What Do Young Adults Expect from the Recreational Use of Ecstasy (3,4-Methylenedioxymethamphetamine/Molly)? A Latent Class Analysis of a Convenience Sample of Dutch Young Adults

Introduction: This study offers insights into Dutch young people's expected social and personal consequences of ecstasy use. Substance use expectancies are assumed to be an essential component in explaining substance use behaviour and, therefore, the development of effective substance use prevention and treatment strategies. Method: Dutch young adults with an online interest in drug-related social media posts were targeted with an online survey about their use of alcohol and drugs. This resulted in a convenience sample (N = 4182, 73.4% female, Mage = 21.11), of which 35.5% had used ecstasy at least once in their life and 29.3% had used ecstasy last year. Latent class analyses were used to identify subgroups based on both positive and negative expectancies of ecstasy use. Cross-class differences were examined using multinomial logistic regression. Results: This study yielded four distinct classes: only negative expectancies (13.6%), high positive and negative expectancies (23.5%), low to moderate positive and negative expectancies (20.6%), and mostly positive expectancies (22.4%). These classes differed significantly in lifetime experience with ecstasy use, intention to use ecstasy, perception of harmfulness and availability, and social norms regarding the use of ecstasy. Conclusion: Findings show that ecstasy use expectancies can be used to create meaningful classes of users and non-users, and that these classes are different enough to warrant varied prevention approaches. Expectancies young people have regarding the use of ecstasy are associated with various ecstasy use-related variables and should be taken into consideration when developing and implementing preventive interventions

Latent Classes of Substance Use in Young Adults–A Systematic Review

Background: This systematic review provides an overview of studies on latent classes related to the substance use among young adults (18–25 years). Identifying these classes helps to detect high-risk groups, setting a base for selective prevention. Methods: This systematic literature review included peer-reviewed studies (published up to February, 2021) that identified latent classes and investigated predictors of latent classes relating to the use of marijuana, alcohol and/or other substances within samples of young adults. Results: Twenty studies (sample sizes N = 171 to N = 21945) met the inclusion criteria. 14 studies identified ‘low-level engagers’, ‘light alcohol and tobacco use’, ‘heavy alcohol and tobacco use’ and ‘heavy use/polysubstance use’ classes. Four studies differentiated within the ‘heavy/polysubstance’ class and found ‘traditional clubdrugs’, ‘hallucinogens’ and ‘wide-range illicit drugs’ classes. Male gender and white race predicted membership of the ‘heavy use/polysubstance use’ class consistently across studies. Other predictors of polysubstance use that were consistent across studies were peer substance use, depressive symptoms, parental drinking and participating in an honor society. Conclusions: The investigated predictors of class membership provide insight into social settings and characteristics that predict heavy use or polysubstance use. They can contribute to the development of effective prevention interventions by allowing for a more targeted approach

MDMA /// Beyond ecstasy

For nearly 40 years, MDMA has been used as a party drug in the Netherlands. Today, more than one in 10 people have used this prohibited substance at least once. Quite separate from this recreational use, MDMA also has a medical use, like ketamine or cannabis. This medical use of MDMA has been the subject of research for nearly half a century. In sum, MDMA is definitely not a novelty in Dutch society; it has been present here for decades. Why, then, should we have a State Commission on MDMA at this specific point in time

Zicht op Evenwicht Landelijke implementatie van een cursus gericht op het verminderen van angst om te vallen bij zelfstandig wonende ouderen

Achtergrond: Zicht op Evenwicht is een effectieve cognitief gedragsmatige groepscursus om bezorgdheid om te vallen en gerelateerd vermijdingsgedrag bij zelfstandig wonende ouderen te verminderen. Dit artikel beschrijft de landelijke implementatiestrategie van deze cursus en de resultaten daarvan. De implementatiestrategie had als doel de cursus in 2009 en 2010 bij minimaal 50 % van 64 thuiszorgorganisaties die zijn aangesloten bij het Landelijk Steunpunt Preventie - Thuiszorg (LSP-T) te implementeren. Methoden: De implementatiestrategie is gebaseerd op de vier fasen van het ‘Replicating Effective Interventions’ (REP)model: randvoorwaarden, preimplementatie, implementatie, en borging en doorontwikkeling. Resultaten: Na voorbereidende implementatieactiviteiten zoals identificeren van belemmerende factoren, consulteren van stakeholders, gereedmaken van cursusmaterialen en training van cursusbegeleiders (n053), is Zicht op Evenwicht in de periode 2009–2010 geïmplementeerd bij 16 van thuiszorgorganisaties van het LSP-T (25 %). Nog eens vijf thuiszorgorganisaties hadden plannen om de cursus aan te bieden. De cursus is in deze periode landelijk 26 keer aangeboden, 19 keer uitgevoerd en heeft 178 cursisten bereikt. Het verschil tussen aanbod en uitvoering is een gevolg van moeizame werving van cursisten. Na de implementatiefase zijn nog eens 16 cursusbegeleiders getraind en verloopt de verspreiding van cursusmaterialen voorspoedig. Conclusie: Het implementatietraject is overeenkomstig de opzet van het REP-model verlopen. Het beoogde implementatiedoel is niet volledig bereikt in de periode van twee jaar,maar de cursus geniet zichtbaar de interesse van ouderen, cursusbegeleiders en thuiszorgorganisaties. De continuering van aandacht voor verspreiding en borging van de cursus in de eerstelijnszorg wordt daarom aanbevolen

A phase 1 study of PARP-inhibitor ABT-767 in advanced solid tumors with BRCA1/2 mutations and high-grade serous ovarian, fallopian tube, or primary peritoneal cancer

Purpose This phase 1 study examined safety, pharmacokinetics (PK), and efficacy of the poly(ADP-ribose) polymerase (PARP) inhibitor ABT-767 in patients with advanced solid tumors and BRCA1/2 mutations or with high-grade serous ovarian, fallopian tube, or primary peritoneal cancer. Methods Patients received ABT-767 monotherapy orally until disease progression or unacceptable toxicity. Dose was escalated from 20mg once daily to 500mg twice daily (BID). Dose-limiting toxicities, recommended phase 2 dose (RP2D), food effect, objective response rate, and biomarkers predicting response were determined. Results Ninety-three patients were treated with ABT-767; 80 had a primary diagnosis of ovarian cancer. ABT-767 demonstrated dose-proportional PK up to 500mg BID and half-life of 2h. Food had no effect on ABT-767 bioavailability. Most common grade 3/4 treatment-related adverse events were nausea, fatigue, decreased appetite, and anemia. Anemia showed dose-dependent increase. RP2D was 400mg BID. Objective response rate by RECIST 1.1 was 21% (17/80) in all evaluable patients and 20% (14/71) in evaluable patients with ovarian cancer. Response rate by RECIST 1.1 and/or CA-125 was 30% (24/80) in patients with ovarian cancer. Mutations in BRCA1 or BRCA2, homologous recombination deficiency (HRD), and platinum sensitivity were associated with tumor response. Median progression-free survival was longer for HRD positive (6.7months) versus HRD negative patients (1.8months) with ovarian cancer. Conclusions ABT-767 had an acceptable safety profile up to the established RP2D of 400mg BID and dose-proportional PK. Patients with BRCA1 or BRCA2 mutation, HRD positivity, and platinum sensitivity were more sensitive to ABT-767

A phase 1 study of PARP-inhibitor ABT-767 in advanced solid tumors with BRCA1/2 mutations and high-grade serous ovarian, fallopian tube, or primary peritoneal cancer

Purpose This phase 1 study examined safety, pharmacokinetics (PK), and efficacy of the poly(ADP-ribose) polymerase (PARP) inhibitor ABT-767 in patients with advanced solid tumors and BRCA1/2 mutations or with high-grade serous ovarian, fallopian tube, or primary peritoneal cancer. Methods Patients received ABT-767 monotherapy orally until disease progression or unacceptable toxicity. Dose was escalated from 20 mg once daily to 500 mg twice daily (BID). Dose-limiting toxicities, recommended phase 2 dose (RP2D), food effect, objective response rate, and biomarkers predicting response were determined. Results Ninety-three patients were treated with ABT-767; 80 had a primary diagnosis of ovarian cancer. ABT-767 demonstrated dose-proportional PK up to 500 mg BID and half-life of ~2 h. Food had no effect on ABT-767 bioavailability. Most common grade 3/4 treatment-related adverse events were nausea, fatigue, decreased appetite, and anemia. Anemia showed dose-dependent increase. RP2D was 400 mg BID. Objective response rate by RECIST 1.1 was 21% (17/80) in all evaluable patients and 20% (14/71) in evaluable patients with ovarian cancer. Response rate by RECIST 1.1 and/or CA-125 was 30% (24/80) in patients with ovarian cancer. Mutations in BRCA1 or BRCA2, homologous recombination deficiency (HRD), and platinum sensitivity were associated with tumor response. Median progression-free survival was longer for HRD positive (6.7 months) versus HRD negative patients (1.8 months) with ovarian cancer. Conclusions ABT-767 had an acceptable safety profile up to the established RP2D of 400 mg BID and dose-proportional PK. Patients with BRCA1 or BRCA2 mutation, HRD positivity, and platinum sensitivity were more sensitive to ABT-767

The diagnosis and treatment of invasive aspergillosis in Dutch haematology units facing a rapidly increasing prevalence of azole-resistance

Patients with haematological malignancies are at risk for invasive fungal diseases (IFD). A survey was conducted in all Dutch academic haematology centres on their current diagnostic, prophylactic and therapeutic approach towards IFD in the context of azole-resistance. In all 8 centres, a haematologist and microbiologist filled in the questionnaire that focused on different subgroups of haematology patients. Fungal prophylaxis during neutropaenia was directed against Candida and consisted of fluconazole and/or amphotericin B suspension. Mould-active prophylaxis was given to acute myeloid leukaemia patients during chemotherapy in 2 of 8 centres. All centres used azole prophylaxis in a subset of patients with graft-versus-host disease. A uniform approach towards the diagnosis and treatment of IFD and in particular azole-resistant Aspergillus fumigatus was lacking. In 2017, all centres agreed to implement a uniform diagnostic and treatment algorithm regarding invasive aspergillosis with a central role for comprehensive diagnostics and PCR-based detection of azole-resistance. This study (DB-MSG 002) will re-evaluate this algorithm when 280 patients have been treated. A heterogeneous approach towards antifungal prophylaxis, diagnosis and treatment was apparent in the Netherlands. Facing triazole-resistance, consensus was reached on the implementation of a uniform diagnostic approach in all 8 centres

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

Participation-based environment accessibility assessment tool (P-BEAAT) in the Zambian context

Purpose: The purpose of this study was to describe the preliminary development and validation of a potential measure for assessing the accessibility of the built environment in Zambia. It was designed to identify environmental features that present barriers to participation for people with mobility limitations (PWML) using mobility devices such as wheelchairs or crutches.Method: The Participation-Based Environment Accessibility Assessment Tool (P-BEAAT) was developed through focus group discussions and personal interviews with 88 PWML from five provinces of Zambia regarding the accessibility of their built environment. The content validity of the P-BEAAT checklist was accomplished through three phases of development with data gathered from 11 focus groups and nine personal interviews. Results: Participants described accessibility barriers which affect their participation in daily life. This information generated the P-BEAAT with 66 items describing eight environmental features with potential for identifying environmental barriers. The P-BEAAT has shown good homogeneity with Cronbach's α score of 0.91. Conclusion: The P-BEAAT was constructed grounded in the reality of people's experiences in Zambia for use in assessing environmental features important in the participation of daily life of PWML pertinent to developing countries. Further clinimetric testing of the properties of the P-BEAAT to establish reliability should be conducted next. Implications for Rehabilitation Identification of barriers in the built environment is a critical element in the process of eliminating obstacles to participation by people with mobility limitations. Accessible built environment facilitates the enhancement of participation of people with mobility limitations. The process of identifying obstacles requires audit/assessment tools to evaluate and measure the presence or absence of barriers to accessibility of the built environment. This study shows that the Participation-Based Environment Accessibility Assessment Tool provides a preliminary checklist to be used in identifying environmental barriers in the process of promoting lifelong participation for people with mobility limitations using wheelchairs or crutches in Zambia