the context of pharmacological GLP-1 receptor activation in patients with T2D. Methods and analysis In this randomised, double-blind, four-arm parallel, placebo-controlled trial, 60 patients with T2D will be included (18-74 of age; on diet and exercise and/or metformin therapy only; glycated haemoglobin 6.5-10.5% (48-91 mmol/mol)). Participants will be randomised to an 8-week run-in period with subcutaneous (s.c.) placebo or semaglutide injections once-weekly (0.5 mg). Participants will then be randomised to 6 weeks' add-on treatment with continuous s.c. placebo or GIP infusion (16 pmol/kg/min). The primary endpoint is change in mean glucose levels (assessed by 14-day continuous glucose monitoring) from the end of the run-in period to end of trial. Ethics and dissemination The present study was approved by the Regional Committee on Health Research Ethics in the Capitol Region of Denmark (identification no. H-20070184) and by the Danish Medicines Agency (EudraCT no. 2020-004774-22). All results, positive, negative and inconclusive, will be disseminated at national and/or international scientific meetings and in peer-reviewed scientific journals.

Objective Ectopic accumulation of cardiac adipose tissue volume (CAT) has been associated with cardiac remodelling and cardiac dysfunction in type 2 diabetes and may be a future therapeutic target. In this substudy from the SIMPLE-trial, we investigated short-term empagliflozin therapy's effects on CAT in patients with type 2 diabetes. Research design and Methods Between 4 April 2017 and 11 May 2020, we randomized 90 patients with type 2 diabetes and established or high risk of cardiovascular disease to 25 mg empagliflozin or placebo for 13 weeks. The substudy focused on change in CAT evaluated by images acquired during 82Rubidium-positron emissions tomography/computed tomography. The analysis included 78 patients who had at least one scan. Furthermore, we report on the relation to the concurrent effects on left ventricular mass, end-diastolic volume and end-systolic volume, body composition and glucometabolic status. Results Mean ± SD baseline CAT was 258.5 ± 117.9 ml. Empagliflozin reduced CAT after 13 weeks by 12.41 ml [95% CI (−23.83 to −0.99), p = .034] as compared with placebo. Similarly, left ventricular mass [−5.16 g, 95% CI (−8.80 to −1.52), p = .006], end-diastolic volume and end-systolic volume decreased with empagliflozin. In addition, significant improvements were observed in body composition, with reduced total fat mass, and in measures of glucose and lipid metabolism. However, no correlation was observed between changes in CAT and changes in cardiac parameters and change in CAT appeared mediated primarily by concurrent change in weight. Conclusions Empagliflozin provides an early reduction of CAT; however, no association was observed with concurrent changes in cardiac volumetrics, Objective: Ectopic accumulation of cardiac adipose tissue volume (CAT) has been associated with cardiac remodelling and cardiac dysfunction in type 2 diabetes and may be a future therapeutic target. In this substudy from the SIMPLE-trial, we investigated short-term empagliflozin therapy's effects on CAT in patients with type 2 diabetes.Research design and Methods: Between 4 April 2017 and 11 May 2020, we randomized 90 patients with type 2 diabetes and established or high risk of cardiovascular disease to 25 mg empagliflozin or placebo for 13 weeks. The substudy focused on change in CAT evaluated by images acquired during (82)Rubidium-positron emissions tomography/computed tomography. The analysis included 78 patients who had at least one scan. Furthermore, we report on the relation to the concurrent effects on left ventricular mass, end-diastolic volume and end-systolic volume, body composition and glucometabolic status.Results: Mean +/- SD baseline CAT was 258.5 +/- 117.9 ml. Empagliflozin reduced CAT after 13 weeks by 12.41 ml [95% CI (-23.83 to -0.99), p = .034] as compared with placebo. Similarly, left ventricular mass [-5.16 g, 95% CI (-8.80 to -1.52), p = .006], end-diastolic volume and end-systolic volume decreased with empagliflozin. In addition, significant improvements were observed in body composition, with reduced total fat mass, and in measures of glucose and lipid metabolism. However, no correlation was observed between changes in CAT and changes in cardiac parameters and change in CAT appeared mediated primarily by concurrent change in weight.Conclusions: Empagliflozin provides an early reduction of CAT; however, no association was observed with concurrent changes in cardiac volumetrics.

Aim: We investigated the effect of 52-week treatment with liraglutide, a glucagon-like peptide 1 receptor agonist, on glucose tolerance and incretin effect in women with previous gestational diabetes mellitus (pGDM). Materials and Methods: Women with overweight/obesity and pGDM were randomized to once daily subcutaneous liraglutide 1.8 mg or placebo for 52 weeks. Participants underwent oral glucose tolerance test (OGTT) and isoglycaemic intravenous glucose infusion at baseline and at 52 weeks, and an additional OGTT after the drug wash-out. Results: In total, 104 women [age: mean ± SD, 38 ± 5 years; fasting plasma glucose (FPG): 5.5 ± 0.4 mmol/L; glycated haemoglobin (HbA1c): 33 ± 4 mmol/mol, bodyweight: 88.2 ± 14.8 kg, body mass index: 31.1 ± 4.3 kg/m2] were assigned to liraglutide (n = 49) or placebo (n = 55). Estimated treatment difference (ETD) for area under curve during OGTT was −173 (95% confidence interval −250 to −97) mmol/L × min, p <.0001, but after wash-out the difference disappeared [ETD 58 (−30 to 146) mmol/L × min, p =.536]. Liraglutide reduced FPG [ETD −0.2 (−0.4 to −0.1) mmol/L, p =.018], HbA1c [−2.2 (−3.5 to −0.8) mmol/mol, p =.018] and bodyweight [−3.9 (−6.2 to −1.6) kg, p =.012]. No change in the incretin effect was observed. The number of women with prediabetes was reduced from 64% to 10% with liraglutide vs. 50% with placebo [adjusted odds ratio 0.10 (0.03-0.32), p =.002]. Conclusions: Treatment with liraglutide for 52 weeks improved glucose tolerance, FPG, HbA1c and bodyweight in women with overweight/obesity and pGDM. Progression to prediabetes while on drug was markedly reduced, but after a 1-week drug wash-out, the effect was lost.

Context The hormone secretin (SCT) is released from intestinal S cells and acts via the SCT receptor (SCTR). Circulating SCT levels increase after Roux-en-Y gastric bypass surgery and have been associated with massive weight loss and high remission rates of type 2 diabetes (T2D) linked to these operations. Exogenous SCT was recently shown to reduce ad libitum food intake in healthy volunteers. Objective To understand SCT biology and its potential role in T2D pathophysiology, we examined the intestinal mucosal expression profile of SCT and SCTR and evaluated the density of S cells along the intestinal tract of individuals with T2D and healthy controls. Methods Using immunohistochemistry and messenger RNA (mRNA) sequencing, we analyzed intestinal mucosa biopsies sampled along the small intestine at 30-cm intervals and from 7 well-defined anatomical sites along the large intestine (during 2 sessions of double-balloon enteroscopy) in 12 individuals with T2D and 12 healthy controls. Results Both groups exhibited a progressive and similar decrease in SCT and SCTR mRNA expression and S-cell density along the small intestine, with reductions of 14, 100, and 50 times, respectively, in the ileum compared to the duodenum (used as reference). Negligible amounts of SCTR and SCT mRNA, as well as low S-cell density, were found in the large intestine. No significant differences were observed between the groups. Conclusion SCT and SCTR mRNA expression and S-cell density were abundant in the duodenum and decreased along the small intestine. Very low SCT and SCTR mRNA levels and S-cell numbers were observed in the large intestine, without aberrations in individuals with T2D compared to healthy controls., BACKGROUND: The hormone secretin (SCT) is released from intestinal S cells and acts via the SCT receptor (SCTR). Circulating SCT levels increase after Roux-en-Y gastric bypass surgery and have been associated with the massive weight loss and the high remission rates of type 2 diabetes (T2D) linked to these operations. Exogenous SCT was recently shown to reduce ad libitum food intake in healthy volunteers. To understand SCT biology and its potential role in T2D pathophysiology, we examined the intestinal mucosal expression profile of SCT and SCTR and evaluated the density of S cells along the intestinal tract of individuals with T2D and healthy controls.METHODS: Using immunohistochemistry and mRNA sequencing, we analyzed intestinal mucosa biopsies sampled along the small intestine at 30 cm intervals and from seven well-defined anatomical sites along the large intestine (during two sessions of double-balloon enteroscopy) in 12 individuals with T2D and 12 healthy controls.RESULTS: Both groups exhibited a progressive and similar decrease in SCT and SCTR mRNA expression and S cell density along the small intestine, with reductions of 14, 100, and 50 times, respectively, in the ileum compared to the duodenum (used as reference). Negligible amounts of SCTR and SCT mRNA, as well as a low S cell density, were found in the large intestine. No significant differences were observed between the groups.CONCLUSIONS: SCT and SCTR mRNA expression and S cell density were abundant in the duodenum and decreased along the small intestine. Very low SCT and SCTR mRNA levels and S cell numbers were observed in the large intestine; without aberrations in individuals with T2D compared to healthy controls.

Context Enteroendocrine N cells secrete neurotensin (NTS). NTS reduces food intake in rodents and may increase insulin release. In humans, postprandial NTS responses increase following Roux-en-Y gastric bypass, associating the hormone with the glucose- and body weight-lowering effects of these procedures. Objective We looked at N cell density and mucosal messenger RNA (mRNA) expression profiles of NTS and NTS receptors in type 2 diabetes (T2D) patients and healthy controls. Methods Using double-balloon enteroscopy, 12 patients with T2D and 12 sex-, age-, and body mass index–matched healthy controls had mucosa biopsies taken from the entire length of the small intestine (at 30-cm intervals) and from 7 anatomically well-defined locations in the large intestine. Biopsies were analyzed using immunohistochemistry and mRNA sequencing. Results N cell density and NTS mRNA expression gradually increased from the duodenum to the ileum, while negligible NTS-positive cells and NTS mRNA expression were observed in the large intestine. NTS receptor 1 and 2 mRNA expression were not detected, but sortilin, a single-pass transmembrane neuropeptide receptor of which NTS also is a ligand, was uniformly expressed in the intestines. Patients with T2D exhibited lower levels of NTS-positive cells and mRNA expression than healthy controls, but this was not statistically significant after adjusting for multiple testing. Conclusion This unique intestinal mapping of N cell density and NTS expression shows increasing levels from the small intestine's proximal to distal end (without differences between patients with T2D and healthy controls), while negligible N-cells and NTS mRNA expression were observed in the large intestine. Sortilin was expressed throughout the intestines in both groups; no NTS receptor 1 or 2 mRNA expression were detected., Context Enteroendocrine N cells secrete neurotensin (NTS). NTS reduces food intake in rodents and may increase insulin release. In humans, postprandial NTS responses increase following Roux-en-Y gastric bypass, associating the hormone with the glucose- and body weight-lowering effects of these procedures. Objective We looked at N cell density and mucosal messenger RNA (mRNA) expression profiles of NTS and NTS receptors in type 2 diabetes (T2D) patients and healthy controls. Methods Using double-balloon enteroscopy, 12 patients with T2D and 12 sex-, age-, and body mass index-matched healthy controls had mucosa biopsies taken from the entire length of the small intestine (at 30-cm intervals) and from 7 anatomically well-defined locations in the large intestine. Biopsies were analyzed using immunohistochemistry and mRNA sequencing. Results N cell density and NTS mRNA expression gradually increased from the duodenum to the ileum, while negligible NTS-positive cells and NTS mRNA expression were observed in the large intestine. NTS receptor 1 and 2 mRNA expression were not detected, but sortilin, a single-pass transmembrane neuropeptide receptor of which NTS also is a ligand, was uniformly expressed in the intestines. Patients with T2D exhibited lower levels of NTS-positive cells and mRNA expression than healthy controls, but this was not statistically significant after adjusting for multiple testing. Conclusion This unique intestinal mapping of N cell density and NTS expression shows increasing levels from the small intestine's proximal to distal end (without differences between patients with T2D and healthy controls), while negligible N-cells and NTS mRNA expression were observed in the large intestine. Sortilin was expressed throughout the intestines in both groups; no NTS receptor 1 or 2 mRNA expression were detected.

Objective: Gastrointestinal-mediated glucose disposal (GIGD) during oral glucose tolerance test (OGTT) reflects the percentage of glucose disposal caused by mechanisms elicited by the oral route of glucose administration. GIGD is reduced in patients with type 2 diabetes (T2D) due to a reduced incretin effect and possibly also due to inappropriate suppression of glucagon after oral glucose. We investigated the effect of glucagon receptor antagonism on GIGD, the incretin effect and glucose excursions in patients with T2D and controls without diabetes. Design: A double-blind, randomised, placebo-controlled crossover study was conducted. Methods: Ten patients with T2D and 10 gender-, age- and BMI-matched controls underwent two 50 g OGTTs and 2 isoglycaemic i.v. glucose infusions, succeeding (~10 h) single-dose administration of 100 mg of the glucagon receptor antagonist LY2409021 or placebo, respectively. Results: Compared to placebo, LY2409021 reduced fasting plasma glucose in patients with T2D and controls. Plasma glucose excursions after oral glucose assessed by baseline-subtracted area under the curve were increased by LY2409021 compared to placebo in both groups, but no effect of LY2409021 on GIGD or the incretin effect was observed. LY2409021 increased fasting glucagon concentrations three-fold compared to placebo concentrations. Conclusions: Glucagon receptor antagonism with LY2409021 had no effect on the impaired GIGD or the impaired incretin effect in patients with T2D and did also not affect these parameters in the controls. Surprisingly, we observed reduced oral glucose tolerance with LY2409021 which may be specific for this glucagon receptor antagonist.

Background: Research in plastic surgery often includes bilateral procedures. This gives rise to issues with clustered data. Clustering is when individual data points within a data set are internally related. However, many authors do not account for clustering within their data, which can lead to incorrect statistical conclusions. Methods: In February of 2020, the authors searched PubMed to investigate the prevalence of reporting issues with bilateral breast procedures in plastic surgery literature. The review focused on breast surgery, as it often involves bilateral procedures and, therefore, clustering. Based on the review, the authors developed guidelines for how to identify and address clustered data. The guidelines were modified by a multidisciplinary group consisting of a biostatistician with expertise in clustered data at the Section of Biostatistics, University of Copenhagen, and three doctors (M.D.s and Ph.D.s) with expertise in statistical analysis and scientific methodology from the Copenhagen University Hospital, Rigshospitalet. Results: A total of 113 studies were included in the review. Seventy-five studies (66 percent) contained clustered data, but only eight studies (11 percent) took clustering into account in the statistical analysis. These results were used to develop the Clustered Data, or CLUDA, reporting guidelines which consist of two sections: one to identify clustering and one for reporting and analyzing clustered data. Conclusions: Clustered data are abundant in plastic surgery literature. The authors propose using the Clustered Data reporting guidelines to identify and report clustered data and consulting with a biostatistician when designing a study.

Background and Objectives: Image-guided quantitative and semi-quantitative assessment of skin can potentially evaluate treatment efficacy. Optical coherence tomography (OCT) and reflectance confocal microscopy (RCM) are ideal for this purpose. This study assessed clinically relevant statistical changes in RCM and OCT features in photoaged skin after light and energy-based therapy. Methods: Novel statistical analyses were performed using OCT and RCM data collected during a previously published trial: a 12-week study of female decollete skin randomized to four areas treated with thulium laser (L), photodynamic therapy (PDT), combined L-PDT, and control. Eight semi-quantitative RCM scores of photodamage and OCT measurements of skin roughness, blood flow, and epidermal thickness (ET) were evaluated and compared to dermoscopy and clinical skin scores. In statistical analysis, estimated treatment difference (ETD) was calculated. Results: Twelve women with moderate to severe photodamage were included. RCM and OCT data demonstrated a trend towards rejuvenation of epidermis with increased ET, changes in skin surface, and improved honeycomb pattern in RCM. In angiographic OCT, non-significant changes towards more regular capillary meshes were shown, which matched a decline in appearance of gross telangiectasias in dermoscopy. Improved skin tone after laser and L-PDT was identified in RCM, showing less edged papillae in 36% and 45%, and lentigo number declined in 55% of patients after treatments in dermoscopy. Based on clinical scores, L-PDT provided the greatest clinical improvement, which corresponded to superior ETD outcomes in ET and edged papillae shown in OCT and RCM, respectively. Conclusion: Objective OCT and RCM assessment of skin rejuvenation was demonstrated in this study. Importantly, image-based improvements corresponded to favorable clinical skin scores and fewer photoaging characteristics in dermoscopy. Importantly, most changes did not reach statistical sign

PURPOSE: To investigate if a combination of topical nonsteroid anti-inflammatory drugs (NSAIDs) and steroids were superior in controlling early postoperative inflammation after cataract surgery compared with topical NSAIDs alone and with dropless surgery where a subtenon depot of steroid was placed during surgery.SETTING: Department of Ophthalmology, Rigshospitalet-Glostrup, Denmark.DESIGN: Prospective randomized controlled trial with masked statistical analyses.METHODS: Patients undergoing phacoemulsification for age-related cataract were randomized to 1 of 5 regimens: ketorolac and prednisolone eyedrops combined (groups Pred+NSAID-Pre [control group] and Pred+NSAID-Post) vs ketorolac monotherapy (groups NSAID-Pre and NSAID-Post) vs subtenon depot of dexamethasone (Dropless group). Drops were used until 3 weeks postoperatively, starting 3 days before surgery in the "Pre" groups and on the day of surgery in the "Post" groups. Aqueous flare was measured at baseline and 3 days postoperatively.RESULTS: 456 participants, mean age 72.1 (SD 7.0) years, 283 (62%) females, were included. Flare increased significantly more in the Dropless group compared with control (Pred+NSAID-Pre), but none of the other groups differed significantly from the control. Intraocular pressure decreased in all groups but significantly less in groups receiving prednisolone eyedrops (Pred+NSAID-Pre and Pred+NSAID-Post) compared with NSAID monotherapy and Drop-less. No differences in postoperative visual acuity were found compared with control.CONCLUSIONS: No differences were found between groups randomized to NSAID monotherapy or combination of NSAID and steroid in controlling early inflammation after cataract surgery but subtenon depot of dexamethasone was less efficient. Initiating prophylactic eyedrops prior to surgery did not influence early postoperative anterior chamber inflammation.