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Lumacaftor/ivacaftor (Orkambi®, LUM/IVA) is indicated for the treatment of cystic fibrosis (CF) patients aged ≥ 2 years with homozygous F580del mutation in the CFTR gene. Triazole fungal agents are used to treat fungal disease in CF. The use of triazoles is limited by pharmacokinetic challenges, such as drug-drug interactions. The most notable drug-drug interaction between triazoles and LUM/IVA is due to strong induction of CYP3A4 and UGT by LUM. In this real-world retrospective observational study, we described the effect of LUM/IVA on the trough concentration of triazoles. Concomitant use of LUM/IVA with itraconazole, posaconazole or voriconazole resulted in subtherapeutic triazole levels in 76% of the plasma samples. In comparison, in patients with triazole agents without LUM/IVA only 30.6% of the plasma samples resulted in subtherapeutic concentrations. Subtherapeutic plasma concentrations of triazoles should be considered in CF patients on LUM/IVA and further research is warranted for other dosing strategies and alternative antifungal therapy.

There is ample evidence showing that childhood maltreatment increases two to three fold the risk of victimization in adulthood. Various risk factors, including posttraumatic stress disorder (PTSD) symptoms, dissociation, self-blame, and alcohol abuse are related to revictimization. Although previous research examined associations between risk factors for revictimization, the evidence is limited and the proposed models mostly include a handful of risk factors. Therefore, it is critical to investigate a more comprehensive model explaining the link between childhood maltreatment and adulthood (re)victimization. Accordingly, this study tested a data-driven theoretical path model consisting of 33 variables (and their associations) that could potentially enhance understanding of factors explaining revictimization. Cross-sectional data derived from a multi-wave study were used for this investigation. Participants (N = 2156, age mean = 19.94, SD = 2.89) were first-year female psychology students in the Netherlands and New Zealand, who responded to a battery of questionnaires and performed two computer tasks. The path model created by structural equation modelling using modification indices showed that peritraumatic dissociation, PTSD symptoms, trauma load, loneliness, and drug use were important mediators. Attachment styles, maladaptive schemas, meaning in life, and sex motives connected childhood maltreatment to adulthood victimization via other factors (i.e., PTSD symptoms, risky sex behavior, loneliness, emotion dysregulation, and sex motives). The model indicated that childhood maltreatment was associated with cognitive patterns (e.g., anxious attachment style), which in turn were associated with emotional factors (e.g., emotion dysregulation), and then with behavioral factors (e.g., risky sex behavior) resulting in revictimization. The findings of the study should be interpreted in the light of the limitations. In particular, the cross-sectional design of

Negative outlooks of our future may foster unwanted and intrusive thoughts. To some extent, individuals have control over their ability to suppress intrusions and downregulate their frequency. Acute stress impairs intentional suppression, leading to an increased frequency of intrusions. The aim of this study was to gain insight into the mechanism underlying stress-induced impairments in intentional suppression of intrusions by investigating the combined and independent roles of the two major stress hormones, noradrenaline and cortisol. Healthy participants (N = 181) were administered propranolol (to block the noradrenergic response), metyrapone (to block the cortisol response), or a placebo before being exposed to the Maastricht Acute Stress Test. Intrusive thoughts of autobiographical future fears were then measured via the Imagine/No-Imagine task. Results demonstrated that the stress response was successfully altered because of the drug and stress manipulations. In all groups, repeated suppression of future fears reduced intrusions. Across the sample, an enhanced decrease over time was associated with greater attenuation of anxiety towards the related fears. The groups did not differ in the total frequency of intrusions. Though, trait anxiety increased the total number of intrusions. Our findings show that stress hormones did not influence the ability to suppress intrusions. However, our results do add support to previous research linking anxiety to memory control deficits. When using autobiographical content, future research should focus on the quality and characteristics of the individual memories to explain more of the variation observed in intentional memory control.

Background Evidence on associations between dairy consumption and incident prediabetes is inconsistent. One potential explanation for heterogeneity is that health behavior and food intake covary with the consumption of various high-fat and low-fat dairy types. Objective The objective was to investigate the associations of total dairy and dairy types with incident prediabetes and to assess how dairy intake is linked with metabolic risk factors, lifestyle behaviors, and foods, as potential explanations for these associations. Methods Overall, 74,132 participants from the prospective population-based Lifelines study were included (mean age, 45.5 ± 12.3 y; 59.7% female). Baseline dairy intake was measured using a validated food frequency questionnaire. Prediabetes at follow-up was defined based on the World Health Organization/International Expert Committee criteria as fasting plasma glucose of 110–125 mg/dL or glycated hemoglobin concentrations of 6.0%–6.5%. Associations were analyzed using Poisson regression models adjusted for social demographics, lifestyle behaviors, family history of diabetes, and food group intake. Interconnections were assessed with mixed graphical model networks. Results At a mean follow-up of 4.1 ± 1.1 y, 2746 participants developed prediabetes (3.7%). In regression analyses, neutral associations were found for most dairy types. Intake of plain milk and low-fat milk were associated with a higher risk of prediabetes in the top compared with bottom quartiles (relative risk [RR]: 1.17; 95% confidence interval [CI]: 1.05, 1.30; P-trend = 0.04 and RR: 1.18; 95% CI: 1.06, 1.31; P-trend =0.01). Strong but nonsignificant effect estimates for high-fat yogurt in relation to prediabetes were found (RR servings/day: 0.80; 95% CI: 0.64, 1.01). The network analysis showed that low-fat milk clustered with energy-dense foods, including bread, meat, and high-fat cheese, whereas high-fat yogurt had no clear link

Purpose Patients with chronic painful chemotherapy-induced peripheral neuropathy (CIPN) may experience a negative impact of CIPN on daily life. They can use various coping (i.e., dealing with symptoms and resulting impairments in general) and self-management (i.e., practical actions to reduce symptoms) strategies to live with their limitations. This paper aimed to examine experienced helpful coping and self-management strategies of patients with chronic painful CIPN. Methods Semi-structured interviews were conducted with twelve patients with chronic painful CIPN. We applied a hybrid deductive-inductive coding approach. ATLAS.ti was used for coding. Results Generated from the data were two themes and nine codes for coping and four themes and 31 codes for self-management strategies. Coping of patients often included active strategies like planning, seeking social support, and acceptance. Additionally, patients often used passive strategies such as focusing on and venting emotions and suppressing competing activities. The most common self-management strategies were mostly passive (i.e., medication, deliberate choice of shoes, resting, sitting, and consulting healthcare professionals) but also active (i.e., exercising) strategies. Conclusion Patients exhibit a great variety of coping and self-management strategies that they perceive as helpful to deal with chronic painful CIPN. However, research has shown that certain strategies are not that helpful or even come with aversive effects. More research into the effectiveness and implementation of psychosocial interventions is needed since it may help patients adopting helping strategies. In addition, healthcare professionals need to refer patients with CIPN in a timely manner to physical therapists, occupational therapists, or rehabilitation teams to reduce or prevent (further) impairments. Implications for Cancer Survivors Patients can consult one of their healthcare

Purpose A significant proportion of cancer patients suffer from chemotherapy-induced peripheral neuropathy (CIPN). This descriptive study aimed to examine patients’ experience of CIPN symptoms, daily limitations, involvement of healthcare professionals, and social support. Methods Cross-sectional data have been collected in the Netherlands via a national online questionnaire comprising closed items only (February 2021). Results Out of 3752 respondents, 1975 received chemotherapy only (i.e., without targeted therapy) and were therefore included. The majority (71.2%) reported symptoms in both hands and feet (e.g., tingling and loss of sensation or diminished sensation). Participants reported most limitations in household chores, social activities, hobbies, sports, walking, and sleeping and least in family/(taking care of) children, cycling, driving, self-care, eating and drinking, and sexuality and intimacy. Many patients indicated that their healthcare professionals informed them about the possibility of CIPN development before treatment (58.4%), and they paid attention to CIPN during and after treatment (53.1%). However, many patients (43%) reported a lack of information on what to do when CIPN develops. Few participants (22%) visited their general practitioner (GP) for CIPN. In general, patients’ social environments sometimes to always showed empathy to patients. Conclusions Symptoms of CIPN are frequently reported and can result in various daily limitations. Support from professionals and peers is crucial in managing CIPN, which is sometimes lacking. Appropriate guidance and support should be provided to patients to decrease the impact of CIPN on daily life. Future research should investigate differences in chemotherapeutic agents and the resulting symptoms and consequences.

Research indicates that fear was an important factor in determining individual responses to COVID-19, predicting relevant behaviors such as compliance to preventive measures (e.g., hand washing) and stress reactions (e.g., poor sleep quality). Given this central role of fear, it is important to understand more about its temporal changes during the COVID-19 pandemic. This article describes a publicly available dataset that contains longitudinal assessment of fear of COVID-19 and other relevant constructs during the first 15 months of the pandemic. Particularly, the dataset contains data from two different samples. The first sample consists predominantly of Dutch respondents (N = 439) who completed a cross-sectional survey in March 2020. The second sample consists of a large-scale longitudinal survey (N = 2000 at T1), including respondents with a broad range of nationalities (though predominantly residing in Europe and North America; 95.6%). The respondents of the second sample completed the survey between April 2020 and August 2020 using the Prolific data collection platform. In addition, one follow-up assessment was completed in June 2021. The measures included in the survey were fear of COVID-19, demographic information (age, gender, country of residence, education level, and working in healthcare), anxious traits (i.e., intolerance of uncertainty, health anxiety, and worrying), media use, self-rated health, perceived ability to prevent infection, and perceived risk for loved ones. Additionally, at the follow-up assessment in June 2021, respondents were asked whether they were vaccinated against COVID-19 or were planning to get vaccinated. The datafiles of this study have been made available through the Open Science Framework and can be freely reused by psychologists, social scientists, and other researchers who wish to investigate the development, correlates, and consequences of fear of COVID-19.

Background Around 30% of cancer survivors suffer from chemotherapy-induced peripheral neuropathy (CIPN) ≥6 months after completion of chemotherapy, which comes with limitations in daily functioning and worsened quality of life(QoL). Treatment options are scarce. Our aim was to develop an online self-help intervention based on Acceptance and Commitment Therapy (ACT) to reduce pain interference in cancer survivors experiencing painful chronic CIPN. Material and methods This article applied a patient-centered design process using the Center for eHealth Research (CeHRes) roadmap. User needs were examined using online semi-structured interviews with patients and experts (N = 23). Interviews were transcribed verbatim and analyzed using thematic analysis. Personas were created based on interviews. Intervention content was based on identified user needs and ACT. Content and design were finalized using low-fidelity prototype testing (N = 5), and high-fidelity prototype testing (N = 7). Results Patients appreciated and agreed with the elements of ACT, had varying guidance needs, and wanted to have autonomy (e.g., moment and duration of use). Additionally, it was important to be aware that patients have had a life-threatening disease which directly relates to the symptoms they experience. Patients reported to prefer a user-friendly and accessible intervention. Similar points also emerged in the expert interviews. The final intervention, named Embrace Pain, includes six sessions. Session content is based on psychoeducation and all ACT processes. Further interpretation of the intervention (such as quotes, guidance, and multimedia choices) is based on the interviews. Conclusion This development demonstrated how a patient-centered design process from a theoretical framework can be applied. Theory-driven content was used as the basis of the intervention. Findings show an online ACT intervention designed for cancer survivors with painful ch

Instrumental learning is controlled by two distinct parallel systems: goal-directed (action-outcome) and habitual (stimulus-response) processes. Seminal research by Schwabe and Wolf (2009, 2010) has demonstrated that stress renders behavior more habitual by decreasing goal-directed control. More recent studies yielded equivocal evidence for a stress-induced shift towards habitual responding, yet these studies used different paradigms to evaluate instrumental learning or used different stressors. Here, we performed exact replications of the original studies by exposing participants to an acute stressor either before (cf. Schwabe and Wolf, 2009) or directly after (cf. Schwabe and Wolf, 2010) an instrumental learning phase in which they had learned that distinct actions led to distinct, rewarding food outcomes (i.e., instrumental learning). Then, following an outcome devaluation phase in which one of the food outcomes was consumed until participants were satiated, action-outcome associations were tested in extinction. Despite successful instrumental learning and outcome devaluation and increased subjective and physiological stress levels following stress exposure, the stress and no-stress groups in both replication studies responded indifferently to valued and devalued outcomes. That is, non-stressed participants failed to demonstrate goal-directed behavioral control, thereby rendering the critical test of a shift from goaldirected to habitual control in the stress group inapt. Several reasons for these replication failures are discussed, including the rather indiscriminate devaluation of outcomes that may have contributed to indifferent responding during extinction, which emphasize the need to further our understanding of the boundary conditions in research aimed at demonstrating a stress-induced shift towards habitual control.

Background Fear is an evolutionary adaptive emotion that serves to protect the organism from harm. Once a threat diminishes, fear should also dissipate as otherwise fear may become chronic and pathological. While actual threat of the COVID-19 pandemic (i.e., number of infections, hospitalizations, and deaths) has substantially varied over the course of the pandemic, it remains unclear whether (subjective) fear has followed a similar pattern. Method To examine the development of fear of COVID-19 during the pandemic and investigate potential predictors of chronic fear, we conducted a large online longitudinal study (N = 2000) using the Prolific platform between April 2020 and June 2021. Participants were voluntary response samples and consisted of residents of 34 different countries. The Fear of the Coronavirus Questionnaire (FCQ) and several other demographic and psychological measures were completed monthly. Results Overall, we find that fear steadily decreased since April 2020. Additional analyses showed that elevated fear was predicted by region (i.e., North America > Europe), anxious traits, gender, risks for loved ones, general health, and media use. Limitations The interpretation of the results of this study is limited by the non-representativeness of the sample and the lack of data points between August 2020 and June 2021. Conclusions This study helps to characterize the trajectory of fear levels throughout the COVID-19 pandemic and establish several relevant predictors of increased fear.

Stress initiates a cascade of (neuro)biological, physiological, and behavioral changes, allowing us to respond to a challenging environment. The human response to acute stress can be studied in detail in controlled settings, usually in a laboratory environment. To this end, many studies employ acute stress paradigms to probe stress-related outcomes in healthy and patient populations. Though valuable, these studies in themselves often have relatively limited sample sizes. We established a data-sharing and collaborative interdisciplinary initiative, the STRESS-NL database, which combines (neuro)biological, physiological, and behavioral data across many acute stress studies in order to accelerate our understanding of the human acute stress response in health and disease (www.stressdatabase.eu). Researchers in the stress field from 12 Dutch research groups of 6 Dutch universities created a database to achieve an accurate inventory of (neuro)biological, physiological, and behavioral data from laboratory-based human studies that used acute stress tests. Currently, the STRESS-NL database consists of information on 5529 individual participants (2281 females and 3348 males, age range 6-99 years, mean age 27.7 ± 16 years) stemming from 57 experiments described in 42 independent studies. Studies often did not use the same stress paradigm; outcomes were different and measured at different time points. All studies currently included in the database assessed cortisol levels before, during and after experimental stress, but cortisol measurement will not be a strict requirement for future study inclusion. Here, we report on the creation of the STRESS-NL database and infrastructure to illustrate the potential of accumulating and combining existing data to allow meta-analytical, proof-of-principle analyses. The STRESS-NL database creates a framework that enables human stress research to take new avenues in explorative and hypothesis-driven data analyses with high statistical power

Background. Regarding sustainability in the intensive care unit (ICU), there is increasing interest in reducing material waste and avoiding unnecessary procedures. Therapeutic drug monitoring (TDM) of vancomycin, using a dedicated tube, is standard clinical care during treatment with vancomycin. Furthermore, in the ICU, on a daily basis, arterial blood gas (ABG) tests are frequently performed throughout the day. After analysis, a variable volume of blood is discarded. Lithium heparin (LiHep) syringes for ABG tests differ from normally used dipotassium ethylenediaminetetraacetic acid (K2EDTA) tubes. The primary objective was to compare both containers and validate the use of LiHep syringes. Secondary objectives were to evaluate the potential impact on saving materials, nursing time, and costs when implementing vancomycin TDM via LiHep syringes. Methods. Vancomycin analysis from sampling in lithium heparin (LiHep) syringes for ABG tests was validated and compared with the concentrations from conventional sampling in K2EDTA tubes. For method comparison, a Bland-Altman plot and Deming regression analysis were performed. The method was validated for inter- and intra-day precision and accuracy. Vancomycin was analyzed by means of the validated method using a particle-enhanced turbidimetric inhibition immunoassay (PETINIA) autoanalyzer. Furthermore, an analysis was conducted to evaluate the potential impact of implementing vancomycin sampling via ABG tests on savings in materials, nursing time, and costs. Results. From 18 patients, 24 plasma samples in both K2EDTA tubes and LiHep syringes were obtained and compared. The mean relative difference between the two containers was -2.0% (-3.0 to -0.93%). Both the Deming regression analysis and the Bland-Altman plot met the acceptance criteria. Potentially, over 1000 blood draws and accompanying materials and packaging can be saved when vancomycin samples are obtained by means of scavenged LiHep syringe

Background About 30% of cancer survivors suffer from chemotherapy-induced peripheral neuropathy (CIPN) ≥6 months after completion of chemotherapy. This condition, for which treatment options are scarce, comes with limitations in daily life functioning and decreased quality of life. The current study examines the effectiveness of an online self-help intervention based on Acceptance and Commitment Therapy (ACT) in comparison to a waiting list condition (WLC) to deal with CIPN. In addition, it examines which factors moderate effects and to what extent the effects differ between guided and unguided ACT intervention. Methods A two-parallel, non-blinded randomized controlled trial (RCT) will be carried out. Adult cancer survivors who experience painful CIPN for at least 3 months and completed chemotherapy at least 6 months ago will be recruited (n=146). In the intervention condition, participants will follow an 8-week self-management course containing 6 modules regarding psychoeducation and ACT processes, including therapeutic email guidance. By means of text and experiential exercises, supplemented with illustrations, metaphors, and audio files, people will learn to carry out value-oriented activities in their daily life with pain. Participants will learn new ways of coping with pain, including reducing pain avoidance and increasing pain acceptance. Participants in the WLC will be invited to follow the intervention without therapeutic guidance 5 months after start. Pain interference is the primary outcome, while psychological distress, quality of life, CIPN symptom severity, pain intensity, psychological flexibility, mindfulness skills, values-based living, and pain catastrophizing will serve as secondary outcomes. All outcome measures will be evaluated at inclusion and baseline, early-intervention, mid-intervention, post-treatment, and 3- and 6-month post-treatment. Qualitative interviews will be conducted post-treatment regarding experiences, usage, u

Vaccines are an important tool for governments and health agencies to contain and curb the Coronavirus Disease-19 (COVID-19) pandemic. However, despite their effectiveness and safeness, a substantial portion of the population worldwide is hesitant to get vaccinated. In the current study, we examined whether fear of COVID-19 predicts vaccination willingness. In a longitudinal study (N = 938), fear for COVID-19 was assessed in April 2020 and vaccination willingness was measured in June 2021. Approximately 11% of our sample indicated that they were not willing to get vaccinated. Results of a logistic regression showed that increased fear of COVID-19 predicts vaccination willingness 14 months later, even when controlling for several anxious personality traits, infection control perceptions, risks for loved ones, self-rated health, previous infection, media use, and demographic variables. These results show that fear of COVID-19 is a relevant construct to consider for predicting and possibly influencing vaccination willingness. Nonetheless, sensitivity and specificity of fear of COVID-19 to predict vaccination willingness were quite low and only became slightly better when fear of COVID-19 was measured concurrently. This indicates that other potential factors, such as perceived risks of the vaccines, probably also play a role in explaining vaccination willingness.

The COVID-19 pandemic has a substantial impact on mental health. Prior reports have shown that depression, anxiety, and stress have increased throughout the pandemic. Nonetheless, not everyone is affected by these negative consequences and some people may be relatively unaffected. In this online study in a predominantly Dutch and Belgian sample (N = 546), we investigated whether positive personality traits such as optimism, mindfulness, and resilience may protect against the negative mental health consequences (i.e., fear of the coronavirus, depression, stress, and anxiety) of the COVID-19 pandemic. We found that fear of COVID-19 was related to higher depression, stress, and anxiety. However, for participants scoring high on mindfulness, optimism, and resilience, this relationship was weakened. In addition to these findings, we present the results of network analyses to explore the network structure between these constructs. These results help to identify possible ways through which psychological well-being can be promoted during the COVID-19 pandemic.

Since the outbreak of the coronavirus disease (COVID-19), several reports have shown that fear relating to COVID-19 has sharply increased. To measure fear of COVID-19, various questionnaires have been developed in parallel. However, fear concerning COVID-19 is not necessarily a uniform construct and the different questionnaires may cover diverse aspects. To examine the underlying structure of fear of COVID-19, we conducted structural equation modelling and network analyses on four scales in an online convenience sample (N = 829). Particularly, the Fear of COVID-19 Scale (Ahorsu et al., 2020), the Fear of the Coronavirus Questionnaire (Mertens et al., 2020), and the COVID Stress Scales (Taylor, Landry, Paluszek, Fergus et al., 2020, Taylor, Landry, Paluszek, Rachor et al., 2020) were included in our study, along with a new scale that also assessed socio-economic worries relating to COVID-19. We found that fear of COVID-19 was best classified into four clusters: Fear of health-related consequences, fear of supplies shortages and xenophobia, fear about socio-economic consequences, and symptoms of fear (e.g., compulsions, nightmares). We also find that a central cluster of items centered on fear of health, which likely represents the core of fear of COVID-19. These results help to characterize fear due to COVID-19 and inform future research.