FDG-PET/CT in indeterminate thyroid nodules: cost-utility analysis alongside a randomised controlled trial.

PURPOSE: To evaluate cost-effectiveness of an [18F]FDG-PET/CT-driven diagnostic workup as compared to diagnostic surgery, for thyroid nodules with Bethesda III/IV cytology. [18F]FDG-PET/CT avoids 40% of futile diagnostic surgeries for benign Bethesda III/IV nodules. METHODS: Lifelong societal costs and quality-adjusted life years (QALYs) were assessed for 132 patients participating in a randomised controlled multicentre trial comparing [18F]FDG-PET/CT to diagnostic surgery. The observed 1-year trial results were extrapolated using a Markov model. The probability of cost-effectiveness was estimated using cost-effectiveness acceptability curves, taking uncertainty about sampling, imputation, and parameters into account. RESULTS: The observed 1-year cost difference of [18F]FDG-PET/CT as compared to diagnostic surgery was - €1000 (95% CI: - €2100 to €0) for thyroid nodule-related care (p = 0.06). From the broader societal perspective, the 1-year difference in total societal costs was - €4500 (- €9200 to €150) (p = 0.06). Over the modelled lifelong period, the cost difference was - €9900 (- €23,100 to €3200) (p = 0.14). The difference in QALYs was 0.019 (- 0.045 to 0.083) at 1 year (p = 0.57) and 0.402 (- 0.581 to 1.385) over the lifelong period (p = 0.42). For a willingness to pay of €50,000 per QALY, an [18F]FDG-PET/CT-driven work-up was the cost-effective strategy with 84% certainty. CONCLUSION: Following the observed reduction in diagnostic surgery, an [18F]FDG-PET/CT-driven diagnostic workup reduced the 1-year thyroid nodule-related and societal costs while sustaining quality of life. It is very likely cost-effective as compared to diagnostic surgery for Bethesda III/IV nodules. TRIAL REGISTRATION NUMBER: This trial is registered with ClinicalTrials.gov: NCT02208544 (5 August 2014), https://clinicaltrials.gov/ct2/show/NCT02208544 .

[18F]FDG-PET/CT to prevent futile surgery in indeterminate thyroid nodules: a blinded, randomised controlled multicentre trial.

PURPOSE: To assess the impact of an [18F]FDG-PET/CT-driven diagnostic workup to rule out malignancy, avoid futile diagnostic surgeries, and improve patient outcomes in thyroid nodules with indeterminate cytology. METHODS: In this double-blinded, randomised controlled multicentre trial, 132 adult euthyroid patients with scheduled diagnostic surgery for a Bethesda III or IV thyroid nodule underwent [18F]FDG-PET/CT and were randomised to an [18F]FDG-PET/CT-driven or diagnostic surgery group. In the [18F]FDG-PET/CT-driven group, management was based on the [18F]FDG-PET/CT result: when the index nodule was visually [18F]FDG-positive, diagnostic surgery was advised; when [18F]FDG-negative, active surveillance was recommended. The nodule was presumed benign when it remained unchanged on ultrasound surveillance. In the diagnostic surgery group, all patients were advised to proceed to the scheduled surgery, according to current guidelines. The primary outcome was the fraction of unbeneficial patient management in one year, i.e., diagnostic surgery for benign nodules and active surveillance for malignant/borderline nodules. Intention-to-treat analysis was performed. Subgroup analyses were performed for non-Hürthle cell and Hürthle cell nodules. RESULTS: Patient management was unbeneficial in 42% (38/91 [95% confidence interval [CI], 32-53%]) of patients in the [18F]FDG-PET/CT-driven group, as compared to 83% (34/41 [95% CI, 68-93%]) in the diagnostic surgery group (p < 0.001). [18F]FDG-PET/CT-driven management avoided 40% (25/63 [95% CI, 28-53%]) diagnostic surgeries for benign nodules: 48% (23/48 [95% CI, 33-63%]) in non-Hürthle cell and 13% (2/15 [95% CI, 2-40%]) in Hürthle cell nodules (p = 0.02). No malignant or borderline tumours were observed in patients under surveillance. Sensitivity, specificity, negative and positive predictive value, and benign call rate (95% CI) of [18F]FDG-PET/CT were 94.1% (80.3-99.3%), 39.8% (30.0-50.2%), 95.1% (83.5-99.4%), 35.2% (25.4-45.9%), and 31.1% (23.3-39.7%), respectively. CONCLUSION: An [18F]FDG-PET/CT-driven diagnostic workup of indeterminate thyroid nodules leads to practice changing management, accurately and oncologically safely reducing futile surgeries by 40%. For optimal therapeutic yield, application should be limited to non-Hürthle cell nodules. TRIAL REGISTRATION NUMBER: This trial is registered with ClinicalTrials.gov: NCT02208544 (5 August 2014), https://clinicaltrials.gov/ct2/show/NCT02208544 .

Cluster randomised trial on the effectiveness of a computerised prompt to refer (back) patients with type 2 diabetes.

AIMS: Information and communications technology (ICT) could support care organisations to cope with the increasing number of patients with diabetes mellitus. We aimed to aid diabetes care providers in allocating patients to the preferred treatment setting (hospital outpatient clinic or primary care practice), by using the Electronic Medical Record (EMR). METHODS: A cluster randomised controlled trial. Physicians in primary and secondary care practices of the intervention group received an advisory message in the EMR during diabetes consultations if patients were treated in the 'incorrect' setting according to national management guidelines. Primary outcome: the proportion of patients that shifted to the correct treatment setting at one year follow-up. RESULTS: 47 (38 primary care and 9 internist) practices and 2778 patients were included. At baseline, 1197 (43.1%) patients were in the correct treatment setting (intervention 599; control 598). Advice most often (68.4%) regarded a consultation with the internist. After one year 12.4% of the patients in the intervention and 10.6% in the control group (p = 0.30) had shifted to the correct setting. Main reasons for not following advice were: 1. physician's preference to consider other treatment options; 2. patients' preferences. CONCLUSIONS: We could not find evidence that using the EMR to send consultation-linked advice to physicians resulted in a shift in patients. Physicians will not follow the advice, at least partly due to patients' preferences.

Diabetes care providers' opinions and working methods after four years of experience with a diabetes patient web portal; a survey among health care providers in general practices and an outpatient clinic.

BACKGROUND: To gain insight into the opinions and working methods of diabetes care providers after using a diabetes web portal for 4 years in order to understand the role of the provider in patients' web portal use. METHODS: Survey among physicians and nurses from general practices and an outpatient clinic, correlated with data from the common web portal. RESULTS: One hundred twenty-eight questionnaires were analysed (response rate 56.6%). Responders' mean age was 46.2 ± 9.8 years and 43.8% were physicians. The majority was of opinion that the portal improves patients' diabetes knowledge (90.6%) and quality of care (72.7%). Although uploading glucose diary (93.6%) and patient access to laboratory and clinical notes (91.2 and 71.0%) were considered important, these features were recommended to patients in only 71.8 and 19.5% respectively. 64.8% declared they informed their patients about the portal and 45.3% handed-out the information leaflet and website address. The portal was especially recommended to type 1 diabetes patients (78.3%); those on insulin (84.3%) and patients aged< 65 years (72.4%). Few found it timesaving (21.9%). Diabetes care providers' opinions were not associated with patients' portal use. CONCLUSIONS: Providers are positive about patients web portals but still not recommend or encourage the use to all patients. There seems room for improvement in their working methods.

Patients' Experiences with and Attitudes towards a Diabetes Patient Web Portal.

OBJECTIVE: A diabetes patient web portal allows patients to access their personal health record and may improve diabetes outcomes; however, patients' adoption is slow. We aimed to get insight into patients' experiences with a web portal to understand how the portal is being used, how patients perceive the content of the portal and to assess whether redesign of the portal might be needed. MATERIALS AND METHODS: A survey among 1500 patients with type 1 and type 2 diabetes with a login to a patient portal. SETTING: 62 primary care practices and one outpatient hospital clinic, using a combined patient portal. We compared patients who requested a login but never used it or once ('early quitters') with patients who used it at least two times ('persistent users'). RESULTS: 632 patients (42.1%) returned the questionnaire. Their mean age was 59.7 years, 63.1% was male and 81.8% had type 2 diabetes. 413 (65.3%) people were persistent users and 34.7% early quitters. In the multivariable analysis, insulin use (OR2.07; 95%CI[1.18-3.62]), experiencing more frequently hyperglycemic episodes (OR1.30;95%CI[1.14-1.49]) and better diabetes knowledge (OR1.02, 95%CI[1.01-1.03]) do increase the odds of being a persistent user. Persistent users perceived the usefulness of the patient portal significantly more favorable. However, they also more decisively declared that the patient portal is not helpful in supporting life style changes. Early quitters felt significantly more items not applicable in their situation compared to persistent users. Both persistent users (69.8%) and early quitters (58.8%) would prefer a reminder function for scheduled visits. About 60% of both groups wanted information about medication and side-effects in their portal. CONCLUSIONS: The diabetes patient web portal might be improved significantly by taking into account the patients' experiences and attitudes. We propose creating separate portals for patients on insulin or not.

Reasons and barriers for using a patient portal: survey among patients with diabetes mellitus.

BACKGROUND: The use of a Web portal for patients with diabetes mellitus to access their own personal health record may result in improved diabetes outcomes. However, the adoption by patients is slow. This may be caused by patient characteristics, but also by the content, layout, and promotion of the portal. Detailed knowledge about this could help increase patients' participation in Web portals. OBJECTIVE: The aim was to study the opinions of patients with diabetes and identify perceived barriers to using a Web portal to optimize its use. METHODS: We conducted a survey among patients with type 1 and type 2 diabetes mellitus from 62 primary care practices and 1 outpatient hospital clinic in the central area of the Netherlands who all used the same electronic health record with a Web portal. Questionnaires about patient characteristics, opinions about reasons for use or nonuse, and about portal content were sent to 1500 patients with a login and 3000 patients without a login to the Web portal. Patient groups were stratified according to login frequency. Demographic and diabetes-related variables were analyzed with multivariable regression analysis. RESULTS: The total response rate was 66.63% (2391/4399); 1390 of 4399 patients (31.60%) were eligible for analysis. There were 413 regular users (login frequency more than once) and 758 nonusers (no login). Most nonusers (72.4%) stated that the main reason for not requesting a login was that they were unaware of the existence of the portal. Other barriers reported by patients were disinterest in managing their own disease (28.5%, 216/758) and feelings of inadequacy with the use of computers and Internet (11.6%, 88/758). Patients treated by a general practitioner were more frequently nonusers compared to patients treated by an internist (78.8%, 666/846 vs 28.3%, 92/325; P<.001) and more users than nonusers became aware of the Web portal through their physician (94.9%, 392/413 vs 48.8%, 102/209; P<.001). Nonusers perceived specific portal content as not as useful as regular users did, especially access to laboratory values (71.7%, 383/534 vs 92.3%, 372/403), rereading clinic visits (61.3%, 320/522 vs 89.6%, 360/402), e-messaging (52.0%, 262/504 vs 74.6%, 299/401), and uploading results to the glucose diary (45.3%, 229/506 vs 74.0%, 288/400; all P<.001). CONCLUSIONS: Our study shows that unawareness of the patient portal is the main barrier of enrollment. Users and nonusers perceive the usefulness of the portal differently and do not have the same recommendations for additional functionalities. To increase patients' participation in a Web portal, the unawareness of its existence and its possibilities need to be addressed by their health care professionals.

Differences between diabetes patients who are interested or not in the use of a patient Web portal.

OBJECTIVE: A patient Web portal allows patients to access their personal health record through the Internet. It may improve diabetes outcomes, but the adoption is unsatisfactory. We examined the differences between patients with and without a login in order to optimize its use. PATIENTS AND METHODS: A survey was conducted among patients from 62 general practices and one outpatient clinic that all use a diabetes Web portal. Between November 2011 and March 2012 questionnaires were sent to 1,500 patients with and 3,000 patients without a login. Patient groups were stratified according to type of diabetes. Demographic and diabetes-related variables were analyzed with multivariable regression analysis. RESULTS: The total response rate was 67%. Fewer than 50% of the patients did request a login. Among 128 patients with type 1 diabetes mellitus, those with a login (89.8%) were younger and more frequently treated by an internist. In 1,262 patients with type 2 diabetes mellitus, fewer patients had a log-in (41.0%), and the likelihood of having a login was independently associated with younger age, male gender, higher educational level, treatment by an internist, longer duration of diabetes, and polypharmacy (all P<0.001). CONCLUSIONS: Patients with type 1 diabetes request a login more frequently than patients with type 2 diabetes, and patients with a login are strikingly different than patients without. The healthcare provider seems to play an important role in patients' Web utilization. Simply promoting use of electronic healthcare methods does not make sense. It is important to address disparities between patient groups to optimize the use of a Web portal.

Nitric oxide synthesis inhibition does not impair water immersion-induced renal vasodilation in humans.

Nitric oxide (NO) is tonically released in the kidney to maintain renal perfusion and adequate sodium and water clearance. Little is known about the role of NO in the renal adaptation to an acute volume challenge. This is important for our understanding of pathophysiologic conditions associated with impaired NO activity. This study examined the effects of NO synthesis inhibition on neurohumoral, renal hemodynamic, and excretory responses to head-out immersion (HOI). Seven healthy men underwent four 7-h clearance studies. One study served as a time control study (placebo infusion), and in one study N(G)-monomethyl-L-arginine (L-NMMA; 3 mg/kg priming dose + 3 mg/kg per h) was infused during hours 2 to 5. In a third and fourth clearance study, HOI was applied from hours 3 to 5, during infusion of either placebo or L-NMMA. To assess the degree of NO synthesis inhibition, the effect of L-NMMA on [(15)N]-arginine-to-[(15)N]-citrulline conversion rate was studied in four others. HOI decreased mean arterial pressure (MAP) from 87 +/- 3 to 76 +/- 2 mmHg and renal vascular resistance (RVR) from 82 +/- 6 to 70 +/- 7 mmHg. min/L, and increased sodium excretion (UNaV) from 110 +/- 27 to 195 +/- 29 micromol/min and flow (UV) from 14.4 +/- 1.4 to 15.8 +/- 1.4 ml/min. L-NMMA caused profound and sustained increases in MAP and RVR and decreases in UNaV and UV. HOI superimposed on L-NMMA infusion decreased the elevated MAP from 93 +/- 4 to 83 +/- 2 mmHg and RVR from 111 +/- 9 to 95 +/- 7 mmHg. min/L, and increased UNaV from 41 +/- 8 to 95 +/- 15 micromol/min and UV from 10.0 +/- 1.1 to 12.7 +/- 1.4 ml/min. The relative changes were not significantly different from the effects of HOI without L-NMMA infusion. HOI decreased plasma renin activity and aldosterone and increased plasma atrial natriuretic peptide and urinary cGMP. L-NMMA decreased urinary cGMP, but did not affect the plasma hormones or the changes induced by HOI. L-NMMA decreased the [(15)N]-arginine-to-[(15)N]-citrulline conversion rate to one-third of baseline. The results indicate that in a state of NO deficiency in humans, the kidney can still respond to an acute volume challenge with vasorelaxation, diuresis, and natriuresis.