Browse

You are looking at 41 - 50 of 5,444 items for

  • User-accessible content x
Clear All
Restricted access

Caroline M J van Kinschot, Vikas R Soekhai, Esther W de Bekker-Grob, W Edward Visser, Robin P Peeters, Tessa M van Ginhoven, and Charlotte van Noord

Objective

Treatment options for Graves’ disease (GD) consist of antithyroid drugs (ATD), radioactive iodine (RAI) and total thyroidectomy (TT). Guidelines recommend to discuss these options with patients, taking into account patients’ preferences. This study aims to evaluate and compare patients’ and clinicians’ preferences and the trade-offs made in choosing treatment.

Design and methods

A discrete choice experiment (DCE) was performed with GD patients with a first diagnosis or recurrence in the previous year, and with clinicians. Participants were offered hypothetical treatment options which differed in type of treatment, rates of remission, severe side effects, permanent voice changes and hypocalcemia. Preference heterogeneity was assessed by latent-class analysis.

Results

In this study, 286 (82%) patients and 61 (18%) clinicians participated in the DCE. All treatment characteristics had a significant effect on treatment choice (P < 0.05). Remission rate was the most important determinant and explained 37 and 35% of choices in patients and clinicians, respectively. Both patients and clinicians preferred ATD over surgery and RAI. A strong negative preference toward RAI treatment was observed in a subclass of patients, whereas clinicians preferred RAI over surgery.

Conclusion

For both patients and clinicians, remission rate was the most important determinant of treatment choice and ATD was the most preferred treatment option. Patients had a negative preference toward RAI compared to alternatives, whereas clinicians preferred RAI over surgery. Clinicians should be aware that their personal attitude toward RAI differs from that of their patients. This study on patients’ and clinicians’ preferences can support shared decision making and thereby improve clinical treatment.

Restricted access

Karolina Zawadzka, Krzysztof Więckowski, Piotr Małczak, Michał Wysocki, Piotr Major, Michał Pędziwiatr, and Magdalena Pisarska-Adamczyk

Objective

Alpha-adrenergic blockade is currently the first choice of preoperative treatment in patients with functional pheochromocytoma and sympathetic paraganglioma. Nevertheless, there is no consensus whether selective or non-selective alpha-blockade is superior for preventing both perioperative hemodynamic instability and complications.

Design

Our study aimed to compare selective and non-selective alpha-blockade through a systematic review with meta-analysis.

Methods

MEDLINE, Embase, Web of Science and Cochrane Library were searched for eligible studies. Randomized and observational studies comparing selective and non-selective alpha-blockade in pheochromocytoma and sympathetic paraganglioma surgery in adults were included. Data on perioperative hemodynamic parameters and postoperative outcomes were extracted.

Results

Eleven studies with 1344 patients were enrolled. Patients receiving selective alpha-blockade had higher maximum intraoperative systolic blood pressure (WMD: 12.14 mmHg, 95% CI: 6.06–18.21, P < 0.0001) compared to those treated with non-selective alpha-blockade. Additionally, in the group pretreated with selective alpha-blockers, intraoperative vasodilators were used more frequently (OR: 2.46, 95% CI 1.44–4.20, P = 0.001). Patients treated with selective alpha-blockers had lower minimum intraoperative systolic blood pressure (WMD: −2.03 mmHg, 95% CI: −4.06 to −0.01, P = 0.05) and shorter length of hospital stay (WMD: −0.58 days, 95% CI: −1.12 to −0.04, P = 0.04). Operative time, overall morbidity and mortality did not differ between the groups.

Conclusions

This meta-analysis shows non-selective alpha-blockade was more effective in preventing intraoperative blood pressure fluctuations while maintaining comparable risk of both intraoperative and postoperative hypotension and overall morbidity.

Free access

Blandine Tramunt, Sarra Smati, Sandrine Coudol, Matthieu Wargny, Matthieu Pichelin, Béatrice Guyomarch, Abdallah Al-Salameh, Coralie Amadou, Sara Barraud, Édith Bigot, Lyse Bordier, Sophie Borot, Muriel Bourgeon, Olivier Bourron, Sybil Charriere, Nicolas Chevalier, Emmanuel Cosson, Bruno Fève, Anna Flaus-Furmaniuk, Pierre Fontaine, Amandine Galioot, Céline Gonfroy-Leymarie, Bruno Guerci, Sandrine Lablanche, Jean-Daniel Lalau, Etienne Larger, Adele Lasbleiz, Bruno Laviolle, Michel Marre, Marion Munch, Louis Potier, Gaëtan Prévost, Eric Renard, Yves Reznik, Dominique Seret-begue, Paul Sibilia, Philippe Thuillier, Bruno Vergès, Jean-Francois Gautier, Samy Hadjadj, Bertrand Cariou, Franck Mauvais-Jarvis, and Pierre Gourdy

Objective:

Male sex is a determinant of severe coronavirus disease-2019 (COVID-19). We aimed to characterize sex differences in severe outcomes in adults with diabetes hospitalized for COVID-19.

Methods:

We performed a sex-stratified analysis of clinical and biological features and outcomes (i.e. invasive mechanical ventilation [IMV], death, intensive care unit [ICU] admission and home discharge at day 7 [D7] or day 28 [D28]) in 2,380 patients with diabetes hospitalized for COVID-19 and included in the nationwide CORONADO observational study (NCT04324736).

Results:

The study population was predominantly male (63.5%). After multiple adjustments, female sex was negatively associated with the primary outcome (IMV and/or death, OR 0.66 [0.49-0.88]), death (OR 0.49 [0.30-0.79]) and ICU admission (OR 0.57 [0.43-0.77]) at D7, but only with ICU admission (OR 0.58 [0.43-0.77]) at D28. Older age and a history of microvascular complications were predictors of death at D28 in both sexes, while chronic obstructive pulmonary disease (COPD) was predictive of death in women only. At admission, CRP, AST and eGFR predicted death in both sexes. Lymphocytopenia was an independent predictor of death in women only, while thrombocytopenia and elevated plasma glucose concentration were predictors of death in men only.

Conclusions:

In patients with diabetes admitted for COVID-19, female sex was associated with lower incidence of early severe outcomes, but did not influence the overall in-hospital mortality, suggesting that diabetes mitigates the female protection from COVID-19 severity. Sex-associated biological determinants may be useful to optimize COVID-19 prevention and management in women and men.

Restricted access

João Pedro Ferreira, Ana Cristina Oliveira, Francisca A Saraiva, Francisco Vasques-Nóvoa, and Adelino Leite-Moreira

Background

Patients with insulin-treated type 2 diabetes (T2D) have a high risk of major adverse cardiovascular events. Sodium-glucose cotransporter inhibitors (SGLTi) improve outcomes without hypoglycaemic risk.

Aims

To study the effect of SGLTi in patients with T2D with and without background insulin treatment in outcome-driven RCTs.

Methods

Random effects models.

Results

A total of 54 374 patients with T2D were included in the analysis, of which 26 551 (48.8%) were treated with insulin. For 3P-MACE in patients without insulin treatment, the HR (95% CI) for the effect of SGLTi vs placebo was 0.93 (0.81–1.05), with moderate heterogeneity (I2 = 49.2%, Q statistic P = 0.11). In insulin-treated patients, the HR (95% CI) was 0.88 (0.82–0.95), without evidence of heterogeneity (I2 =0.0%, Q statistic P =0.91). The pooled effect evidenced a 10% reduction of 3P-MACE with SGLTi (HR: 0.90, 95% CI: 0.85–0.96), without SGLTi-by-insulin interaction P = 0.53. For the composite outcome of HF hospitalisation or cardiovascular death in patients without insulin treatment, the HR (95% CI) for the effect of SGLTi vs placebo was 0.77 (0.61-0.92), with marked heterogeneity (I2 = 66.8%, Q statistic P = 0.02). In insulin-treated patients, the HR (95% CI) was 0.77 (0.68–0.86), without significant heterogeneity (I2 = 31.7%, Q statistic P = 0.25). The pooled effect evidenced a 23% reduction of HF hospitalisations or cardiovascular death with SGLTi (HR: 0.77, 95% CI: 0.68–0.85), without SGLTi-by-insulin interaction P = 0.98.

Conclusion

SGLTi reduces cardiovascular events regardless of insulin use. However, the treatment effect is more homogeneous among insulin-treated patients, supporting the use of SGLTi for the treatment of patients with T2D requiring insulin for glycaemic control.

Restricted access

Jan W Eriksson, Robin Visvanathar, Joel Kullberg, Robin Strand, Stanko Skrtic, Simon Ekström, Mark Lubberink, Martin H Lundqvist, Petros Katsogiannos, Maria J Pereira, and Håkan Ahlström

Objective

To obtain direct quantifications of glucose turnover, volumes and fat content of several tissues in the development of type 2 diabetes (T2D) using a novel integrated approach for whole-body imaging.

Design and methods

Hyperinsulinemic–euglycemic clamps and simultaneous whole-body integrated [18F]FDG-PET/MRI with automated analyses were performed in control (n = 12), prediabetes (n = 16) and T2D (n = 13) subjects matched for age, sex and BMI.

Results

Whole-body glucose uptake (Rd) was reduced by approximately 25% in T2D vs control subjects, and partitioning to brain was increased from 3.8% of total Rd in controls to 7.1% in T2D. In liver, subcutaneous AT, thigh muscle, total tissue glucose metabolic rates (MRglu) and their % of total Rd were reduced in T2D compared to control subjects. The prediabetes group had intermediate findings. Total MRglu in heart, visceral AT, gluteus and calf muscle was similar across groups. Whole-body insulin sensitivity assessed as glucose infusion rate correlated with liver MRglu but inversely with brain MRglu. Liver fat content correlated with MRglu in brain but inversely with MRglu in other tissues. Calf muscle fat was inversely associated with MRglu only in the same muscle group.

Conclusions

This integrated imaging approach provides detailed quantification of tissue-specific glucose metabolism. During T2D development, insulin-stimulated glucose disposal is impaired and increasingly shifted away from muscle, liver and fat toward the brain. Altered glucose handling in the brain and liver fat accumulation may aggravate insulin resistance in several organs.

Restricted access

Nèle F Lenders, Adam C Wilkinson, Stephen J Wong, Tint T Shein, Richard J Harvey, Warrick J Inder, Peter E Earls, and Ann I McCormack

Objective

The clinical utility and prognostic value of WHO 2017 lineage-based classification of pituitary tumours have not been assessed. This study aimed to (1) determine the clinical utility of transcription factor analysis for classification of pituitary tumours and (2) determine the prognostic value of improved lineage-based classification of pituitary tumours.

Methods

This was a retrospective evaluation of patients who underwent surgical resection of pituitary tumours at St Vincent’s Public and Private Hospitals, Sydney, Australia between 1990 and 2016. Included patients were at least 18 years of age and had complete histopathological data, forming the 'histological cohort'. Patients with at least 12 months of post-surgical follow-up were included in the subgroup 'clinical cohort'. The diagnostic efficacy of transcription factor immunohistochemistry in conjunction with hormone immunohistochemistry was compared with hormone immunohistochemistry alone. The prognostic value of identifying 'higher-risk' histological subtypes was assessed.

Results

There were 171 patient tumour samples analyzed in the histological cohort. Of these, there were 95 patients forming the clinical cohort. Subtype diagnosis was changed in 20/171 (12%) of tumours. Within the clinical cohort, there were 21/95 (22%) patients identified with higher-risk histological subtype tumours. These were associated with tumour invasiveness (P = 0.050), early recurrence (12–24 months, P = 0.013), shorter median time to recurrence (49 (IQR: 22.5–73.0) vs 15 (IQR: 12.0–25.0) months, P = 0.005) and reduced recurrence-free survival (P = 0.031).

Conclusions

Application of transcription factor analysis, in addition to hormone immunohistochemistry, allows for refined pituitary tumour classification and may facilitate an improved approach to prognostication.

Restricted access

Tero Varimo, Yafei Wang, Päivi J Miettinen, Kirsi Vaaralahti, Matti Hero, and Taneli Raivio

Objective

The role of miRNA as endocrine regulators is emerging, and microRNA mir-30b has been reported to repress Mkrn3. However, the expression of miR-30b during male puberty has not been studied.

Design and methods

Circulating relative miR-30b expression was assessed in sera of 26 boys with constitutional delay of growth and puberty (CDGP), treated with low-dose testosterone (T) (n =11) or aromatase inhibitor letrozole (Lz) (n =15) for 6 months and followed up to 12 months (NCT01797718). The associations between the relative expression of miR-30b and hormonal markers of puberty were evaluated.

Results

During the 12 months of the study, circulating miR-30b expression increased 2.4 ± 2.5 (s.d.) fold (P = 0.008) in all boys, but this change did not correlate with corresponding changes in LH, testosterone, inhibin B, FSH, or testicular volume (P = 0.25-0.96). Lz-induced activation of the hypothalamic–pituitary–gonadal (HPG) axis was associated with more variable miR-30b responses at 3 months (P < 0.05), whereas those treated with T exhibited significant changes in relative miR-30b levels in the course the study (P < 0.01–0.05).

Conclusions

Circulating miR-30b expression in boys with CDGP increases in the course of puberty, and appears to be related to the activity of the HPG axis.

Restricted access

Meena Bandhakavi, Amy Wanaguru, Loveline Ayuk, Jeremy M Kirk, Timothy G Barrett, Melanie Kershaw, Wolfgang Högler, and Nicholas J Shaw

Introduction

Autosomal recessive forms of pseudohypoaldosteronism are caused by genetic defects in the epithelial sodium channel. Little is known about the long-term outcome and medication needs during childhood and adolescence.

Objective

This study reports a single-centre experience of children affected with this ultra-rare condition over a 37-year period.

Methods

We report the clinical presentation, growth, neuro-development, associated conditions, mortality and medication dosing and administration for 12 affected children from eight families.

Results

All children were presented within the first 2 weeks of life with life-threatening, severe hyperkalaemia and hyponatraemia. All parents were consanguineous and of South Asian, Middle Eastern or African ethnic origin. Eight children had homozygous mutations in the SCNN1A and SCNN1G genes, encoding the epithelial sodium channel subunits alpha and gamma, respectively, including one novel mutation. Three children died (25%) and two (16%) had severe neurological impairment post-cardiac arrest secondary to hyperkalaemia. One affected female had a successful pregnancy at the age of 28 years.

Conclusion

Despite high mortality and morbidity in this condition, survival with normal physical and neurological outcome is possible, justifying intensive management to prevent electrolyte imbalance.

Restricted access

Danielle M Richman, Christine E Cherella, Jessica R Smith, Biren P Modi, Benjamin Zendejas, Mary C Frates, and Ari J Wassner

Objective

Surgical resection is recommended for cytologically indeterminate pediatric thyroid nodules due to their intermediate malignancy risk. We evaluated the utility of ultrasound characteristics for refining malignancy risk to inform the management of these nodules.

Design

Retrospective cohort study (2004–2019).

Methods

We analyzed consecutive thyroid nodules with indeterminate fine-needle aspiration cytology (Bethesda category III, IV, or V) in pediatric patients (<19 years). We assessed the association of demographic and sonographic characteristics with malignancy risk among all indeterminate nodules and within each Bethesda category.

Results

Eighty-seven cytologically indeterminate nodules were identified in 78 patients. Bethesda category was III in 56 nodules (64%), IV in 12 (14%), and V in 19 (22%). The malignancy rate was 46/87 (53%) overall, and 23/56 (41%), 8/12 (75%), and 15/19 (79%) in Bethesda III, IV, and V nodules, respectively. Malignancy rate was higher in solitary nodules (67% vs 37%, P = 0.004) and nodules with irregular margins (100% vs 44%, P < 0.001) or calcifications (82% vs 43%, P = 0.002). American College of Radiology Thyroid Imaging, Reporting and Data System (ACR TI-RADS) risk level TR5 was associated with a higher rate of malignancy than lower TI-RADS risk levels (80% vs 42%, P = 0.002). Within individual Bethesda categories, TI-RADS risk level was not associated with malignancy. No sonographic feature had a negative predictive value for malignancy greater than 80%.

Conclusions

In pediatric thyroid nodules with indeterminate cytology, some sonographic features – including higher ACR TI-RADS risk level – are associated with malignancy, but these associations are unlikely to alter clinical management in most cases.

Restricted access

Martina Behanova, Judith Haschka, Jochen Zwerina, Thomas C Wascher, Berthold Reichardt, Klaus Klaushofer, and Roland Kocijan

Objective

Patients with diabetes have an increased risk of osteoporosis and shorter life expectancy. Hip fracture (HF) is the most serious consequence of osteoporosis and is associated with increased mortality risk. We aimed to assess the association of antidiabetic medications with HF and the post-hip fracture mortality risk among diabetic patients ≥50 years.

Design

In this nationwide case-control study 53 992 HF cases and 112 144 age-, sex- and region-matched non-hip fracture controls were analyzed. A cohort of hip-fractured diabetic patients were followed-up for an all-cause mortality.

Methods

We defined three groups of diabetic patients based on a prescription of antidiabetic medications: group 1 treated with insulin monotherapy (G1DM), group 2 (G2DM) treated with blood glucose-lowering drugs (BGLD) only, group 3 on a combined BGLD and insulin therapy (G3DM). We applied logistic regression and Cox regression.

Results

We identified 2757 G1DM patients, 15 310 G2DM patients, 3775 G3DM patients and 144 294 patients without any antidiabetic treatment. All three groups of diabetic patients had increased odds of HF compared to controls. G1DM patients aged 50–64 years (aOR: 4.80, 95% CI: 3.22–7.17) and G3DM patients (aOR: 1.39, 95% CI: 1.02–1.88) showed the highest HF odds, whereas G2DM patients had 18% decrease in HF odds than their non-diabetic controls (aOR: 0.82, 95% CI: 0.69–0.99). All diabetic patients had increased post-hip fracture mortality risk compared to non-diabetic controls. The highest mortality hazard was observed in G1DM patients, being greater for women than men (HR: 1.71, 95% CI: 1.55–1.89 and HR: 1.44, 95% CI: 1.27–1.64, respectively).

Conclusions

Antidiabetic medications increase the probability of HF. Diabetic patients, who sustained HF have a higher mortality risk than non-diabetic patients.