High accuracy of a blood ctDNA-based multimodal test to detect colorectal cancer.

BACKGROUND: Detection of circulating tumor DNA (ctDNA) is a minimally invasive and convenient blood-based screening strategy that may increase effectiveness of colorectal cancer (CRC) screening. PATIENTS AND METHODS: A novel multimodal ctDNA-based blood assay that integrates genomics, epigenomics and fragmentomics, as well as proteomics in a refined version, was tested in blood samples from two cohorts: (i) consecutive fecal immunochemical test (FIT)-positive individuals from the CRC Barcelona stool-based screening program; (ii) patients diagnosed with CRC. Primary endpoint was the performance of the test to detect CRC at different tumor-node-metastasis (TNM) stages. Secondary endpoint was the ability of the test to detect advanced precancerous lesions (advanced adenoma or advanced serrated lesion). RESULTS: A total of 623 blood samples were analyzed in the primary analysis. Sensitivity and specificity of the assay to detect CRC was 93% and 90%, respectively. The sensitivity of CRC detection according to TNM stages was 84% for stage I, 94% for stage II and 96% for stage III (70/73) (P< 0.024). Sensitivity to detect advanced precancerous lesions was 23% with a refined version of the test (including protein and updating bioinformatic thresholding). CONCLUSION: A blood-based multimodal ctDNA assay detected CRC with high accuracy. This minimally invasive, accessible and convenient assay may help to increase the effectiveness of CRC screening.

Relationship between obsessive compulsive symptomatology and severity of psychotic symptoms in schizophrenia: Meta-analysis and meta-regression analysis.

BACKGROUND: Schizophrenia patients often show obsessive-compulsive symptoms (OCS) and obsessive-compulsive disorder (OCD) and their presence has been associated with poorer prognosis. However, the impact of OCS/OCD on psychotic severity remains unclear. The aim of this study is twofold: 1) to investigate the effect of OCS/OCD on the severity of positive, negative, and global psychotic symptoms of schizophrenia patients and 2) to analyze the effect of patient and study-related covariates on moderating this relationship. METHODS: A systematic review and meta-analysis (SRMA) of studies comparing the severity of psychotic symptoms among schizophrenia patients with and without OCS/OCD was performed. Standardized mean difference (SMD) was calculated for positive, negative, and global psychotic symptoms. The difference of SMD (Diff SMD) was calculated to analyze the effect of covariates on study outcomes using meta-regression. RESULTS: Sixty-seven studies involving 7740 patients were included. Patients with schizophrenia and OCS/OCD showed a slightly higher severity of positive (SMD = 0.17, p value = 0.0089) and global psychotic symptoms (SMD = 0.24, p value = 0.0104) than patients without OCS/OCD but no differences in negative symptoms were found between groups (SMD = 0.11, p value = 0.0367). Only one covariate "proportion of patients without antipsychotics (AP)" was found to modify the effect on psychotic severity (Diff SMD = -0.008, p value = 0.002). CONCLUSIONS: Comorbid OCS/OCD in schizophrenia has, at most, a minor impact on psychotic severity. Variability in this effect was considerable and was poorly explained by the covariates analyzed.

Perceptions from nurses, surgeons, and anesthetists about the use and benefits of the surgical checklist in a teaching hospital.

OBJECTIVE: To assess attitudes and perceptions from nursing staff, surgeons and anesthetists about compliance, utility, and impact on patient's safety of the surgical checklist in a teaching hospital. We also aimed to identify improvement opportunities for strengthening the usefulness of the checklist in the operating theater. METHODS: We carried out a questionnaire-based an observational cross-sectional study. A questionnaire was distributed to operating room staff, including nursing staff, surgeons, and anesthetists. In addition to the information about surgical checklist, We also collected information regarding years of experience in the operating theater. Fisher's exact was used to compare proportions in each statement. Group discussion meetings with key professionals were held to jointly assess the results, propose improvement actions, and evaluate their feasibility. RESULTS: The overall response rate was 36.2% (131/362). Nursing staff was perceived as the most supportive group in the use of surgical checklist. A 64.3% of surgeons considered that using the checklist prevented adverse events vs 84.2% and 85.7% among anesthetists and nurses, respectively; p=0.028. Junior staff showed a supportive attitude toward the use of surgical checklist, considering it as a tool that gives them confidence. We ended up with a list of improvement actions aiming at strengthening the surgical checklist reliability and compliance. CONCLUSIONS: The perception of the surgical checklist usefulness as a tool to prevent adverse events was moderate among surgeons, but well appreciated by junior staff. Nursing staff were especially critical regarding compliance and support by other professionals. To reinforce the usefulness perception of the surgical checklist it is needed to increase the involvement of all professionals, especially senior staff and surgical leaders.

[Factors that influence compliance with hand hygiene in healthcare professionals: A concept mapping study]. / Factores que influyen en el cumplimiento de la higiene de manos en profesionales sanitarios: un estudio de mapeo de conceptos.

OBJECTIVE: To identify factors that may influence hand hygiene compliance by professional category and clinical department. MATERIALS AND METHODS: Use was made of concept mapping methodology, a tool that combines a qualitative analysis with a quantitative statistical analysis, in order to identify the most influential and important factors for the fulfilment of hand hygiene in 2 clinical departments (Infectious and General Surgery) of the Hospital del Mar. RESULTS: The study included a total of 42 volunteer professionals from General Surgery (6 doctors and 10 nurses) and from Infectious Diseases (11 doctors and 10 nurses) clinical departments, as well as 5 hospital porters. High correlations of influential and important factors for hand hygiene compliance were observed between nurses and doctors in the Infectious Diseases Department (r=0.93 vs. r=0.69, respectively). In contrast, the correlation was lower among surgical professionals (r=-0.17 for influence and r=0.51 for importance). Professionals identified the most influential factors in compliance as training and adequate resources, taking into account professional category and clinical department. CONCLUSION: The design of interventions to improve compliance with hand hygiene should take into account the perceptions of different professionals in order to adapt actions to each professional group.

Detection of incident breast and colorectal cancer cases from an administrative healthcare database in Catalonia, Spain.

OBJECTIVE: To validate the Catalan minimum basic data set (MBDS) of hospital discharges as an information source for detecting incident breast (BC) and colorectal cancer (CRC), against the Hospital del Mar Cancer Registry (RTHMar) in Barcelona (Spain) as the gold standard. METHODS: Using ASEDAT software (Analysis, Selection and Extraction of Tumour Data), we identified Catalan public hospital discharge abstracts in patients with a first-time diagnosis of BC and CRC in the years 2005, 2008, and 2011, aggregated by unique patient identifiers and sorted by date. Once merged with the RTHMar database and anonymized, tumour-specific algorithms were validated to extract data on incident cases, tumour stage, surgical treatment, and date of incidence. RESULTS: MBDS had a respective sensitivity and positive predictive value (PPV) of 78.0% (564/723) and 90.5% (564/623) for BC case detection; and 83.9% (387/461) and 94.9% (387/408) for CRC case detection. The staging algorithms overestimated the proportion of local-stage cases and underestimated the regional-stage cases in both cancers. When loco-regional stage and surgery were combined, sensitivity and PPV reached 98.3% and 99.8%, respectively, for BC and 96.4% and 98.4% for CRC. The differences between dates of incidence between RTHMar and MBDS were greater for BC cases without initial surgery, whereas they were generally smaller and homogeneous for CRC cases. CONCLUSIONS: The MBDS is a valid and efficient instrument to improve the completeness of a hospital-based cancer registry (HBCR), particularly in BC and CRC, which require hospitalization and are predominantly surgical.

Dissemination of health technologies: Trends in the use of diagnostic test in breast cancer screening.

OBJECTIVE: To analyse trends in the use of diagnostic test in breast cancer screening programs in Spain. MATERIALS AND METHODS: Retrospective study of 542,695 women who had undergone at least one screening mammogram in any of the screening centres of three administrative regions in Spain, between 1996 and 2011. Process measures were: overall recall rate, overall invasive test rate, and rates of each type of invasive test (fine-needle aspiration biopsy, core-needle biopsy and surgical biopsy). As results measures were included detection of benign lesions rate, ductal in situ cancer rate and invasive cancer rate. Adjusted by age rates were estimated year by year for each measure and, also, the annual percent of change and its corresponding joint points. RESULTS: Core-needle biopsy rates decreased between 1996 and 1999 and changed trends in 1999-2011 with an increase of 4.9% per year. Overall recall rate declined by 4.6% from 1999 to 2004, invasive test rate declined between 1996 and 2004 by 24.3%. Fine-needle aspiration biopsy rate changes were: a 22.4% declined per year (1996-1998), and 13.5% declined per year (1998-2005). Benign lesions rate decreased from 1996 to 2011, 21.4% per year (1996-2001) and 6.0% (2001-2011). Ductal carcinoma in situ and invasive cancer had no-statistically significant changes. CONCLUSION: The introduction of core-needle biopsy was slow and not concurrent with the reduction in the use of other diagnostic tests, but also represented a reduction in the rate of overall diagnostic tests and in the detection rate of benigns lesions without affecting the cancer detection rates.

Discontinuation of pharmacological treatment of children and adolescents with attention deficit hyperactivity disorder: meta-analysis of 63 studies enrolling 11,788 patients.

BACKGROUND: The risk-benefit balance of pharmacological treatment for children and adolescents with ADHD and the factors that moderate this relationship are unclear. METHODS: A systematic review and meta-analysis of randomised, placebo-controlled clinical trials (RPCCTs) investigating the efficacy of pharmacological treatment in children or adolescents with ADHD was carried out. Meta-analysis of treatment discontinuation, clinician-, parent- and teacher-rated efficacy and adverse events was performed. The effect of covariates was studied. RESULTS: Sixty-three studies were included. Ten drugs were investigated, with atomoxetine and methylphenidate the most frequently studied. RPCCTs had mostly a short duration (7.9 weeks). All-cause treatment discontinuation was lower with pharmacological treatment than placebo (OR = 0.68). Pharmacological treatment was more efficacious than placebo independently of the rater (clinician, standardised mean difference (SMD) 0.74; parent, SMD = 0.63; or teacher, SMD = 0.75). Evidence of publication bias was found for clinician-rated efficacy, especially in industry-sponsored RPCCT. Psychostimulants showed a higher efficacy and were associated with a better outcome on treatment discontinuation than non-stimulant drugs. Efficacy was smaller in RPCCTs for which a psychiatric comorbid disorder was an inclusion criterion, was larger in studies with a commercial sponsorship and showed a negative association with treatment length. CONCLUSIONS: In the short term, pharmacological treatment provides moderate-high symptom relief, is safe and shows lower treatment discontinuation than placebo, suggesting a suitable risk-benefit balance, particularly with psychostimulants. The efficacy is lower in patients with a comorbid psychiatric disorder and should be assessed periodically, as it appears to reduce over time. Publication bias of clinician-rated efficacy in studies with a commercial sponsor is suggested.

Cumulative risk of breast cancer screening outcomes according to the presence of previous benign breast disease and family history of breast cancer: supporting personalised screening.

BACKGROUND: Our aim was to assess the cumulative risk of false-positive screening results, screen-detected cancer, and interval breast cancer in mammography screening among women with and without a previous benign breast disease and a family history of breast cancer. METHODS: The cohort included 42 928 women first screened at the age of 50-51 years at three areas of the Spanish Screening Programme (Girona, and two areas in Barcelona) between 1996 and 2011, and followed up until December 2012. We used discrete-time survival models to estimate the cumulative risk of each screening outcome over 10 biennial screening exams. RESULTS: The cumulative risk of false-positive results, screen-detected breast cancer, and interval cancer was 36.6, 5.3, and 1.4 for women with a previous benign breast disease, 24.1, 6.8, and 1.6% for women with a family history of breast cancer, 37.9, 9.0, and 3.2%; for women with both a previous benign breast disease and a family history, and 23.1, 3.2, and 0.9% for women without either of these antecedents, respectively. CONCLUSIONS: Women with a benign breast disease or a family history of breast cancer had an increased cumulative risk of favourable and unfavourable screening outcomes than women without these characteristics. A family history of breast cancer did not increase the cumulative risk of false-positive results. Identifying different risk profiles among screening participants provides useful information to stratify women according to their individualised risk when personalised screening strategies are discussed.

Clinical guideline for the treatment of dual pathology in the adult population.

Editorial del vol 28-1.

Efficacy, safety and variability in pharmacotherapy for adults with attention deficit hyperactivity disorder: a meta-analysis and meta-regression in over 9000 patients.

RATIONALE: The factors underlying the variability in the results of randomized, placebo-controlled clinical trials (RPCCT) assessing pharmacological interventions for adults with attention deficit hyperactivity disorder (ADHD) are not fully understood. METHODS: A systematic review and meta-analysis of RPCCT comparing pharmacological treatment and placebo in adults with ADHD was carried out. The study outcomes were all-cause treatment discontinuation, efficacy on ADHD symptoms, and safety. Patient-, intervention-, and study design-related covariates were collected. Meta-regression methods were applied. RESULTS: Forty-four studies involving 9952 patients were included. All-cause treatment discontinuation was slightly higher with pharmacological treatment than with placebo (odds ratio (OR) = 1.18; 95 % confidence interval (CI) 1.02, 1.36; p = 0.003). A better outcome on all-cause treatment discontinuation was observed in studies that provided concomitant psychotherapy when compared to those that did not (rate of OR (ROR) = 0.68, p = 0.048). Pharmacological treatment was efficacious for reducing ADHD symptoms (standardized mean difference (SMD) = 0.45; 95 % CI 0.37, 0.52; p < 0.00001), with stronger intervention effects found in studies investigating stimulant drugs (difference of SMD (Diff SMD) = 0.18, p = 0.017), in shorter studies (Diff SMD = -0.01, p = 0.044), and when clinician-rated scales were used (Diff SMD = 0.44, p < 0.0001). Pharmacological treatment was associated with more frequent adverse events (AEs) (OR = 2.29; 95 % CI 1.97, 2.66; p = 0.006). Studies with a lead-in phase and with a higher proportion of patients previously treated with stimulants were associated with a better safety outcome (ROR = 0.59, p = 0.017; ROR = 0.98, p = 0.036, respectively). CONCLUSION: Pharmacological treatment provides mild symptom improvement but is associated with frequent AEs and higher treatment discontinuation than placebo, particularly when no concomitant psychotherapy is administered. Stimulants appear more efficacious than non-stimulant drugs and the former should be preferred over the latter. The efficacy of pharmacological treatment should be monitored over time because it may decrease progressively.

Pharmacological treatment of attention deficit hyperactivity disorder with co-morbid drug dependence.

BACKGROUND: Drug dependence is frequent in patients with attention deficit hyperactivity disorder (ADHD). Nevertheless, the efficacy and safety of pharmacological treatments in this population are unclear. METHODS: A systematic review with meta-analysis was performed. Randomised placebo-controlled clinical trials investigating the efficacy of pharmacological treatment in patients with co-occurring ADHD and substance use disorder (SUD) were included. ADHD symptom severity, drug abstinence and all-cause treatment discontinuation were the primary study endpoints. The effects of patient-, intervention- and study-related covariates over the primary outcomes were investigated by means of meta-regression. RESULTS: Thirteen studies were included, enrolling a total of 1,271 patients. A small to moderate reduction of ADHD symptoms was found. Meta-regression analysis identified the presence of a lead-in period as a covariate associated with reduced efficacy. Conversely, no beneficial effect was observed either on drug abstinence or treatment discontinuation. The efficacy on ADHD symptoms was smaller in studies with a lead-in period. A positive correlation between the efficacy for ADHD and that for SUD was found. CONCLUSIONS: The efficacy of pharmacological interventions for co-occurring ADHD and SUD has been little investigated. Mixed results were obtained: while pharmacological interventions improved ADHD symptoms, no beneficial effect on drug abstinence or on treatment discontinuation was noted. The strength of the recommendation of pharmacological treatment for co-occurring ADHD and SUD is therefore modest. The study was registered with the international prospective register of systematic reviews (PROSPERO): CRD 4212003414.

Desarrollo y validación de un algoritmo para identificar recidivas de cáncer a partir de bases de datos hospitalarias / Development and validation of an algorithm to identify cancer recurrences from hospital data bases

Objetivos. Los registros de tumores hospitalarios y las bases de datos hospitalarias son una fuente de información valiosa y eficiente para la investigación de recidivas de cáncer. El objetivo de este estudio fue desarrollar y validar algoritmos para identificar recidivas de cáncer de mama. Métodos. Estudio observacional retrospectivo de casos de cáncer de mama del registro de tumores de un centro hospitalario universitario de tercer nivel diagnosticados entre 2003 y 2009. A partir del cruce de bases de datos hospitalarias y la construcción de definiciones operativas se obtuvieron diferentes algoritmos de probable recidiva de cáncer con su correspondiente sensibilidad, especificidad, valor predictivo positivo y valor predictivo negativo. Resultados. Se identificaron 1.523 pacientes diagnosticados de cáncer entre 2003 y 2009. La solicitud de gammagrafía ósea tras 6 meses desde el primer tratamiento oncológico obtuvo la mayor sensibilidad (53,8%) y valor predictivo negativo (93,8%), y la realización de una prueba de anatomía patológica tras 6 meses desde el diagnóstico obtuvo la mayor especificidad (93,8%) y valor predictivo negativo (92,6%). La combinación de definiciones aumentó la especificidad y el valor predictivo positivo pero disminuyó la sensibilidad. Conclusiones. Se elaboraron diferentes algoritmos diagnósticos cuyas definiciones pueden ser útiles según los intereses y recursos del investigador. Un mayor valor predictivo positivo podría interesar para una estimación rápida del número de casos, y un mayor valor predictivo negativo para dar una estimación más exacta si se dispone de mayores recursos. Estos algoritmos se configuran como una herramienta versátil y adaptable a otros tumores y a las necesidades del investigador (AU)

Objectives. Hospital cancer registries and hospital databases are valuable and efficient sources of information for research into cancer recurrences. The aim of this study was to develop and validate algorithms for the detection of breast cancer recurrence. Methods. A retrospective observational study was conducted on breast cancer cases from the cancer registry of a third level university hospital diagnosed between 2003 and 2009. Different probable cancer recurrence algorithms were obtained by linking the hospital databases and the construction of several operational definitions, with their corresponding sensitivity, specificity, positive predictive value and negative predictive value. Results. A total of 1,523 patients were diagnosed of breast cancer between 2003 and 2009. A request for bone gammagraphy after 6 months from the first oncological treatment showed the highest sensitivity (53.8%) and negative predictive value (93.8%), and a pathology test after 6 months after the diagnosis showed the highest specificity (93.8%) and negative predictive value (92.6%). The combination of different definitions increased the specificity and the positive predictive value, but decreased the sensitivity. Conclusions. Several diagnostic algorithms were obtained, and the different definitions could be useful depending on the interest and resources of the researcher. A higher positive predictive value could be interesting for a quick estimation of the number of cases, and a higher negative predictive value for a more exact estimation if more resources are available. It is a versatile and adaptable tool for other types of tumors, as well as for the needs of the researcher (AU)

[Development and validation of an algorithm to identify cancer recurrences from hospital data bases]. / Desarrollo y validación de un algoritmo para identificar recidivas de cáncer a partir de bases de datos hospitalarias.

OBJECTIVES: Hospital cancer registries and hospital databases are valuable and efficient sources of information for research into cancer recurrences. The aim of this study was to develop and validate algorithms for the detection of breast cancer recurrence. METHODS: A retrospective observational study was conducted on breast cancer cases from the cancer registry of a third level university hospital diagnosed between 2003 and 2009. Different probable cancer recurrence algorithms were obtained by linking the hospital databases and the construction of several operational definitions, with their corresponding sensitivity, specificity, positive predictive value and negative predictive value. RESULTS: A total of 1,523 patients were diagnosed of breast cancer between 2003 and 2009. A request for bone gammagraphy after 6 months from the first oncological treatment showed the highest sensitivity (53.8%) and negative predictive value (93.8%), and a pathology test after 6 months after the diagnosis showed the highest specificity (93.8%) and negative predictive value (92.6%). The combination of different definitions increased the specificity and the positive predictive value, but decreased the sensitivity. CONCLUSIONS: Several diagnostic algorithms were obtained, and the different definitions could be useful depending on the interest and resources of the researcher. A higher positive predictive value could be interesting for a quick estimation of the number of cases, and a higher negative predictive value for a more exact estimation if more resources are available. It is a versatile and adaptable tool for other types of tumors, as well as for the needs of the researcher.

Temporal trends in canine leishmaniosis in the Balearic Islands (Spain): a veterinary questionnaire. Prospective canine leishmaniosis survey and entomological studies conducted on the Island of Minorca, 20 years after first data were obtained.

Leishmaniosis is present in the Mediterranean region of Europe, where Leishmania infantum is responsible for the disease, dogs are the main reservoir, and sand flies of the Phlebotomus genus, subgenus Larroussius, are proven vectors. Some areas, including Minorca in the Balearic Islands, are considered free of the disease, despite the presence of vectors. However, in the context of the current expansion of canine leishmaniosis in parts of Europe, an epidemiological study using a veterinary questionnaire was carried out to establish the current situation of the disease in the Balearic Islands. While 50% of veterinarians thought that the incidence of canine leishmaniosis had not changed over time, 26.2% perceived an increasing trend, mainly those from Minorca, where most of the veterinarians polled (88.1%) considered the new diagnosed cases as autochthonous. A cross-sectional serological study performed in this island gave a seroprevalence rate of 24%. Seroprevalence among animals of local origin and with no history of movements to endemic areas was 31%. The presence of autochthonous canine leishmaniosis in Minorca was not correlated with an increase in vector density. The environmental and climatic factors that influenced the distribution and density of Phlebotomus perniciosus on the island and the possible causes of the apparent emergence of canine leishmaniosis in Minorca are discussed.

Cumulative risk of cancer detection in breast cancer screening by protocol strategy.

BACKGROUND: There is little information on the individual risk of screen-detected cancer in women over successive participations. This study aimed to estimate the 10-year cumulative breast cancer detection risk (ductal carcinoma in situ and invasive carcinoma) in a population-based breast cancer screening program according to distinct protocol strategies. A further aim was to determine which strategies maximized the cancer detection risk and how this risk was affected by the radiologic protocol variables. METHODS: Data were drawn from a retrospective cohort of women from nine population-based screening programs in Spain from 1990 to 2006. We used logistic regression with discrete intervals to estimate the cumulative detection risk at 10 years of follow-up according to radiologic variables and protocol strategies. RESULTS: In women starting screening at the age of 45-59 years, the cumulative risk of screen-detected cancer at 10 years ranged from 11.11 to 16.71 per 1,000 participants according to the protocol strategy. The cumulative detection risk for overall cancer and invasive cancer was the highest with strategies using digital mammography, double reading, and two projections (16.71 and 12.07 ‰, respectively). For ductal carcinoma in situ, cumulative detection risk was the highest with strategies using screen-film, double reading, and two projections (2.32 ‰). The risk was the lowest with strategies using screen-film mammography, single reading, and two projections. CONCLUSIONS: This study found that at least eleven cancers are detected per 1,000 women screened in the first 10 years of follow-up. Enhanced knowledge of the variability in cumulative risk of screen-detected cancer could improve protocol strategies.

Risk factors for cocaine-induced psychosis in cocaine-dependent patients.

Cocaine consumption can induce transient psychotic symptoms, expressed as paranoia or hallucinations. Cocaine induced psychosis (CIP) is common but not developed in all cases. This is the first European study on the relationship between CIP, consumption pattern variables and personality disorders. We evaluated 173 cocaine-dependent patients over 18 years; mostly males, whose average age was 33.6 years (SD=7.8). Patients attending an outpatient addictions department were enrolled in the study and subsequently systematically evaluated using SCID I and SCID II interviews for comorbid disorders, a clinical interview for psychotic symptoms and EuropASI for severity of addiction. A high proportion of cocaine dependent patients reported psychotic symptoms under the influence of cocaine (53.8%), the most frequently reported being paranoid beliefs and suspiciousness (43.9%). A logistic regression analysis was performed, finding that a model consisting of amount of cocaine consumption, presence of an antisocial personality disorder and cannabis dependence history had 66.2% sensitivity 75.8% specificity predicting the presence of CIP. In our conclusions, we discuss the relevance of evaluating CIP in all cocaine dependent-patients, and particularly in those fulfilling the clinical profile derived from our results. These findings could be useful for a clinical approach to the risks of psychotic states in cocaine-dependent patients.