Effectiveness and cost-effectiveness of a cluster-randomized prenatal lifestyle counseling trial: A seven-year follow-up

There is a link between the pregnancy and its long-term influence on health and susceptibility to future chronic disease both in mother and offspring. The objective was to determine whether individual counseling on physical activity and diet and weight gain at five antenatal visits can prevent type 2 diabetes mellitus (T2DM) and overweight or improve glycemic parameters, among all at-risk-mothers and their children. Another objective was to evaluate whether gestational lifestyle intervention was cost-effective as measured with mother's sickness absence and quality-adjusted life years (QALY). This study was a seven-year follow-up study for women, who were enrolled to the antenatal cluster-randomized controlled trial (RCT). Analysis of the outcome included all women whose outcome was available, in addition with subgroup analysis including women adherent to all lifestyle aims. A total of 173 women with their children participated to the study, representing 43% (173/399) of the women who finished the original RCT. Main outcome measures were: T2DM based on medication use or fasting blood glucose or oral glucose tolerance test (OGTT), body mass index (BMI), glycosylated hemoglobin (HbA1c). None of the women were diagnosed to have T2DM. HbA1c or fasting blood glucose differences were not found among mothers or children. Differences in BMI were non-significant among mothers (Intervention 27.3, Usual care 28.1 kg/m2, p = 0.33) and children (I 21.3 vs U 22.5 kg/m2, p = 0.07). Children's BMI was significantly lower among adherent group (I 20.5 vs U 22.5, p = 0.04). The mean total cost per person was 30.6% lower in the intervention group than in the usual care group (I €2,944 vs. U €4,243; p = 0.74). Intervention was cost-effective in terms of sickness absence but not in QALY gained i.e. if society is willing to pay additional €100 per one avoided sickness absence day; there is a 90% probability of the intervention arm to be cost-effective. Long-term effectiveness of antenatal lifestyle counseling was not shown, in spite of possible effect on children's BMI. Cost-effectiveness of the intervention in terms of sickness absence may have larger societal impact.Public Library of Science open acces

PET/CT to detect adverse reactions to metal debris in patients with metal-on-metal hip arthroplasty: an exploratory prospective study

Metal-on-metal (MoM) bearings in total hip arthroplasties and hip resurfacing arthroplasties have recently shown a new type of complication: adverse reactions to metal debris (ARMD). ARMD is characterized by local severe inflammation and tissue necrosis leading to implant failures. The gluteal muscle region is important for the patient outcome after revision surgery. This prospective positron emission tomography/computed tomography (PET/CT) study was undertaken to evaluate the characteristics of 2-deoxy-2-[18 F]fluoro-d-glucose ([18 F]FDG) and [68 Ga]Gallium citrate ([68 Ga]Citrate) PET/CT in ARMD patients. [18 F]FDG and [68 Ga]Citrate PET/CT were performed in 18 hip arthroplasty patients: 12 ARMD patients (with 16 MoM hips) and six arthroplasty controls without ARMD. Tracer uptake was evaluated visually, and maximum standardized uptake (SUVmax ) was measured in the gluteal muscle region. ARMD severity was graded by metal artefact reduction sequence-magnetic resonance imaging (MARS-MRI). Periprosthetic [18 F]FDG uptake was observed in 15 of 16 hips, [68 Ga]Citrate uptake in three of 16 hips, respectively. The distribution of tracer uptake resembled infection in three hips. In the gluteal muscle region, the SUVmax of [18 F]FDG was significantly greater in hips with moderate and severe ARMD compared with the controls (P = 0·009 for [18 F]FDG and P = 0·217 for [68 Ga]Citrate). In patients who needed revision surgery, an intraoperative finding of gluteal muscle necrosis was associated with increased local SUVmax as detected by preoperative [18 F]FDG (P = 0·039), but not by [68 Ga]Citrate (P = 0·301). In conclusion, the inflammatory reaction to metal debris in hip arthroplasty patients is best visualized with [18 F]FDG

Regulation of human brown adipose tissue by adenosine and A2A receptors – studies with [15O]H2O and [11C]TMSX PET/CT

PurposeBrown adipose tissue (BAT) has emerged as a potential target to combat obesity and diabetes, but novel strategies to activate BAT are needed. Adenosine and A2A receptor (A2AR) agonism activate BAT in rodents, and endogenous adenosine is released locally in BAT as a by-product of noradrenaline, but physiological data from humans is lacking. The purpose of this pilot study was to investigate the effects of exogenous adenosine on human BAT perfusion, and to determine the density of A2ARs in human BAT in vivo for the first time, using PET/CT imaging.MethodsHealthy, lean men (n = 10) participated in PET/CT imaging with two radioligands. Perfusion of BAT, white adipose tissue (WAT) and muscle was quantified with [15O]H2O at baseline, during cold exposure and during intravenous administration of adenosine. A2AR density of the tissues was quantified with [11C]TMSX at baseline and during cold exposure.ResultsAdenosine increased the perfusion of BAT even more than cold exposure (baseline 8.3 ± 4.5, cold 19.6 ± 9.3, adenosine 28.6 ± 7.9 ml/100 g/min, p 11C]TMSX in BAT was significantly lower during cold exposure compared to baseline. In cold, low [11C]TMSX binding coincided with high concentrations of noradrenaline.ConclusionsAdenosine administration caused a maximal perfusion effect in human supraclavicular BAT, indicating increased oxidative metabolism. Cold exposure increased noradrenaline concentrations and decreased the density of A2AR available for radioligand binding in BAT, suggesting augmented release of endogenous adenosine. Our results show that adenosine and A2AR are relevant for activation of human BAT, and A2AR provides a future target for enhancing BAT metabolism.</div

A Comparative 68Ga-Citrate and 68Ga-Chloride PET/CT Imaging of Staphylococcus aureus Osteomyelitis in the Rat Tibia

There may be some differences in the in vivo behavior of Ga-68-chloride and Ga-68-citrate leading to different accumulation profiles. This study compared Ga-68-citrate and Ga-68-chloride PET/CT imaging under standardized experimental models. Methods. Diffuse Staphylococcus aureus tibial osteomyelitis and uncomplicated bone healing rat models were used (n = 32). Two weeks after surgery, PET/CT imaging was performed on consecutive days using Ga-68-citrate or Ga-68-chloride, and tissue accumulation was confirmed by ex vivo analysis. In addition, peripheral quantitative computed tomography and conventional radiography were performed. Osteomyelitis was verified by microbiological analysis and specimens were also processed for histomorphometry. Results. In PET/CT imaging, the SUVmax of Ga-68-chloride and Ga-68-citrate in the osteomyelitic tibias (3.6 +/- 1.4 and 4.7 +/- 1.5, resp.) were significantly higher (P = 0.0019 and P = 0.0020, resp.) than in the uncomplicated bone healing (2.7 +/- 0.44 and 2.5 +/- 0.49, resp.). In osteomyelitic tibias, the SUVmax of Ga-68-citrate was significantly higher than the uptake of Ga-68-chloride (P = 0.0017). In animals with uncomplicated bone healing, no difference in the SUVmax of Ga-68-chloride or Ga-68-citrate was seen in the operated tibias. Conclusions. This study further corroborates the use of Ga-68-citrate for PET imaging of osteomyelitis

Head-to-Head Comparison of 68Ga-Citrate and 18F-FDG PET/CT for Detection of Infectious Foci in Patients with Staphylococcus aureus Bacteraemia

Purpose. This study evaluated the potential of 68Ga-citrate positron emission tomography/computed tomography (PET/CT) for the detection of infectious foci in patients with Staphylococcus aureus bacteraemia by comparing it with 2-[18F]fluoro-2-deoxy--glucose (18F-FDG) PET/CT. Methods. Four patients admitted to hospital due to S. aureus bacteraemia underwent both 18F-FDG and 68Ga-citrate whole-body PET/CT scans to detect infectious foci. Results. The time from hospital admission and the initiation of antibiotic treatment to the first PET/CT was 4–10 days. The time interval between 18F-FDG and 68Ga-citrate PET/CT was 1–4 days. Three patients had vertebral osteomyelitis (spondylodiscitis) and one had osteomyelitis in the toe; these were detected by both 18F-FDG (maximum standardised uptake value [SUVmax 6.0 ± 1.0] ) and 68Ga-citrate (SUVmax 6.8 ± 3.5, P = 0.61). Three patients had soft tissue infectious foci, with more intense 18F-FDG uptake (SUVmax 6.5 ± 2.5) than 68Ga-citrate uptake (SUVmax 3.9 ± 1.2, P = 0.0033). Conclusions. Our small cohort of patients with S. aureus bacteraemia revealed that 68Ga-citrate PET/CT is comparable to 18F-FDG PET/CT for detection of osteomyelitis, whereas 18F-FDG resulted in a higher signal for the detection of soft tissue infectious foci.</p

Head-to-Head Comparison of 68

Purpose. This study evaluated the potential of 68Ga-citrate positron emission tomography/computed tomography (PET/CT) for the detection of infectious foci in patients with Staphylococcus aureus bacteraemia by comparing it with 2-[18F]fluoro-2-deoxy-D-glucose (18F-FDG) PET/CT. Methods. Four patients admitted to hospital due to S. aureus bacteraemia underwent both 18F-FDG and 68Ga-citrate whole-body PET/CT scans to detect infectious foci. Results. The time from hospital admission and the initiation of antibiotic treatment to the first PET/CT was 4–10 days. The time interval between 18F-FDG and 68Ga-citrate PET/CT was 1–4 days. Three patients had vertebral osteomyelitis (spondylodiscitis) and one had osteomyelitis in the toe; these were detected by both 18F-FDG (maximum standardised uptake value [SUVmax] 6.0±1.0) and 68Ga-citrate (SUVmax  6.8±3.5, P=0.61). Three patients had soft tissue infectious foci, with more intense 18F-FDG uptake (SUVmax  6.5±2.5) than 68Ga-citrate uptake (SUVmax  3.9±1.2, P=0.0033). Conclusions. Our small cohort of patients with S. aureus bacteraemia revealed that 68Ga-citrate PET/CT is comparable to 18F-FDG PET/CT for detection of osteomyelitis, whereas 18F-FDG resulted in a higher signal for the detection of soft tissue infectious foci

68Ga-Citrate Positron Emission Tomography of Healthy Men: Whole-Body Biodistribution Kinetics and Radiation Dose Estimates

68Ga-citrate has one of the simplest chemical structures of all 68Ga-radiopharmaceuticals, and its clinical use is justified by the proven medical applications using its isotope-labeled compound 67Ga-citrate. To support broader application of 68Ga-citrate in medical diagnosis, further research is needed to gain clinical data from healthy volunteers. In this work, we studied the biodistribution of 68Ga-citrate and subsequent radiation exposure from it in healthy males. Methods: 68Ga-citrate was prepared with an acetone-based radiolabeling procedure compliant with Good Manufacturing Practices. Six healthy males (age 41 ± 12 years, mean ± SD) underwent sequential whole-body PET/CT scans after an injection of 204 ± 8 MBq of 68Ga-citrate. Serial arterialized venous blood samples were collected during PET imaging and the radioactivity concentration was measured with a gamma counter. Urinary voids were collected and measured. The Medical Internal Radiation Dose (MIRD) bladder-voiding model with a 3.5 hour voiding interval was used. A model using a 70 kg adult male and MIRD schema was used to estimate absorbed doses in target organs and effective doses. Calculations were performed using OLINDA/EXM 2.0 software. Results: Radioactivity clearance from the blood was slow, and relatively high radioactivity concentrations were observed over the whole of the 3 hour measuring period. Although radioactivity excretion via urine was rather slow (biological half-time, 69 ± 24 hours), the highest decay-corrected concentrations in urinary bladder contents were measured at 90 and 180 minute time points. Moderate concentrations were also seen in kidneys, liver, and spleen. The source organs showing the largest residence times were muscle, liver, lung, and heart contents. The heart wall received the highest absorbed dose of 0.077 ± 0.008 mSv/MBq. The mean effective dose (ICRP 103) was 0.021 ± 0.001 mSv/MBq. Conclusion: PET imaging with 68Ga-citrate is associated with modest radiation exposure. A 200 MBq injection of 68Ga-citrate results in an effective radiation dose of 4.2 mSv, which is in the same range as other 68Ga-labeled tracers. This suggests the feasibility of clinical studies using 68Ga-citrate imaging in humans and the possibility of performing multiple scans in the same subjects across the course of a year.</p