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Background: Healthcare organizations measure costs for business operations but do not routinely incorporate costs in decision-making on the value of care., Aim: Provide guidance on how to use costs in value-based healthcare (VBHC) delivery at different levels of the healthcare system., Setting and Participants: Integrated practice units (IPUs) for diabetes mellitus (DM) and for acute myocardial infarction (AMI) at the Leiden University Medical Center and a collaboration of seven breast cancer IPUs of the Santeon group, all in the Netherlands., Program Description and Evaluation: VBHC aims to optimize care delivery to the patient by understanding how costs relate to outcomes. At the level of shared decision-making between patient and clinician, yearly check-up consultations for DM type I were analyzed for patient-relevant costs. In benchmarking among providers, quantities of cost drivers for breast cancer care were assessed in scorecards. In continuous learning, cost-effectiveness analysis was compared with radar chart analysis to assess the value of telemonitoring in outpatient follow-up., Discussion: Costs vary among providers in healthcare, but also between provider and patient. The joint analysis of outcomes and costs using appropriate methods helps identify and optimize the aspects of care that drive desired outcomes and value., (© 2023. The Author(s).)

Perceptual sensitivity for dyspnea (i.e. breathlessness) is often quantified using the slope of magnitude estimations plotted against the physical stimulus intensities of respiratory loads. This study investigated whether this slope and its stability varies as a function of (1) affective versus sensory aspects of dyspnea, and (2) interindividual differences in Fear of Suffocation. Eighty-three healthy women performed a load magnitude estimation task twice one week apart. Resistive loads of increasing magnitude (0-2.4-5-7.4-12.4-20 cmH 2 0/l/s) were repeatedly presented for a single flow-targeted inspiration. One group rated the intensity of loads, another their unpleasantness. Neither slopes nor intercepts differed between sensory versus affective aspects of dyspnea. Intercepts were lower in the second compared to the first session. Fear of Suffocation was associated with flatter slopes. Test-retest reliabilities were low to moderate suggesting that perceptual sensitivity to dyspnea is less stable than commonly assumed., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Introduction: Lockdown measures have a profound effect on many aspects of daily life relevant for diabetes self-management. We assessed whether lockdown measures, in the context of the COVID-19 pandemic, differentially affect perceived stress, body weight, exercise and related this to glycemic control in people with type 1 and type 2 diabetes., Research Design and Methods: We performed a short-term observational cohort study at the Leiden University Medical Center. People with type 1 and type 2 diabetes ≥18 years were eligible to participate. Participants filled out online questionnaires, sent in blood for hemoglobin A1c (HbA1c) analysis and shared data of their flash or continuous glucose sensors. HbA1c during the lockdown was compared with the last known HbA1c before the lockdown., Results: In total, 435 people were included (type 1 diabetes n=280, type 2 diabetes n=155). An increase in perceived stress and anxiety, weight gain and less exercise was observed in both groups. There was improvement in glycemic control in the group with the highest HbA1c tertile (type 1 diabetes: -0.39% (-4.3 mmol/mol) (p<0.0001 and type 2 diabetes: -0.62% (-6.8 mmol/mol) (p=0.0036). Perceived stress was associated with difficulty with glycemic control (p<0.0001)., Conclusions: An increase in perceived stress and anxiety, weight gain and less exercise but no deterioration of glycemic control occurs in both people with relatively well-controlled type 1 and type 2 diabetes during short-term lockdown measures. As perceived stress showed to be associated with glycemic control, this provides opportunities for healthcare professionals to put more emphasis on psychological aspects during diabetes care consultations., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: Sex differences in cardiometabolic risk factors and their management in type 2 diabetes (T2D) have not been fully identified. Therefore, we aimed to examine differences in cardiometabolic risk factor levels, pharmacological treatment and achievement of risk factor control between women and men with T2D., Research Design and Methods: Cross-sectional data from the Dutch Diabetes Pearl cohort were used (n=6637, 40% women). Linear and Poisson regression analyses were used to examine sex differences in cardiometabolic risk factor levels, treatment, and control., Results: Compared with men, women had a significantly higher body mass index (BMI) (mean difference 1.79 kg/m 2 (95% CI 1.49 to 2.08)), while no differences were found in hemoglobin A 1c (HbA 1c ) and systolic blood pressure (SBP). Women had lower diastolic blood pressure (-1.94 mm Hg (95% CI -2.44 to -1.43)), higher total cholesterol (TC) (0.44 mmol/L (95% CI 0.38 to 0.51)), low-density lipoprotein cholesterol (LDL-c) (0.26 mmol/L (95% CI 0.22 to 0.31)), and high-density lipoprotein cholesterol (HDL-c) sex-standardized (0.02 mmol/L (95% CI 0.00 to 0.04)), and lower TC:HDL ratio (-0.29 (95% CI -0.36 to -0.23)) and triglycerides (geometric mean ratio 0.91 (95% CI 0.85 to 0.98)). Women had a 16% higher probability of being treated with antihypertensive medication in the presence of high cardiovascular disease (CVD) risk and elevated SBP than men (relative risk 0.84 (95% CI 0.73 to 0.98)), whereas no sex differences were found for glucose-lowering medication and lipid-modifying medication. Among those treated, women were less likely to achieve treatment targets of HbA 1c (0.92 (95% CI 0.87 to 0.98)) and LDL-c (0.89 (95% CI 0.85 to 0.92)) than men, while no differences for SBP were found., Conclusions: In this Dutch T2D population, women had a slightly different cardiometabolic risk profile compared with men and a substantially higher BMI. Women had a higher probability of being treated with antihypertensive medication in the presence of high CVD risk and elevated SBP than men, and were less likely than men to achieve treatment targets for HbA 1c and LDL levels., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY. Published by BMJ.)

Panic disorder is characterized by the paroxysmal occurrence and fear of bodily symptoms. In recent years it has been proposed that patients "learn" to fear cardiorespiratory sensations through interoceptive conditioning. This study sought to model the initial stage of this process in healthy volunteers (N=44) using mild cardiac sensations. An additional aim was to explore whether anxiety sensitivity - a known risk factor for panic disorder - modulates such interoceptive learning. Infusions of pentagastrin and saline were used to manipulate the presence versus absence of cardiac sensations, respectively, and served as conditioned stimuli in a differential interoceptive conditioning paradigm. Inhalation of 35% CO 2 -enriched air served as the panicogenic, unconditioned stimulus (UCS). In half of the participants ("prepared" condition), cardiac sensations caused by pentagastrin were followed by inhalation of CO 2 -enriched air (penta CS+), whereas the absence of such sensations (saline) was followed by room air (saline CS-). The reversed combination ("unprepared" condition) was used in the other half of the participants. Conditioning effects showed up for self-reported UCS-expectancy, but not for skin conductance and anxiety ratings. Only participants from the prepared group learned to expect the UCS, and differential learning was impaired with higher scores on anxiety sensitivity. Expectancy learning was more easily established towards the presence compared to the absence of cardiac sensations, whereas the reverse effect was observed for safety learning. Modeling impaired discriminatory learning and the moderating effect of anxiety sensitivity provides new insight in the development of panic disorder., (Copyright © 2016 Elsevier B.V. and ECNP. All rights reserved.)

Potentially life-threatening interoceptive sensations easily engage the behavioral defensive system. Resulting fear and anxiety toward interoceptive threat are functionally distinct states that are hypothesized to play a prominent role in the etiology of panic disorder. The present study aimed to investigate whether fear- and anxiety-potentiated startle responses occur to predictable and unpredictable interoceptive threat, respectively. Therefore, we modified the NPU threat test (Schmitz & Grillon, ) and replaced the aversive electrocutaneous stimulus with an aversive interoceptive stimulus (a breathing occlusion, making it briefly impossible to breathe). Healthy participants (N = 48) underwent three instructed conditions. A visual cue signaled the occlusion in the predictable condition (P), whereas another cue was unrelated to the occurrence of the occlusion in the unpredictable condition (U). The safe condition (N) also had a visual cue, but no occlusion. Both fear- and anxiety-potentiated startle blink responses were observed in response to predictable and unpredictable respiratory threat, respectively. The current study presents and validates the NPU respiratory threat test (NPUr) as an ecologically valid paradigm to study both anxiety and fear in response to a panic-relevant interoceptive threat. The paradigm allows future testing of contextual generalization, investigation of different clinical groups, and more explicit comparisons of defensive responding to interoceptive versus exteroceptive threats., (© 2016 Society for Psychophysiological Research.)

Fear reduction obtained during a fear extinction procedure can generalize from the extinction stimulus to other perceptually similar stimuli. Perceptual generalization of fear extinction typically follows a perceptual gradient, with increasing levels of fear reduction the more a stimulus resembles the extinction stimulus. The current study aimed to investigate whether perceptual generalization of fear extinction can be observed also after a retention interval of 24h. Fear was acquired to three geometrical figures of different sizes (CS(+), CS1(+) and CS2(+)) by consistently pairing them with a short-lasting suffocation experience (US). Three other geometrical figures that were never followed by the US served as control stimuli (CS(-), CS1(-), CS2(-)). Next, only the CS(+) was extinguished by presenting it in the absence of the US. One day later, fear responses to all stimuli were assessed without any US-presentation. Outcome measures included startle blink EMG, skin conductance, US expectancy, respiratory rate and tidal volume. On day 2 spontaneous recovery of fear was observed in US expectancy and tidal volume, but not in the other outcomes. Evidence for the retention of fear extinction generalization was present in US expectancy and skin conductance, but a perceptual gradient in the retention of generalized fear extinction could not be observed., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Interoceptive fear conditioning (IFC), fear generalization and a lack of safety learning have all been hypothesized to play a role in the pathogenesis of panic disorder, but have never been examined in a single paradigm. The present study aims to investigate whether healthy participants (N=43) can learn both fear and safety to an interoceptive sensation, and whether such learning generalizes to other, similar sensations. Two intensities of inspiratory breathing impairment (induced by two pressure threshold loads of 6 and 25 cm H2O) served as interoceptive conditional stimuli (CSs) in a differential conditioning paradigm. An inspiratory occlusion was used as the unconditioned stimulus (US). Generalization was tested 24h after conditioning, using four generalization stimuli with intensities in-between CS+ and CS- (GSs: 8-10.5-14-18.5 cm H2O). Measures included US-expectancy, startle blink EMG responses, electrodermal activity and respiration. Perceptual discrimination of interoceptive CSs and GSs was explored with a discrimination task prior to acquisition and after generalization. Results indicate that differential fear learning was established for US-expectancy ratings. The group with a low intensity CS+ and a high intensity CS- showed the typical pattern of differential fear responding and a similarity-based generalization gradient. In contrast, the high intensity CS+ and low intensity CS- group showed impaired differential learning and complete generalization of fear. Our findings suggest that interoceptive fear learning and generalization are modulated by stimulus intensity and that the occurrence of discriminatory learning is closely related to fear generalization., (Copyright © 2015. Published by Elsevier Ltd.)

This study aimed to investigate whether interindividual differences in autonomic inhibitory control predict safety learning and fear extinction in an interoceptive fear conditioning paradigm. Data from a previously reported study (N = 40) were extended (N = 17) and re-analyzed to test whether healthy participants' resting heart rate variability (HRV) - a proxy of cardiac vagal tone - predicts learning performance. The conditioned stimulus (CS) was a slight sensation of breathlessness induced by a flow resistor, the unconditioned stimulus (US) was an aversive short-lasting suffocation experience induced by a complete occlusion of the breathing circuitry. During acquisition, the paired group received 6 paired CS-US presentations; the control group received 6 explicitly unpaired CS-US presentations. In the extinction phase, both groups were exposed to 6 CS-only presentations. Measures included startle blink EMG, skin conductance responses (SCR) and US-expectancy ratings. Resting HRV significantly predicted the startle blink EMG learning curves both during acquisition and extinction. In the unpaired group, higher levels of HRV at rest predicted safety learning to the CS during acquisition. In the paired group, higher levels of HRV were associated with better extinction. Our findings suggest that the strength or integrity of prefrontal inhibitory mechanisms involved in safety- and extinction learning can be indexed by HRV at rest.

Adequate perception of bodily sensations is essential to protect health. However, misinterpretation of signals from within the body is common and can be fatal, for example, in asthma or cardiovascular disease. We suggest that placing interoceptive stimuli into interoceptive categories (e.g., the category of symptoms vs. the category of benign sensations) leads to perceptual generalization effects that may underlie misinterpretation. In two studies, we presented stimuli inducing respiratory effort (respiratory loads) either organized into categories or located on a continuous dimension. We found pervasive effects of categorization on magnitude estimations, affective stimulus evaluations, stimulus recognition, and breathing behavior. These findings indicate the need for broadening perspectives on interoception to include basal processes of stimulus organization, in order for interoceptive bias to be understood. The results are relevant to a wide range of interoception-related phenomena, from emotion to symptom perception.

Recent research considers distress (in)tolerance as an essential component in the development of various forms of psychopathology. A behavioral task frequently used to assess distress tolerance is the breath holding task. Although breath holding time (BHT) has been associated with behavioral outcomes related to inhibitory control (e.g., smoking cessation), the relationship among breath holding and direct measures of executive control has not yet been thoroughly examined. The present study aims to assess (a) the BHT-task's test-retest reliability in a 1-year follow-up and (b) the relationship between a series of executive function tasks and breath holding duration. One hundred and thirteen students completed an initial BHT assessment, 58 of which also completed a series of executive function tasks [the Wisconsin Card Sorting Test (WCST), the Parametric Go/No-Go task and the N-back memory updating task]. A subsample of these students (N = 34) repeated the breath holding task in a second session 1 year later. Test-retest reliability of the BHT-task over a 1-year period was high (r = 0.67, p < 0.001), but none of the executive function tasks was significantly associated with BHT. The rather moderate levels of unpleasantness induced by breath holding in our sample may suggest that other processes (physiological, motivational) besides distress tolerance influence BHT. Overall, the current findings do not support the assumption of active inhibitory control in the BHT-task in a healthy sample. Our findings suggest that individual differences (e.g., in interoceptive or anxiety sensitivity) should be taken into account when examining the validity of BHT as a measure of distress tolerance.