Effectiveness of a digital alcohol moderation intervention as an add-on to depression treatment for young adults: study protocol of a multicentre pragmatic randomized controlled trial

Background: Depressive disorders and problematic drinking often co-occur, also among young adults. These co-occurring conditions are associated with various negative health outcomes compared to both conditions alone. Early intervention by addressing alcohol use and depressive symptoms simultaneously in the same treatment might improve both conditions. However, evidence on the (cost-) effectiveness of digital combined depression and alcohol interventions for young adults is currently insufficient. We therefore developed an add-on digital alcohol moderation adherence-focussed guided intervention to complement treatment as usual (TAU) for depressive disorders. The digital intervention is a web-app, including 6 modules based on motivational interviewing and cognitive behavioural therapy. This study aims to evaluate the (cost-)effectiveness of a digital alcohol moderation intervention + TAU compared to TAU on alcohol and depression outcomes among young adults with co-occurring depressive disorders and problematic alcohol use.Methods: One hundred fifty-six participants, aged 18-35 years, with problematic alcohol use and a diagnosed depressive disorder will participate in a pragmatic multicentre two-arm randomized controlled trial. Problematic alcohol use is operationalised as scoring >= 5 for women and >= 8 for men on the Alcohol Use Disorder Identification Test (AUDIT). Participants will be randomized to either the experimental group (digital alcohol intervention + TAU) or control group (TAU only). Participants will be recruited at three Dutch mental health care centres and through social media. Assessments take place at baseline and after 3, 6 and 12 months post-randomization. The primary outcome is treatment response at 6-month follow-up, operationalized as a composite score that combines alcohol use and depression measures and indicates whether treatment has been successful or not. Secondary outcomes are depressive symptoms and alcohol use (i.e. number of weekly standard drinks and AUDIT score). An economic evaluation will be conducted alongside the trial.Discussion: This study evaluates the (cost-) effectiveness of an add-on digital alcohol moderation intervention for young adults who are in treatment for depressive disorders. If proven effective, the digital intervention could be implemented in mental health care and improve treatment for people with co-occurring depressive disorders and problematic alcohol use.</div

Lifestyle interventions for people with a severe mental illness living in supported housing:A systematic review and meta-analysis

Although supported housing facilities (SHF) appear to be an ideal setting for supporting people with severe mental illness (SMI) to obtain a healthier lifestyle, little is known about the effects of lifestyle interventions in SHF and the factors contributing to successful implementation. We performed a systematic review and meta-analysis to assess the effect of lifestyle interventions on mental and physical health in people with SMI in SHF, and reviewed which intervention factors contribute to successful implementation. A meta-analysis using a random effects model was undertaken. Discussions were reviewed to identify factors that foster successful implementation. Of 7401 identified studies, 9 RCTs (n = 1260) were included for the systematic review and 8 (n = 1187) for the meta-analysis. Improvements in weight (n = 3), BMI (n = 1), 6-Min Walk Test (n = 1) and metabolic criteria (n = 2) were seen. In the meta-analysis we only found a small effect for a decrease in waist circumference. Reviewing factors involved with the implementation showed that the most successfully implemented interventions were multidisciplinary and integrated into standard care. In conclusion, we found limited evidence for the effectiveness of lifestyle interventions on physical health for those living in SHF. To reliably examine the effects on mental and physical health, more studies with high involvement of staff and participants are needed

Cardiorespiratory fitness and self-reported physical activity levels of referring mental healthcare professionals, and their attitudes and referral practices related to exercise and physical health

BACKGROUND: Physical activity (PA) interventions can improve mental and physical health of people with mental illness, especially when delivered by qualified exercise professionals. Also, the behaviour, engagement and support of referring mental healthcare professionals (HCP) seem essential, but research is scarce. We aimed to study HCP physical fitness and PA, and associations with their attitudes and referral practices related to physical health and PA interventions. METHODS: HCP at the Dutch Association for Psychiatry congress (2019) were invited to an online questionnaire (demographic/work characteristics, stress, PA levels, knowledge/attitudes regarding PA, referral practices) and cycle ergometer test. Strongest associations were analysed using linear and logistic regression. RESULTS: Of the 115 HCP who completed the questionnaire (40 also completed the ergometer test), 43% (n = 50) met PA guidelines (i.e., ≥150min moderate-to-vigorous PA and ≥2x bone/muscle-strengthening exercises/week). Women, HCP interns/residents and HCP experiencing more stress were less active and less likely to meet PA guidelines. Conversely, there were positive associations with personal experience with an exercise professional. Knowledge/attitudes on physical health and PA were positive. HCP were more likely to refer patients to PA interventions if they met PA guidelines (OR = 2.56, 95%BI = 0.85-7.13) or had higher beliefs that exercise professionals can increase adherence to PA interventions (OR = 3.72, 95%BI = 1.52-9.14). LIMITATIONS: Mainly psychiatrists, affecting generalizability. CONCLUSIONS: HCP report the importance and relevance of PA in mental healthcare. Despite strong evidence and guidance for PA interventions in prevention and treatment, referral to such interventions partly depends on the PA behaviour and attitude of patient's physician/clinician

Statin use is not associated with improved progression free survival in cetuximab treated KRAS mutant metastatic colorectal cancer patients: results from the CAIRO2 study.

Statins may inhibit the expression of the mutant KRAS phenotype by preventing the prenylation and thus the activation of the KRAS protein. This study was aimed at retrospectively evaluating the effect of statin use on outcome in KRAS mutant metastatic colorectal cancer patients (mCRC) treated with cetuximab. Treatment data were obtained from patients who were treated with capecitabine, oxaliplatin bevacizumab ± cetuximab in the phase III CAIRO2 study. A total of 529 patients were included in this study, of whom 78 patients were on statin therapy. In patients with a KRAS wild type tumor (n = 321) the median PFS was 10.3 vs. 11.4 months for non-users compared to statin users and in patients with a KRAS mutant tumor (n = 208) this was 7.6 vs. 6.2 months, respectively. The hazard ratio (HR) for PFS for statin users was 1.12 (95% confidence interval 0.78-1.61) and was not influenced by treatment arm, KRAS mutation status or the KRAS*statin interaction. Statin use adjusted for covariates was not associated with increased PFS (HR = 1.01, 95% confidence interval 0.71-1.54). In patients with a KRAS wild type tumor the median OS for non-users compared to statin users was 22.4 vs. 19.8 months and in the KRAS mutant tumor group the OS was 18.1 vs. 14.5 months. OS was significantly shorter in statin users versus non-users (HR = 1.54; 95% confidence interval 1.06-2.22). However, statin use, adjusted for covariates was not associated with increased OS (HR = 1.41, 95% confidence interval 0.95-2.10). In conclusion, the use of statins at time of diagnosis was not associated with an improved PFS in KRAS mutant mCRC patients treated with chemotherapy and bevacizumab plus cetuximab

Effectiveness of a digital alcohol moderation intervention as an add-on to depression treatment for young adults:study protocol of a multicentre pragmatic randomized controlled trial

Background: Depressive disorders and problematic drinking often co-occur, also among young adults. These co-occurring conditions are associated with various negative health outcomes compared to both conditions alone. Early intervention by addressing alcohol use and depressive symptoms simultaneously in the same treatment might improve both conditions. However, evidence on the (cost-) effectiveness of digital combined depression and alcohol interventions for young adults is currently insufficient. We therefore developed an add-on digital alcohol moderation adherence-focussed guided intervention to complement treatment as usual (TAU) for depressive disorders. The digital intervention is a web-app, including 6 modules based on motivational interviewing and cognitive behavioural therapy. This study aims to evaluate the (cost-)effectiveness of a digital alcohol moderation intervention + TAU compared to TAU on alcohol and depression outcomes among young adults with co-occurring depressive disorders and problematic alcohol use. Methods: One hundred fifty-six participants, aged 18–35 years, with problematic alcohol use and a diagnosed depressive disorder will participate in a pragmatic multicentre two-arm randomized controlled trial. Problematic alcohol use is operationalised as scoring ≥5 for women and ≥ 8 for men on the Alcohol Use Disorder Identification Test (AUDIT). Participants will be randomized to either the experimental group (digital alcohol intervention + TAU) or control group (TAU only). Participants will be recruited at three Dutch mental health care centres and through social media. Assessments take place at baseline and after 3, 6 and 12 months post-randomization. The primary outcome is treatment response at 6-month follow-up, operationalized as a composite score that combines alcohol use and depression measures and indicates whether treatment has been successful or not. Secondary outcomes are depressive symptoms and alcohol use (i.e. number of weekly standard drinks and AUDIT score). An economic evaluation will be conducted alongside the trial. Discussion: This study evaluates the (cost-) effectiveness of an add-on digital alcohol moderation intervention for young adults who are in treatment for depressive disorders. If proven effective, the digital intervention could be implemented in mental health care and improve treatment for people with co-occurring depressive disorders and problematic alcohol use. Trial registration: Pre-registered on October 29, 2019 in The Netherlands Trial Register (NL8122)

Kaplan-Meier plots for progression free survival for patients with KRAS wild type (19 statin-users and 145 nonusers) and KRAS mutant (16 statin-users and 83 nonusers) tumors treated with capecitabine, oxaliplatin, bevacizumab and cetuximab.

<p>Kaplan-Meier plots for progression free survival for patients with KRAS wild type (19 statin-users and 145 nonusers) and KRAS mutant (16 statin-users and 83 nonusers) tumors treated with capecitabine, oxaliplatin, bevacizumab and cetuximab.</p

Patient Characteristics.

<p>Patient Characteristics.</p

Overview of the mevalonate pathway and the inhibition of HMG-CoA by statins.

<p><i>Mevalonate pathway causes prenylation of ras, N-glycosylation of EGFR and membrane and steroidsynthesis. Statins have inhibitory effects on the mevalonate pathway and thus on prenylation of k-ras. Abbreviations: Acetyl-CoA, Acetyl coenzyme A; EGFR, epidermal growth factor receptor; FTase, farnesyltransferase; GTase, geranylgeranyltransferase; HMG-CoA (reductase), 3-hydroxy-3-methyl-glutaryl-CoA reductase; -PP, -pyrophosphate.</i></p

Statin Use Is Not Associated with Improved Progression Free Survival in Cetuximab Treated KRAS Mutant Metastatic Colorectal Cancer Patients: Results from the CAIRO2 Study

Statins may inhibit the expression of the mutant KRAS phenotype by preventing the prenylation and thus the activation of the KRAS protein. This study was aimed at retrospectively evaluating the effect of statin use on outcome in KRAS mutant metastatic colorectal cancer patients (mCRC) treated with cetuximab. Treatment data were obtained from patients who were treated with capecitabine, oxaliplatin bevacizumab ± cetuximab in the phase III CAIRO2 study. A total of 529 patients were included in this study, of whom 78 patients were on statin therapy. In patients with a KRAS wild type tumor (n = 321) the median PFS was 10.3 vs. 11.4 months for non-users compared to statin users and in patients with a KRAS mutant tumor (n = 208) this was 7.6 vs. 6.2 months, respectively. The hazard ratio (HR) for PFS for statin users was 1.12 (95% confidence interval 0.78-1.61) and was not influenced by treatment arm, KRAS mutation status or the KRAS*statin interaction. Statin use adjusted for covariates was not associated with increased PFS (HR = 1.01, 95% confidence interval 0.71-1.54). In patients with a KRAS wild type tumor the median OS for non-users compared to statin users was 22.4 vs. 19.8 months and in the KRAS mutant tumor group the OS was 18.1 vs. 14.5 months. OS was significantly shorter in statin users versus non-users (HR = 1.54; 95% confidence interval 1.06-2.22). However, statin use, adjusted for covariates was not associated with increased OS (HR = 1.41, 95% confidence interval 0.95-2.10). In conclusion, the use of statins at time of diagnosis was not associated with an improved PFS in KRAS mutant mCRC patients treated with chemotherapy and bevacizumab plus cetuximab