Autofluorescence-guided hemithyroidectomy in a low-volume thyroid institution with no experience in parathyroid surgery: randomized clinical trial.

BACKGROUND: Recent studies suggest that low-volume surgeons with no experience in parathyroid surgery are at increased risk of causing parathyroid gland damage during thyroid surgery. The aim of this RCT was to evaluate the impact of using autofluorescence in hemithyroidectomy on parathyroid gland identification and preservation in a low-volume institution with no experience in parathyroid surgery. METHODS: Patients referred for hemithyroidectomy were randomized 1 : 1 to either autofluorescence-guided hemithyroidectomy (the near-infrared autofluorescence group) or conventional hemithyroidectomy (the control group). The primary outcome was parathyroid gland identification rate. Secondary outcomes were the rate of parathyroid gland autotransplantation and the rate of inadvertent parathyroid gland excision. RESULTS: A total of 170 patients were randomized to either autofluorescence-guided hemithyroidectomy (84 patients) or conventional hemithyroidectomy (86 patients). In the near-infrared autofluorescence group, 81.0% of parathyroid glands were identified, compared with 57.0% in the control group (P < 0.001). Autofluorescence enabled parathyroid gland visualization before the naked eye in 46.3% of cases. Surgeons had lower confidence in the parathyroid gland identification process in the control group than in the near-infrared autofluorescence group (59.1% versus 87.5% respectively; P < 0.001). In the near-infrared autofluorescence group, the parathyroid gland autotransplantation rate was initially high, but declined over time. There was no difference in the rate of inadvertent parathyroid gland excision. CONCLUSION: Autofluorescence guidance significantly improved the parathyroid gland identification rate in hemithyroidectomy in a low-volume institution with no experience in parathyroid surgery and provided an increase in surgical confidence. The pattern of parathyroid gland autotransplantation in autofluorescence-guided surgery indicates the presence of a learning curve. REGISTRATION NUMBER: NCT05044351 (http://www.clinicaltrials.gov).

Damage to the parathyroid glands is common during thyroid surgery. The main reason for that is that they can be difficult to see during surgery. The aim of this study was to see if the use of a new near-infrared camera during thyroid surgery could make it easier to see the parathyroid glands. Patients, where removal of part of their thyroid gland was planned, were randomly assigned to one of two groups. In the first group, the near-infrared camera was used, whereas it was not used in the other group. When the near-infrared camera was used, more parathyroid glands were found and the surgeons felt more secure in their handling of parathyroid glands.

Metabolic Sequelae and All-Cause Mortality in Chronic Pancreatitis With and Without Prior Acute Pancreatitis: A Nationwide Population-Based Cohort Study.

OBJECTIVES: To investigate the risk of metabolic sequelae and all-cause mortality in a population-based cohort of chronic pancreatitis (CP) patients with and without prior acute pancreatitis (AP). METHODS: We used nationwide health registries to identify all Danish residents (>18 years) with incident CP from 2000-2018. Information on AP/CP diagnoses, metabolic sequelae (post-pancreatitis diabetes mellitus (PPDM), exocrine pancreatic dysfunction (EPD), and osteoporosis), and all-cause mortality were obtained from Danish national health registries. CP cases were stratified based on the presence of AP prior to CP diagnosis. The risk of metabolic sequelae and all-cause mortality was expressed as hazard ratios (HRs) with 95% confidence intervals (CIs), calculated using multivariate Cox proportional hazards models. RESULTS: A total of 9655 CP patients were included. Among CP patients, 3913 (40.5%) had a prior AP diagnosis. Compared to patients without a history of AP, patients with prior AP had a decreased risk of death (HR 0.79 (95% CI, 0.74-0.84)), which was largely confined to the initial period after CP diagnosis. Patients with prior AP had an increased risk of PPDM (HR 1.53 (95% CI, 1.38-1.69)), which persisted for up to a decade after CP diagnosis. No overall differences in risk were observed for EPD (HR 0.97 (95% CI, 0.87-1.07)) and osteoporosis (HR 0.87 (95% CI, 0.74-1.02)). CONCLUSIONS: This nationwide study revealed that the majority of CP patients have no prior episode(s) of AP, indicating that an attack of AP sensitizing the pancreas is not essential for CP development. CP patients with and without prior AP have different risk profiles of PPDM and all-cause mortality.

Adherence to newer second-line oral antidiabetic drugs among people with type 2 diabetes-A systematic review.

The adherence to oral antidiabetic drugs (OADs) among people with type 2 diabetes (T2D) is suboptimal. However, new OADs have been marketed within the last 10 years. As these new drugs differ in mechanism of action, treatment complexity, and side effects, they may influence adherence. Thus, the aim of this study was to assess the adherence to newer second-line OADs, defined as drugs marketed in 2012-2022, among people with T2D. A systematic review was performed in CINAHL, Cochrane Trials, Embase, PubMed, PsycINFO, and Scopus. Articles were included if they were original research of adherence to newer second-line OADs and reported objective adherence quantification. The quality of the articles was assessed using JBI's critical appraisal tools. The overall findings were reported according to the preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidelines and summarized in a narrative synthesis. All seven included articles were European retrospective cohort studies investigating alogliptin, canagliflozin, dapagliflozin, empagliflozin, and unspecified types of SGLT2i. Treatment discontinuation and medication possession ratio (MPR) were the most frequently reported adherence quantification measures. Within the first 12 months of treatment, 29%-44% of subjects on SGLT2i discontinued the treatment. In terms of MPR, 61.7%-94.9% of subjects on either alogliptin, canagliflozin, dapagliflozin, empagliflozin or an unspecified SGLT2i were adherent. The two investigated adherence quantification measures, treatment discontinuation and MPR, suggest that adherence to the newer second-line OADs may be better than that of older OADs. However, a study directly comparing older and newer OADs should be done to verify this.

Serum osteoglycin is stable during various glycemic challenges in healthy men.

PURPOSE: Osteoglycin is hypothesized to be metabolically active and may enhance insulin action. We hypothesized that osteoglycin levels increase during hyperglycemia as a physiological response to enhance the effects of insulin. METHODS: Eight healthy males were included in a cross-over study consisting of three study days following an 8 h fast. First, we performed an oral glucose tolerance test (OGTT); second, an isoglycemic intravenous glucose infusion (IIGI); and third, a control period consisting of a three hour fast. We analyzed blood samples for circulating osteoglycin levels during the study days. Repeated measures ANOVA was performed to compare levels of s-osteoglycin between OGTT, IIGI, and the fasting control. RESULTS: There were no differences in baseline osteoglycin levels among study days (p > 0.05). We observed no significant changes neither in absolute s-osteoglycin levels by time (p = 0.14) nor over time by study day (p = 0.99). Likewise, we observed no significant changes in percentage s-osteoglycin levels neither by time (p = 0.11) nor over time by study day (p = 0.89). CONCLUSION: We found that s-osteoglycin levels were stable for three hours during OGTT, IIGI, and fasting in healthy males. Based on the present study, circulating s-osteoglycin levels may be measured independently of fasting or non-fasting conditions. Furthermore, circulating physiological levels of glucose and insulin did not affect s-osteoglycin levels.

Low-grade inflammation in persons with recently diagnosed type 2 diabetes: The role of abdominal adiposity and putative mediators.

AIMS: To determine the magnitude of the association between abdominal adiposity and low-grade inflammation in persons with recently diagnosed type 2 diabetes (T2D) and to determine to what extent this association is mediated by low physical activity level, hyperinsulinaemia, hyperglycaemia, dyslipidaemia, hypertension, and comorbidities. MATERIALS AND METHODS: We measured waist circumference, clinical characteristics, and inflammatory markers i.e. tumour necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and high-sensitivity C-reactive protein (hsCRP), in >9000 persons with recently diagnosed T2D. We applied multiple mediation analysis using structural equation modelling, with adjustment for age and sex. RESULTS: Waist circumference as a proxy for abdominal adiposity was positively associated with all inflammatory markers. Hence, a one-standard deviation (SD) increase in waist circumference (SD = 15 cm) was associated with a 22%, 35%, and 46% SD increase in TNF-α (SD = 1.5 pg/mL), IL-6 (SD = 4.4 pg/mL), and hsCRP (SD = 6.9 mg/L), respectively. The level of hyperinsulinaemia assessed by fasting C-peptide was quantitatively the most important mediator, accounting for 9%-25% of the association between abdominal adiposity and low-grade inflammation, followed by low physical activity (5%-7%) and high triglyceride levels (2%-6%). Although mediation of adiposity-induced inflammation by greater comorbidity and higher glycated haemoglobin levels reached statistical significance, their impact was minor (1%-2%). CONCLUSIONS: In persons with recently diagnosed T2D, there was a clear association between abdominal adiposity and low-grade inflammation. A considerable part (20%-40%) of this association was mediated by other factors, with hyperinsulinaemia as a potentially important driver of adiposity-induced inflammation in T2D.

Hypoparathyroidism following total thyroidectomy: high rates at a low-volume, non-parathyroid institution.

Background: Hypoparathyroidism following total thyroidectomy is globally the most common complication to thyroid surgery. The reported complication rates vary widely and might be highly dependent on the surgical experience. In this study we aimed to evaluate the rate of hypoparathyroidism following primary total thyroidectomy at a low-volume institution that only performs thyroid surgery and does not have any experience with parathyroid surgery. Methods: Retrospective cohort study. All patients undergoing primary total thyroidectomy at the ENT-Department, Goedstrup Hospital, Denmark, over a 5-year period (2016-2020) were identified through the procedure codes for total thyroidectomy. Medical records, pathology reports, biochemical and medical histories were fully assessed for each patient. The primary endpoint was the rate of hypoparathyroidism- both immediate and permanent. Secondary outcomes were parathyroid gland identification rates, rates of parathyroid gland autotransplantation, and rates of inadvertent parathyroid gland excision. Results: A total of 89 patients were included in the final analysis. A total of 33 patients (37.1%) experienced immediate hypoparathyroidism following surgery, while 30 patients (33.7%) still were on active vitamin D two months postoperatively. One year following surgery, 28 patients (31.5%) were still on active vitamin D and were considered as having permanent hypoparathyroidism. Sixty-one percent of the parathyroid glands were identified intraoperatively, and 19% of the patients experienced parathyroid autotransplantation. Inadvertent parathyroid gland excision occurred for 21% of the patients and was associated with a significantly increased risk of permanent hypoparathyroidism (RR = 2.99; 95% CI: 1.36 - 6.62, p = 0.005). Conclusion: Both transient and permanent hypoparathyroidism following total thyroidectomy at a low-volume, non-parathyroid institution occurred with much higher frequencies than previously reported. The elevated rates were most likely due to the low-volume, non-parathyroid nature of the surgeons which in part was mirrored in low parathyroid gland identifications rates, and high rates of autotransplantation and inadvertent parathyroid gland excision.

Association between Glucose-lowering Treatments and Risk of Diabetic Retinopathy in People with Type 2 Diabetes: A Nationwide Cohort Study.

INTRODUCTION: Glycaemic variability is possibly linked to the development of diabetic retinopathy, and newer second-line glucose-lowering treatments in type 2 diabetes might reduce glycaemic variability. AIM: This study aimed to investigate whether newer second-line glucose-lowering treatments are associated with an alternative risk of developing diabetic retinopathy in people with type 2 diabetes. METHODS: A nationwide cohort of people with type 2 diabetes on second-line glucose-lowering treatment regimens in 2008-2018 was extracted from the Danish National Patient Registry. Adjusted time to diabetic retinopathy was estimated with a Cox Proportional Hazards model. The model was adjusted for age, sex, diabetes duration, alcohol abuse, treatment start year, education, income, history of late-diabetic complications, history of non-fatal major adverse cardiovascular events, history of chronic kidney disease, and history of hypoglycaemic episodes. RESULTS: Treatment regimens of metformin + basal insulin (HR: 3.15, 95% CI: 2.42-4.10) and metformin + glucagon-like peptide-1 receptor agonist (GLP-1-RA, HR: 1.46, 95% CI: 1.09-1.96) were associated with an increased risk of diabetic retinopathy compared with metformin + dipeptidyl peptidase-4 inhibitors (DPP-4i). Treatment with metformin + sodium-glucose cotransporter-2 inhibitor (SGLT2i, HR: 0.77, 95% CI: 0.28-2.11) was associated with the numerically lowest risk of diabetic retinopathy compared with all regimens investigated. CONCLUSION: Findings from this study indicate that basal insulin and GLP-1-RA are suboptimal second- line choices for people with type 2 diabetes at risk of developing diabetic retinopathy. However, many other considerations concerning the choice of second-line glucose-lowering treatment for type 2 diabetes patients should be taken into account.

Fracture patterns in adult onset type 1 diabetes and associated risk factors - A nationwide cohort study.

OBJECTIVE: This study aimed to determine the hazard ratios (HR) for various fracture sites and identify associated risk factors in a cohort of relatively healthy adult people with newly diagnosed type 1 diabetes (T1D). METHODS: The study utilized data from the UK Clinical Practice Research Datalink GOLD (1987-2017). Participants included people aged 20 and above with a T1D diagnosis code (n = 3281) and a new prescription for insulin. Controls without diabetes were matched based on sex, year of birth, and practice. Cox regression analysis was conducted to estimate HRs for any fracture, major osteoporotic fractures (MOFs), and peripheral fractures (lower-arm and lower-leg) in people with T1D compared to controls. Risk factors for T1D were examined and included sex, age, diabetic complications, medication usage, Charlson comorbidity index (CCI), hypoglycemia, previous fractures, falls, and alcohol consumption. Furthermore, T1D was stratified by duration of disease and presence of microvascular complications. RESULTS: The proportion of any fracture was higher in T1D (10.8 %) than controls (7.3). Fully adjusted HRs for any fracture (HR: 1.43, CI95%: 1.17-1.74), MOFs (HR: 1.46, CI95%: 1.04-2.05), and lower-leg fractures (HR: 1.37, CI95%: 1.01-1.85) were statistically significantly increased in people with T1D compared to controls. The primary risk factor across all fracture sites in T1D was a previous fracture. Additional risk factors at different sites included previous falls (HR: 1.64, CI95%: 1.17-2.31), antidepressant use (HR: 1.34, CI95%: 1.02-1.76), and anxiolytic use (HR: 1.54, CI95%: 1.08-2.29) for any fracture; being female (HR: 1.65, CI95%: 1.14-2.38) for MOFs; the presence of retinopathy (HR: 1.47, CI95%: 1.02-2.11) and previous falls (HR: 2.04, CI95%: 1.16-3.59) for lower-arm and lower-leg fractures, respectively. Lipid-lowering medication use decreased the risk of MOFs (HR: 0.66, CI95%: 0.44-0.99). Stratification of T1D by disease duration showed that the relative risk of any fracture in T1D did not increase with longer diabetes duration (0-4 years: HR: 1.52, CI95%: 1.23-1.87; 5-9 years: HR: 1.30, CI95%: 0.99-1.71; <10 years: HR: 1.07, CI95%: 0.74-1.55). Similar patterns were observed for other fracture sites. Moreover, the occurrence of microvascular complications in T1D was linked to a heightened risk of fractures in comparison to controls. However, when considering the T1D cohort independently, the association was not statistically significant. CONCLUSION: In a cohort of relatively healthy and newly diagnosed people with T1D HRs for any fracture, MOFs, and lower-leg fractures compared to controls were increased. A previous fracture was the most consistent risk factor for a subsequent fracture, whereas retinopathy was the only diabetes related one. We postulate a potential initial fracture risk, succeeded by a subsequent risk reduction, which might potentially increase in later years due to the accumulation of complications and other factors.

The co-existence of peripheral and vestibular neuropathy in diabetes: a cross-sectional study.

PURPOSE: Diabetic neuropathy can lead to decreased peripheral sensation and motor neuron dysfunction associated with impaired postural control and risk of falling. However, the relationship between decreased peripheral sensation and impaired vestibular function in diabetes mellitus is poorly investigated. Therefore, the aim of this study was to investigate the relationship between peripheral and autonomic measurements of diabetic neuropathy and measurements of vestibular function. METHODS: A total of 114 participants with type 1 diabetes (n = 52), type 2 diabetes (n = 51) and controls (n = 11) were included. Vestibular function was evaluated by video head impulse testing. Peripheral neuropathy was assessed by quantitative sensory testing and nerve conduction. Autonomic neuropathy using the COMPASS 31 questionnaire. Data were analyzed according to data type and distribution. RESULTS: Measurements of vestibular function did not differ between participants with type 1 diabetes, type 2 diabetes or controls (all p-values above 0.05). Subgrouping of participants according to the involvement of large-, small- or autonomic nerves did not change this outcome. Correlation analyses showed a significant difference between COMPASS 31 and right lateral gain value (ρ = 0.23, p = 0.02,), while no other significant correlations were found. CONCLUSION: Diabetic neuropathy does not appear to impair vestibular function in diabetes, by means of the VOR. CLINICAL TRIALS: NCT05389566, May 25th, 2022.

Fracture patterns and associated risk factors in pediatric and early adulthood type 1 diabetes: Findings from a nationwide retrospective cohort study.

PURPOSE: People with pediatric and early adulthood type 1 diabetes (T1D) might have a higher fracture risk at several sites compared to the general population. Therefore, we assessed the hazard ratios (HR) of various fracture sites and determined the risk factors associated with fractures among people with newly diagnosed childhood and adolescence T1D. METHODS: All people from the UK Clinical Practice Research Datalink GOLD (1987-2017), below 20 years of age with a T1D diagnosis code (n = 3100) and a new insulin prescription, were included and matched 1:1 by sex, age, and practice to a control without diabetes. Cox regression was used to estimate HRs of any, major osteoporotic fractures (MOFs) and peripheral fractures (lower-arm and lower-legs) for people with T1D compared to controls. The analyses were adjusted for sex, age, diabetic complications, medication (glucocorticoids, anti-depressants, anxiolytics, bone medication, anti-convulsive), Charlson-comorbidity-index (CCI), hypoglycemia, falls and alcohol. T1D was further stratified by diabetes duration, presence of diabetic microvascular complications (retinopathy, nephropathy, and neuropathy) and boys versus girls. RESULTS: The crude HRs for any fracture (HR: 1.30, CI95%: 1.11-1.51), lower-arm (HR: 1.22, CI95%: 1.00-1.48), and lower-leg fractures (HR: 1.54, CI95%: 1.11-2.13) were statistically significant increase in T1D compared to controls, but the effect disappeared in the adjusted analyses. For MOFs, no significant differences were seen. Risk factors in the T1D cohort were few, but the most predominantly one was a previous fracture (any fracture: HR: 2.00, CI95%: 1.70-2.36; MOFs: HR: 1.89, CI95%: 1.44-2.48, lower- arm fractures: HR: 2.08, CI95%: 1.53-2.82 and lower-leg fractures: HR: 2.08, CI95%: 1.34-3.25). Others were a previous fall (any fracture: HR: 1.54, CI95%: 1.20-1.97), hypoglycemia (Any fracture: HR: 1.46, CI95%: 1.21-1.77 and lower-leg fractures: HR: 2.34, CI95%: 1.47-3.75), and anxiolytic medication (Any fracture: HR: 1.52, CI95%: 1.10-2.11). Whereas girls had a lower risk compared to boys (Any fracture: HR: 0.78, CI95%: 0.67-0.90 and lower-arm fractures; HR: 0.51, CI95%: 0.38-0.68). The risk of any fracture in T1D did not increase with longer diabetes duration compared to controls (0-4 years: HR: 1.20, CI95%: 1.00-1.44; 5-9 years: HR: 1.17, CI95%: 0.91-1.50; <10 years: HR: 0.83, CI95%: 0.54-1.27). Similar patterns were observed for other fracture sites. Furthermore, one complication compared to none in T1D correlated with a higher fracture risk (1 complication: HR: 1.42, CI95%: 1.04-1.95). CONCLUSION: The overall fracture risk was not increased in pediatric and early adulthood T1D; instead, it was associated with familiar risk factors and specific diabetes-related ones.

Metformin treatment is associated with reduced risk of hypoglycaemia, major adverse cardiovascular events, and all-cause mortality in patients with post-pancreatitis diabetes mellitus: a nationwide cohort study.

OBJECTIVE: Post-pancreatitis diabetes mellitus (PPDM) is a frequent complication of pancreatitis and is associated with an increased risk of adverse outcomes. Metformin is recommended for the treatment of PPDM, but evidence of its risk-benefit profile is limited. In a pharmaco-epidemiologic study, we investigated the association between metformin treatment and adverse outcomes in patients with PPDM. DESIGN AND METHODS: In a Danish nationwide population-based cohort study, we included adults (≥18 years) with incident PPDM or type 2 diabetes between 2009 and 2018. Post-pancreatitis diabetes mellitus was categorised into acute and chronic subtypes (PPDM-A and PPDM-C). Associations between metformin treatment and severe hypoglycaemia, major adverse cardiovascular events (MACE), and all-cause mortality were examined across the diabetes subgroups using Cox regression analysis. Treatments with metformin, insulin, and other glucose-lowering therapies were handled as time-varying exposures. RESULTS: We included 222 337 individuals with new-onset type 2 diabetes and 3781 with PPDM, of whom 2305 (61%) were classified as PPDM-A and 1476 (39%) as PPDM-C. Treatment with metformin was associated with a lower risk of severe hypoglycaemia (adjusted hazard ratio [HR] 0.41, 95% CI 0.27-0.62, P < .0001), MACE (HR 0.74, 95% CI 0.60-0.92, P = .0071), and all-cause mortality (HR 0.56, 95% CI 0.49-0.64, P < .0001) in patients with PPDM. In sensitivity analyses and among individuals with type 2 diabetes, metformin treatment exhibited comparable trends of risk reduction. CONCLUSIONS: Metformin is associated with a lower risk of adverse outcomes, including all-cause mortality in patients with PPDM, supporting the use of metformin as a glucose-lowering therapy for these patients.

Evaluation of a phosphate kinetics model in hemodialysis therapy-Assessment of the temporal robustness of model predictions.

In-depth understanding of intra- and postdialytic phosphate kinetics is important to adjust treatment regimens in hemodialysis. We aimed to modify and validate a three-compartment phosphate kinetic model to individual patient data and assess the temporal robustness. Intradialytic phosphate samples were collected from the plasma and dialysate of 12 patients during two treatments (HD1 and HD2). 2-h postdialytic plasma samples were collected in four of the patients. First, the model was fitted to HD1 samples from each patient to estimate the mass transfer coefficients. Second, the best fitted model in each patient case was validated on HD2 samples. The best model fits were determined from the coefficient of determination (R2 ) values. When fitted to intradialytic samples only, the median (interquartile range) R2 values were 0.985 (0.959-0.997) and 0.992 (0.984-0.994) for HD1 and HD2, respectively. When fitted to both intra- and postdialytic samples, the results were 0.882 (0.838-0.929) and 0.963 (0.951-0.976) for HD1 and HD2, respectively. Eight patients demonstrated a higher R2 value for HD2 than for HD1. The model seems promising to predict individual plasma phosphate in hemodialysis patients. The results also show good temporal robustness of the model. Further modifications and validation on a larger sample are needed.

A Three-Step Data-Driven Methodology to Assess Adherence to Basal Insulin Therapy in Patients With Insulin-Treated Type 2 Diabetes.

BACKGROUND: While health care providers (HCPs) are generally aware of the challenges concerning insulin adherence in adults with insulin-treated type 2 diabetes (T2D), data guiding identification of insulin nonadherence and understanding of injection patterns have been limited. Hence, the aim of this study was to examine detailed injection data and provide methods for assessing different aspects of basal insulin adherence. METHOD: Basal insulin data recorded by a connected insulin pen and prescribed doses were collected from 103 insulin-treated patients (aged ≥18 years) with T2D from an ongoing clinical trial (NCT04981808). We categorized the data and analyzed distributions of correct doses, increased doses, reduced doses, and missed doses to quantify adherence. We developed a three-step model evaluating three aspects of adherence (overall adherence, adherence distribution, and dose deviation) offering HCPs a comprehensive assessment approach. RESULTS: We used data from a connected insulin pen to exemplify the use of the three-step model to evaluate overall, adherence, adherence distribution, and dose deviation using patient cases. CONCLUSION: The methodology provides HCPs with detailed access to previously limited clinical data on insulin administration, making it possible to identify specific nonadherence behavior which will guide patient-HCP discussions and potentially provide valuable insights for tailoring the most appropriate forms of support.

The impact of CHOP versus bendamustine on bone mineral density in patients with indolent lymphoma enrolled in the GALLIUM study.

Standard CHOP treatment includes a high cumulative dose of prednisone, and studies have shown increased fracture risk following CHOP. It is unclear whether reductions in bone mineral density (BMD) are caused by glucocorticoids or by the combination with chemotherapy. Our objective was to determine the effect of obinutuzumab (G)/rituximab (R)-bendamustine versus G/R-CHOP on BMD in follicular lymphoma patients. Patients in this GALLIUM post hoc study were ≥60 years old and in complete remission at induction treatment completion (ITC), following treatment with G or R in combination with bendamustine or CHOP. To assess BMD, Hounsfield units (HU) were measured in lumbar vertebra L1 on annual computed tomography. Furthermore, vertebral compression fractures were recorded. Of 173 patients included, 59 (34%) received CHOP and 114 (66%) received bendamustine. At baseline, there was no difference in HU between groups. The mean HU decrease from baseline to ITC was 27.8 after CHOP and 17.3 after bendamustine, corresponding to a difference of 10.4 (95% CI: 3.2-17.6). Vertebral fractures were recorded in 5/59 patients receiving CHOP and in 2/114 receiving bendamustine. CHOP was associated with a significant greater decrease in BMD and more frequent fractures. These results suggest that prophylaxis against BMD loss should be considered.

Effects of Incretin Therapy on Skeletal Health in Type 2 Diabetes-A Systematic Review.

Diabetes poses a significant risk to bone health, with Type 1 diabetes (T1D) having a more detrimental impact than Type 2 diabetes (T2D). The group of hormones known as incretins, which includes gastric inhibitory peptide (GIP) and glucagon-like peptide 1 (GLP-1), play a role in regulating bowel function and insulin secretion during feeding. GLP-1 receptor agonists (GLP-1 RAs) are emerging as the primary treatment choice in T2D, particularly when atherosclerotic cardiovascular disease is present. Dipeptidyl peptidase 4 inhibitors (DPP-4is), although less potent than GLP-1 RAs, can also be used. Additionally, GLP-1 RAs, either alone or in combination with GIP, may be employed to address overweight and obesity. Since feeding influences bone turnover, a relationship has been established between incretins and bone health. To explore this relationship, we conducted a systematic literature review following the PRISMA guidelines. While some studies on cells and animals have suggested positive effects of incretins on bone cells, turnover, and bone density, human studies have yielded either no or limited and conflicting results regarding their impact on bone mineral density (BMD) and fracture risk. The effect on fracture risk may vary depending on the choice of comparison drug and the duration of follow-up, which was often limited in several studies. Nevertheless, GLP-1 RAs may hold promise for people with T2D who have multiple fracture risk factors and poor metabolic control. Furthermore, a potential new area of interest is the use of GLP-1 RAs in fracture prevention among overweight and obese people. Based on this systematic review, existing evidence remains insufficient to support a positive or a superior effect on bone health to reduce fracture risk in people with T2D. © 2023 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.

Sex- and Age Group-Specific Fracture Incidence Rates Trends for Type 1 and 2 Diabetes Mellitus.

The incidence of major osteoporotic fractures has declined in men and women in Western countries over the last two decades. Although fracture risk is higher in persons with diabetes mellitus, trends of fractures remain unknown in men and women with diabetes. We investigated the trends in fracture incidence rates (IRs) in men and women with type 1 diabetes mellitus (T1D) and type 2 diabetes mellitus (T2D) in Denmark between 1997 and 2017. We identified men and women aged 18+ years who sustained a fracture (excluding skull and facial fractures) between 1997 and 2017 using the Danish National Patient Registry. We calculated sex-specific IRs of fractures per 10,000 person-years separately in persons with T1D, T2D, or without diabetes. Furthermore, we compared median IRs of the first 5 years (1997-2002) to the median IRs of the last 5 years (2012-2017). We identified 1,235,628 persons with fractures including 4863 (43.6% women) with T1D, 65,366 (57.5% women) with T2D, and 1,165,399 (54.1% women) without diabetes. The median IRs of fractures declined 20.2%, 19.9%, and 7.8% in men with T1D, T2D, and without diabetes, respectively (p-trend <0.05). The median IRs decreased 6.4% in women with T1D (p-trend = 0.35) and 25.6% in women with T2D (p-trend <0.05) but increased 2.3% in women without diabetes (p-trend = 0.08). Fracture IRs decreased in men with both diabetes types and only in women with T2D, highlighting the need for further attention behind the stable trend observed in women with T1D. © 2023 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.

The TRH test provides valuable information in the diagnosis of central hypothyroidism in patients with known pituitary disease and low T4 levels.

Objective: To evaluate the value of the thyrotropin-releasing hormone (TRH) test in the diagnosis of central hypothyroidism (CH) in patients with pituitary disease. Methods: Systematic evaluation of 359 TRH tests in patients with pituitary disease including measurements of thyroxine (T4), TBG-corrected T4 (T4corr), baseline TSH (TSH0) and relative or absolute TSH increase (TSHfold, TSHabsolute). Results: Patients diagnosed with CH (n=39) show comparable TSH0 (p-value 0.824) but lower T4corr (p-value <0.001) and lower TSH increase (p-value <0.001) compared to patients without CH. In 54% (42 of 78 cases) of patients with low T4corr, the CH diagnosis was rejected based on a high TSHfold. In these cases, a spontaneous increase and mean normalization in T4corr (from 62 to 73 nmol/L, p-value <0.001) was observed during the follow-up period (7.6 ± 5.0 years). Three of the 42 patients (7%) were started on replacement therapy due to spontaneous deterioration of thyroid function after 2.8 years. Patients diagnosed with CH reported significantly more symptoms of hypothyroidism (p-value 0.005), although, symptoms were reported in most patients with pituitary disease. The TRH test did not provide clinical relevant information in patients with normal T4 or patients awaiting pituitary surgery (78%, 281 of 359). There were only mild and reversible adverse effects related to the TRH test except for possibly one case (0.3%) experiencing a pituitary apoplexy. Conclusion: The TRH test could be reserved to patients with pituitary disease, low T4 levels without convincing signs of CH. Approximately 50% of patients with a slightly decreased T4 were considered to have normal pituitary thyroid function based on the TRH test results.

Personalized Prediction of Change in Fasting Blood Glucose Following Basal Insulin Adjustment in People With Type 2 Diabetes: A Proof-of-Concept Study.

AIMS: For people with type 2 diabetes treated with basal insulin, suboptimal glycemic control due to clinical inertia is a common issue. Determining the optimal basal insulin dose can be difficult, as it varies between individuals. Thus, insulin titration can be slow and cautious which may lead to treatment fatigue and non-adherence. A model that predicts changes in fasting blood glucose (FBG) after adjusting basal insulin dose may lead to more optimal titration, reducing some of these challenges. OBJECTIVE: To predict the change in FBG following adjustment of basal insulin in people with type 2 diabetes using a machine learning framework. METHODS: A multiple linear regression model was developed based on 786 adults with type 2 diabetes. Data were divided into training (80%) and testing (20%) sets using a ranking approach. Forward feature selection and fivefold cross-validation were used to select features. RESULTS: Participants had a mean age of approximately 59 years, a mean duration of diabetes of 12 years, and a mean HbA1c at screening of 65 mmol/mol (8.1%). Chosen features were FBG at week 2, basal insulin dose adjustment from week 2 to 7, trial site, hemoglobin level, and alkaline phosphatase level. The model achieved a relative absolute error of 0.67, a Pearson correlation coefficient of 0.74, and a coefficient of determination of 0.55. CONCLUSIONS: A model using FBG, insulin doses, and blood samples can predict a five-week change in FBG after adjusting the basal insulin dose in people with type 2 diabetes. Implementation of such a model can potentially help optimize titration and improve glycemic control.

Implementation of a coagulation component into a phosphate kinetics model in haemodialysis therapy: A tool for detection of clotting problems?

A coagulation component should be considered in phosphate kinetics modelling because intradialytic coagulation of the extracorporeal circuit and dialyser might reduce phosphate removal in haemodialysis. Thus, the objective of this study was to add and evaluate coagulation as an individual linear clearance reduction component to a promising three-compartment model assuming progressive intradialytic clotting. The model was modified and validated on intradialytic plasma and dialysate phosphate samples from 12 haemodialysis patients collected during two treatments (HD1 and HD2) at a Danish hospital ward. The most suitable clearance reduction in each treatment was identified by minimizing the root mean square error (RMSE). The model simulations with and without clearance reduction were compared based on RMSE and coefficient of determination (R2 ) values. Improvements were found for 17 of the 24 model simulations when clearance reduction was added to the model. The slopes of the clearance reduction were in the range of 0.011-0.632/h. Three improvements were found to be statistically significant (|observed z value| > 1.96). A very significant correlation (R2  = 0.708) between the slopes for HD1 and HD2 was found. Adding the clearance reduction component to the model seems promising in phosphate kinetics modelling and might be explained, at least in part, by intradialytic coagulation. In future studies, the model might be developed further to serve as a potentially useful tool for the quantitative detection of clotting problems in haemodialysis. NEW FINDINGS: What is the central question of this study? The aim was to add an intradialytic coagulation component to a modified version of a promising three-compartment phosphate kinetics model. The hypothesis was that circuit and dialyser clotting can be modelled by an individual linear phosphate clearance reduction component during haemodialysis treatment. What is the main finding and its importance? Improvements were found for 17 of 24 model simulations when clearance reduction was added to the model. Thus, the kinetics model seems promising and could be a useful tool for the quantitative detection of clotting problems in haemodialysis patients.

A Systematic Review of Cost-Effectiveness Studies of Newer Non-Insulin Antidiabetic Drugs: Trends in Decision-Analytical Models for Modelling of Type 2 Diabetes Mellitus.

BACKGROUND: We performed a systematic overview of the cost-effectiveness analyses (CEAs) comparing Non-insulin antidiabetic drugs (NIADs) with other NIADs for the treatment of type 2 diabetes mellitus (T2DM), using decision-analytical modelling (DAM), focusing on both the economic results and the underlying methodological choices. METHODS: Eligible studies were CEAs using DAM to compare NIADs within the glucagon-like peptide-1 (GLP1) receptor agonists, sodium-glucose cotransporter-2 (SGLT2) inhibitors, or dipeptidyl peptidase-4 (DPP4) inhibitor classes with other NIADs within those classes for the treatment of T2DM. The PubMed, Embase and Econlit databases were searched from 1 January 2018 to 15 November 2022. Two reviewers screened the studies for relevance by titles and abstracts and then for eligibility via full-text screening, extracted the data from the full texts and appendices, and then stored the data in a spreadsheet. RESULTS: The search yielded 890 records and 50 studies were eligible for inclusion. The studies were mainly based on a European setting (60%). Industry sponsorship was found in 82% of studies. The CORE diabetes model was used in 48% of the studies. GLP1 and SGLT2 products were the main comparators in 31 and 16 studies, respectively, while one study had DPP4 and two had no easily discernible main comparator. Direct comparison between SGLT2 and GLP1 occurred in 19 studies. At a class level, SGLT2 dominated GLP1 in six studies and was cost effective against GLP1 once as part of a treatment pathway. GLP1 was cost effective in nine studies and not cost effective against SGLT2 in three studies. At a product level, oral and injectable semaglutide, and empagliflozin, were cost effective against other within-class products. Injectable and oral semaglutide were more frequently found cost effective in these comparisons, with some conflicting results. Most of the modelled cohorts and treatment effects were sourced from randomised controlled trials. The following model assumptions varied depending on the class of the main comparator: choice of and reasoning behind risk equations, the time until the treatment switch, and how often the comparators were discontinued. Diabetes-related complications were emphasised on par with quality-adjusted life-years as model outputs. The main quality issues were regarding the description of alternatives, the perspective of analysis, the measurement of costs and consequences, and patient subgroups. CONCLUSION: The included CEAs using DAMs have limitations that hinder their ability to inform decision makers on the cost-effective choice: lack of updated reasoning behind the choice of key model assumptions, over-reliance on risk equations based on older treatment practices, and sponsorship bias. The question of which NIAD is cost effective for the treatment of which T2DM patient is a pressing one and the answer remains unclear.