Purpose: Assessing renal perfusion in-vivo is challenging and quantitativeinformation regarding renal hemodynamics is hardly incorporated in medicaldecision-making while abnormal renal hemodynamics... Show morePurpose: Assessing renal perfusion in-vivo is challenging and quantitativeinformation regarding renal hemodynamics is hardly incorporated in medicaldecision-making while abnormal renal hemodynamics might play a crucial rolein the onset and progression of renal disease. Combining physiological stimuliwith rubidium-82 positron emission tomography/computed tomography (82 RbPET/CT) offers opportunities to test the kidney perfusion under various condi-tions. The aim of this study is: (1) to investigate the application of a one-tissuecompartment model for measuring renal hemodynamics with dynamic 82 RbPET/CT imaging, and (2) to evaluate whether dynamic PET/CT is sensitiveto detect differences in renal hemodynamics in stress conditions compared toresting state.Methods: A one-tissue compartment model for the kidney was applied to car-diac 82 Rb PET/CT scans that were obtained for ischemia detection as part ofclinical care. Retrospective data, collected from 17 patients undergoing dynamicmyocardial 82 Rb PET/CT imaging in rest, were used to evaluate various CT-based volumes of interest (VOIs) of the kidney. Subsequently, retrospectivedata, collected from 10 patients (five impaired kidney functions and five controls)undergoing dynamic myocardial 82 Rb PET/CT imaging, were used to evaluateimage-derived input functions (IDIFs), PET-based VOIs of the kidney, extractionfractions, and whether dynamic 82 Rb PET/CT can measure renal hemodynam-ics differences using the renal blood flow (RBF) values in rest and after exposureto adenosine pharmacological stress.Results: The delivery rate (K1 ) values showed no significant (p = 0.14) differ-ence between the mean standard deviation (SD) K1 values using one CT-basedVOI and the use of two, three, and four CT-based VOIs, respectively 2.01(0.32),1.90(0.40), 1.93(0.39), and 1.94(0.40) mL/min/mL. The ratio between RBF inrest and RBF in pharmacological stress for the controls were overall significantlylower compared to the impaired kidney function group for both PET-based delin-eation methods (region growing and iso-contouring), with the smallest medianinterquartile range (IQR) of 0.40(0.28–0.66) and 0.96(0.62–1.15), respectively(p < 0.05). The K1 of the impaired kidney function group were close to1.0 mL/min/mL. Show less
PurposeThe aim of this study was to investigate the biodistribution of (super-)selective trans-arterial radioembolization (TARE) with holmium-166 microspheres (166Ho-MS), when administered as... Show morePurposeThe aim of this study was to investigate the biodistribution of (super-)selective trans-arterial radioembolization (TARE) with holmium-166 microspheres (166Ho-MS), when administered as adjuvant therapy after RFA of HCC 2-5 cm. The objective was to establish a treatment volume absorbed dose that results in an absorbed dose of >= 120 Gy on the hyperemic zone around the ablation necrosis (i.e., target volume).MethodsIn this multicenter, prospective dose-escalation study in BCLC early stage HCC patients with lesions 2-5 cm, RFA was followed by (super-)selective infusion of 166Ho-MS on day 5-10 after RFA. Dose distribution within the treatment volume was based on SPECT-CT. Cohorts of up to 10 patients were treated with an incremental dose (60 Gy, 90 Gy, 120 Gy) of 166Ho-MS to the treatment volume. The primary endpoint was to obtain a target volume dose of >= 120 Gy in 9/10 patients within a cohort.ResultsTwelve patients were treated (male 10; median age, 66.5 years (IQR, [64.3-71.7])) with a median tumor diameter of 2.7 cm (IQR, [2.1-4.0]). At a treatment volume absorbed dose of 90 Gy, the primary endpoint was met with a median absorbed target volume dose of 138 Gy (IQR, [127-145]). No local recurrences were found within 1-year follow-up.ConclusionAdjuvant (super-)selective infusion of 166Ho-MS after RFA for the treatment of HCC can be administered safely at a dose of 90 Gy to the treatment volume while reaching a dose of >= 120 Gy to the target volume and may be a favorable adjuvant therapy for HCC lesions 2-5 cm.Trial registrationClinicaltrials.gov NCT03437382. (registered: 19-02-2018) Show less
Kullberg, M.L.J.; Schoorl, M.; Oprel, D.A.C.; Hoeboer, C.M.; Smit, F.; Does, W. van der; ... ; Hout, W. van den 2023
Background: Prolonged exposure (PE) is an effective treatment for post-traumatic stress disorder (PTSD).Objective: This study aimed to analyse the cost-effectiveness of three exposure-based... Show moreBackground: Prolonged exposure (PE) is an effective treatment for post-traumatic stress disorder (PTSD).Objective: This study aimed to analyse the cost-effectiveness of three exposure-based treatments in patients with childhood abuse-related PTSD.Method: A net–benefit analysis was conducted alongside a pragmatic randomized controlled trial with participants (N = 149) randomized to three conditions: PE (n = 48), intensified PE (i-PE, n = 51), and phase-based PE [Skills Training in Affective and Interpersonal Regulation (STAIR) + PE, n = 50]. Assessments took place at baseline (T0), post-treatment (T3), 6 month follow-up (T4), and 12 month follow-up (T5). Costs stemming from healthcare utilization and productivity losses were estimated using the Trimbos/iMTA questionnaire for Costs associated with Psychiatric Illness. Quality-adjusted life-years (QALYs) were based on the 5-level EuroQoL 5 Dimensions (EQ-5D-5L) using the Dutch tariff. Missing values of costs and utilities were multiply imputed. To compare i-PE to PE and STAIR + PE to PE, pair-wise unequal-variance t-tests were conducted. Net–benefit analysis was used to relate costs to QALYs and to draw acceptability curves.Results: Intervention costs did not differ across the three treatment conditions. Total medical costs, productivity losses, total societal costs, and EQ-5D-5L-based QALYs did not differ between treatment conditions either (all p > .10). At the relevant €50,000/QALY threshold, the probability of one treatment being more cost-effective than another was 32%, 28%, and 40% for PE, i-PE, and STAIR-PE, respectively.Conclusion: Three equally effective treatments were compared and no differences in cost-effectiveness between treatments were found. Therefore, we advocate the implementation and adoption of any of the treatments and endorse shared decision making. Show less
Vuijk, F.A.; Shahbazi, S.F.; Noortman, W.A.; Velden, F.H.P. van; Dibbets-Schneider, P.; Marinelli, A.W.K.S.; ... ; Geus-Oei, L.F. de 2023
ObjectiveIn this pilot study, we investigated the feasibility of response prediction using digital [F-18]FDG PET/computed tomography (CT) and multiparametric MRI before, during, and after... Show moreObjectiveIn this pilot study, we investigated the feasibility of response prediction using digital [F-18]FDG PET/computed tomography (CT) and multiparametric MRI before, during, and after neoadjuvant chemoradiation therapy in locally advanced rectal cancer (LARC) patients and aimed to select the most promising imaging modalities and timepoints for further investigation in a larger trial. MethodsRectal cancer patients scheduled to undergo neoadjuvant chemoradiation therapy were prospectively included in this trial, and underwent multiparametric MRI and [F-18]FDG PET/CT before, 2 weeks into, and 6-8 weeks after chemoradiation therapy. Two groups were created based on pathological tumor regression grade, that is, good responders (TRG1-2) and poor responders (TRG3-5). Using binary logistic regression analysis with a cutoff value of P <= 0.2, promising predictive features for response were selected. ResultsNineteen patients were included. Of these, 5 were good responders, and 14 were poor responders. Patient characteristics of these groups were similar at baseline. Fifty-seven features were extracted, of which 13 were found to be promising predictors of response. Baseline [T2: volume, diffusion-weighted imaging (DWI): apparent diffusion coefficient (ADC) mean, DWI: difference entropy], early response (T2: volume change, DWI: ADC mean change) and end-of-treatment presurgical evaluation MRI (T2: gray level nonuniformity, DWI: inverse difference normalized, DWI: gray level nonuniformity normalized), as well as baseline (metabolic tumor volume, total lesion glycolysis) and early response PET/CT (Delta maximum standardized uptake value, Delta peak standardized uptake value corrected for lean body mass), were promising features. ConclusionBoth multiparametric MRI and [F-18]FDG PET/CT contain promising imaging features to predict response to neoadjuvant chemoradiotherapy in LARC patients. A future larger trial should investigate baseline, early response, and end-of-treatment presurgical evaluation MRI and baseline and early response PET/CT. Show less
Vuijk, F.A.; Shahbazi, S.F.; Noortman, W.A.; Velden, F.H.P. van; Dibbets-Schneider, P.; Marinelli, A.W.K.S.; ... ; Geus-Oei, L.F. de 2023
Objective In this pilot study, we investigated the feasibility of response prediction using digital [18F]FDG PET/computed tomography (CT) and multiparametric MRI before, during, and after... Show moreObjective In this pilot study, we investigated the feasibility of response prediction using digital [18F]FDG PET/computed tomography (CT) and multiparametric MRI before, during, and after neoadjuvant chemoradiation therapy in locally advanced rectal cancer (LARC) patients and aimed to select the most promising imaging modalities and timepoints for further investigation in a larger trial.Methods Rectal cancer patients scheduled to undergo neoadjuvant chemoradiation therapy were prospectively included in this trial, and underwent multiparametric MRI and [18F]FDG PET/CT before, 2 weeks into, and 6–8 weeks after chemoradiation therapy. Two groups were created based on pathological tumor regression grade, that is, good responders (TRG1-2) and poor responders (TRG3-5). Using binary logistic regression analysis with a cutoff value of P ≤ 0.2, promising predictive features for response were selected.Results Nineteen patients were included. Of these, 5 were good responders, and 14 were poor responders. Patient characteristics of these groups were similar at baseline. Fifty-seven features were extracted, of which 13 were found to be promising predictors of response. Baseline [T2: volume, diffusion-weighted imaging (DWI): apparent diffusion coefficient (ADC) mean, DWI: difference entropy], early response (T2: volume change, DWI: ADC mean change) and end-of-treatment presurgical evaluation MRI (T2: gray level nonuniformity, DWI: inverse difference normalized, DWI: gray level nonuniformity normalized), as well as baseline (metabolic tumor volume, total lesion glycolysis) and early response PET/CT (Δ maximum standardized uptake value, Δ peak standardized uptake value corrected for lean body mass), were promising features.Conclusion Both multiparametric MRI and [18F]FDG PET/CT contain promising imaging features to predict response to neoadjuvant chemoradiotherapy in LARC patients. A future larger trial should investigate baseline, early response, and end-of-treatment presurgical evaluation MRI and baseline and early response PET/CT. Show less
Chen, L.L.; Burgt, A. van de; Smit, F.; Audhoe, R.S.; Boer, S.M. de; Velden, F.H.P. van; Geus-Oei, L.F. de 2023
ObjectiveSince the end of 2019, the coronavirus disease 2019 (COVID-19) virus has infected millions of people, of whom a significant group suffers from sequelae from COVID-19, termed long COVID. As... Show moreObjectiveSince the end of 2019, the coronavirus disease 2019 (COVID-19) virus has infected millions of people, of whom a significant group suffers from sequelae from COVID-19, termed long COVID. As more and more patients emerge with long COVID who have symptoms of fatigue, myalgia and joint pain, we must examine potential biomarkers to find quantifiable parameters to define the underlying mechanisms and enable response monitoring. The aim of this study is to investigate the potential added value of [F-18]FDG-PET/computed tomography (CT) for this group of long COVID patients. MethodsFor this proof of concept study, we evaluated [F-18]FDG-PET/CT scans of long COVID patients and controls. Two analyses were performed: semi-quantitative analysis using target-to-background ratios (TBRs) in 24 targets and total vascular score (TVS) assessed by two independent nuclear medicine physicians. Mann-Whitney U-test was performed to find significant differences between the two groups. ResultsThirteen patients were included in the long COVID group and 25 patients were included in the control group. No significant differences (P < 0.05) were found between the long COVID group and the control group in the TBR or TVS assessment. ConclusionAs we found no quantitative difference in the TBR or TVS between long COVID patients and controls, we are unable to prove that [F-18]FDG is of added value for long COVID patients with symptoms of myalgia or joint pain. Prospective cohort studies are necessary to understand the underlying mechanisms of long COVID. Show less
Chen, L.L.; Burgt, A. van de; Smit, F.; Audhoe, R.S.; Boer, S.M. de; Velden, F.H.P. van; Geus-Oei, L.F. de 2023
Objective Since the end of 2019, the coronavirus disease 2019 (COVID-19) virus has infected millions of people, of whom a significant group suffers from sequelae from COVID-19, termed long COVID.... Show moreObjective Since the end of 2019, the coronavirus disease 2019 (COVID-19) virus has infected millions of people, of whom a significant group suffers from sequelae from COVID-19, termed long COVID. As more and more patients emerge with long COVID who have symptoms of fatigue, myalgia and joint pain, we must examine potential biomarkers to find quantifiable parameters to define the underlying mechanisms and enable response monitoring. The aim of this study is to investigate the potential added value of [18F]FDG-PET/computed tomography (CT) for this group of long COVID patients.Methods For this proof of concept study, we evaluated [18F]FDG-PET/CT scans of long COVID patients and controls. Two analyses were performed: semi-quantitative analysis using target-to-background ratios (TBRs) in 24 targets and total vascular score (TVS) assessed by two independent nuclear medicine physicians. Mann–Whitney U-test was performed to find significant differences between the two groups.Results Thirteen patients were included in the long COVID group and 25 patients were included in the control group. No significant differences (P < 0.05) were found between the long COVID group and the control group in the TBR or TVS assessment.Conclusion As we found no quantitative difference in the TBR or TVS between long COVID patients and controls, we are unable to prove that [18F]FDG is of added value for long COVID patients with symptoms of myalgia or joint pain. Prospective cohort studies are necessary to understand the underlying mechanisms of long COVID. Show less
Kullberg, M.L.J.; Schoorl, S.M.D.; Oprel, D.A.C.; Hoeboer, C.M.; Smit, F.; Does, A.J.W. van der; ... ; Hout, W. van den 2023
Simple Summary Prostate-specific membrane antigen (PSMA)-targeted PET/CT imaging is increasingly being used for (re)staging in prostate cancer. Although PSMA suggests specificity to prostate cancer... Show moreSimple Summary Prostate-specific membrane antigen (PSMA)-targeted PET/CT imaging is increasingly being used for (re)staging in prostate cancer. Although PSMA suggests specificity to prostate cancer, previous preclinical studies and case reports have shown this protein to be overexpressed by multiple other tumor types. This study aims to investigate the applicability of a PSMA-targeted PET/CT tracer to detect gastrointestinal cancers, including colon, pancreatic and gastric cancer. Current imaging modalities frequently misjudge disease stage in colorectal, gastric and pancreatic cancer. As treatment decisions are dependent on disease stage, incorrect staging has serious consequences. Previous preclinical research and case reports indicate that prostate-specific membrane antigen (PSMA)-targeted PET/CT imaging might provide a solution to some of these challenges. This prospective clinical study aims to assess the feasibility of [F-18]DCFPyL PET/CT imaging to target and visualize primary colon, gastric and pancreatic cancer. In this prospective clinical trial, patients with colon, gastric and pancreatic cancer were included and underwent both [F-18]DCFPyL and [F-18]FDG PET/CT scans prior to surgical resection or (for gastric cancer) neoadjuvant therapy. Semiquantitative analysis of immunohistochemical PSMA staining was performed on the surgical resection specimens, and the results were correlated to imaging parameters. The results of this study demonstrate detection of the primary tumor by [F-18]DCFPyL PET/CT in 7 out of 10 patients with colon, gastric and pancreatic cancer, with a mean tumor-to-blood pool ratio (TBR) of 3.3 and mean SUVmax of 3.6. However, due to the high surrounding uptake, visual distinction of these tumors was difficult, and the SUVmax and TBR on [F-18]FDG PET/CT were significantly higher than on [F-18]DCFPyL PET/CT. In addition, no correlation between PSMA expression in the resection specimen and SUVmax on [F-18]DCFPyL PET/CT was found. In conclusion, the detection of several gastrointestinal cancers using [F-18]DCFPyL PET/CT is feasible. However, low tumor expression and high uptake physiologically in organs/background hamper the clear distinction of the tumor. As a result, [F-18]FDG PET/CT was superior in detecting colon, gastric and pancreatic cancers. Show less
Purpose To investigate the biodistribution of holmium-166 microspheres (Ho-166-MS) when administered after radiofrequency ablation (RFA) of early-stage hepatocellular carcinoma (HCC). The aim is to... Show morePurpose To investigate the biodistribution of holmium-166 microspheres (Ho-166-MS) when administered after radiofrequency ablation (RFA) of early-stage hepatocellular carcinoma (HCC). The aim is to establish a perfused liver administration dose that results in a tumoricidal dose of holmium-166 on the hyperaemic zone around the ablation necrosis (i.e. target volume). Materials and Methods This is a multicentre, prospective, dose-escalation study in HCC patients with a solitary lesion 2-5 cm, or a maximum of 3 lesions of <= 3 cm each. The day after RFA patients undergo angiography and cone-beam CT (CBCT) with (super)selective infusion of technetium-99 m labelled microalbumin aggregates (Tc-99m-MAA). The perfused liver volume is segmented from the CBCT and Ho-166-MS is administered to this treatment volume 5-10 days later. The dose of holmium-166 is escalated in a maximum of 3 patient cohorts (60 Gy, 90 Gy and 120 Gy) until the endpoint is reached. SPECT/CT is used to determine the biodistribution of holmium-166. The endpoint is met when a dose of >= 120 Gy has been reached on the target volume in 9/10 patients of a cohort. Secondary endpoints include toxicity, local recurrence, disease-free and overall survival. Discussion This study aims to find the optimal administration dose of adjuvant radioembolization with Ho-166-MS after RFA. Ultimately, the goal is to bring the efficacy of thermal ablation up to par with surgical resection for early-stage HCC patients. Show less
Purpose To investigate the biodistribution of holmium166 microspheres (166Ho-MS) when administered after radiofrequency ablation (RFA) of early-stage hepatocellular carcinoma (HCC). The aim is to... Show morePurpose To investigate the biodistribution of holmium166 microspheres (166Ho-MS) when administered after radiofrequency ablation (RFA) of early-stage hepatocellular carcinoma (HCC). The aim is to establish a perfused liver administration dose that results in a tumoricidal dose of holmium-166 on the hyperaemic zone around the ablation necrosis (i.e. target volume). Materials and Methods This is a multicentre, prospective, dose-escalation study in HCC patients with a solitary lesion 2–5 cm, or a maximum of 3 lesions of B 3 cm each. The day after RFA patients undergo angiography and conebeam CT (CBCT) with (super)selective infusion of technetium-99 m labelled microalbumin aggregates (99mTcMAA). The perfused liver volume is segmented from the CBCT and 166Ho-MS is administered to this treatment volume 5–10 days later. The dose of holmium-166 is escalated in a maximum of 3 patient cohorts (60 Gy, 90 Gy and 120 Gy) until the endpoint is reached. SPECT/CT is used to determine the biodistribution of holmium-166. The endpoint is met when a dose of C 120 Gy has been reached on the target volume in 9/10 patients of a cohort. Secondary endpoints include toxicity, local recurrence, disease-free and overall survival. Discussion This study aims to find the optimal administration dose of adjuvant radioembolization with 166Ho-MS after RFA. Ultimately, the goal is to bring the efficacy of thermal ablation up to par with surgical resection for earlystage HCC patients. Show less
Bruggen, W. van der; Vriens, D.; Meier, M.E.; Smit, F.; Winter, E.M.; Geus-Oei, L.F. de; Appelman-Dijkstra, N.M. 2022
Background: A previous randomized controlled trial in older adults with anxiety symptoms found no differences between a brief blended Acceptance and Commitment Therapy (ACT) intervention and brief... Show moreBackground: A previous randomized controlled trial in older adults with anxiety symptoms found no differences between a brief blended Acceptance and Commitment Therapy (ACT) intervention and brief face-to-face Cognitive Behavior Therapy (CBT) regarding anxiety symptom severity at posttreatment and 12-month follow-up. A health-economic evaluation comparing these interventions has not yet been conducted. Objective: This study examined the one-year cost-effectiveness and cost-utility of blended ACT compared to face-to-face CBT for older adults with anxiety symptoms. Methods: The economic evaluation was embedded in a randomized controlled trial comparing blended ACT to CBT in 314 older adults with mild to moderately severe anxiety symptoms. Data were collected at baseline and 3, 6 and 12 months post baseline. For the cost-effectiveness analysis, treatment response was defined as a reliable improvement in anxiety symptom severity (measured with the Generalized Anxiety Disorder-7) between baseline and 12-month follow-up. To assess cost-utility, quality-adjusted life years (QALYs) were computed using EuroQol-5 Dimensions-5 Levels-5 utility scores. Analyses took the societal perspective, including both healthcare costs and productivity costs. Incremental cost-effectiveness ratios were calculated using 2500 bootstraps of seemingly unrelated regression equations of costs and effects. Sensitivity analyses were performed to assess the robustness of the findings. Results: Differences between the blended ACT group and CBT group in treatment response and QALYs were statistically insignificant and clinically irrelevant. The ACT intervention was associated with an average per-participant cost reduction of (sic)466 ($593) compared to CBT, which resulted from lower productivity costs in the blended ACT group. From a healthcare perspective, the ACT intervention was associated with higher costs (by (sic)71 ($90)) than CBT. Conclusions: The results do not indicate that from a health-economic perspective blended ACT should be preferred over CBT in the treatment of older adults with anxiety symptoms. The findings support a model of shared decision making, where clinicians and patients collaboratively decide on the preferred intervention, based on ethical-medical, practical and personal considerations. Show less
Psychological problems like procrastination, perfectionism, low self-esteem, test anxiety and stress are common among college students. There are evidence-based interventions available for these... Show morePsychological problems like procrastination, perfectionism, low self-esteem, test anxiety and stress are common among college students. There are evidence-based interventions available for these problems that not only have direct effects on these problems, but also indirect effects on mental disorders such as depression and anxiety disorders. Targeting these psychological problems may offer new opportunities to prevent and treat mental disorders in a way that is less stigmatizing to students. In this study we examined the association of five psychological problems with five common mental disorders (panic, generalized anxiety, bipolar, major depressive, and substance use disorder) in a sample of 2,449 students from two Dutch universities. Psychological problems were measured with one item for each problem and mental disorders were measured with the Composite International Diagnostic Interview Screening Scales. Associations were examined with Poisson regression models as relative risks (RR) of the disorders as a function of the psychological problems. The population attributable fraction (PAF) indicates by what percentage the prevalence of the mental disorder would be reduced if the psychological problem was addressed successfully by an intervention. Especially generalized anxiety disorder was strongly associated with psychological problems (strong associations with stress and low self-esteem and moderately with test anxiety). The group with three or more psychological problems had a strongly increased risk for generalized anxiety (RR = 11.25; 95% CI: 7.51-16.85), and a moderately increase risk for major depression (RR = 3.22; 95% CI: 2.63-3.95), panic disorder (RR = 3.19; 95% CI: 1.96-5.20) and bipolar disorder (RR = 3.66; 95% CI: 2.40-5.58). The PAFs for having any of the psychological problems (one or more) were considerable, especially for generalized anxiety (60.8%), but also for panic disorder (35.1%), bipolar disorder (30.6%) and major depression (34.0%). We conclude that common psychological problems are associated with mental disorders and with each other. After adjustment, psychological problems are associated with different patterns of mental disorders. If the impact of the psychological problems could be taken away, the prevalence of several mental disorders would be reduced considerably. The psychological problems may provide a promising target to indirectly prevent and intervene in psychopathology in hard to reach college students with mental disorders. Show less
Bruggen, W. van der; Vriens, D.; Meier, M.E.; Smit, F.; Winter, E.M.; Geus-Oei, L.F. de; Appelman-Dijkstra, N.M. 2021
Context: The correlation between fibrous dysplasia/McCune-Albright syndrome (FD/MAS) skeletal disease burden on Na[F-18]F positron emission tomography-computed tomography (PET-CT) and serum bone... Show moreContext: The correlation between fibrous dysplasia/McCune-Albright syndrome (FD/MAS) skeletal disease burden on Na[F-18]F positron emission tomography-computed tomography (PET-CT) and serum bone turnover markers (BTMs) was recently described. The effect of treatment on lesional fluoride burden in FD/MAS is unknown.Objective: To investigate treatment response measurements in patients with FD/MAS who underwent Na[F-18]F-PET-CT and treatment with antiresorptives.Methods: Observational case series at an academic center of expertise for rare bone diseases. Fifteen consecutive patients were observed with FD/MAS with baseline and follow-up Na[F-18]F-PET-CT parameters of healthy bone and FD lesions, BTMs, and pain scores at start of denosumab (n=8) treatment and non-denosumab patients (n=7). On Na[F-18]F-PET-CT the volumetric measures of FD burden (fluoride tumor volume [FTV]) and "fraction affected skeleton" (FAS) represented the portion of the skeleton affected. This was correlated with BTMs and pain.Results: Disease activity decreased significantly, with FTV 361 cm(3) to 97 cm(3) (P=.018) in denosumab-treated patients, but not in non-denosumab patients (P=.249). Serum P1NP and alkaline phosphatase (ALP) decreased significantly: 82 ng/mL vs 55 ng/mL (P=.023) and 119 IU/L vs 84 IU/L (P=.020), respectively. In denosumab-treated patients pain scores improved leading to pain medication reduction. This correlated with lesional uptake, but healthy bone activity did not change. BTMs and FTV correlated positively (P1NP r=0.730, P<.001; and ALP r=0.406, P=.006), as did change in BTMs and FTV: P1NP (P=0.032) and ALP (P=0.024). FAS strongly correlated with treatment-induced decrease in ALP (P=.027) and P1NP (P=.009).Conclusion: Na[F-18]F-PET-CT captured treatment-induced lesional changes which correlated with BTMs and pain reduction. Therefore Na[F-18]F-PET-CT can be used as an objective local parameter of response to denosumab treatment in FD/MAS. Show less
Bruggen, W. van der; Vriens, D.; Meier, M.E.; Smit, F.; Winter, E.M.; Geus-Oei, L.F. de; Appelman-Dijkstra, N.M. 2021
Context The correlation between fibrous dysplasia/McCune-Albright syndrome (FD/MAS) skeletal disease burden on Na[F-18]F positron emission tomography-computed tomography (PET-CT) and serum bone... Show moreContext The correlation between fibrous dysplasia/McCune-Albright syndrome (FD/MAS) skeletal disease burden on Na[F-18]F positron emission tomography-computed tomography (PET-CT) and serum bone turnover markers (BTMs) was recently described. The effect of treatment on lesional fluoride burden in FD/MAS is unknown.Objective To investigate treatment response measurements in patients with FD/MAS who underwent Na[F-18]F-PET-CT and treatment with antiresorptives.Methods Observational case series at an academic center of expertise for rare bone diseases. Fifteen consecutive patients were observed with FD/MAS with baseline and follow-up Na[F-18]F-PET-CT parameters of healthy bone and FD lesions, BTMs, and pain scores at start of denosumab (n = 8) treatment and non-denosumab patients (n = 7). On Na[F-18]F-PET-CT the volumetric measures of FD burden (fluoride tumor volume [FTV]) and "fraction affected skeleton" (FAS) represented the portion of the skeleton affected. This was correlated with BTMs and pain.Results Disease activity decreased significantly, with FTV 361 cm(3) to 97 cm(3) (P = .018) in denosumab-treated patients, but not in non-denosumab patients (P = .249). Serum P1NP and alkaline phosphatase (ALP) decreased significantly: 82 ng/mL vs 55 ng/mL (P = .023) and 119 IU/L vs 84 IU/L (P = .020), respectively. In denosumab-treated patients pain scores improved leading to pain medication reduction. This correlated with lesional uptake, but healthy bone activity did not change. BTMs and FTV correlated positively (P1NP r = 0.730, P < .001; and ALP r = 0.406, P = .006), as did change in BTMs and FTV: P1NP (P = 0.032) and ALP (P = 0.024). FAS strongly correlated with treatment-induced decrease in ALP (P = .027) and P1NP (P = .009).Conclusion Na[F-18]F-PET-CT captured treatment-induced lesional changes which correlated with BTMs and pain reduction. Therefore Na[F-18]F-PET-CT can be used as an objective local parameter of response to denosumab treatment in FD/MAS. Show less
Witlox, M.; Garnefski, N.; Kraaij, V.; Waal, M.W.M. de; Smit, F.; Bohlmeijer, E.; Spinhoven, P. 2021
Background: Anxiety symptoms in older adults are prevalent and disabling but often go untreated. Most trials on psychological interventions for anxiety in later life have examined the effectiveness... Show moreBackground: Anxiety symptoms in older adults are prevalent and disabling but often go untreated. Most trials on psychological interventions for anxiety in later life have examined the effectiveness of face-to-face cognitive behavioral therapy (CBT). To bridge the current treatment gap, other treatment approaches and delivery formats should also be evaluated.Objective: This study is the first to examine the effectiveness of a brief blended acceptance and commitment therapy (ACT) intervention for older adults with anxiety symptoms, compared with a face-to-face CBT intervention. Methods: Adults aged between 55-75 years (n=314) with mild to moderately severe anxiety symptoms were recruited from general practices and cluster randomized to either blended ACT or face-to-face CBT. Assessments were performed at baseline (T0), posttreatment (T1), and at 6- and 12-month follow-ups (T2 and T3, respectively). The primary outcome was anxiety symptom severity (Generalized Anxiety Disorder-7). Secondary outcomes were positive mental health, depression symptom severity, functional impairment, presence of Diagnostic and Statistical Manual of Mental Disorders V anxiety disorders, and treatment satisfaction. Results: Conditions did not differ significantly regarding changes in anxiety symptom severity during the study period (T0-T1: B=.18, P=.73; T1-T2: B=-.63, P=.26; T1-T3: B=-.33, P=.59). Large reductions in anxiety symptom severity (Cohen d >= 0.96) were found in both conditions post treatment, and these were maintained at the 12-month follow-up. The rates of clinically significant changes in anxiety symptoms were also not different for the blended ACT group and CBT group (chi(2)(1)=0.2, P=.68). Regarding secondary outcomes, long-term effects on positive mental health were significantly stronger in the blended ACT group (B=.27, P=.03, Cohen d=0.29), and treatment satisfaction was significantly higher for blended ACT than CBT (B=3.19, P<.001, Cohen d=0.78). No other differences between the conditions were observed in the secondary outcomes.Conclusions: The results show that blended ACT is a valuable treatment alternative to CBT for anxiety in later life. Show less
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