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Abstract BackgroundIn our aging population, primary care is under pressure to remain accessible to all. Effective use of digital health care could potentially lower general practitioners’ (GPs) workload. Some general practices are already implementing a digital health platform as a primary method to contact their patients. However, it is unknown how older people experience this novel way to communicate with their GP. ObjectiveThe aim of this study was to study the experiences of patients aged 65 years and older in general practices who use digital health as a primary communication tool. The secondary aims were to identify barriers and facilitators for the use of digital health care and whether a practice focus on digital health influences older patients’ choice to enlist. MethodsWe invited all patients aged 65 years and older at 2 general practices in Amsterdam that work with a novel digital health platform. We used purposive sampling to select a heterogeneous group of patients in terms of age, sex, level of education, digital literacy, and experiences with the digital app of their general practice. We conducted 18 semistructured interviews from May through July 2023. All interviews were audio-recorded, transcribed, coded, and thematically analyzed. ResultsWe generated three themes: (1) experiences of older people with digital health care in general practice, (2) impact of individual factors on digital health experiences, and (3) reasons for choosing a digitally oriented general practice. Participants reported both positive and negative experiences. The main perceived advantages of the digital health platform were increased accessibility, direct GP contact without an intermediary, and saving time through asynchronous communication. The disadvantages mentioned were log-in difficulties and problems with the automated explanatory questionnaire. Individual factors such as age, digital literacy, and expectations of general practice care seemed to impact people’s experiences and could act as barriers or facilitators for using digital health. Reasons for older patients to enlist at a general practice were mainly practical. The digital orientation of the practice hardly played a role in this choice. ConclusionsOlder patients in general practice see benefits to using a digital health platform that offers 2-way chat-based communication between the patient and GP. We found that individual factors such as skills, norms and values, attitudes toward digitalization, and expectations of general practice care impacted older patients’ experiences with digital health care. For many older participants, the digital profile of the general practice did not play a role in their choice to enlist. Further improvement of digital health platforms will be necessary to ensure digital health for all in general practice.

Background: : Qualitative research shows barriers in access to healthcare for persons with a migration background, possibly leading to healthcare inequalities. We aimed to compare healthcare use between older community-dwelling persons with a migration background and native Dutch persons with dementia. Methods: : Observational cohort study using electronic health records of NIVEL Primary Care Database (2013–2014) linked to nationwide administrative registries managed by Statistics Netherlands. We included all community-dwelling persons with dementia in the Netherlands aged 65 years and older. Negative binomial and logistic regression analyses were conducted to assess differences in healthcare use outcomes. The largest migrant groups (persons born in Surinam, Turkey and Morocco) were studied separately. Results: : 138,864 persons with dementia were included in the study, whereof 3,991 persons with a migration background and 132,477 native Dutch persons. Moroccan-born persons showed 1.46 higher odds of having an unplanned hospital admission compared to native Dutch persons (95 % Confidence Interval [CI] 1.22–1.74). Persons with a migration background used less professional home care (Odds Ratio [OR] 0.55, 95 %CI 0.51–0.59), and received less home visits from their general practitioner (OR 0.50, 95 %CI 0.43–0.57) than native Dutch persons. Moroccan-born persons had more often an out-of-hours general practitioner consultation compared to native Dutch persons (Incidence Rate Ratio 1.36, 95 %CI 1.18–1.57). Conclusions: : We found significant quantitative differences in healthcare use between persons with a migration background and native Dutch persons with dementia. Further research is needed to gain insight into the reasons of these differences, with consideration of specific migration background.

Abstract Background Among older people undiagnosed and untreated vision impairment and blindness are common. The leading causes are uncorrected refractive errors and cataracts. Vision problems are associated with a lower quality of life, several health problems, and a higher chance of falling accidents and fractures. To eliminate avoidable vision impairment and blindness, targeted eye screening programs are recommended. Older patients, receiving home healthcare, have not yet been considered as a population at risk who could benefit from eye screening. Methods A cluster-randomized controlled trial will be conducted to investigate the cost-effectiveness and cost-utility of online nurse-assisted eye screening in home healthcare, compared to care as usual, in reducing avoidable vision impairment. A healthcare and societal perspective will be used. The study will be performed in collaboration with several home healthcare organizations in the Netherlands. The online eye screening consists of near and distance visual acuity, followed by an Amsler grading test. Measurements in both groups will take place at baseline and after 6 and 12 months of follow-up. A total of 240 participants will be recruited. Older men and women (65 +), who receive home-based nursing and are cognitively able to participate, will be included. The primary outcome will be the change of two lines or more on the Colenbrander-1 M visual acuity chart between baseline and 12-month follow-up. Discussion An eye screening for populations at risk contributes to the detection of undiagnosed and untreated vision impairment. This may reduce the health-related consequences of vision loss and the high economic burden associated with vision impairment. Trial registration ClinicalTrials.gov NCT06058637. Registered on 27 September 2023.

Aim To evaluate the effectiveness, feasibility and acceptability of a multicomponent intervention for improving personal continuity for older patients in general practice.Design A cluster randomised three-wedged, pragmatic trial during 18 months.Setting 32 general practices in the Netherlands.Participants 221 general practitioners (GPs), practice assistants and other practice staff were included. Practices were instructed to include a random sample of 1050 patients aged 65 or older at baseline and 12-month follow-up.Intervention The intervention took place at practice level and included opTimise persOnal cOntinuity for oLder (TOOL)-kit: a toolbox containing 34 strategies to improve personal continuity.Outcomes Data were collected at baseline and at six 3-monthly follow-up measurements. Primary outcome measure was experienced continuity of care at the patient level measured by the Nijmegen Continuity Questionnaire (NCQ) with subscales for personal continuity (GP knows me and GP shows commitment) and team/cross-boundary continuity at 12-month follow-up. Secondary outcomes were measured in GPs, practice assistants and other practice staff and included work stress and satisfaction and perceived level of personal continuity. In addition, a process evaluation was undertaken among GPs, practice assistants and other practice staff to assess the acceptability and feasibility of the intervention.Results No significant effect of the intervention was observed on NCQ subscales GP knows me (adjusted mean difference: 0.05 (95% CI −0.05 to 0.15), p=0.383), GP shows commitment (0.03 (95% CI −0.08 to 0.14), p=0.668) and team/cross-boundary (0.01 (95% CI −0.06 to 0.08), p=0.911). All secondary outcomes did not change significantly during follow-up. Process evaluation among GPs, practice assistants and other practice staff showed adequate acceptability of the intervention and partial implementation due to the COVID-19 pandemic and a high perceived workload.Conclusion Although participants viewed TOOL-kit as a practical and accessible toolbox, it did not improve personal continuity as measured with the NCQ. The absence of an effect may be explained by the incomplete implementation of TOOL-kit into practice and the choice of general outcome measures instead of outcomes more specific for the intervention.Trial registration number International Clinical Trials registry Platform (ICTRP), trial NL8132 (URL: ICTRP Search Portal (who.int).

Introduction Vertigo is a prevalent and burdensome symptom. More than 80% of patients with vertigo are primarily treated by their general practitioner (GP) and are never referred to a medical specialist. Despite this therapeutic responsibility, the GP’s diagnostic toolkit has serious limitations. All recommended tests lack empirical evidence, because a diagnostic accuracy study on vestibular disorders (‘How well does test x discriminate between patients with or without target condition y?’) has never been performed in general practice. The VERtigo DIagnosis study aims to fill this gap.Methods and analysis We will perform a diagnostic accuracy study on vertigo of primary vestibular origin in general practice to assess the discriminative ability of history taking and physical examination. We will compare all index tests with a respective reference standard. We will focus on five target conditions that account for more than 95% of vertigo diagnoses in general practice: (1) benign paroxysmal positional vertigo, (2) vestibular neuritis, (3) Ménière’s disease, (4) vestibular migraine (VM) and (5) central causes other than VM. As these five target conditions have a different pathophysiology and lack one generally accepted gold standard, we will use consensus diagnosis as a construct reference standard. Data for each patient, including history, physical examination and additional tests as recommended by experts in an international Delphi procedure, will be recorded on a standardised form and independently reviewed by a neurologist and otorhinolaryngologist. For each patient, the reviewers have to decide about the presence/absence of each target condition. We will calculate sensitivity, specificity, predictive values, likelihood ratios and diagnostic ORs, followed by decision rules for each target condition.Ethics and dissemination The study obtained approval from the Vrije Universiteit Medical Center Medical Ethical Review Committee (reference: 2022.0817—NL83111.029.22). We will publish our findings in peer-reviewed international journals.Trial registration number ISRCTN97250704.

Abstract Background Vestibular rehabilitation is a safe and effective exercise-based treatment for patients with chronic vestibular symptoms. However, it is underused in general practice. Internet-based vestibular rehabilitation (Vertigo Training), which has proven to be effective as well, was developed to increase uptake. We now aim to improve the quality of care for patients with vestibular symptoms by carrying out a nationwide implementation of Vertigo Training. We will evaluate the effect of this implementation on primary care. Methods Our implementation study consists of three successive phases: 1) We will perform a retrospective observational cohort study and a qualitative interview study to evaluate the current management of patients with vestibular symptoms in primary care, in particular anti-vertigo drug prescriptions, and identify areas for improvement. We will use the results of this phase to tailor our implementation strategy to the needs of general practitioners (GPs) and patients. 2) This phase entails the implementation of Vertigo Training using a multicomponent implementation strategy, containing: guideline adaptations; marketing strategy; pharmacotherapeutic audit and feedback meetings; education; clinical decision support; and local champions. 3) In this phase, we will evaluate the effect of the implementation in three ways. a. Interrupted time series. We will use routine primary care data from adult patients with vestibular symptoms to compare the number of GP consultations for vestibular symptoms, referrals for vestibular rehabilitation, prescriptions for anti-vertigo drugs, and referrals to physiotherapy and secondary care before and after implementation. b. Prospective observational cohort study. We will extract data from Vertigo Training to investigate the usage and the characteristics of participants. We will also determine whether these characteristics are associated with successful treatment. c. Qualitative interview study. We will conduct interviews with GPs to explore their experiences with the implementation. Discussion This is one of the first studies to evaluate the effect of a nationwide implementation of an innovative treatment on Dutch primary care. Implementation strategies have been researched before, but it remains unclear which ones are the most effective and under what conditions. We therefore expect to gain relevant insights for future projects that aim to implement innovations in primary care.

BackgroundFew studies have considered the life-course development of depressive symptoms in relation to life transitions in early-adulthood and whether these might affect depressive trajectories differently depending on specific indicators of parental socioeconomic status (SES). In the present work, we explore these questions using the adolescent pathway model as a guiding framework to test socially differential exposure, tracking and vulnerability of the effects of life transitions on depressed mood across different socioeconomic backgrounds.MethodsLatent growth modeling was used to estimate the associations between indicators of parental SES (parental education and household income) and depressed mood from age 13 to 40 with life transitions (leaving the parental home, leaving the educational system, beginning cohabitation, attaining employment) as pathways between the two. Our analyses were based on a 27-year longitudinal dataset (n = 1242) of a Norwegian cohort with 10 time points in total. To make socioeconomic comparisons, three groups (low, mid, and high) were made for parental education and income respectively.ResultsDepressed mood decreased from age 13 to 40. The low and high parental education groups showed a stable difference in depressed mood during early adolescence, which decreased in young adulthood and then increased slightly in mid-adulthood. The low household income group showed higher depressed mood across young adulthood compared to the medium and higher household income groups. For life transitions, leaving the parental home and beginning cohabitation was associated with an added downturn of the trajectory of depressed mood when adjusting for other transitions. However, adolescents with high parental education showed a relatively stronger decrease in depressed mood when leaving the parental home. Similarly, adolescents with a high household income showed a relatively stronger decrease in depressed mood when leaving the educational system.ConclusionsDepressed mood decreased over time and developed differently depending on parental education and household income. Life transitions were generally associated with reductions in depressed mood across time, but lower SES youths were not found to be more socially vulnerable these effects.

Abstract Background Therapy dropout poses a major challenge. Considerable research has been conducted on predictors of dropout, however none in the context of primary mental health services in Norway. The purpose of this study was to investigate which client characteristics can predict dropout from the service Prompt Mental Health Care (PMHC). Methods We performed a secondary analysis of a Randomized Controlled Trial (RCT). Our sample consisted of 526 adult participants receiving PMHC-treatment in the municipalities of Sandnes and Kristiansand, between November 2015 to August 2017. Using logistic regression, we investigated the association between nine client characteristics and dropout. Results The dropout rate was 25.3%. The adjusted analysis indicated that older clients had a lower odds ratio (OR) of dropping out compared to younger clients (OR = 0.43, [95% CI = 0.26, 0.71]). Moreover, clients with higher education had a lower odds ratio of dropping out compared to clients with lower levels of education (OR = 00.55, 95% CI [0.34, 0.88]), while clients who were unemployed were more likely to drop-out as compared the regularly employed (OR = 2.30, [95% CI = 1.18, 4.48]). Finally, clients experiencing poor social support had a higher odds ratio of dropping out compared to clients who reported good social support (OR = 1.81, [95% CI = 1.14, 2.87]). Sex, immigrant background, daily functioning, symptom severity and duration of problems did not predict dropout. Conclusion The predictors found in this prospective study might help PMHC-therapists identify clients at risk of dropout. Strategies for preventing dropout are discussed.

Abstract Background While frank discussion of suicidal thoughts in patients with depression is important for the prevention of suicide, suicide exploration of General Practitioners (GPs) is suboptimal. This study aimed to assess whether an intervention that prompts pop-up screens nudges GPs to more frequently explore suicidal thoughts over the course of two years. Methods From January 2017 to December 2018, the intervention was incorporated in the information system of the Dutch general practice sentinel network. New registration of an episode of depression triggered a pop-up screen referring to a questionnaire about GPs’ behaviour with regard to exploring suicidal thoughts. In two years, 625 questionnaires were completed by GPs and analysed using multilevel logistic regression analyses. Results Compared to the first year, GPs were 50% more likely to explore suicidal thoughts among patients in the second year (OR 1.48; 95%CI 1.01–2.16). When adjusting for patients’ gender and age we found that the effect of the pop-up screens disappeared (OR 1.33; 95% CI 0.90–1.97). Suicide exploration occurred less frequently in women than in men (OR 0.64; 95% CI 0.43–0.98) and in older compared to younger patients (OR 0.97; 95% CI 0.96–0.98 per year older). In addition, 26% of variation in suicide exploration was because of differences in general practice. There was no evidence that general practices developed differently over time. Conclusions Although low cost and easy to administer, the pop-up system was not effective in nudging GPs to explore suicidality more frequently. We encourage studies to test whether implementing these nudges as part of a multifaceted approach will lead to a stronger effect. Moreover, we recommend researchers to include more variables, such as work experience or previous mental health training, to better understand the effects of the intervention on GPs’ behaviour.

Abstract Background Marital status is a robust correlate of disordered gambling, but few studies have examined the direction of this association. Methods The present study used a case–control design by including all adults receiving their first gambling disorder (GD) diagnosis between January 2008 to December 2018 (Norwegian Patient Registry, n = 5,121) and compared them against age and gender matched individuals with other somatic/psychiatric illnesses (Norwegian Patient Registry, n = 27,826) and a random sample from the general population (FD-Trygd database, n = 26,695). The study examined marital status before GD, getting divorced as a risk factor for future GD, and becoming married as a protective factor of future GD. Results The findings indicated an 8–9 percentage points higher prevalence of unmarried people and about a 5 percentage points higher prevalence of separation/divorce among those that subsequently experienced GD compared to controls. Logistic regressions showed that transition through divorce was associated with higher odds of future GD compared to illness controls (odds ratio [OR] = 2.89, 95% CI [2.41, 3.45]) and the general population (OR = 2.83 [2.36, 3.38]). Logistic regressions also showed that transition through marriage was associated with lower odds of future GD compared to illness controls (OR = 0.62, CI [0.55, 0.70]) and the general population (OR = 0.57, CI [0.50, 0.64]). Conclusions Social bonds have previously been shown to impact physical and mental health, and the findings of the study emphasize the importance of considering social network history and previous relationship dissolution among individuals with GD.

Abstract Background Whether long-term symptom improvement is maintained after treatment in services such as the Norwegian Prompt Mental Health Care (PMHC) and the English Improving Access to Psychological Therapies is not yet known. In this prospective study, we investigate whether improvements observed at 6-month follow-up are maintained at 24- and 36-month follow-up among clients who received PMHC. Method Data from the treatment arm of the randomized controlled trial of PMHC were used (n = 459). The main outcomes were (reliable) recovery rate and symptoms of depression (PHQ-9) and anxiety (GAD-7). Primary outcome data at 24- and 36-months follow-up were available for 47% and 39% of participants, respectively. Secondary outcomes were work participation, functional status, health-related quality of life, and positive mental well-being. Sensitivity analyses with regard to missing data assumptions were conducted for the primary continuous outcomes. Results Improvements were maintained at 24- and 36-month follow-up for symptoms of depression and anxiety, (reliable) recovery rate, and health-related quality of life. Small linear improvements since 6-month follow-up were observed for work participation, functional status, and positive mental well-being. Sensitivity analyses did not substantially alter the findings for symptoms of depression and anxiety mentioned above. Conclusions Our findings support the long-term effectiveness of PMHC, but results should be interpreted with caution due to lacking follow-up data at 24- and 36-month in the control group, and substantial attrition.

Non-pharmaceutical interventions, including promotion of social distancing, have been applied extensively in managing the COVID-19 pandemic. Understanding cognitive and psychological factors regulating precautionary behavior is important for future management. The present study examines the importance of selected factors as predictors of having visited or intended to visit crowded places. Six online questionnaire-based waves of data collection were conducted in April–October 2020 in a Norwegian panel (≥18 years). Sample size at Wave 1 was 1,400. In the present study, “Visited or intended to visit crowded places” for different types of locations were the dependent variables. Predictors included the following categories of items: Perceived response effectiveness, Self-efficacy, Vulnerability, Facilitating factors and Barriers. Data were analyzed with frequency and percentage distributions, descriptives, correlations, principal components analysis, negative binomial-, binary logistic-, and multiple linear regression, and cross-lagged panel models. Analyses of dimensionality revealed that a distinction had to be made between Grocery stores, a location visited by most, and locations visited by few (e.g., “Pub,” “Restaurants,” “Sports event”). We merged the latter set of variables into a countscore denoted as “Crowded places.” On the predictor side, 25 items were reduced to eight meanscores. Analyses of data from Wave 1 revealed a rather strong prediction of “Crowded places” and weaker associations with “Supermarket or other store for food.” Across waves, in multiple negative binomial regression models, three meanscore predictors turned out to be consistently associated with “Crowded places.” These include “Response effectiveness of individual action,” “Self-efficacy with regard to avoiding people,” and “Barriers.” In a prospective cross-lagged model, a combined Response effectiveness and Self-efficacy score (Cognition) predicted behavior (“Visited or intended to visit crowded places”) prospectively and vice versa. The results of this study suggest some potential to reduce people's visits to crowded locations during the pandemic through health education and behavior change approaches that focus on strengthening individuals' perceived response effectiveness and self-efficacy.

Abstract Background Accurate identification of older persons at risk of unplanned hospital visits can facilitate preventive interventions. Several risk scores have been developed to identify older adults at risk of unplanned hospital visits. It is unclear whether risk scores developed in one country, perform as well in another. This study validates seven risk scores to predict unplanned hospital admissions and emergency department (ED) visits in older home care recipients from six countries. Methods We used the IBenC sample (n = 2446), a cohort of older home care recipients from six countries (Belgium, Finland, Germany, Iceland, Italy and The Netherlands) to validate four specific risk scores (DIVERT, CARS, EARLI and previous acute admissions) and three frailty indicators (CHESS, Fried Frailty Criteria and Frailty Index). Outcome measures were unplanned hospital admissions, ED visits or any unplanned hospital visits after 6 months. Missing data were handled by multiple imputation. Performance was determined by assessing calibration and discrimination (area under receiver operating characteristic curve (AUC)). Results Risk score performance varied across countries. In Iceland, for any unplanned hospital visits DIVERT and CARS reached a fair predictive value (AUC 0.74 [0.68–0.80] and AUC 0.74 [0.67–0.80]), respectively). In Finland, DIVERT had fair performance predicting ED visits (AUC 0.72 [0.67–0.77]) and any unplanned hospital visits (AUC 0.73 [0.67–0.77]). In other countries, AUCs did not exceed 0.70. Conclusions Geographical validation of risk scores predicting unplanned hospital visits in home care recipients showed substantial variations of poor to fair performance across countries. Unplanned hospital visits seem considerably dependent on healthcare context. Therefore, risk scores should be validated regionally before applied to practice. Future studies should focus on identification of more discriminative predictors in order to develop more accurate risk scores.

Abstract Background Continuity of care, in particular personal continuity, is a core principle of general practice and is associated with many benefits such as a better patient-provider relationship and lower mortality. However, personal continuity is under pressure due to changes in society and healthcare. This affects older patients more than younger patients. As the number of older patients will double the coming decades, an intervention to optimise personal continuity for this group is highly warranted. Methods Following the UK Medical Research Council framework for complex Interventions, we will develop and evaluate an intervention to optimise personal continuity for older patients in general practice. In phase 0, we will perform a literature study to provide the theoretical basis for the intervention. In phase I we will define the components of the intervention by performing surveys and focus groups among patients, general practitioners, practice assistants and practice nurses, concluded by a Delphi study among members of our group. In phase II, we will test and finalise the intervention with input from a pilot study in two general practices. In phase III, we will perform a stepped wedge cluster randomised pragmatic trial. The primary outcome measure is continuity of care from the patients’ perspective, measured by the Nijmegen Continuity Questionnaire. Secondary outcome measures are level of implementation, barriers and facilitators for implementation, acceptability and feasibility of the intervention. In phase IV, we will establish the conditions for large-scale implementation. Discussion This is the first study to investigate an intervention for improving personal continuity for older patients in general practice. If proven effective, our intervention will enable General practitioners to improve the quality of care for their increasing population of older patients. The pragmatic design of the study will enable evaluation in real-life conditions, facilitating future implementation. Trial registration number Netherlands Trial Register, trial NL8132 . Registered 2 November 2019.

Introduction Surgical site infections (SSIs) are among the most common complications after abdominal surgery and develop in approximately 20% of patients. These patients suffer a 12% increase in mortality, underlying the need for strategies reducing SSI. Perioperative antibiotic prophylaxis is paramount for SSI prevention in major abdominal surgery. Yet, intraoperative redosing criteria are subjective and whether patients benefit from it remains unclear.Methods and analysis The REpeat versus SIngle ShoT Antibiotic prophylaxis in major Abdominal Surgery (RESISTAAS I) study is a single-centre, prospective, observational study investigating redosing of antibiotic prophylaxis in 300 patients undergoing major abdominal surgery. Adult patients scheduled for major abdominal surgery will be included. Current practice of redosing regarding number and time period will be recorded. Postoperative SSIs, nosocomial infections, clinically relevant infection-associated bacteria, postoperative antibiotic treatment, in addition to other clinical, pharmacological and economical outcomes will be evaluated. Differences between groups will be analysed with analysis of covariance.Ethics and dissemination RESISTAAS I will be conducted in accordance with the Declaration of Helsinki and internal, national and international standards of GCP. The Medical Ethics Review Board of Heidelberg University has approved the study prior to initiation (S-404/2021). The study has been registered on 7 February 2022 at German Clinical Trials Register, with identifier DRKS00027892. We plan to disseminate the results of the study in a peer-reviewed journal.Trial registration German Clinical Trials Register (DRKS): DRKS00027892.

Various studies have reported insufficient beta-lactam concentrations in critically ill patients. The optimal dosing strategy for beta-lactams in critically ill patients, particularly in septic patients, is an ongoing matter of discussion. This retrospective study aimed to evaluate the success of software-guided empiric meropenem dosing (CADDy, Calculator to Approximate Drug-Dosing in Dialysis) with subsequent routine meropenem measurements and expert clinical pharmacological interpretations. Adequate therapeutic drug exposure was defined as concentrations of 8–16 mg/L, whereas concentrations of 16–24 mg/L were defined as moderately high and concentrations >24 mg/L as potentially harmful. A total of 91 patients received meropenem as a continuous infusion (229 serum concentrations), of whom 60% achieved 8–16 mg/L, 23% achieved 16–24 mg/L, and 10% achieved unnecessarily high and potentially harmful meropenem concentrations >24 mg/L in the first 48 h using the dosing software. No patient showed concentrations p ≤ 0.05) enhanced to 70%. No patient had meropenem concentrations >24 mg/L with TDM-guided dose adjustments. The combined use of dosing software and consecutive TDM promised a high rate of adequate therapeutic drug exposures of meropenem in patients with sepsis and septic shock.

Abstract The scope of extracorporeal membrane oxygenation (ECMO) is expanding, nevertheless, pharmacokinetics in patients receiving cardiorespiratory support are fairly unknown leading to unpredictable drug concentrations. Currently, there are no clear guidelines for antibiotic dosing during ECMO. This study aims to evaluate the pharmacokinetics (PK) of cefazolin in patients undergoing ECMO treatment. Total and unbound plasma cefazolin concentration of critically ill patients on veno-arterial ECMO were determined. Observed PK was compared to dose recommendations calculated by an online available, free dosing software. Concentration of cefazolin varied broadly despite same dosage in all patients. The mean total and unbound plasma concentration were high showing significantly (p = 5.8913 E−09) greater unbound fraction compared to a standard patient. Cefazolin clearance was significantly (p = 0.009) higher in patients with preserved renal function compared with CRRT. Based upon the calculated clearance, the use of dosing software would have led to lower but still sufficient concentrations of cefazolin in general. Our study shows that a “one size fits all” dosing regimen leads to excessive unbound cefazolin concentration in these patients. They exhibit high PK variability and decreased cefazolin clearance on ECMO appears to compensate for ECMO- and critical illness-related increases in volume of distribution.

BackgroundGiven that relapse is common in patients in remission from anxiety and depressive disorders, relapse prevention is needed in the maintenance phase. Although existing psychological relapse prevention interventions have proven to be effective, they are not explicitly based on patients’ preferences. Hence, we developed a blended relapse prevention program based on patients’ preferences, which was delivered in primary care practices by mental health professionals (MHPs). This program comprises contact with MHPs, completion of core and optional online modules (including a relapse prevention plan), and keeping a mood and anxiety diary in which patients can monitor their symptoms. ObjectiveThe aims of this study were to provide insight into (1) usage intensity of the program (over time), (2) the course of symptoms during the 9 months of the study, and (3) the association between usage intensity and the course of symptoms. MethodsThe Guided E-healTh for RElapse prevention in Anxiety and Depression (GET READY) program was guided by 54 MHPs working in primary care practices. Patients in remission from anxiety and depressive disorders were included. Demographic and clinical characteristics, including anxiety and depressive symptoms, were collected via questionnaires at baseline and after 3, 6, and 9 months. Log data were collected to assess the usage intensity of the program. ResultsA total of 113 patients participated in the study. Twenty-seven patients (23.9%) met the criteria for the minimal usage intensity measure. The core modules were used by ≥70% of the patients, while the optional modules were used by

Abstract Background In critically ill patients, tigecycline (TGC) remains an important therapeutic option due to its efficacy against multiresistant Gram-positive and Gram-negative bacteria. TGC is metabolized and eliminated predominantly by the liver. Critical illness-induced liver failure may have a profound impact on the pharmacokinetic of TGC. In the present study, we aimed to establish a link between the degree of liver dysfunction and TGC plasma concentration using the novel maximum liver function capacity (LiMAx) test, as a dynamic liver function test. Materials/methods The prospective study included 33 patients from a surgical ICU with the clinical indication for antibiotic therapy with TGC. The patients received 100 mg loading dose of TGC followed by intermittent standard doses of 50 mg q12. Blood samples for TGC plasma concentration were collected at 0.3, 2, 5, 8 and 11.5 h in a steady-state condition after at least 36 h post-standard dosage. The results were analyzed by means of a high-performance liquid chromatography (HPLC) method. Within the same day, the LiMAx test was carried out and routine blood parameters were measured. Results Peak plasma concentrations of TGC were significantly higher in patients with severe liver failure (LiMAx 300 µg/kg/h). The pharmacokinetic curves revealed higher values in severe liver failure at any measured point. Moreover, LiMAx and total bilirubin were the only liver-related parameters that correlated with TGC C max. Conclusions The present study demonstrates a high variability of TGC plasma concentrations in critically ill patients. The results show a significant correlation between the degree of liver dysfunction, measured by the LiMAx test, and TGC C max. LiMAx test may be a helpful tool beyond others for adjusting the required dosage of hepatic metabolized antibiotics in critically ill patients. Trial registry DRKS—German clinical trials register; Trial registration number: DRKS00008888; Date of registration: 07-17-2015; Date of enrolment of the first participant to the trial: 12-10-2015

BackgroundIdentification of community-dwelling older adults at risk of unplanned hospitalizations is of importance to facilitate preventive interventions. Our objective was to review and appraise the methodological quality and predictive performance of prediction models for predicting unplanned hospitalizations in community-dwelling older adults.Methods and findingsWe searched MEDLINE, EMBASE and CINAHL from August 2013 to January 2021. Additionally, we checked references of the identified articles for the inclusion of relevant publications and added studies from two previous reviews that fulfilled the eligibility criteria. We included prospective and retrospective studies with any follow-up period that recruited adults aged 65 and over and developed a prediction model predicting unplanned hospitalizations. We included models with at least one (internal or external) validation cohort. The models had to be intended to be used in a primary care setting. Two authors independently assessed studies for inclusion and undertook data extraction following recommendations of the CHARMS checklist, while quality assessment was performed using the PROBAST tool. A total of 19 studies met the inclusion criteria. Prediction horizon ranged from 4.5 months to 4 years. Most frequently included variables were specific medical diagnoses (n = 11), previous hospital admission (n = 11), age (n = 11), and sex or gender (n = 8). Predictive performance in terms of area under the curve ranged from 0.61 to 0.78. Models developed to predict potentially preventable hospitalizations tended to have better predictive performance than models predicting hospitalizations in general. Overall, risk of bias was high, predominantly in the analysis domain.ConclusionsModels developed to predict preventable hospitalizations tended to have better predictive performance than models to predict all-cause hospitalizations. There is however substantial room for improvement on the reporting and analysis of studies. We recommend better adherence to the TRIPOD guidelines.

Abstract Background Sepsis is a life-threatening organ dysfunction caused by a dysregulated host response to infection with a hospital mortality in excess of 40%. Along with insufficient and delayed empirical antimicrobial therapy, inappropriate antimicrobial exposure has been identified to negatively affect patient outcomes. Receipt of prolonged infusion (i.e. extended or continuous infusion) of piperacillin/tazobactam (TZP) improves antimicrobial exposure and is associated with reduced mortality in patients with sepsis. Using therapeutic drug monitoring (TDM) with dosing tailored to the altered pharmacokinetics of the individual patient to avoid under- and overdosing may be a further strategy to improve patient outcomes. This current trial will address the question whether a TDM-guided therapy with TZP administered by continuous infusion will result in a greater resolution of organ dysfunction and hence better clinical outcome compared to continuous infusion of the total daily dose of TZP without TDM. Methods The study is an investigator-initiated, multi-centre, parallel-group, single-blinded, randomised controlled trial. The trial will be conducted in several centres across Germany. Adult patients (aged ≥ 18 years) with severe sepsis or septic shock will be eligible for study participation. Participants will be randomly assigned to receive either TZP by continuous infusion guided by daily TDM of piperacillin (experimental group) or by continuous infusion without TDM guidance (total daily dose in normal renal function 13.5 g TZP) (control group). The pharmacokinetic (PK)/pharmacodynamic (PD) target will be 100% f T>4MIC (percentage of time during a dosing interval that the free [f] drug concentration exceeds 4 times the minimum inhibitory concentration). The primary efficacy endpoint is the change in mean total Sequential Organ Failure Assessment score from day 1 after randomisation until day 10 or discharge from the intensive care unit or death, whichever comes first. Secondary outcomes include mortality, clinical cure, microbiological cure, overall antibiotic use, individual components of the primary outcome, adverse events and analysis of PK and (PD) indices. Discussion This trial will assess for the first time whether continuous infusion of TZP guided by daily TDM in patients with sepsis will result in a greater resolution of organ dysfunction and hence better clinical outcome compared to continuous infusion without TDM. Trial registration German Clinical Trials Register (GermanCTR), DRKS00011159. Registered on 10 October 2016.

Abstract Background Identifying factors that can influence young peoples’ physical activity and sedentary behaviors is important for the development of effective interventions. The family structure in which children grow up may be one such factor. As the prevalence of single parent and reconstituted families have increased substantially over the last decades, the objective of this study was to examine whether these family structures are differentially associated with young people’s MVPA, participation in organized sports and screen-time activities (screen-based passive entertainment, gaming, other screen-based activities) as compared to traditional nuclear families. Methods The data stem from the 2013/2014 “Health Behaviour in School- aged Children (HBSC) study”. A large Norwegian sample of 11–16 years old students (n = 4509) participated. Cluster-adjusted regression models were estimated using full information maximum likelihood with robust standard errors (MLR). Results After adjusting for covariates, living with a single parent was negatively associated with days/week with 60 min MVPA (b = −.39, 95%CI: −.58, −.20), and positively associated with hours/weekday of total screen time (b = .50, 95%CI: .08, .93). Young people living with a single parent were also more likely to report no participation in organized sports (OR = 1.40, 95%CI: 1.09, 1.79). Living in a reconstituted family was negatively associated with days/week with 60 min MVPA (b = −.31, 95%CI: −.53, −.08), and positively associated with hours/weekday of total screen time (b = .85, 95%CI: .37, 1.33). For all outcomes, the interaction effects of family structure with sex, and with having siblings were not statistically significant. For material affluence, a significant interaction effect was found for participation in organized sports (χ2 [4] =13.9, p = .008). Those living in a reconstituted family with low or high material affluence had an increased risk for not participating in organized sports whereas those with medium material affluence did not. Conclusion This study suggests that living with a single parent or in reconstituted families was unfavorably associated with physical activity, sport participation and screen-based behaviors among Norwegian youth. The findings indicate that family structure could be an important factor to take into account in the development and testing of interventions. More in-depth research is needed to identify the mechanisms involved.

Abstract Background Since anxiety and depressive disorders often recur, self-management competencies are crucial for improving the long-term course of anxiety and depressive disorders. However, few relapse prevention programmes are available that focus on improving self-management. E-health combined with personal contact with a mental health professional in general practice might be a promising approach for relapse prevention. In this protocol, the GET READY (Guided E-healTh for RElapse prevention in Anxiety and Depression) study will be described in which a relapse prevention programme is developed, implemented and evaluated. The aim of the study is to determine patients’ usage of the programme and the associated course of their symptoms, to examine barriers and facilitators of implementation, and to assess patients’ satisfaction with the programme. Methods Participants are discharged from mental healthcare services, and are in complete or partial remission. They receive access to an E-health platform, combined with regular contact with a mental health professional in general practices. Online questionnaires will be completed at baseline and after 3, 6 and 9 months. Also, semi-structured qualitative individual interviews and focus group interviews will be conducted with patients and mental health professionals. Discussion This mixed-methods observational cohort study will provide insights into the use of a relapse prevention programme in relation to the occurrence of symptoms, as well as in its implementation and evaluation. Using the results of this study, the relapse prevention programme can be adapted in accordance with the needs of patients and mental health professionals. If this programme is shown to be acceptable, a randomized controlled trial may be conducted to test its efficacy. Trial registration Retrospectively registered in the Netherlands Trial Register (NTR7574; 25 October 2018).

Background: No studies have examined the underlying structure or predictive validity of the Cognitive Therapy Adherence and Competence Scale (CTACS). Examining the structure of the CTACS is of great relevance because it could provide information on what constitutes competence in CBT, and whether some underlying factors are more important for predicting treatment outcomes than others. This study investigates the psychometric properties of the Norwegian version of CTACS and its associations with treatment outcomes in a sample of primary care clients who received CBT for anxiety and/or depression.Method: Independent assessors rated audiotaped therapy sessions (early, mid and late in treatment) in a sample of 132 primary care clients (mean [SD] age = 34.8 [11.8], 63.6% women), participating in the Prompt Mental Health Care trial. Outcomes were symptoms of anxiety and depression assessed by patient self-report questionnaires. Structural validity was examined by means of confirmatory and exploratory factor analyses (CFA/EFA), whereas longitudinal associations with treatment outcome were explored by adopting multilevel modeling.Results: No evidence was found for the divergent validity of the constructs competence and adherence as indicated by a very high correlation between these two subscales in CTACS (0.97). Regarding reliability, ICCs for the mean score of the full competence scale and its associated subscales were generally good to excellent (0.70–0.80), although the subscale measuring the quality of the therapeutic relationship was relatively low (0.44). Internal consistency was overall acceptable, but our CFA models did not provide an acceptable fit for the pre-specified one-factor and four-factor solutions. EFA results were difficult to interpret, with a sub-optimal three-factor solution providing best model fit and only two meaningful factors [CBT specific skills (α = 0.82) and session structure (α = 0.59)]. Overall, the results indicated no evidence for the scales' predictive validity.Conclusion: Our findings point to several psychometric problems of the CTACS that may limit both its research and clinical utility. The importance of providing empirical evidence for both reliability and validity aspects of scales are discussed and suggestions for future research are provided.

Dalbavancin is emerging as a promising alternative in the ambulant treatment of gram-positive infections that require long-term antibiotic treatment such as osteomyelitis, prosthetic joint infections, and endocarditis. The aim of the current study was to develop and validate a simple, rapid, and cost-effective high-performance liquid chromatography–ultraviolet spectrometry (HPLC–UV) method for the quantification of dalbavancin. Sample clean-up included a protein precipitation protocol, followed by chromatographic separation on a reverse phase HPLC column (C-18) with gradient elution of the mobile phase. Quantification was performed with the internal standard (caffeine) method. Linear relationships between peak area responses and drug concentrations were obtained in the range of 12.5–400 mg/L. The variation coefficient of precision and the bias of accuracy (both inter- and intraday) were less than 10%. The limit of quantification (LOQ) was 12.5 mg/L. The simple and reliable HPLC–UV assay described is a powerful tool for routine therapeutic drug monitoring (TDM) of dalbavancin in human serum in clinical laboratories. With a total process time of approximately 20 min, it allows for accurate and selective quantification up to the expected pharmacokinetic peak concentrations. The method was successfully used to analyze subsequent serum samples of three patients and showed good performance in monitoring serum levels.

Extracorporeal membrane oxygenation (ECMO) is utilized to temporarily sustain respiratory and/or cardiac function in critically ill patients. Ciprofloxacin is used to treat nosocomial infections, but data describing the effect of ECMO on its pharmacokinetics is lacking. Therefore, a prospective, observational trial including critically ill adults (n = 17), treated with ciprofloxacin (400 mg 8–12 hourly) during ECMO, was performed. Serial blood samples were collected to determine ciprofloxacin concentrations to assess their pharmacokinetics. The pharmacometric modeling was performed (NONMEM®) and utilized for simulations to evaluate the probability of target attainment (PTA) to achieve an AUC0–24/MIC of 125 mg·h/L for ciprofloxacin. A two-compartment model most adequately described the concentration-time data of ciprofloxacin. Significant covariates on ciprofloxacin clearance (CL) were plasma bicarbonate and the estimated glomerular filtration rate (eGFR). For pathogens with an MIC of ≤0.25 mg/L, a PTA of ≥90% was attained. However, for pathogens with an MIC of ≥0.5 mg/L, plasma bicarbonate ≥ 22 mmol/L or eGFR ≥ 10 mL/min PTA decreased below 90%, steadily declining to 7.3% (plasma bicarbonate 39 mmol/L) and 21.4% (eGFR 150 mL/min), respectively. To reach PTAs of ≥90% for pathogens with MICs ≥ 0.5 mg/L, optimized dosing regimens may be required.

Background: Internet-based vestibular rehabilitation (VR) with physiotherapy support, known as blended VR, was effective in reducing vestibular symptoms in a recent randomised controlled trial. Blended VR is a complex intervention comprised of physiotherapeutic visits, the vertigo training website, and VR exercises. Because of these interacting components, it is important to understand how blended VR works, for whom it works best, and how it should ideally be delivered. Aim: To investigate the experiences of both patients and physiotherapists with blended internet-based VR. Design & setting: A qualitative interview study was performed with patients who received blended internet-based VR with physiotherapy support, and physiotherapists who provided this support. Method: Semi-structured interviews were conducted with 14 patients and eight physiotherapists after the 6-month follow-up of the randomised trial. All interviews were audio-recorded, transcribed, and thematically analysed. Results: According to both patients and physiotherapists, the physiotherapist visits were useful in providing personal attention, helping patients safely execute exercises, and improving patients’ adherence to therapy. Some patients said they did not need physiotherapist support and, according to physiotherapists, both the necessity and the optimal way to deliver guidance differed greatly between patients. The Vertigo Training website and exercises provided patients with a sense of control over their symptoms. Patients reported that the VR exercises were easy to perform and most patients continued to use them long after the trial ended. Conclusion: In blended VR, physiotherapeutic visits appear to offer benefits above the vertigo training website and VR exercises alone. Physiotherapy support may best be used when individually tailored.

Objectives To evaluate the cost-effectiveness of stand-alone and blended internet-based vestibular rehabilitation (VR) in comparison with usual care (UC) for chronic vestibular syndromes in general practice.Design Economic evaluation alongside a three-armed, individually randomised controlled trial.Setting 59 Dutch general practices.Participants 322 adults, aged 50 years and older with a chronic vestibular syndrome.Interventions Stand-alone VR consisted of a 6-week, internet-based intervention with weekly online sessions and daily exercises. In blended VR, this intervention was supplemented with face-to-face physiotherapy support. UC group participants received usual general practice care without restrictions.Main outcome measures Societal costs, quality-adjusted life years (QALYs), Vertigo Symptom Scale—Short Form (VSS-SF), clinically relevant response (≥3 points VSS-SF improvement).Results Mean societal costs in both the stand-alone and blended VR groups were statistically non-significantly higher than in the UC group (mean difference (MD) €504, 95% CI −1082 to 2268; and €916, 95% CI −663 to 2596). Both stand-alone and blended VR groups reported non-significantly more QALYs than the UC group (MD 0.02, 95% CI −0.00 to 0.04; and 0.01, 95% CI −0.01 to 0.03), and significantly better VSS-SF Scores (MD 3.8 points, 95% CI 1.7 to 6.0; and 3.3 points, 95% CI 1.3 to 5.2). For stand-alone VR compared with UC, the probability of cost-effectiveness was 0.95 at a willingness-to-pay ratio of €24 161/QALY, €600/point improvement in VSS-SF and €8000/clinically relevant responder in VSS-SF. For blended VR versus UC, the probability of cost-effectiveness was 0.95 at a willingness-to-pay ratio of €123 335/QALY, €900/point improvement in VSS-SF and €24 000/clinically relevant responder in VSS-SF.Conclusion Stand-alone and blended internet-based VR non-significantly increased QALYs and significantly reduced vestibular symptoms compared with UC, while costs in both groups were non-significantly higher. Stand-alone VR has the highest probability to be cost-effective compared with UC.Trial registration number The Netherlands Trial Register NTR5712.

Objective To investigate the prevalence of, and associations between, prenatal and perinatal risk factors and developmental vulnerability in twins at age 5.Design Retrospective cohort study using bivariate and multivariable logistic regression.Setting Western Australia (WA), 2002–2015.Participants 828 twin pairs born in WA with an Australian Early Development Census (AEDC) record from 2009, 2012 or 2015.Main outcome measures The AEDC is a national measure of child development across five domains. Children with scores

Objectives To develop and internally validate prediction models to assess treatment success of both stand-alone and blended online vestibular rehabilitation (VR) in patients with chronic vestibular syndrome.Design Secondary analysis of a randomised controlled trial.Setting 59 general practices in The Netherlands.Participants 202 adults, aged 50 years and older with a chronic vestibular syndrome who received either stand-alone VR (98) or blended VR (104). Stand-alone VR consisted of a 6-week, internet-based intervention with weekly online sessions and daily exercises. In blended VR, the same intervention was supplemented with physiotherapy support.Main outcome measures Successful treatment was defined as: clinically relevant improvement of (1) vestibular symptoms (≥3 points improvement Vertigo Symptom Scale—Short Form); (2) vestibular-related disability (>11 points improvement Dizziness Handicap Inventory); and (3) both vestibular symptoms and vestibular-related disability. We assessed performance of the predictive models by applying calibration plots, Hosmer-Lemeshow statistics, area under the receiver operating characteristic curves (AUC) and applied internal validation.Results Improvement of vestibular symptoms, vestibular-related disability or both was seen in 121, 81 and 64 participants, respectively. We generated predictive models for each outcome, resulting in different predictors in the final models. Calibration for all models was adequate with non-significant Hosmer-Lemeshow statistics, but the discriminative ability of the final predictive models was poor (AUC 0.54 to 0.61). None of the identified models are therefore suitable for use in daily general practice to predict treatment success of online VR.Conclusion It is difficult to predict treatment success of internet-based VR and it remains unclear who should be treated with stand-alone VR or blended VR. Because we were unable to develop a useful prediction model, the decision to offer stand-alone or blended VR should for now be based on availability, cost effectiveness and patient preference.Trial registration number The Netherlands Trial Register NTR5712.

Abstract Background Prompt mental health care (PMHC) is a Norwegian initiative, inspired by the English ‘Improving Access to Psychological Therapy’ (IAPT), aimed to provide low-threshold access to primary care treatment for persons with symptoms of anxiety and depression. The objectives of the present study are to describe the PMHC service, to examine changes in symptoms of anxiety and depression following treatment and to identify predictors of change, using data from the 12 first pilot sites. Methods A prospective cohort design was used. All participants were asked to complete questionnaires at baseline, before each treatment session and at the end of treatment. Effect sizes (ES) for pre-post changes and recovery rates were calculated based on the Patient Health Questionnaire and the Generalized Anxiety Disorder scale. Multiple imputation (MI) was used in order to handle missing data. We examined predictors through latent difference score models and reported the contribution of each predictor level in terms of ES. Results In total, N = 2512 clients received treatment at PMHC between October 2014 and December 2016, whereof 61% consented to participate. The changes from pre- to post-treatment were large for symptoms of both depression (ES = 1.1) and anxiety (ES = 1.0), with an MI-based reliable recovery rate of 58%. The reliable recovery rate comparable to IAPT based on last-observation-carried-forward was 48%. The strongest predictors for less improvement were having immigrant background (ES change depression − 0.27, ES change anxiety − 0.26), being out of work at baseline (ES change depression − 0.18, ES change anxiety − 0.35), taking antidepressants (ES change anxiety − 0.36) and reporting bullying as cause of problems (ES change depression − 0.29). Taking sleep medication did on the other hand predict more improvement (ES change depression 0.23, ES change anxiety 0.45). Conclusions Results in terms of clinical outcomes were promising, compared to both the IAPT pilots and other benchmark samples. Though all groups of clients showed substantial improvements, having immigrant background, being out of work, taking antidepressant medication and reporting bullying as cause stood out as predictors of poorer treatment response. Altogether, PMHC was successfully implemented in Norway. Areas for improvement of the service are discussed.

Abstract Background Due to the raised public awareness of Lyme Borreliosis (LB), its increased incidence and the increased availability of serological tests, the demand for diagnostic testing on LB has increased. This may affect the diagnostic behaviour of general practitioners (GPs). Aim of our study was to describe GPs’ diagnostic behaviour when suspecting LB. Methods In this descriptive study from January 2010 to June 2015, we used the anonymized electronic medical records of 56,996 patients registered in 12 general practices in Amsterdam, The Netherlands. The target population was identified by means of an extensive search strategy, based on International Classification of Primary Care (ICPC-1) codes, free text and diagnostic test codes. All contacts related to LB were included in the analysis. Results 2311 patients were included, accounting for 3861 LB contacts and 2619 LB episodes. The distribution of LB contacts showed annual peaks during spring and summer. Serological testing was performed in 36.4% of LB episodes and was mostly requested in patients presenting with general symptoms (71.4%). Unnecessary testing often occurred and only 5.9% of the tests turned out to be positive by immunoblot. From January 2010 to June 2015, no significant differences were found in the number of requested serological tests. The level of serological testing during LB episodes differed significantly between the general practices (19.2% to 75.8%). Conclusions Contrary to clinical guidelines, GPs regularly requested serology even when there was a low suspicion of LB. The development of an easy-to-use diagnostic algorithm may decrease overuse of diagnostic tests and thereby reduce overtreatment of LB.

Effective antibiotic therapy of cerebral infections such as meningitis or ventriculitis is hindered by low penetration into the cerebrospinal fluid (CSF). Because continuous infusion of meropenem and vancomycin and routine therapeutic drug monitoring (TDM) have been proposed to optimize antimicrobial exposure in ventriculitis patients, an individualized dosing strategy was implemented in our department. We present a retrospective analysis of meropenem and vancomycin concentrations in serum and CSF in the first nine ventriculitis patients treated with continuous infusion and TDM-guided dose optimization aiming at 20–30 mg/L. Median initial dosing was 8.8 g/24 h meropenem and 4.25 g/24 h vancomycin, respectively, resulting in median serum concentrations of 21.3 mg/L for meropenem and 24.5 mg/L for vancomycin and CSF concentrations of 3.4 mg/L for meropenem and 1.7 mg/L for vancomycin. Median CSF penetration was 15% for meropenem and 7% for vancomycin. With initial dosing, all but one patient achieved CSF concentrations above 1 mg/L. Dose adjustment according to TDM ensured sufficient CSF concentrations in all patients within 48 h of treatment. Given the limited penetration, continuous infusion of meropenem and vancomycin based on renal function and TDM-guided dose optimization appears a reasonable approach to attain sufficient CSF concentrations in ventriculitis patients.

1.1 Based on the initial data from Table 1 there were errors in the original article [...]

Optimization of antibiotic dosing is a treatment intervention that is likely to improve outcomes in severe infections. The aim of this retrospective study was to describe the therapeutic exposure of steady state piperacillin concentrations (cPIP) and clinical outcome in critically ill patients with sepsis or septic shock who received continuous infusion of piperacillin with dosing personalized through software-guided empiric dosing and therapeutic drug monitoring (TDM). Therapeutic drug exposure was defined as cPIP of 32–64 mg/L (2–4× the ‘MIC breakpoint’ of Pseudomonas aeruginosa). Of the 1544 patients screened, we included 179 patients (335 serum concentrations), of whom 89% achieved the minimum therapeutic exposure of >32 mg/L and 12% achieved potentially harmful cPIP > 96 mg/L within the first 48 h. Therapeutic exposure was achieved in 40% of the patients. Subsequent TDM-guided dose adjustments significantly enhanced therapeutic exposure to 65%, and significantly reduced cPIP > 96 mg/L to 5%. Mortality in patients with cPIP > 96 mg/L (13/21; 62%) (OR 5.257, 95% CI 1.867–14.802, p = 0.001) or 64–96 mg/L (30/76; 45%) (OR 2.696, 95% CI 1.301–5.586, p = 0.007) was significantly higher compared to patients with therapeutic exposure (17/72; 24%). Given the observed variability in critically ill patients, combining the application of dosing software and consecutive TDM increases therapeutic drug exposure of piperacillin in patients with sepsis and septic shock.

Abstract Background Mental well-being is an important, yet understudied, area of research, partly due to lack of appropriate population-based measures. The Warwick-Edinburgh Mental Well-being Scale (WEMWBS) was developed to meet the needs for such a measure. This article assesses the psychometric properties of the Norwegian version of the WEMWBS, and its short-version (SWEMWBS) among a sample of primary health care patients who participated in the evaluation of Prompt Mental Health Care (PMHC), a novel Norwegian mental health care program aimed to increase access to treatment for anxiety and depression. Methods Forward and back-translations were conducted, and 1168 patients filled out an electronic survey including the WEMWBS, and other mental health scales. The original dataset was randomly divided into a training sample (≈70%) and a validation sample (≈30%). Parallel analysis and confirmatory factor analysis were carried out to assess construct validity and precision. The final models were cross-validated in the validation sample by specifying a model with fixed parameters based on the estimates from the trainings set. Criterion validity and measurement invariance of the (S)WEMWBS were examined as well. Results Support was found for the single factor hypothesis in both scales, but similar to previous studies, only after a number of residuals were allowed to correlate (WEMWBS: CFI = 0.99; RMSEA = 0.06, SWEMWBS: CFI = .99; RMSEA = 0.06). Further analyses showed that the correlated residuals did not alter the meaning of the underlying construct and did not substantially affect the associations with other variables. Precision was high for both versions of the WEMWBS (>.80), and scalar measurement invariance was obtained for gender and age group. The final measurement models displayed adequate fit statistics in the validation sample as well. Correlations with other mental health scales were largely in line with expectations. No statistically significant differences were found in mean latent (S)WEMWBS scores for age and gender. Conclusion Both WEMWBS scales appear to be valid and precise instruments to measure mental well-being in primary health care patients. The results encourage the use of mental well-being as an outcome in future epidemiological, clinical, and evaluation studies, and may as such be valuable for both research and public health practice.

Objective: To investigate the use of canalith repositioning manoeuvres and vestibular rehabilitation (VR) by GPs and to assess reasons for not using these techniques in patients with vertigo. Design: Online survey. Setting: GPs in the western and central part of the Netherlands. Subjects and method: Of GPs, 1169 were approached to participate in the survey. A sample of 426 GPs filled out the questionnaire (36.4% response rate). The 22-item questionnaire contained both multiple choice and free-text questions on the Epley manoeuvre, the Brandt-Daroff exercises and VR. Results of the survey were descriptively analyzed. Main outcome measures: The use of the Epley manoeuvre, the Brandt-Daroff exercises and VR by GPs; reasons that deter GPs from using these techniques. Results: The repositioning manoeuvres (Epley manoeuvre and Brandt-Daroff exercises) were used by approximately half of all GPs (57.3 and 50.2%), while only a small group of GPs applied VR (6.8%). The most important reason for GPs not to use the Epley manoeuvre, Brandt-Daroff exercises and VR was that they did not know how to perform the technique (49.5, 89.6 and 92.4%). Conclusions: Despite the proven effectiveness, repositioning manoeuvres and VR are remarkably underused by Dutch GPs. Not knowing how to perform the technique is the most important reason for GPs not to use these techniques. Efforts should be made to increase the knowledge and skills of GPs regarding canalith repositioning manoeuvres and VR. Key points • Dizziness is a common symptom with limited therapeutic options. • Canalith repositioning manoeuvres and vestibular rehabilitation represent the best treatment options currently available for vertigo. • Canalith repositioning manoeuvres and vestibular rehabilitation are still widely underused by GPs. • The most important reason for GPs not to use these techniques is that they do not know how to perform them. • Efforts should be made to increase the knowledge and skills of GPs regarding canalith repositioning manoeuvres and vestibular rehabilitation.

ObjectivesPrompt Mental Health Care (PMHC) is the Norwegian version of the England’s Improving Access to Psychological Therapies (IAPT). Both programs have been associated with substantial symptom reductions from pre- to post-treatment. The present study extends these findings by investigating symptom levels at 12 months post-treatment, as well as treatment outcome in relation to low- vs. high-intensity treatment forms.Design and Outcome MeasuresA prospective cohort design was used. All participants (n = 1530) were asked to complete the Patient Health Questionnaire-9 (PHQ-9) and the Generalized Anxiety Disorder-7 questionnaire (GAD-7) at baseline, before each session during treatment, at final treatment, and at 12 months post-treatment. Cohen’s d was used as effect size measure. Sensitivity analyses were conducted to examine the impact of the high missing data rates at post-treatment (≈44%) and 12 months post-treatment (≈58%).ResultsA large symptom reduction was seen from baseline to 12 months post-treatment for both PHQ (d = −0.98) and GAD (d = −0.94). Improvements observed at post-treatment were largely maintained at 12 months post-treatment (PHQ (Δd = 0.10) and GAD (Δd = 0.09). Recovery rates decreased only slightly from 49.5% at post-treatment to 45.0% at follow-up. Both low- and high-intensity treatment forms were associated with substantial and lasting symptoms reductions (−1.26 ≤ d ≤ −0.73). Sensitivity analyses did not substantially alter the main results.ConclusionThe findings suggest long-lasting effects of the PMHC program and encourage the use of low-intensity treatment forms in PMHC like settings.

Cefiderocol is a new siderophore-cephalosporin for the treatment of multi-drug resistant Gram-negative pathogens. As a reserve agent, it will and should be used primarily in critically ill patients in the upcoming years. Due to the novelty of the substance little data on the pharmacokinetics in critically ill patients with septic shock and renal failure (including continuous renal replacement therapy and cytokine adsorber therapy) is available. We performed therapeutic drug monitoring in a cohort of five patients treated with cefiderocol, to improve the knowledge on pharmacokinetics in this vulnerable patient population. As expected for a cephalosporin with predominantly renal elimination the maintenance dose could be reduced in patients with renal impairment or on continuous renal replacement therapy. The manufacturer’s dosing instructions were sufficient to achieve a drug level well above the MIC. However, the addition of a cytokine adsorber might reduce serum levels substantially, so that in this context therapeutic drug monitoring and dose adjustment are recommended.

Cefiderocol is a new siderophore cephalosporin approved for the treatment of multidrug resistant bacteria including activity against carbapenem-resistant Enterobacterales and Pseudomonas aeruginosa. As cephalosporins are known for their high pharmacokinetic variability in critically ill patients, cefiderocol therapeutic drug monitoring might become a valuable tool. Therefore, we aimed to develop and validate a simple, rapid, cost-effective high performance liquid chromatography (HPLC) method for the quantification of cefiderocol in serum. Samples were treated for protein precipitation followed by chromatographic separation on a reverse phase column (HPLC C-18) with gradient elution of the mobile phase. Cefiderocol was detected via UV absorption and quantification was performed with the internal standard (metronidazole) method. The calibration range showed linearity from 4 to 160 mg/L. The intra and interday precision was less than 10% with a recovery rate of 81%. The method was successfully used for the analysis of subsequent serum samples of critically ill patients and showed good performance in monitoring serum levels and optimizing antibiotic therapy.

Objective: For general practitioners (GPs) dizziness is a challenging condition to deal with. Data on the management of dizziness in older patients are mostly lacking. Furthermore, it is unknown whether GPs attempt to decrease Fall Risk Increasing Drugs (FRIDs) use in the management of dizziness in older patients. The aim of this study is to gain more insight into GP’s management of dizziness in older patients, including FRID evaluation and adjustment. Design: Data were derived from electronic medical records, obtained over a 12-month period in 2013. Setting: Forty-six Dutch general practices. Patients: The study sample comprised of 2812 older dizzy patients of 65 years and over. Patients were identified using International Classification of Primary Care codes and free text. Main outcome measures: Usual care was categorized into wait-and-see strategy (no treatment initiated); education and advice; additional testing; medication adjustment; and referral. Results: Frequently applied treatments included a wait-and-see strategy (28.4%) and education and advice (28.0%). Additional testing was performed in 26.8%; 19.0% of the patients were referred. Of the patients 87.2% had at least one FRID prescription. During the observation period, GPs adjusted the use of one or more FRIDs for 11.7% of the patients. Conclusion: This study revealed a wide variety in management strategies for dizziness in older adults. The referral rate for dizziness was high compared to prior research. Although many older dizzy patients use at least one FRID, FRID evaluation and adjustment is scarce. We expect that more FRID adjustments may reduce dizziness and dizziness-related impairment. Key Points It is important to know how general practitioners manage dizziness in older patients in order to assess potential cues for improvement. This study revealed a wide variety in management strategies for dizziness in older patients. There was a scarcity in Fall Risk Increasing Drug (FRID) evaluation and adjustment. The referral rate for dizziness was high compared with previous research.

OBJECTIVES:Dizziness is common in older people. Physicians are often unable to identify a specific cause for dizziness in older people, even after an extensive diagnostic work-up. A prognosis-oriented approach, i.e. treating modifiable risk factors for an unfavourable course of dizziness, may reduce dizziness-related impairment in older people in primary care. DESIGN:Cluster randomized controlled trial. SETTING:45 primary care practices in The Netherlands. PARTICIPANTS:168 participants aged ≥65y who consulted their general practitioner for dizziness and experienced significant dizziness-related impairment (Dizziness Handicap Inventory (DHI) ≥30). Participants were part of to the intervention group (n = 83) or control group (n = 85), depending on whether they were enlisted in an intervention practice or in a control practice. INTERVENTIONS:The multifactorial intervention consisted of: medication adjustment in case of ≥3 prescribed fall-risk-increasing drugs (FRIDs) and/or stepped mental health care in case of anxiety disorder and/or depression and/or exercise therapy in case of impaired functional mobility. The intervention was compared to usual care. OUTCOME MEASURES:The primary outcome was dizziness-related impairment. Secondary outcomes were quality of life (QoL), dizziness frequency, fall frequency, anxiety and depression, use of FRIDs. RESULTS:Intention-to-treat analysis showed no significant intervention effect on dizziness-related impairment (DHI score difference -0.69 [95% CI -5.66;4.28]; p = 0.79). The intervention proved effective in reducing the number of FRIDs (FRID difference -0.48 [95% CI -0.89;-0.06]; p = 0.02). No significant intervention effects were found on other secondary outcomes. The uptake of and adherence to the interventions was significantly lower in patients eligible for ≥2 interventions compared to patients eligible for one intervention (p

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Continuity of care is a core value of primary health care. (1-4) It is highly valued by patients and general practitioners (GPs). (5,6) According to the late Barbara Starfield, continuity [...]