The cerebellum and psychological trauma: A systematic review of neuroimaging studies.

Psychological trauma is highly prevalent among psychiatric disorders, however, the relationship between trauma, neurobiology and psychopathology is not yet fully understood. The cerebellum has been recognized as a crucial structure for cognition and emotion, however, it has been relatively ignored in the literature of psychological trauma, as it is not considered as part of the traditional fear neuro-circuitry. The aim of this review is to investigate how psychological trauma affects the cerebellum and to make conclusive remarks on whether the cerebellum forms part of the trauma-affected brain circuitry. A total of 267 unique records were screened and 39 studies were included in the review. Structural cerebellar alterations and aberrant cerebellar activity and connectivity in trauma-exposed individuals were consistently reported across studies. Early-onset of adverse experiences was associated with cerebellar alterations in trauma-exposed individuals. Several studies reported alterations in connectivity between the cerebellum and nodes of large-brain networks, which are implicated in several psychiatric disorders, including the default mode network, the salience network and the central executive network. Also, trauma-exposed individuals showed altered resting state and task based cerebellar connectivity with cortical and subcortical structures that are involved in emotion and fear regulation. Our preferred interpretation of the results is through the lens of the Universal Cerebellar Transform, the hypothesis that the cerebellum, given its homogeneous cytoarchitecture, performs a common computation for motor, cognitive and emotional functions. Therefore, trauma-induced alterations in this computation might set the ground for a variety of psychiatric symptoms.

Impact of COVID-19 lockdown on individuals under treatment for substance use disorders: Risk factors for adverse mental health outcomes.

BACKGROUND: Individuals with Substance Use Disorders (SUD), are vulnerable to the psychological consequences of the COVID-19 pandemic. This is the first study to assess risk factors of adverse mental health outcomes during lockdown in a SUD population. METHODS: This was a cross-sectional study, conducted through an online survey that was completed by 303 individuals with SUD, attended in the Addiction Unit of University of Barcelona Clínic Hospital. Sociodemographic and clinical data were collected and descriptive analyses were carried out. Depending on whether individuals reported a worsening or no change/improvement in anxiety and depression symptoms during lockdown, the sample was divided in two groups. A logistic regression was then carried out to identify risk factors associated with adverse mental health outcomes. RESULTS: Overall, frequency of use for the majority of individuals with SUD remained stable during lockdown in comparison to the pre-lockdown era, although a reduction was found in frequency of tobacco, alcohol, cannabis and cocaine use in a small fraction of individuals with SUD. Symptoms of clinical anxiety were found in 58.7% of the sample while 48.2% of participants scored above the clinical threshold for depression. In addition, 50.3% of the sample reported a deterioration in depression and anxiety symptoms during lockdown that was associated with the following risk factors: previous trauma-exposure, female gender, distress and isolation, income reduction and alcohol use. CONCLUSION: A high percentage of patients with SUD experienced adverse mental health outcomes during lockdown that were associated with several risk factors, which should be taken into account in policy making and prevention strategies, as well as in clinical practice, in order to provide personalized care to SUD patients during the time of the pandemic.

Cannabis use the week before admission to psychiatric in-patient service as a marker of severity.

OBJECTIVE: To evaluate if cannabis dose recorded as standard joint unit (SJU) consumed before admission and other related factors have an influence on psychiatric inpatient's symptom severity and clinical outcomes. METHODS: Cross-sectional study in an acute psychiatric inpatient unit including 106 individuals. Quantity of cannabis was measured as SJU and symptoms severity through the Brief Psychiatric Rating Scale (BPRS). Secondary outcomes (e.g. length of stay) were also assessed. Bivariate analyses and multivariate analyses were performed to determine the effect of SJU consumed before admission on measures of clinical severity. RESULTS: Point prevalence of cannabis use before admission was 25.5%. Mean BPRS score was 55.8 (SD = 16.1); and 62.9 (SD = 11.1) among cannabis users. A low degree positive correlation between SJU consumed the week before admission and BPRS score (rs = 0.28, p = 0.03) was found. In the multivariate analyses both main diagnostic group, Schizophrenia and other psychotic disorders vs. others (Bipolar and Unipolar Affective Disorders and Addictive disorders) (B = 8.327; 95% CI 4.976-11.677) and need of PRN ("pre re nata" or when necessary) administration of antipsychotics and benzodiazepines (B = 12.13; 95% CI 6.868-17.393) were significant predictors, both increasing BPRS score. CONCLUSIONS: The study did not find a correlation between SJU consumed last week and psychiatric severity. On the other hand, individuals with psychotic disorders reported a higher prevalence of cannabis use the week before admission and displayed higher BPRS scores, which points to the need for the development of tailored interventions for high-risk groups. The SJU is a useful quantification tool suitable for further clinical research.

The blind men and the elephant: Systematic review of systematic reviews of cannabis use related health harms.

Cannabis is the third most used psychoactive substance worldwide. The legal status of cannabis is changing in many Western countries, while we have very limited knowledge of the public health impact of cannabis-related harms. There is a need for a summary of the evidence of harms and risks attributed to cannabis use, in order to inform the definition of cannabis risky use. We have conducted a systematic review of systematic reviews, aiming to define cannabis-related harms. We included systematic reviews published until July 2018 from six different databases and following the PRISMA guidelines. To assess study quality we applied the AMSTAR 2 tool. A total of 44 systematic reviews, including 1,053 different studies, were eligible for inclusion. Harm was categorized in three dimensions: mental health, somatic harm and physical injury (including mortality). Evidence shows a clear association between cannabis use and psychosis, affective disorders, anxiety, sleep disorders, cognitive failures, respiratory adverse events, cancer, cardiovascular outcomes, and gastrointestinal disorders. Moreover, cannabis use is a risk factor for motor vehicle collision, suicidal behavior and partner and child violence. Cannabis use is a risk factor for several medical conditions and negative social consequences. There is still little data on the dose-dependency of these effects; evidence that is essential in order to define, from a public health perspective, what can be considered risky use of cannabis. This definition should be based on quantitative and qualitative criteria that informs and permits the evaluation of current approaches to a regulated cannabis market.

Dabigatrán en pacientes con lesión miocárdica después de cirugía no cardiaca. A propósito del estudio MANAGE / Dabigatran in patients with myocardial injury after non-cardiac surgery. Report on the MANAGE trial

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Improving screening and brief intervention activities in primary health care: Secondary analysis of professional accuracy based on the AUDIT-C.

INTRODUCTION AND OBJECTIVE: The ODHIN trial found that training and support and financial reimbursement increased the proportion of patients that were screened and given advice for their heavy drinking in primary health care. However, the impact of these strategies on professional accuracy in delivering screening and brief advice is underresearched and is the focus of this paper. METHOD: From 120 primary health care units (24 in each jurisdiction: Catalonia, England, the Netherlands, Poland, and Sweden), 746 providers participated in the baseline and the 12-week implementation periods. Accuracy was measured in 2 ways: correctness in completing and scoring the screening instrument, AUDIT-C; the proportion of screen-negative patients given advice, and the proportion of screen-positive patients not given advice. Odds ratios of accuracy were calculated for type of profession and for intervention group: training and support, financial reimbursement, and internet-based counselling. RESULTS: Thirty-two of 36 711 questionnaires were incorrectly completed, and 65 of 29 641 screen-negative patients were falsely classified. At baseline, 27% of screen-negative patients were given advice, and 22.5% screen-positive patients were not given advice. These proportions halved during the 12-week implementation period, unaffected by training. Financial reimbursement reduced the proportion of screen-positive patients not given advice (OR = 0.56; 95% CI, 0.31-0.99; P < .05). CONCLUSION: Although the use of AUDIT-C as a screening tool was accurate, a considerable proportion of risky drinkers did not receive advice, which was reduced with financial incentives.

La anemia como factor de riesgo quirúrgico en cirugía vascular. Algoritmos de diagnóstico y tratamiento / Anaemia as surgical risk factor in vascular surgery. Diagnostic and treatment algorithms

La anemia es una entidad clínica que se detecta frecuentemente en la evaluación preoperatoria, especialmente en pacientes de edad avanzada. Se asocia a un aumento de la morbimortalidad perioperatoria, así como a una mayor probabilidad de transfusión de sangre alogénica (TSA), con los riesgos que ello implica. Aunque la anemia puede ser multifactorial y difícil de tipificar en algunos casos, sus causas más frecuentes son las deficiencias nutricionales (hierro, ácido fólico y vitamina B12) y la anemia por enfermedad crónica o anemia inflamatoria. En el paciente candidato a cirugía vascular arterial la prevalencia de anemia preoperatoria se sitúa alrededor del 50%. Además, uno de cada 3 pacientes presenta anemia en los 3 meses previos a la cirugía. El estado inflamatorio, inherente al proceso crónico vascular, y las pérdidas sanguíneas quirúrgicas favorecen la predisposición a padecer anemia. La anemia, como factor de mal pronóstico perioperatorio, exige su diagnóstico y tratamiento. Se proponen algoritmos para el manejo de la anemia, diferenciando la cirugía programada de la urgente. Se destaca la administración preferente de hierro por vía intravenosa en los períodos preoperatorio y postoperatorio precoz (AU)

Anaemia is a clinical condition that is frequently detected in the pre-operative evaluation, particularly in elderly patients. Anaemia is associated with increased peri-operative morbidity and mortality, as well as a greater likelihood of allogeneic blood transfusion, along with the risks involved. Although anaemia can be due to many factors and difficult to establish in some cases, its most common causes are nutritional deficiencies (iron, folic acid, and vitamin B12) and anaemia of chronic inflammatory disease. In patient candidates for arterial vascular surgery, preoperative anaemia prevalence is around 50%. In addition, one out of three patients has anaemia in the 3 months prior to surgery. The inflammatory condition, inherent to chronic vascular processes, and surgical blood loss favours the predisposition to anaemia. Anaemia, as factor of poor peri-operative prognosis, requires diagnosis and treatment. Algorithms are proposed for managing the anaemia, differentiating scheduled from urgent surgery. The administration of IV iron should be in the preoperative and early postoperative periods (AU)

Alcohol Dependence, Co-occurring Conditions and Attributable Burden.

AIMS: Alcohol dependence is associated with high rates of co-occurring disorders which impact health-related quality of life (HRQoL) and add to the cost-of-illness. This study investigated the burden of alcohol dependence and associated co-occurring conditions on health and productivity. METHODS: A cross-sectional survey was conducted in eight European countries. Physicians (Psychiatrists and General Practitioners) completed patient record forms, which included assessment of co-occurring conditions, and patients completed matching self-completion forms. Drinking risk level (DRL) was calculated and the relationship between DRL, co-occurring conditions, work productivity, hospitalisations and rehabilitation stays was explored. RESULTS: Data were collected for 2979 alcohol-dependent patients (mean age 48.8 ± 13.6 years; 70% male). In total, 77% of patients suffered from moderate-to-severe co-occurring psychiatric and/or somatic conditions. High DRL was significantly associated with depression, greater work productivity losses, increased hospitalisations and rehabilitation stays. Co-occurring conditions were significantly associated with poorer HRQoL and decreased work productivity, with a statistical trend towards an increased frequency of rehabilitation stays. CONCLUSIONS: Alcohol-dependent patients manifest high rates of co-occurring psychiatric and somatic conditions, which are associated with impaired work productivity and HRQoL. The continued burden of illness observed in these already-diagnosed patients suggests an unmet need in both primary and secondary care.

Who receives treatment for alcohol use disorders in the European Union? A cross-sectional representative study in primary and specialized health care.

BACKGROUND: Alcohol use disorders (AUDs) are highly prevalent in Europe, but only a minority of those affected receive treatment. It is therefore important to identify factors that predict treatment in order to reframe strategies aimed at improving treatment rates. METHODS: Representative cross-sectional study with patients aged 18-64 from primary health care (PC, six European countries, n=8476, data collection 01/13-01/14) and from specialized health care (SC, eight European countries, n=1762, data collection 01/13-03/14). For descriptive purposes, six groups were distinguished, based on type of DSM-IV AUD and treatment setting. Treatment status (yes/no) for any treatment (model 1), and for SC treatment (model 2) were main outcome measures in logistic regression models. RESULTS: AUDs were prevalent in PC (12-month prevalence: 11.8%, 95% confidence interval (CI): 11.2-12.5%), with 17.6% receiving current treatment (95%CI: 15.3-19.9%). There were clear differences between the six groups regarding key variables from all five predictor domains. Prediction of any treatment (model 1) or SC treatment (model 2) was successful with high overall accuracy (both models: 95%), sufficient sensitivity (model 1: 79%/model 2: 76%) and high specificity (both models: 98%). The most predictive single variables were daily drinking level, anxiety, severity of mental distress, and number of inpatient nights during the last 6 months. CONCLUSIONS: Variables from four domains were highly predictive in identifying treatment for AUD, with SC treatment groups showing very high levels of social disintegration, drinking, comorbidity and functional losses. Earlier intervention and formal treatment for AUD in PC should be implemented to reduce these high levels of adverse outcomes.

Ácido acetilsalicílico y clonidina en el perioperatorio de pacientes intervenidos de cirugía no cardíaca (estudio POISE-2) / Perioperative acetylsalicylic acid and clonidine in noncardiac surgery patients (POISE-2 trial)

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Assessment of cannabis use disorders: a systematic review of screening and diagnostic instruments.

BACKGROUND: Cannabis use and misuse have become a public health problem. There is a need for reliable screening and assessment tools to identify harmful cannabis use at an early stage. We conducted a systematic review of published instruments used to screen and assess cannabis use disorders. METHOD: We included papers published until January 2013 from seven different databases, following the PRISMA guidelines and a predetermined set of criteria for article selection. Only tools including a quantification of cannabis use and/or a measurement of the severity of dependence were considered. RESULTS: We identified 34 studies, of which 25 included instruments that met our inclusion criteria: 10 scales to assess cannabis use disorders, seven structured interviews, and eight tools to quantify cannabis use. Both cannabis and substance use scales showed good reliability and were validated in specific populations. Structured interviews were also reliable and showed good validity parameters. Common limitations were inadequate time-frames for screening, lack of brevity, undemonstrated validity for some populations (e.g., psychiatric patients, female gender, adolescents), and lack of relevant information that would enable routine use (e.g., risky use, regular users). Instruments to quantify consumption did not measure grams of the psychoactive compounds, which hampered comparability among different countries or regions where tetrahydrocannabinol concentrations may differ. CONCLUSIONS: Current instruments available for assessing cannabis use disorders need to be further improved. A standard cannabis unit should be studied and existing instruments should be adapted to this standard unit in order to improve cannabis use assessment.

Nalmefene and its use in alcohol dependence.

Nalmefene is the first available drug approved in the E.U. to reduce alcohol use in alcohol-dependent patients. Reduction in alcohol use in heavy drinkers diminishes mortality risk and socio-economic burden. Nalmefene has shown efficacy at 6 months in alcohol-dependent patients with high or very high drinking risk levels in reducing total alcohol consumption (-7.6 g/day [95% confidence interval (CI): -11.6 to -3.5]; P = 0.0003), heavy drinking days (-2.00 days/month [95% CI: -3.00 to -1.00]; P ⟨ 0.00001) and other secondary outcome measures such as γ-glutamyl transferase, alanine aminotransferase, drinking risk level and Clinical Global Impression. It is generally well tolerated and has limited contraindications and interactions. As-needed dosage is a novel concept in the addictions field, which may overcome limitations of traditional regimens. In the pivotal trials, nalmefene was taken 52% of the days and compliance with the as-needed treatment regimen was good (above 80% of the days) in 68% of the nalmefene-treated patients. A new pharmacological approach combined with a brief psychosocial intervention for alcoholism is available and appears to be feasible, safe and efficacious.

The tangible common denominator of substance use disorders: a reply to commentaries to Rehm et al. (2013a).

In response to our suggestion to define substance use disorders via 'heavy use over time', theoretical and conceptual issues, measurement problems and implications for stigma and clinical practice were raised. With respect to theoretical and conceptual issues, no other criterion has been shown, which would improve the definition. Moreover, heavy use over time is shown to be highly correlated with number of criteria in current DSM-5. Measurement of heavy use over time is simple and while there will be some underestimation or misrepresentation of actual levels in clinical practice, this is not different from the status quo and measurement of current criteria. As regards to stigma, research has shown that a truly dimensional concept can help reduce stigma. In conclusion, 'heavy use over time' as a tangible common denominator should be seriously considered as definition for substance use disorder.

Mortality of bullous pemphigoid in the first year after diagnosis: a retrospective study in a Spanish medical centre.

BACKGROUND: Prognosis of patients with bullous pemphigoid (BP) is controversial, with a 1-year mortality rate ranging from 6% to 48%. OBJECTIVE: To determine the mortality rate of a large cohort of patients with BP and to identify prognostic factors associated with early mortality. METHODS: Patients diagnosed with BP between January 1, 1990 and December 31, 2010 in a referral unit for blistering skin diseases at a university hospital in Spain were studied retrospectively. Outcome measures were mortality rate during the first year after diagnosis, standardized mortality rate and poor prognostic factors. RESULTS: A total of 101 patients were included in the study. The mean patient age at diagnosis was 77.8 years, and 52 (51.5%) were men. Overall mortality during the first year was 12.9%. We found a standardized mortality ratio of 2.33 [CI95 = (1.25-4.03)]. Advanced age (patient group >80 years old) was the only risk factor for lethal outcome found, with a multivariate risk estimate of 1.09 [CI95 = (1.02-1.16)]. No significant association with mortality was detected for comorbidities, hospitalization history or treatment received for BP. CONCLUSIONS: We found an increased mortality of our BP patients compared with the general population. The mortality rate of BP patients was 2.3 times the expected rate. Observed mortality rate was lower than described in previous European studies. Advanced age impacts the prognosis of patients with BP. Specific treatment for BP appeared not to influence survival.

Treatment of bullous pemphigoid with low-dose oral cyclophosphamide: a case series of 20 patients.

BACKGROUND: Cyclophosphamide has been commonly used for the treatment of pemphigus vulgaris and mucous membrane pemphigoid with satisfactory results. Published data of this therapeutic approach for bullous pemphigoid are scant and showed significant morbidity and mortality. OBJECTIVE: To assess the clinical efficacy and safety of low-dose oral cyclophosphamide (CFM) (50-100 mg/day) in patients with refractory bullous pemphigoid. METHODS: We conducted a retrospective study including patients with bullous pemphigoid treated with CFM in the department of Dermatology in the Hospital Clínic of Barcelona, Spain. RESULTS: Complete response was observed in 11 (58%) over 19 evaluable patients. Cyclophosphamide at 50 mg/day was enough to achieve clinical remission in eight of these patients. Partial response was observed in four (21%) more patients. Bone marrow suppression appeared in 12 (60%) patients, but treatment discontinuation was only required in three (15%) cases. Gastrointestinal intolerance occurred in one (5%) patient. One patient died during therapy from heart failure (not attributed to CFM) and another patient developed acute myeloid leukaemia 1.5 years after CFM therapy. CONCLUSIONS: In our series, CFM had a marked therapeutic effect in bullous pemphigoid. These results of efficacy are similar to those described in other autoimmune blistering skin diseases. Only a few patients had to discontinue their treatment due to adverse effects. Therefore, we consider that low-dose oral CFM can be valuable therapeutic alternative in elderly patients with moderate-to-severe bullous pemphigoid.

Defining substance use disorders: do we really need more than heavy use?

AIMS: The aim of the study was to explore whether the concept of heavy substance use over time can be used as definition of substance use disorder. METHODS: Narrative review. RESULTS: Heavy use over time clearly underlies the neurobiological changes associated with current thinking of substance use disorders. In addition, there is evidence that heavy use over time can explain the majority of social problems and of burden of disease (morbidity and mortality). A definition of substance use disorders via heavy use over time would avoid some of the problems of current conceptualizations, for instance the cultural specificity of concepts such as loss of control. Finally, stressing the continuum of use may avoid the high level of stigmatization currently associated with substance use disorders. CONCLUSION: 'Heavy substance use over time' seems to be a definition of substance use disorders in line with results of basic research and epidemiology. Additionally, it reduces stigmatization. This approach should thus be further explored.

Simultaneous versus delayed treatment of tobacco dependence in alcohol-dependent outpatients.

INTRODUCTION: There is a high prevalence of smoking among heavy drinkers, which is often forgotten even though it has important health consequences. AIM: To evaluate the effects that providing an intensive tobacco cessation treatment simultaneously with alcohol dependence treatment versus delayed treatment (first alcohol and 6 months later tobacco) has on alcohol and tobacco consumption. METHODS: Ninety-two alcohol-dependent smokers were randomized into either a simultaneous group, in which treatment was given concurrently for quitting both alcohol and tobacco, or a delayed group, in which help to quit smoking was given after 6 months. RESULTS: No differences were found in alcohol abstinence rates in time-to-first relapse or in cumulative abstinence at 6 months. Smoking cessation rates were low overall, but better at 3 months in the simultaneous group, although differences later disappeared. DISCUSSION: Participation in a smoking cessation program does not impair alcohol outcomes, at least during the first 6 months.