Destination Matters More: Relapse following Hospital-Based Treatment of Substance Use Disorders With and Without Co-Occurring Disorders.

OBJECTIVES: Addressing substance use in psychiatric care encounters significant barriers, but the emergence of specialized services offers an opportunity to advance and scale up the integration of addiction services within psychiatric settings. However, research gaps still exist in this field, particularly in understanding the substance relapse rates of people with co-occurring disorders after a psychiatric hospitalization. This study aimed to investigate and compare the relapse rates of patients under inpatient care with exclusively addiction-related issues and those with co-occurring disorders after a hospitalization in a psychiatric ward and gain insights into differences in outcomes for these two patient groups. METHODS: This retrospective analysis examined electronic medical records of patients admitted to the Acute Psychiatry Ward of the Hospital Clinic of Barcelona with a substance use disorder diagnosis between January 2019 and February 2021. Cox regression was used to identify variables independently associated with the first relapse episode. RESULTS: From a total of 318 admissions (79.2% with psychiatric comorbidity), 76.1% relapsed during the study follow-up, with a median survival time of 54 days. Younger age, female gender, voluntary admission, and outpatient follow-up were independently associated with relapse. The presence of a co-occurring disorder was not associated with relapse. CONCLUSION: This study highlights the need for interventions aimed at improving post-discharge abstinence rates for addiction-related hospitalizations. It also challenges the notion that co-occurring disorders automatically imply a worsened prognosis and emphasizes the importance of addressing addiction and psychiatric comorbidity in a comprehensive, integrated, and specialized manner.

Quitline nurses' experiences in providing telephone-based smoking cessation help to mental health patients: A mixed methods study.

WHAT IS KNOWN ON THE SUBJECT?: Quitlines are known to be effective in helping people quit smoking, including those with mental health conditions. It is particularly important to address smoking in this population as the prevalence of smoking ranges from 40% to 75%. However, professionals working in quitlines often face barriers due to their limited training and resources to effectively support these smokers quit, especially if they are not mental health professionals. Therefore, training programmes should be developed to enhance their knowledge and skills in providing smoking cessation support to this vulnerable population. WHAT THE PAPER ADDS TO EXISTING KNOWLEDGE?: The '061 QUIT-MENTAL study' evaluated the efficacy of a proactive telephone-based intervention for smoking cessation among smokers with severe mental health disorders. Conducted through a quitline service in Catalonia, Spain, the study focused on training non-mental health specialized nurses and other health professionals to provide evidence-based interventions for promoting smoking cessation among individuals with mental health disorders. The objective of this study is to assess the changes in nurses' knowledge and readiness to treat smokers with mental health conditions, while also capturing their insights and perceptions regarding the facilitators and barriers to providing smoking cessation interventions. The training and insights of the nurses were integral to conducting this research and providing valuable information for the future sustainability of such interventions. This is particularly important as quitlines hold the potential to offer cessation support to these patients at the community level. WHAT ARE THE IMPLICATIONS FOR PRACTICE?: While the training programme was successful in improving non-mental health specialized nurses' knowledge and motivation skills to help patients with mental health disorders quit smoking, they encountered obstacles in delivering this intervention over the phone. These difficulties were mainly due to challenges in reaching participants and delivering the intervention as detailed in the protocol. The study highlights the need of reducing barriers for providers in attending to these patients, particularly if they are non-mental health specialized professionals. By minimizing the stigmatization associated with caring for mentally ill individuals and promoting coordination with specialists, innovative approaches may be introduced to alleviate the burden of tobacco-related diseases among this population. ABSTRACT: Introduction The viewpoint of those who implement a programme for the first time is crucial for understanding its impact and ensuring its long-term viability. The 061 QUIT-MENTAL study was a pragmatic randomized controlled trial evaluating a proactive telephone-based intervention addressed to mental health patients conducted by non-psychiatric specialized nurses. Aim We assessed nurses' knowledge of smoking cessation interventions addressed to this population before and after receiving training and their insights after delivering the intervention. Method Mixed methods study: (1) Pre-post evaluation to assess self-reported knowledge, self-efficacy and opinions about smoking cessation. (2) In-depth interviews with key nurses to ascertain their perceptions regarding the impact of the training received in delivering the study intervention. Results The training enhanced nurses' knowledge of psychological and pharmacological resources to aid these patients, as well as their ability to increase their motivation to quit. However, nurses reported difficulties in delivering population-based interventions to individuals with mental health disorders. These challenges primarily arose from participants being hard to reach, exhibiting low motivation to quit, struggling to comprehend instructions or follow recommendations, and nurses feeling unsure about their capacity to assist individuals with mental illnesses in quitting, despite the training they received. Discussion Despite the training and protocol designed to facilitate the delivery of the intervention, nurses faced difficulties in providing population-based interventions to individuals with mental health disorders. Implications for Practice Future quitline programmes aimed at the population with mental health disorders should strive to reduce barriers for providers in attending to these patients, particularly if they are non-mental health specialized professionals. By minimizing the stigmatization associated with caring for mentally ill individuals and promoting coordination with specialists, innovative approaches may be introduced to alleviate the burden of tobacco-related diseases among this population.

Recent Advances in the Catalytic Synthesis of the Cyclopentene Core.

Five-membered carbocycles are ubiquitously found in natural products, pharmaceuticals, and other classes of organic compounds. Within this category, cyclopentenes deserve special attention due to their prevalence as targets and as well as key intermediates for synthesizing more complex molecules. Herein, we offer an overview summarizing some significant recent advances in the catalytic assembly of this structural motif. A great variety of synthetic methodologies and strategies are covered, including transition metal-catalyzed or organocatalyzed processes. Both inter- and intramolecular transformations are documented. On this ground, our expertise in the application of C-H functionalization reactions oriented towards the formation of this ring and its subsequent selective functionalization is embedded.

C-H Activation of Unbiased C(sp3 )-H Bonds: Gold(I)-Catalyzed Cycloisomerization of 1-Bromoalkynes.

Selective functionalization of non-activated C(sp3 )-H bonds is a major challenge in chemistry, so functional groups are often used to enhance reactivity. Here, we present a gold(I)-catalyzed C(sp3 )-H activation of 1-bromoalkynes without any sort of electronic, or conformational bias. The reaction proceeds regiospecifically and stereospecifically to the corresponding bromocyclopentene derivatives. The latter can be readily modified, comprising an excellent library of diverse 3D scaffolds for medicinal chemistry. In addition, a mechanistic study has shown that the reaction proceeds via a so far unknown mechanism: a concerted [1,5]-H shift / C-C bond formation involving a gold-stabilized vinylcation-like transition state.

The dietary sweetener sucralose is a negative modulator of T cell-mediated responses.

Artificial sweeteners are used as calorie-free sugar substitutes in many food products and their consumption has increased substantially over the past years1. Although generally regarded as safe, some concerns have been raised about the long-term safety of the consumption of certain sweeteners2-5. In this study, we show that the intake of high doses of sucralose in mice results in immunomodulatory effects by limiting T cell proliferation and T cell differentiation. Mechanistically, sucralose affects the membrane order of T cells, accompanied by a reduced efficiency of T cell receptor signalling and intracellular calcium mobilization. Mice given sucralose show decreased CD8+ T cell antigen-specific responses in subcutaneous cancer models and bacterial infection models, and reduced T cell function in models of T cell-mediated autoimmunity. Overall, these findings suggest that a high intake of sucralose can dampen T cell-mediated responses, an effect that could be used in therapy to mitigate T cell-dependent autoimmune disorders.

Tobacco cessation among smokers under substance use treatment for alcohol and/or cannabis: study protocol and pilot study.

BACKGROUND: Approximately 80% of people with a substance use disorder (SUD) are smokers. Starting SUD treatment offers the opportunity to also quit smoking. The ACT-ATAC project aims to identify the predictors associated with smoking cessation among persons treated for alcohol and/or cannabis use disorder in Barcelona. This manuscript reports its methodology and the experience of carrying it out during the COVID-19 pandemic. METHODS: Mixed methods project with three substudies. Substudy 1 (S1) comprises heterogeneous discussion groups among clinicians. S2 has two prospective cohorts composed of smokers under treatment for alcohol and/or cannabis use disorder and the clinicians in charge of these patients. Participating smokers will be followed for 12 months and interviewed about their substance use and the tobacco cessation services received using the Spanish version of the users' Knowledge, Attitudes, and Services (S-KAS) scale. The clinicians will be asked about their self-reported practices in smoking cessation using the Knowledge, Attitudes, and Practices (S-KAP) scale. S3 comprises heterogeneous discussion groups with smokers. Data will be triangulated using qualitative and quantitative analyses. To facilitate the recruitment process, the researchers have introduced several strategies (design clear protocols, set monthly online meetings, extend the project, provide gift cards, etc.). DISCUSSION: The results of S1 were used to develop the questionnaires. S2 required some adjustments due to the COVID-19 pandemic, particularly the follow-up interviews being conducted by phone instead of face-to-face, and the recruitment rhythm was lower than expected. Recruitment will last until reaching at least 200-250 users. The fieldwork could not have been possible without the collaboration of the ACT-ATAC team and the introduction of several strategies. Trial registration The ACT-ATAC project has been successfully registered at Clinicaltrials.gov [NCT04841655].

Cell-specific bioorthogonal tagging of glycoproteins.

Altered glycoprotein expression is an undisputed corollary of cancer development. Understanding these alterations is paramount but hampered by limitations underlying cellular model systems. For instance, the intricate interactions between tumour and host cannot be adequately recapitulated in monoculture of tumour-derived cell lines. More complex co-culture models usually rely on sorting procedures for proteome analyses and rarely capture the details of protein glycosylation. Here, we report a strategy termed Bio-Orthogonal Cell line-specific Tagging of Glycoproteins (BOCTAG). Cells are equipped by transfection with an artificial biosynthetic pathway that transforms bioorthogonally tagged sugars into the corresponding nucleotide-sugars. Only transfected cells incorporate bioorthogonal tags into glycoproteins in the presence of non-transfected cells. We employ BOCTAG as an imaging technique and to annotate cell-specific glycosylation sites in mass spectrometry-glycoproteomics. We demonstrate application in co-culture and mouse models, allowing for profiling of the glycoproteome as an important modulator of cellular function.

Intramolecular activation of strong Si-O bonds by gold(I): regioselective synthesis of 3-bromo-2-silylbenzofurans.

The high reactivity of gold-vinylidene complexes, generated in situ by [1,2]-bromine shift from the corresponding 1-bromoalkynes, allows the activation of one of the strongest bonds in organic chemistry (Si-O), strategically placed at the ortho-position. In this way, the synthesis of 3-bromo-2-silylbenzofuranes is achieved in good yields. Several substituents with different electronic properties and substitution patterns are well tolerated on the tethering aromatic ring as well as a number of silyl groups on the O-atom. A preliminary mechanistic study is compatible with the participation of gold vinylidene intermediate species. The synthetic applicability of the obtained scaffolds was preliminarily showcased by orthogonal C-C bond forming transformations.

Phosphatidylethanol (PEth) for Monitoring Sobriety in Liver Transplant Candidates: Preliminary Results of Differences Between Alcohol-Related and Non-Alcohol-Related Cirrhosis Candidates.

BACKGROUND Monitoring sobriety is mandatory for liver transplant (LT) candidates with alcohol-related cirrhosis in Germany. Prior to listing, abstinence of 6 months is required. However, little is known about biomarker performance in alcohol-related cirrhosis. Routine testing of ethyl glucuronide in urine (uEtG) or hair (hEtG) is prone to manipulation or is unfeasible in anuria. Phosphatidylethanol (PEth) in dried-blood spots is a promising alternative. We compared PEth with routine parameters and self-reports in alcohol-related and non-alcohol-related cirrhosis at our transplant center. MATERIAL AND METHODS All patients received self-report questionnaires (AUDIT & TLFB). Blood, urine and hair samples, as well as PEth dried-blood spots were drawn at baseline. In addition, survival analyses were conducted. RESULTS Out of 66 patients, 53 were listed for LT and 13 were candidates not listed so far. An alcohol-use disorder was found in 25 patients. Positive results for uEtG, hEtG, and PEth were found in 5/65, 9/65, and 34/66 cases, respectively. PEth positivity was found in 52% of patients with alcohol-related cirrhosis, while 53% of patients with other liver diseases were positive. While uEtG, hEtG, and TLFB correlated with higher PEth values, active waiting list status was significantly correlated with negative PEth values. During the mean follow-up of 41.15 months, 23 patients were transplanted (34.9%). None of the biomarkers significantly predicted survival. CONCLUSIONS PEth can importantly assist abstinence monitoring in LT candidates due to its high validity and objectivity. The high percentage of patients with alcohol consumption in the non-alcoholic liver disease cohort underscores the importance of testing all transplant candidates.

GREM1 is required to maintain cellular heterogeneity in pancreatic cancer.

Pancreatic ductal adenocarcinoma (PDAC) shows pronounced epithelial and mesenchymal cancer cell populations1-4. Cellular heterogeneity in PDAC is an important feature in disease subtype specification3-5, but how distinct PDAC subpopulations interact, and the molecular mechanisms that underlie PDAC cell fate decisions, are incompletely understood. Here we identify the BMP inhibitor GREM16,7 as a key regulator of cellular heterogeneity in pancreatic cancer in human and mouse. Grem1 inactivation in established PDAC in mice resulted in a direct conversion of epithelial into mesenchymal PDAC cells within days, suggesting that persistent GREM1 activity is required to maintain the epithelial PDAC subpopulations. By contrast, Grem1 overexpression caused an almost complete 'epithelialization' of highly mesenchymal PDAC, indicating that high GREM1 activity is sufficient to revert the mesenchymal fate of PDAC cells. Mechanistically, Grem1 was highly expressed in mesenchymal PDAC cells and inhibited the expression of the epithelial-mesenchymal transition transcription factors Snai1 (also known as Snail) and Snai2 (also known as Slug) in the epithelial cell compartment, therefore restricting epithelial-mesenchymal plasticity. Thus, constant suppression of BMP activity is essential to maintain epithelial PDAC cells, indicating that the maintenance of the cellular heterogeneity of pancreatic cancer requires continuous paracrine signalling elicited by a single soluble factor.

Acceptability and participation predictors for a pragmatic randomized controlled trial to test a smoking cessation intervention after discharge from mental health wards.

BACKGROUND AND AIM: Hospitalization is an ideal time to promote smoking cessation, but interventions are limited for supporting cessation maintenance after discharge. This study aimed to evaluate the acceptability of participating in a trial that tested the efficacy of an intensive telephone-based intervention for smokers after discharge. METHODS: Adult smokers admitted to mental health wards of six hospitals were invited to participate in the trial. We studied the study acceptance/decline rates by analyzing the characteristics of participants (e.g., sex, age, psychiatric disorder, smoking pattern) and hospitals (e.g., size, tobacco control implementation). We calculated adjusted odds ratios (aOR) to assess predictors of non-participation. RESULTS: Of 530 smokers that met the study inclusion criteria, 55.5% (n = 294) agreed to participate. Participant and non-participants were not different in sex, age, or psychiatric diagnosis. Compared to non-participants, participants had made more attempts to quit in the past year (66.1% vs 33.9%; p < 0.001) and reported higher abstinence rates during the hospital stay (66.7% vs. 33.3%; p = 0.05). Participation rates by hospital varied from 30.9% to 82.0% (p < 0.001). Predictors of non-participation were not having attempted to quit in the last year (aOR=2.42; 95%CI: 1.66-3.53) and low level of tobacco control in the hospital (aOR range: 1.79-6.39, p < 0.05). CONCLUSIONS: A telephone-based intervention to promote smoking cessation after discharge was accepted by half of the smokers with mental health disorders. Smokers that had attempted to quit previously and those that stayed in hospitals with a strong tobacco control policy were more likely to participate in the trial.

Comparative transcriptomic analysis reveals translationally relevant processes in mouse models of malaria.

Recent initiatives to improve translation of findings from animal models to human disease have focussed on reproducibility but quantifying the relevance of animal models remains a challenge. Here, we use comparative transcriptomics of blood to evaluate the systemic host response and its concordance between humans with different clinical manifestations of malaria and five commonly used mouse models. Plasmodium yoelii 17XL infection of mice most closely reproduces the profile of gene expression changes seen in the major human severe malaria syndromes, accompanied by high parasite biomass, severe anemia, hyperlactatemia, and cerebral microvascular pathology. However, there is also considerable discordance of changes in gene expression between the different host species and across all models, indicating that the relevance of biological mechanisms of interest in each model should be assessed before conducting experiments. These data will aid the selection of appropriate models for translational malaria research, and the approach is generalizable to other disease models.

Primary care provider expectations of addiction services and patients in Spain.

BACKGROUND: Primary care (PC) is crucial in the care of substance use disorder (SUD) patients. However, the relationship between PC and addiction settings is complex and collaboration issues stand out. Available evidence suggests that integration of SUD and PC services can improve physical and mental health of SUD patients and reduce health expenses. OBJECTIVE: To explore the experiences, views and attitudes of PC professionals towards the interaction between PC and SUD services. METHODS: Twenty-seven GPs took part in three focus groups. The focus group sessions were audio-taped, transcribed verbatim and analysed using reflexive thematic analysis. Recurrent themes were identified. RESULTS: Four main themes were devised: (1) Differences and specificities of SUD patients, (2) Interaction between providers of PC and addiction services, (3) Patient management (4) Addiction stigma. These main themes reflect the consideration that SUD patients are a specific group with specific care needs that yield specific challenges to GPs themselves. Improved training, availability of a shared medical record system, increased feedback between GP and addiction specialists and the efficiency of the circuit are to be considered the main priority for the majority of the participants. CONCLUSIONS: An efficient and effective referral circuit, with increased feedback and shared medical records is considered key to GPs. Its implementation should keep in mind the specific features of both SUD patients and GPs.

Recent Advances on the Halo- and Cyano-Trifluoromethylation of Alkenes and Alkynes.

Incorporation of fluorine into organic molecules is a well-established strategy in the design of advanced materials, agrochemicals, and pharmaceuticals. Among numerous modern synthetic approaches, functionalization of unsaturated bonds with simultaneous addition of trifluoromethyl group along with other substituents is currently one of the most attractive methods undergoing wide-ranging development. In this review article, we discuss the most significant contributions made in this area during the last decade (2012-2021). The reactions reviewed in this work include chloro-, bromo-, iodo-, fluoro- and cyano-trifluoromethylation of alkenes and alkynes.

Ventricular, atrial, and outflow tract heart progenitors arise from spatially and molecularly distinct regions of the primitive streak.

The heart develops from 2 sources of mesoderm progenitors, the first and second heart field (FHF and SHF). Using a single-cell transcriptomic assay combined with genetic lineage tracing and live imaging, we find the FHF and SHF are subdivided into distinct pools of progenitors in gastrulating mouse embryos at earlier stages than previously thought. Each subpopulation has a distinct origin in the primitive streak. The first progenitors to leave the primitive streak contribute to the left ventricle, shortly after right ventricle progenitor emigrate, followed by the outflow tract and atrial progenitors. Moreover, a subset of atrial progenitors are gradually incorporated in posterior locations of the FHF. Although cells allocated to the outflow tract and atrium leave the primitive streak at a similar stage, they arise from different regions. Outflow tract cells originate from distal locations in the primitive streak while atrial progenitors are positioned more proximally. Moreover, single-cell RNA sequencing demonstrates that the primitive streak cells contributing to the ventricles have a distinct molecular signature from those forming the outflow tract and atrium. We conclude that cardiac progenitors are prepatterned within the primitive streak and this prefigures their allocation to distinct anatomical structures of the heart. Together, our data provide a new molecular and spatial map of mammalian cardiac progenitors that will support future studies of heart development, function, and disease.

Mid and long-term effects of a SBIRT program for at-risk drinkers attending to an emergency department. Follow-up results from a randomized controlled trial.

BACKGROUND AND IMPORTANCE: SBIRT programs (Screening Brief Intervention and Referral to Treatment) for at-risk drinkers in emergency departments (ED) have shown to be effective, particularly at short term. In this article, we report mid and long-term follow-up results of a specialized SBIRT program. A short-term follow-up after 1.5 months showed encouraging results, with more than a 20% greater reduction of at-risk drinking in the intervention group and more than double of successful referrals to specialized treatment. OBJECTIVE: We aimed to evaluate the mid and long-term efficacy of an SBIRT program conducted by psychiatrist specialists in addictive disorders and motivational interviewing in the ED of a tertiary hospital. DESIGN, SETTINGS AND PARTICIPANTS: We conducted a secondary analysis of a previously published randomized controlled trial of an SBIRT program conducted by alcohol specialists for at-risk drinkers presenting to the ED, measured with the AUDIT-C scale. INTERVENTION OR EXPOSURE: Patients were randomized into two groups, with the control group receiving two leaflets: one regarding alcohol use and the other giving information about the study protocol. The intervention group received the same leaflets as well as a brief motivational intervention on alcohol use and, where appropriate, a referral to specialized treatment. OUTCOMES MEASURE AND ANALYSIS: Long-term assessment primary outcome was the proportion of at-risk alcohol use measured by AUDIT-C scale. The main effectiveness analysis at 18 weeks and 12 months' follow-up was conducted with multilevel logistic regression analyses. Missing values were imputed with the last observation carried forward. MAIN RESULTS: Of 200 patients included in the study, 133 (66.5%) and 131 (65.5%) completed 18 weeks and 1-year follow-up respectively. Although the proportion of risky drinkers was substantially lower in the intervention group (38.5 vs. 57.4% at 4.5 months and 58.5 vs 68.2% at 1 year), these results did not reach statistical significance (OR = 2.15; CI, 0.87-5.33). CONCLUSIONS: In this secondary analysis for mid- and long-term effects of a specialized SBIRT program, there was no significant difference in the reduction of risky drinkers at 18 weeks and 1 year. The small size of the studied sample and the low retention rate precluded any significant conclusion, although point estimates suggest a positive effect. Overall, SBIRT programs are an effective tool to reduce alcohol use at short time and to refer patients to specialized treatment; however, its effects seem to decay over time.

Abstinence Among Alcohol Use Disorder Patients During the COVID-19 Pandemic: Insights From Spain.

BACKGROUND: Patients with alcohol use disorder (AUD) are likely to suffer disproportionate harms related to the COVID-19 pandemic and related policy measures. While many surveys have been conducted, most are focused on drinking changes in the general population and validation with biological markers is lacking. METHOD: We performed a retrospective cohort study among patients with AUD attending a urine drug screening program. With mixed-effects logistic regression models, we assessed the probability of screening positive for ethyl glucuronide according to patients' main clinical characteristics and time of analysis (either prior to or after a lockdown was implemented in Spain). RESULTS: A total of 362 patients provided 2,040 urine samples (1,295 prior to lockdown, 745 during lockdown). The mean age of participants was 52.0 years (SD 12.6), and 69.2% were men. Of the 43% of patients tested for other drugs 22% screened positive. After adjusting for all covariates, the odds of screening positive for ethyl glucuronide during lockdown almost doubled (OR = 1.99, 95% CI 1.20 to 3.33, p = 0.008). Other significant covariates included testing positive for other drugs (OR = 10.79, 95% CI 4.60 to 26.97) and length of treatment (OR = 0.59, 95% CI 0.47 to 0.74). CONCLUSIONS: Our data support an association between the lockdown due to COVID-19 and increased alcohol use in patients with AUD. Thus, addiction healthcare systems could face significant challenges ahead. In light of these findings, it is essential to evaluate prospectively how patients with AUD are affected by the pandemic and how health systems respond to their needs.