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Co-occurrence of depression and a substance use disorder (SUD) in patients who present dual diagnoses has been long recognized as an important consideration in clinical practice. This review synthesizes the evidence of pharmacological and psychosocial interventions for comorbid depressive disorders and SUDs while providing clinical recommendations about the best interventions to address these patients. The best evidence from randomized controlled trials was used to evaluate treatment options. The strength of recommendations was described using the GRADE approach. Our results suggest that 1) In patients with depression and alcohol consumption, the administration of non-selective serotonin reuptake inhibitor (SSRI) antidepressants instead of SSRI is recommended for improvement of depressive symptoms (strong recommendation). Neither SSRI (strong recommendation) nor non-SSRI (weak recommendation) antidepressants are recommended for reduction in alcohol consumption. 2) In patients with depression and cannabis use, the use of venlafaxine is not recommended (weak recommendation). 3) In patients with depression and cocaine consumption, the use of SSRI antidepressants for improving depressive symptoms (weak recommendation) or to reduce cocaine use is not recommended (strong recommendation). The use of non-SSRI antidepressants is only recommended for improving depressive symptoms (strong recommendation). 4) The administration of bupropion to reduce nicotine consumption is not recommended (strong recommendation). 5) Regarding psychological treatment, in patients with depression and co-occurring alcohol disorder, both pharmacotherapy and cognitive behavioural therapy have positive effects on internalizing symptoms and in reducing alcohol consumption (weak recommendation). Our review suggests the need for more research in this area and for larger, multisite, randomized studies to provide more definite evidence.

Assessing the long-term risk of breast cancer after diagnosis of benign breast disease by mammography is of utmost importance to design personalised screening strategies. We analysed individual-level data from 778,306 women aged 50-69 years with at least one mammographic screening participation in any of ten breast cancer screening centers in Spain from 1996 to 2015, and followed-up until 2017. We used Poisson regression to compare the rates of incident breast cancer among women with and without benign breast disease. During a median follow-up of 7.6 years, 11,708 (1.5%) women had an incident of breast cancer and 17,827 (2.3%) had a benign breast disease. The risk of breast cancer was 1.77 times higher among women with benign breast disease than among those without (95% CI: 1.61 to 1.95). The relative risk increased to 1.99 among women followed for less than four years, and remained elevated for two decades, with relative risk 1.96 (95% CI: 1.32 to 2.92) for those followed from 12 to 20 years. Benign breast disease is a long-term risk factor for breast cancer. Women with benign breast disease could benefit from closer surveillance and personalized screening strategies.

Although correct diagnosis and management of patients with schizophrenia and a comorbid substance use disorder (SUD) would determine a decrease in morbidity and mortality in these patients, development of efficient therapeutic strategies is still pending. We present recommendations on the pharmacological and psychological management of these patients following the 'PICO' structure (Patient-Intervention-Comparison-Outcomes). Evaluation of the quality of studies and summary of the evidence for each question was performed following the recommendations of the GRADE (Grading of Recommendations, Assessment, Development and Evaluation) working group. Our results suggest: 1) In patients with schizophrenia and cannabis use disorder, it is not possible to recommend one antipsychotic drug over another (between olanzapine, risperidone or haloperidol) for improving psychotic symptoms, reducing cannabis use, or improving pragmatic variables (weak recommendation). Clozapine cannot be recommended to reduce cannabis use (weak recommendation). 2) In patients with schizophrenia and cocaine use disorder we recommend haloperidol over olanzapine to reduce craving (moderate recommendation), and olanzapine over haloperidol to improve motor side effects in these patients (moderate recommendation). 3) In patients with schizophrenia and alcohol use disorder while naltrexone is recommended to reduce alcohol use (in terms of reducing alcohol craving) (weak recommendation), there is insufficient evidence to make any recommendation on the use of adjuvant acamprosate (weak recommendation). 4) In patients with schizophrenia and nicotine use disorder, adjuvant bupropion and varenicline are recommended for reducing nicotine use and nicotine abstinence (strong/moderate recommendation). 5) In patients with schizophrenia and polydrug use disorder, second-generation over first-generation antipsychotic drugs and olanzapine over other second-generation antipsychotics are recommended to improve psychotic symptoms (moderate/weak recommendation).

Substantial evidence has confirmed the high comorbidity between Attention-Deficit/Hyperactivity Disorder (ADHD) and a substance use disorder (SUD). This review synthesizes the pharmacological and psychosocial interventions conducted in ADHD and SUDs, and provides clinical recommendations using the GRADE approach. Our results suggest: 1) In patients with ADHD and alcohol use, atomoxetine is recommended to reduce ADHD symptoms (weak recommendation) and alcohol craving (weak recommendation). 2) In patients with ADHD and cannabis use disorder, atomoxetine is recommended to improve ADHD symptoms (weak recommendation), not to reduce cannabis use (weak recommendation). 3) In patients with ADHD and cocaine use disorder, methylphenidate is not recommended to improve ADHD symptoms or to reduce cocaine use (weak recommendation). 4) In patients with ADHD and comorbid nicotine use disorder, methylphenidate is recommended to improve ADHD symptoms (weak recommendation). Psychoestimulants, such as methylphenidate or lisdexamfetamine dimesylate, are not recommended to reduce nicotine use (weak recommendation). 5) Regarding patients with ADHD and any SUD, the use of psychostimulants is recommended to improve ADHD symptoms (weak recommendation), not to reduce substance use (weak recommendation) or to improve retention to treatment (strong recommendation). In these patients, the use of atomoxetine is recommended to improve ADHD symptoms (weak recommendation), not to decrease substance use (weak recommendation) or to improve retention to treatment (strong recommendation). Atomoxetine and psychostimulants appear to be safe in patients with any SUD (strong recommendation). Our review suggests the need for more research in this area and for larger, multisite, randomized studies to provide more definite and conclusive evidence.

BACKGROUND: High placebo response in ADHD can reduce medication-placebo differences, jeopardizing the development of new medicines. This research aims to 1) determine placebo response in ADHD, 2) compare the accuracy of meta-regression and MetaForest in predicting placebo response, and 3) determine the covariates associated with placebo response. METHODS: A systematic review with meta-analysis (SRMA) of RPCCTs investigating pharmacological interventions for ADHD was performed. Placebo response was defined as the change from baseline in ADHD symptom severity assessed according to the 18-item, clinician-rated, DSM-based rating scale. The effect of study design-, intervention- and patient-related covariates in predicting placebo response was studied by means of meta-regression and MetaForest. RESULTS: Ninety-four studies including 6,614 patients randomized to placebo were analysed. Overall, placebo response was -8.9 points, representing a 23.1% reduction in the severity of ADHD symptoms. Cross-validated accuracy metrics for meta-regression were R 2 = 0.0012 and RMSE = 3.3219 for meta-regression and 0.0382 and 3.2599 for MetaForest. Placebo response amongst ADHD patients increased by 63% between 2001 and 2020 and was larger in the US than in other regions of the world. CONCLUSIONS: Strong placebo response was found in ADHD patients. Both meta-regression and MetaForest showed poor performance in predicting placebo response. ADHD symptom improvement with placebo has markedly increased over the last two decades and is grater in the US than the rest of the world.

Background Diagnostic mammography projections (DxMM) have been traditionally used in the assessment of women recalled after a suspicious screening mammogram. Digital breast tomosynthesis (DBT) reduces the tissue overlap effect, thus improving image assessment. Some studies have suggested DBT might replace DxMM with at least equivalent performance. Objective To evaluate the replacement of DxMM with DBT in women recalled at screening. Methods We searched PubMed, EMBASE, and the Cochrane Library databases to identify diagnostic paired cohort studies or RCTs comparing DBT vs DxMM, published in English that: reported accuracy outcomes, recruited women recalled for assessment at mammography screening, and included a reference standard. Subgroup analysis was performed over lesion characteristics. We provided pooled accuracy estimates and differences between tests using a quadrivariate model. We assessed the certainty of the evidence using the GRADE approach. Results We included ten studies that reported specificity and sensitivity. One study included 7060 women while the remaining included between 52 and 738 women. DBT compared with DxMM showed a pooled difference for the sensitivity of 2% (95% CI 1%-3%) and a pooled difference for the specificity of 6% (95%CI 2%-11%). Restricting the analysis to the six studies that included women with microcalcification lesions gave similar results. In the context of a prevalence of 21% of breast cancer (BC) in recalled women, DBT probably detects 4 (95% CI 2-6) more BC cases and has 47 (95%CI 16-87) fewer false-positive results per 1000 assessments. The certainty of the evidence was moderate due to risk of bias. Conclusion The evidence in the assessment of screen-recalled findings with DBT is sparse and of moderate certainty. DBT probably has higher sensitivity and specificity than DxMM. Women, health care providers and policymakers might value as relevant the reduction of false-positive results and related fewer invasive diagnostic procedures with DBT, without missing BC cases.

Objective: To determine the relationship between treatment duration and the efficacy of pharmacological treatment for reducing ADHD symptoms. Method: We conducted a systematic review of randomized, double-blind, placebo-controlled clinical trials investigating the efficacy of pharmacological interventions in patients with ADHD. The last bibliographic search was performed in April 15, 2019. The effect of treatment duration on efficacy was studied using meta-regression. Results: A total of 87 studies lasting from 3 to 28 weeks were included. Pharmacological treatment improved ADHD symptom severity by -7.35 points. Treatment duration did not moderate the efficacy of pharmacological treatment. Consistent results were found for psychostimulant drugs, methylphenidate, amphetamine derivatives, atomoxetine, and a2-agonists. A negative correlation was found between baseline ADHD severity efficacy (Coefficient = -.250, p = .013). Conclusion: The efficacy of pharmacological treatment for ADHD remains stable over time. A greater efficacy in more severe patients is suggested.

AimsTo perform a systematic review of observational studies on the epidemiology of drug-related death (DRD) in patients requiring hospitalisation or while hospitalised (hospital-acquired DRD). MethodsWe conducted a systematic review of observational studies investigating the occurrence rate of DRD episodes among deceased inpatients. Two independent researchers assessed eligibility criteria, extracted data and evaluated the risk of bias. Both quality assessment and meta-analysis were performed. ResultsFrom 1351 identified potential studies, 6 retrospective studies were included. DRD occurrences rates were 7.3% (95% confidence interval [CI] 4.1-12.5) among deceased inpatients and 0.13% (95% CI 0.04-0.40) among hospitalised patients. During hospitalisation, acquired-DRD represented 2.7% (95% CI 1.0-6.9) of inpatient deaths and occurred in 0.05% (95% CI 0.01-0.23) of hospitalised patients. However, these estimates have to be viewed with caution because there was significant heterogeneity (I-2 >97%). None of the studies were considered to be at high risk of bias according to the criteria of the NIH Quality Assessment Tool. The most common adverse drug reactions related to death were haemorrhages due to antithrombotic drugs (39%, 95% CI 26.5-53.2) and infections in drug-immunosuppressed patients (27.5%, 95% CI 16.7-41.7). ConclusionWe found that the DRD occurrence rate of deceased hospital inpatients has been infrequently studied in Europe. Our findings suggest that drugs are an important cause of death in hospitals. The limited number of studies in European countries stresses the need for more research in this area.

Description: The European Commission Initiative for Breast Cancer Screening and Diagnosis guidelines (European Breast Guidelines) are coordinated by the European Commission's Joint Research Centre. The target audience for the guidelines includes women, health professionals, and policymakers. Methods: An international guideline panel of 28 multidisciplinary members, including patients, developed questions and corresponding recommendations that were informed by systematic reviews of the evidence conducted between March 2016 and December 2018. GRADE (Grading of Recommendations Assessment, Development and Evaluation) Evidence to Decision frameworks were used to structure the process and minimize the influence of competing interests by enhancing transparency. Questions and recommendations, expressed as strong or conditional, focused on outcomes that matter to women and provided a rating of the certainty of evidence. Recommendations: This synopsis of the European Breast Guidelines provides recommendations regarding organized screening programs for women aged 40 to 75 years who are at average risk. The recommendations address digital mammography screening and the addition of hand-held ultrasonography, automated breast ultrasonography, or magnetic resonance imaging compared with mammography alone. The recommendations also discuss the frequency of screening and inform decision making for women at average risk who are recalled for suspicious lesions or who have high breast density.