Automated mobile virtual reality cognitive behavior therapy for aviophobia in a natural setting: a randomized controlled trial.

BACKGROUND: Access to evidence-based psychological treatment is a challenge worldwide. We assessed the effectiveness of a fully automated aviophobia smartphone app treatment delivered in combination with a $5 virtual reality (VR) viewer. METHODS: In total, 153 participants from the Dutch general population with aviophobia symptoms and smartphone access were randomized in a single-blind randomized controlled trial to either an automated VR cognitive behavior therapy (VR-CBT) app treatment condition (n = 77) or a wait-list control condition (n = 76). The VR-CBT app was delivered over a 6-week period in the participants' natural environment. Online self-report assessments were completed at baseline, post-treatment, at 3-month and at 12-month follow-up. The primary outcome measure was the Flight Anxiety Situations Questionnaire (FAS). Analyses were based on intent-to-treat. RESULTS: A significant reduction of aviophobia symptoms at post-test for the VR-CBT app compared with the control condition [p < 0.001; d = 0. 98 (95% CI 0.65-1.32)] was demonstrated. The dropout rate was 21%. Results were maintained at 3-month follow-up [within-group d = 1.14 (95% CI 0.46-1.81)] and at 12-month follow-up [within-group d = 1.12 (95% CI 0.46-1.79)]. Six participants reported adverse effects of cyber sickness symptoms. CONCLUSIONS: This study is the first to show that fully automated mobile VR-CBT therapy delivered in a natural setting can maintain long-term effectiveness in reducing aviophobia symptoms. In doing so, it offers an accessible and scalable evidence-based treatment solution that can be applied globally at a fraction of the cost of current treatment alternatives.

[Online schema therapy: a cross-sectional survey among Dutch therapists]. / Schematherapie via beeldbellen; crosssectioneel onderzoek onder therapeuten.

BACKGROUND: Long waiting lists exist for the treatment of personality disorders, which can be shortened by using videoconference treatment. During the COVID-19 pandemic, by necessity, videoconferencing was used to provide schema therapy, a specific treatment for personality disorders. AIM: To investigate therapist experience of schema therapy via videoconferencing during the pandemic. METHOD: In an observational cross-sectional study, 83 schema therapists completed a questionnaire about the period prior to, and during the COVID-19 pandemic. We investigated their experience, use of, and attitude toward videoconferencing, as well as the extent to which the effectiveness of videoconferencing and face to face (F2F) schema therapy for personality disorders was found to be comparable. RESULTS: Schema therapists rated their experience with videoconferencing therapy for personality disorders during the COVID-19 pandemic positively, its use increased during this period, and therapists’ attitudes became more positive. However, the majority found videoconferencing therapy less effective than F2F treatment. Almost half of the therapists used shorter sessions or adapted exercises during videoconferencing therapy. CONCLUSION: Although therapists were increasingly positive about video conferencing therapy, they believed that F2F treatment is more effective. Randomized efficacy studies of videoconferencing therapy compared to F2F therapy are needed, also examining patients’ experiences with both forms.

Economic evaluations of Internet interventions for mental health: a systematic review.

BACKGROUND: Internet interventions are assumed to be cost-effective. However, it is unclear how strong this evidence is, and what the quality of this evidence is. METHOD: A comprehensive literature search (1990-2014) in Medline, EMBASE, the Cochrane Central Register of Controlled Trials, NHS Economic Evaluations Database, NHS Health Technology Assessment Database, Office of Health Economics Evaluations Database, Compendex and Inspec was conducted. We included economic evaluations alongside randomized controlled trials of Internet interventions for a range of mental health symptoms compared to a control group, consisting of a psychological or pharmaceutical intervention, treatment-as-usual (TAU), wait-list or an attention control group. RESULTS: Of the 6587 abstracts identified, 16 papers met the inclusion criteria. Nine studies featured a societal perspective. Results demonstrated that guided Internet interventions for depression, anxiety, smoking cessation and alcohol consumption had favourable probabilities of being more cost-effective when compared to wait-list, TAU, group cognitive behaviour therapy (CBGT), attention control, telephone counselling or unguided Internet CBT. Unguided Internet interventions for suicide prevention, depression and smoking cessation demonstrated cost-effectiveness compared to TAU or attention control. In general, results from cost-utility analyses using more generic health outcomes (quality of life) were less favourable for unguided Internet interventions. Most studies adhered reasonably to economic guidelines. CONCLUSIONS: Results of guided Internet interventions being cost-effective are promising with most studies adhering to publication standards, but more economic evaluations are needed in order to determine cost-effectiveness of Internet interventions compared to the most cost-effective treatment currently available.

Predictors of treatment dropout in self-guided web-based interventions for depression: an 'individual patient data' meta-analysis.

BACKGROUND: It is well known that web-based interventions can be effective treatments for depression. However, dropout rates in web-based interventions are typically high, especially in self-guided web-based interventions. Rigorous empirical evidence regarding factors influencing dropout in self-guided web-based interventions is lacking due to small study sample sizes. In this paper we examined predictors of dropout in an individual patient data meta-analysis to gain a better understanding of who may benefit from these interventions. METHOD: A comprehensive literature search for all randomized controlled trials (RCTs) of psychotherapy for adults with depression from 2006 to January 2013 was conducted. Next, we approached authors to collect the primary data of the selected studies. Predictors of dropout, such as socio-demographic, clinical, and intervention characteristics were examined. RESULTS: Data from 2705 participants across ten RCTs of self-guided web-based interventions for depression were analysed. The multivariate analysis indicated that male gender [relative risk (RR) 1.08], lower educational level (primary education, RR 1.26) and co-morbid anxiety symptoms (RR 1.18) significantly increased the risk of dropping out, while for every additional 4 years of age, the risk of dropping out significantly decreased (RR 0.94). CONCLUSIONS: Dropout can be predicted by several variables and is not randomly distributed. This knowledge may inform tailoring of online self-help interventions to prevent dropout in identified groups at risk.

Carbapenemase-producing Enterobacteriaceae in Europe: a survey among national experts from 39 countries, February 2013.

The spread of carbapenemase-producing Enterobacteriaceae (CPE) is a threat to healthcare delivery, although its extent differs substantially from country to country. In February 2013, national experts from 39 European countries were invited to self-assess the current epidemiological situation of CPE in their country. Information about national management of CPE was also reported. The results highlight the urgent need for a coordinated European effort on early diagnosis, active surveillance, and guidance on infection control measures.

Is guided self-help as effective as face-to-face psychotherapy for depression and anxiety disorders? A systematic review and meta-analysis of comparative outcome studies.

BACKGROUND: Although guided self-help for depression and anxiety disorders has been examined in many studies, it is not clear whether it is equally effective as face-to-face treatments.MethodWe conducted a meta-analysis of randomized controlled trials in which the effects of guided self-help on depression and anxiety were compared directly with face-to-face psychotherapies for depression and anxiety disorders. A systematic search in bibliographical databases (PubMed, PsycINFO, EMBASE, Cochrane) resulted in 21 studies with 810 participants. RESULTS: The overall effect size indicating the difference between guided self-help and face-to-face psychotherapy at post-test was d=-0.02, in favour of guided self-help. At follow-up (up to 1 year) no significant difference was found either. No significant difference was found between the drop-out rates in the two treatments formats. CONCLUSIONS: It seems safe to conclude that guided self-help and face-to-face treatments can have comparable effects. It is time to start thinking about implementation in routine care.

Surveillance of hospitalisations for 2009 pandemic influenza A(H1N1) in the Netherlands, 5 June - 31 December 2009.

We analysed and reported on a weekly basis clinical and epidemiological characteristics of patients hospitalised in the Netherlands for the 2009 pandemic influenza A(H1N1) using information from the national mandatory notification system. The notification criteria changed on 15 August 2009 from all possible, probable and confirmed cases to only laboratory-confirmed pandemic influenza hospitalisations and deaths. In the period of comprehensive case-based surveillance (until 15 August), 2% (35/1,622) of the patients with pandemic influenza were hospitalised. From 5 June to 31 December 2009, a total of 2,181 patients were hospitalised. Of these, 10% (219/2,181) were admitted to an intensive care unit (ICU) and 53 died. Among non-ICU hospitalised patients, 56% (961/1,722) had an underlying medical condition compared with 70% (147/211) of the patients in ICU and 46 of the 51 fatal cases for whom this information was reported. Most common complications were dehydration among non-ICU hospitalised patients and acute respiratory distress syndrome among patients in ICU and patients who died. Children under the age of five years had the highest age-specific hospitalisation rate (62.7/100,000), but relatively few were admitted to an ICU (1.7/100,000). Characteristics and admission rates of hospitalised patients were comparable with reports from other countries and previous influenza seasons. The national notification system was well suited to provide weekly updates of relevant monitoring information on the severity of the pandemic for professionals, decision makers, the media and the public, and could be rapidly adapted to changing information requirements.

Epidemiology and control of influenza A(H1N1)v in the Netherlands: the first 115 cases.

Introductions of the new influenza A(H1N1) variant virus in the Netherlands led to enhanced surveillance and infection control. By 24 June 2009, 115 cases were reported, of whom 44% were indigenously acquired. Severity of disease is similar to reports elsewhere. Our point estimate of the effective reproductive number (Re) for the initial phase of the influenza A(H1N1)v epidemic in the Netherlands was below one. Given that the Re estimate is based on a small number of indigenous cases and a limited time period, it needs to be interpreted cautiously.

0Phobia - towards a virtual cure for acrophobia: study protocol for a randomized controlled trial.

BACKGROUND: Virtual reality exposure therapy (VRET) has been shown to be as effective as traditional forms of in vivo exposure therapy for the treatment of specific phobias. However, as with in vivo exposure, VRET still involves relatively high costs and limited accessibility which makes it prohibitive for a large part of the population. Innovative methods using smartphone applications (apps) may improve accessibility and scalability of VRET. The aim of this study is to evaluate 0Phobia, a gamified self-guided VRET for acrophobia that is delivered through a smartphone app in combination with rudimentary cardboard virtual reality (VR) goggles. METHODS/DESIGN: Participants (N = 180, aged 18-65 years) with acrophobia symptoms will be recruited from the Dutch general population and randomized to either 0Phobia (n = 90) or a waitlist control condition (n = 90). 0Phobia will be delivered over a period of 3 weeks and includes psychoeducation, VR exposure, cognitive techniques, monitoring of symptoms, and relapse prevention. The primary outcome measure will be the Acrophobia Questionnaire. Secondary outcome measures will include user-friendliness, symptoms of anxiety, depression, and mastery. Assessments will take place online at baseline, directly after the intervention (post test) and at follow-up (3 months). DISCUSSION: This study capitalizes on novel technology and recent scientific advances to develop an affordable and scalable treatment modality. TRIAL REGISTRATION: Netherlands Trial Register: NTR6442 . Registered on 29 June 2017.

Inhibition of the in vivo conversion of androstenedione to estrone by the aromatase inhibitor vorozole in healthy postmenopausal women.

Vorozole is a new, potent, and highly selective nonsteroidal aromatase inhibitor, which in animal and human studies was found to be about 1000-fold more potent than aminoglutethimide. Almost all aromatase-inhibiting activity resides in the dextro-enantiomer currently undergoing clinical trials. A marked decrease in circulating estrogens was found in several studies of healthy premenopausal women and male volunteers treated with the racemate, referred to as vorozole racemate. To further evaluate the aromatase-inhibiting potency of this drug, the in vivo conversion of androstenedione to estrone was studied in 12 healthy postmenopausal women. Four h after a single oral dose of vorozole racemate, [14C]androstenedione and [3H]estrone were infused at a constant rate for 2 h. Women were randomized to receive vorozole racemate orally in one of three different doses, i.e., 1, 2.5, and 5 mg, in a double-blind protocol. Each woman acted as her own control in an identical experiment with a placebo carried out 2-4 weeks either before or after the test with vorozole racemate. In the urine, collected for 4 days after each experiment, estrogens were extracted and purified until a constant 3H/14C ratio of estrone was achieved. The percentage conversion of androstenedione to estrone in the 12 placebo experiments was 2.19 +/- 0.60% (mean +/- SD, n = 12). Following a single administration of vorozole racemate, the conversion decreased to 0.14 +/- 0.04%. The percentage inhibition was 93.0 +/- 2.5 (n = 4) following administration of 1 mg vorozole racemate; administration of 2.5 or 5 mg resulted in an inhibition percentage of 93.2 +/- 1.6 or 94.4 +/- 1.2, respectively. It is concluded that a single oral dose of 1-5 mg vorozole racemate results in an almost complete inhibition of in vivo aromatase activity.

Inhibition of breast cancer tissue aromatase activity and estrogen concentrations by the third-generation aromatase inhibitor vorozole.

In about one-third of advanced breast cancers, estrogen deprivation causes tumor regression. Estrogen concentrations in tumor tissue seem to depend largely on local production. The aromatase enzyme complex is thought to be the key enzyme in this respect. In the present study, the effect of the new third-generation nonsteroidal aromatase inhibitor vorozole (Rivizor) on tumor tissue aromatase activity and estrogen concentrations was evaluated. During 7 days preceding mastectomy, 11 postmenopausal breast cancer patients were treated with 2.5 mg of vorozole once daily. Eight patients could be evaluated. Intratumoral aromatase activity and estrone and estradiol levels were measured and compared to the values of nine untreated postmenopausal breast cancer patients. In treated patients, median tissue aromatase activity was 89% lower than that in controls (P < 0.001). Similarly, median tissue estrone and estradiol concentrations were 64 and 80% lower, respectively, in treated patients (P = 0.001 and P < 0.05, respectively). These results support the hypothesis that depleting the tumor of estrogens, thus impairing estrogenic stimulation, is an important mechanism in the antitumor activity of aromatase inhibitors.

E-care 4 caregivers - an online intervention for nonprofessional caregivers of patients with depression: study protocol for a pilot randomized controlled trial.

BACKGROUND: Nonprofessional caregivers are highly important in the everyday life of patients with depression. Yet, they may experience increased levels of burden, stress, depression, and anxiety. Therefore, there is a need for interventions that relieve symptoms and are accessible and time-efficient. This paper describes the protocol of a pilot study to evaluate (1) the feasibility of an online self-management intervention, E-care 4 caregivers, for the nonprofessional caregiver of patients with depression, and (2) the initial effects of E-care 4 caregivers on psychological distress, subjective burden, symptoms of anxiety and depression, and quality of life. METHODS/DESIGN: The study is a randomized controlled trial in which we are comparing the E-care 4 caregivers online intervention with a wait list control group. Eighty-four nonprofessional caregivers of patients with depression aged 18 years or older are being recruited from among the general population. Feasibility is determined by semistructured telephone interviews evaluating the subjects' satisfaction with the intervention and by using a questionnaire on the user-friendliness of the system. The primary outcome measure used to examine the initial effects of the intervention is psychological distress. Secondary outcome measures are subjective burden, symptoms of anxiety and depression, level of mastery, and quality of life. Assessments will be done at baseline and 6 weeks later. Statistical analysis of the effects of the intervention will be carried out on the basis of the intention-to-treat principle. DISCUSSION: E-care 4 caregivers could potentially benefit nonprofessional caregivers, as well as patients and professionals indirectly. TRIAL REGISTRATION: Netherlands Trial Register identifier: NTR5268 . Registered on 30 June 2015.

Monitoring the spread of meticillin-resistant Staphylococcus aureus in The Netherlands from a reference laboratory perspective.

BACKGROUND: In The Netherlands, efforts to control meticillin-resistant Staphylococcus aureus (MRSA) in hospitals have been largely successful due to stringent screening of patients on admission and isolation of those that fall into defined risk categories. However, Dutch hospitals are not free of MRSA, and a considerable number of cases are found that do not belong to any of the risk categories. Some of these may be due to undetected nosocomial transmission, whereas others may be introduced from unknown reservoirs. AIM: Identifying multi-institutional clusters of MRSA isolates to estimate the contribution of potential unobserved reservoirs in The Netherlands. METHODS: We applied a clustering algorithm that combines time, place, and genetics to routine data available for all MRSA isolates submitted to the Dutch Staphylococcal Reference Laboratory between 2008 and 2011 in order to map the geo-temporal distribution of MRSA clonal lineages in The Netherlands. FINDINGS: Of the 2966 isolates lacking obvious risk factors, 579 were part of geo-temporal clusters, whereas 2387 were classified as MRSA of unknown origin (MUOs). We also observed marked differences in the proportion of isolates that belonged to geo-temporal clusters between specific multi-locus variable number of tandem repeat analysis (MLVA) clonal complexes, indicating lineage-specific transmissibility. The majority of clustered isolates (74%) were present in multi-institutional clusters. CONCLUSION: The frequency of MRSA of unknown origin among patients lacking obvious risk factors is an indication of a largely undefined extra-institutional but genetically highly diverse reservoir. Efforts to understand the emergence and spread of high-risk clones require the pooling of routine epidemiological information and typing data into central databases.

The population structure of Staphylococcus aureus in China and Europe assessed by multiple-locus variable number tandem repeat analysis; clues to geographical origins of emergence and dissemination.

To compare the genetic population structure of Staphylococcus aureus from China and Europe, 1294 human isolates were characterized by multiple-locus variable number tandem repeat analysis (MLVA). In total, MLVA identified 17 MLVA complexes (MCs), comprising 260 MLVA types (MTs) among the Chinese isolates and 372 MTs among the European isolates. The five most frequent MCs among the Chinese isolates belonged to MC398, MC5 subclade a, MC8, MC437 and MC7 and made up 55% of the sample. For the European isolates, the five most frequent MCs consisted of MC5 subclade a, MC45, MC8, MC30 and MC22, which accounted for 64% of the sample. Phylogeographic analysis of the major MCs shared between China and Europe points to a European origin of MC8 but cannot provide a consistent signal for MC5 subclade a, probably indicating a different origin. Diversity and frequency distributions of other lineages were also compared. Altogether, this study provides the first snapshot of two extant populations of S. aureus from Europe and China, and important clues on the emergence and dissemination of different lineages of S. aureus.

Occurrence, regulation, and significance of progesterone receptors in human meningioma.

The abundant expression of progesterone receptors (PR) in human meningiomas is well established. It is unknown, however, how PR expression is regulated, especially since estrogen receptors (ER) are virtually absent in these tumors. At the mRNA level, ER splice variants occur in meningioma but these appear not to be involved in the apparently autonomous PR expression. In an earlier study, because other ER-inducible proteins were either not expressed at all (pS2) or were expressed at a very low level compared to their expression in breast cancer (Cathepsin-D), the authors have postulated that the autonomous PR expression in meningioma is PR promoter-related rather than ER-related and have studied PR expression in cultured meningioma cells. PR levels appeared to decrease rapidly in vitro in monolayer as well as in three dimensional spheroid cultures. Culture conditions thus are not yet sufficient for the quantitative evaluation of PR expression. To evaluate whether PR deterioration is associated with cell turnover (meningiomas grow much faster in vitro than in vivo), the relationship between expression of the apoptotic proteins Bcl-2 and Bax and PR expression was investigated. Bcl-2 expression was found to be highest in meningioma with low PR levels, and in breast cancer tissue with high PR levels. Bax expression was not related to PR expression in any of the two tissues. Given the potential benefit of antiprogestin treatment and the occurrence in meningiomas of a protein capable of binding to the estrogen-responsive element, the expression of PR in meningioma remains a fascinating phenomenon which requires further investigation.

Dispersal of antibiotic-resistant high-risk clones by hospital networks: changing the patient direction can make all the difference.

BACKGROUND: Patients who seek treatment in hospitals can introduce high-risk clones of hospital-acquired, antibiotic-resistant pathogens from previous admissions. In this manner, different healthcare institutions become linked epidemiologically. All links combined form the national patient referral network, through which high-risk clones can propagate. AIM: To assess the influence of changes in referral patterns and network structure on the dispersal of these pathogens. METHODS: Hospital admission data were mapped to reconstruct the English patient referral network, and 12 geographically distinct healthcare collectives were identified. The number of patients admitted and referred to hospitals outside their collective was measured. Simulation models were used to assess the influence of changing network structure on the spread of hospital-acquired pathogens. FINDINGS: Simulation models showed that decreasing the number of between-collective referrals by redirecting, on average, just 1.5 patients/hospital/day had a strong effect on dispersal. By decreasing the number of between-collective referrals, the spread of high-risk clones through the network can be reduced by 36%. Conversely, by creating supra-regional specialist centres that provide specialist care at national level, the rate of dispersal can increase by 48%. CONCLUSION: The structure of the patient referral network has a profound effect on the epidemic behaviour of high-risk clones. Any changes that affect the number of referrals between healthcare collectives, inevitably affect the national dispersal of these pathogens. These effects should be taken into account when creating national specialist centres, which may jeopardize control efforts.

Predictors and moderators of response to internet-delivered Interpersonal Psychotherapy and Cognitive Behavior Therapy for depression.

BACKGROUND: By identifying which predictors and moderators lead to beneficial outcomes, accurate selection of the best initial treatment will have significant benefits for depressed individuals. METHOD: An automated, fully self-guided randomized controlled internet-delivered noninferiority trial was conducted comparing two new interventions (Interpersonal Psychotherapy [IPT; n=620] and Cognitive Behavioral Therapy [CBT; n=610]) to an active control intervention (MoodGYM; n=613) over a period of 4 weeks to spontaneous visitors of an internet-delivered therapy website (e-couch). A range of putative predictors and moderators (socio-demographic characteristics [age, gender, marital status, education level], clinical characteristics [depression/anxiety symptoms, disability, quality of life, medication use], skills [mastery and dysfunctional attitudes] and treatment preference) were assessed using internet-delivered self-report measures at baseline and immediately following treatment and at six months follow-up. Analyses were conducted using Mixed Model Repeated Measures (MMRM). RESULTS: Female gender, lower mastery and lower dysfunctional attitudes predicted better outcome at post-test and/or follow-up regardless of intervention. No overall differential effects for condition on depression as a function of outcome were found. However, based on time-specific estimates, a significant interaction effect of age was found. For younger people, internet-delivered IPT may be the preferred treatment choice, whereas older participants derive more benefits from internet-delivered CBT programs. LIMITATIONS: Although the sample of participants was large, power to detect moderator effects was still lacking. CONCLUSIONS: Different e-mental health programs may be more beneficial for specific age groups. The findings raise important possibilities for increasing depression treatment effectiveness and improving clinical practice guidelines for depression treatment of different age groups.