Drastic reduction of false positive species in samples of insects by intersecting the default output of two popular metagenomic classifiers.

The use of high-throughput sequencing to recover short DNA reads of many species has been widely applied on biodiversity studies, either as amplicon metabarcoding or shotgun metagenomics. These reads are assigned to taxa using classifiers. However, for different reasons, the results often contain many false positives. Here we focus on the reduction of false positive species attributable to the classifiers. We benchmarked two popular classifiers, BLASTn followed by MEGAN6 (BM) and Kraken2 (K2), to analyse shotgun sequenced artificial single-species samples of insects. To reduce the number of misclassified reads, we combined the output of the two classifiers in two different ways: (1) by keeping only the reads that were attributed to the same species by both classifiers (intersection approach); and (2) by keeping the reads assigned to some species by any classifier (union approach). In addition, we applied an analytical detection limit to further reduce the number of false positives species. As expected, both metagenomic classifiers used with default parameters generated an unacceptably high number of misidentified species (tens with BM, hundreds with K2). The false positive species were not necessarily phylogenetically close, as some of them belonged to different orders of insects. The union approach failed to reduce the number of false positives, but the intersection approach got rid of most of them. The addition of an analytic detection limit of 0.001 further reduced the number to ca. 0.5 false positive species per sample. The misidentification of species by most classifiers hampers the confidence of the DNA-based methods for assessing the biodiversity of biological samples. Our approach to alleviate the problem is straightforward and significantly reduced the number of reported false positive species.

Relative species abundance estimation in artificial mixtures of insects using mito-metagenomics and a correction factor for the mitochondrial DNA copy number.

Mito-metagenomics (MMG) is becoming an alternative to amplicon metabarcoding for the assessment of biodiversity in complex biological samples using high-throughput sequencing. Whereas MMG overcomes the biases introduced by the PCR step in the generation of amplicons, it is not yet a technique free of shortcomings. First, as the reads are obtained from shotgun sequencing, a very low proportion of reads map into the mitogenomes, so a high sequencing effort is needed. Second, as the number of mitogenomes per cell can vary among species, the relative species abundance (RSA) in a mixture could be wrongly estimated. Here, we challenge the MMG method to estimate the RSA using artificial libraries of 17 insect species whose complete genomes are available on public repositories. With fresh specimens of these species, we created single-species libraries to calibrate the bioinformatic pipeline and mixed-species libraries to estimate the RSA. Our results showed that the MMG approach confidently recovers the species list of the mixtures, even when they contain congeneric species. The method was also able to estimate the abundance of a species across different samples (within-species estimation) but failed to estimate the RSA within a single sample (across-species estimation) unless a correction factor accounting for the variable number of mitogenomes per cell was used. To estimate this correction factor, we used the proportion of reads mapping into mitogenomes in the single-species libraries and the lengths of the whole genomes and mitogenomes.

Development of a multiprimer metabarcoding approach to understanding trophic interactions in agroecosystems.

To understand trophic interactions and the precise ecological role of each predatory species, it is important to know which arthropod and plant resources are used by generalist predators in agroecosystems. Molecular approaches, such as the use of high-throughput sequencing (HTS), play a key role in identifying these resources. This study develops a multiprimer metabarcoding approach for screening the most common trophic interactions of two predatory arthropods with contrasting morphologies, Rhagonycha fulva (Coleoptera: Cantharidae) and Anthocoris nemoralis (Hemiptera: Anthocoridae) collected from a peach crop. To reduce the time and cost of this metabarcoding approach, we first evaluated the effect of using two different predator-pools of different size (10 and 23 individuals of the same species). We also used our system to analyze the performance of one and two primer pairs in the same library. Our results show that the analysis of 23 individuals together with the use of two primer pairs in the same library optimize the HTS analysis. Using these best-performing conditions, we then analyzed the entire bodies of field-collected predators as well as the washing solutions used to clean the insect bodies. We were able to identify both gut content (i.e., diet) and external pollen load (i.e., on the insects' bodies). This study also demonstrates the importance of washing predatory insects' bodies prior to HTS analysis when the target species have a considerable size (>10 mm) and hairy structures. This metabarcoding approach has significant potential for the study of trophic links in agriculture, revealing expected and unexpected trophic relationships.

Genotype by sequencing: An alternative new method to amplicon metabarcoding and shotgun metagenomics for the assessment of eukaryote biodiversity.

The use of high-throughput DNA sequencing (HTS) has revolutionized the assessment of biodiversity in plant and animal communities. There are two main approaches to estimate the identity and the relative species abundance (RSA) in complex mixtures using HTS: amplicon metabarcoding and shotgun metagenomics. While amplicon metabarcoding targets one or a few genomic regions, shotgun metagenomics randomly explores the genome of the species. In this issue of Molecular Ecology Resources, Wagemaker et al. (2021) present a new method, multi-species Genotyping by Sequencing (msGBS), as an alternative middle ground between metabarcoding and metagenomics. They apply the technique to mixtures of plant roots and report the remarkable capacity of msGBS to estimate the RSA. If validated in other laboratories and biological communities, msGBS might become a third method to explore the biodiversity of biological communities, especially of plants, where current techniques are struggling to get sufficient taxonomic resolution.

Ten-Year Follow-Up of Clinical Governance Implementation in Primary Care: Improving Screening, Diagnosis and Control of Cardiovascular Risk Factors.

Current improvement strategies for the control of cardiovascular risk factors (CRFs) in Europe are based on quality management policies. With the aim of understanding the effect of interventions delivered by primary healthcare systems, we evaluated the impact of clinical governance on cardiovascular health after ten years of implementation in Catalonia. A cohort study that included 1878 patients was conducted in 19 primary care centres (PCCs). Audits that comprised 13 cardiovascular health indicators were performed and general practitioners received periodic (annual, biannual or monthly) feedback about their clinical practice. We evaluated improvement in screening, diagnosis and control of the main CRFs and the effects of the feedback on cardiovascular risk (CR), incidence of cardiovascular disease (CVD) and mortality, comparing baseline data with data at the end of the study (after a 10-year follow-up). The impact of the intervention was assessed globally and with respect to feedback frequency. General improvement was observed in screening, percentage of diagnoses and control of CRFs. At the end of the study, few clinically significant differences in CRFs were observed between groups. However, the reduction in CR was greater in the group receiving high frequency feedback, specifically in relation to smoking and control of diabetes and cholesterol (Low Density Lipoprotein (LDL) and High Density Lipoprotein (HDL)). A protective effect of having a cardiovascular event (hazard ratio (HR) = 0.64, 95% confidence interval (CI) = 0.44-0.94) or death (HR = 0.55, 95% CI = 0.35-0.88) was observed in patients from centres where general practitioners received high frequency feedback. Additionally, these PCCs presented improved cardiovascular health indicators and lower incidence and mortality by CVD, illustrating the impact of this intervention.

The choice of universal primers and the characteristics of the species mixture determine when DNA metabarcoding can be quantitative.

DNA metabarcoding is a technique used to survey biodiversity in many ecological settings, but there are doubts about whether it can provide quantitative results, that is, the proportions of each species in the mixture as opposed to a species list. While there are several experimental studies that report quantitative metabarcoding results, there are a similar number that fail to do so. Here, we provide the rationale to understand under what circumstances the technique can be quantitative. In essence, we simulate a mixture of DNA of S species with a defined initial abundance distribution. In the simulated PCR, each species increases its concentration following a certain amplification efficiency. The final DNA concentration will reflect the initial one when the efficiency is similar for all species; otherwise, the initial and final DNA concentrations would be poorly related. Although there are many known factors that modulate amplification efficiency, we focused on the number of primer-template mismatches, arguably the most important one. We used 15 common primers pairs targeting the mitochondrial COI region and the mitogenomes of ca. 1,200 insect species. The results showed that some primers pairs produced quantitative results under most circumstances, whereas some other primers failed to do so. In conclusion, depending on the primer pair used in the PCR amplification and on the characteristics of the mixture analysed (i.e., high species richness, low evenness), DNA metabarcoding can provide a quantitative estimate of the relative abundances of different species.

Impact of depression and/or anxiety on the presentation of cardiovascular events in a cohort with metabolic syndrome. StreX project: Five years of follow-up.

OBJECTIVES: To determine the role of anxiety and depression on the incidence of cardiovascular events (CVE) in a Catalonian population with metabolic syndrome (MetS) over a five-year follow-up according to the number/type of MetS criteria. METHODS: Prospective study to determine the incidence of CVE according to the presence of anxiety and depression disorders among individuals with different combinations of clinical traits of the MetS. SETTING: Primary Care, Catalonia (Spain). SUBJECTS: 35-75 years old fulfilling MetS criteria without CVE at the initiation of follow-up (2009). We studied 16 MetS phenotypes [NCEP-ATPIII criteria] based on the presence of depression/anxiety. The primary endpoint was the incidence of CVE at five years. RESULTS: We analyzed 401,743 people with MetS (17.2% of the population); 8.7% had depression, 16.0% anxiety and 3.8% both. 14.5% consumed antidepressants and 20.8% tranquilizers. At the 5-year follow-up, the incidence of CVE was 5.5%, being 6.4% in men and 4.4% in women. On comparing individuals with and without depression the incidence of CVE was 6.7% vs. 5.3%, respectively (p<0.01), being 5.5% in both groups in relation to anxiety. CONCLUSION: Depression and anxiety play a role in the poor prognosis of patients with MetS. In Catalonia, the two predominant MetS phenotypes do not include obesity as a criterion.

[Lesions Detected in Six Spanish Colorectal Cancer Screening Population Based Programmes. CRIBEA Project. Spain]. / Lesiones detectadas en seis programas poblacionales de cribado de cáncer colorrectal en España. Proyecto CRIBEA.

OBJECTIVE: In this study, the results of six Colorectal Cancer Screening Population Programmes are shown (Catalonia, Valence, Murcia, Cantabria, the Basque Country and the Canary Islands collected between 2005 and 2012. These programmes use the faeces occult blood test (FOBt) biennial. Objective: To determine and compare the results of lesions detected by the programmes, participation, sex, age and test used. METHODS: Retrospective cohort study based on people invited, aged between 50-74 years, in at least a complete round. Lesions considered: Advanced Adenomas (AA), Colorectal Invasive Cancer (CRC) and both of them, known as Advanced Neoplasia (AN). Logistic Regression and time trends are used. RESULTS: 1,995,719 of invitations registered, with an average participation-rate of 46.7%. 21,228 Advanced Neoplasias (2,813 CRC and 18,415 AA). Differences in detection rates observed between programmes (varying from 15.1‰ to 35.8‰ between participants). Participation rates were related to lesions' detection rates (OR 1.25 in 40-60% of participation). . Inmunochemical qualitative test showed an OR of 4.79 and quantitative test an OR of 7.30 over the guaiac test. Men showed an OR of 2.73 with respect to women. In 2012 the Advanced Neoplasia rate for women and men was 33.1 and 14.2 by 1,000 participants. CONCLUSIONS: The test used was the most important factor for detecting lesions. Time trends showed an increase in detected lesions caused by the change of the type of test in 2010.

OBJETIVO: En este estudio se presentan los resultados de seis programas poblacionales de cribado de cáncer colorrectal desde 2005 a 2012 (Cataluña, Valencia, Murcia, Cantabria, País Vasco y Canarias) que utilizan diferentes tipos de test de cribado de sangre oculta en heces (SOH) bienal. El objetivo fue describir y comparar los resultados en cuanto a lesiones detectadas tanto por programa, participación, sexo, edad, tipo de test y comunidad autónoma. METODOS: Estudio de cohorte retrospectivo de las personas participantes en al menos una ronda completa cuya edad estaba comprendida entre los 50 y los 74 años. Lesiones consideradas: adenomas avanzados (AA), cáncer aolorrectal invasivo (CCR) y la suma de ambos, neoplasia avanzada (NA). Se realizó un nálisis de regresión logística y estudio de tendencias temporales. RESULTADOS: Se obtuvieron 1.995.719 participaciones, lo que supuso el 46,7% de las invitaciones a participar. Se detectaron 21.228 neoplasias avanzadas (2.813 CCR y 18.415 AA). Se observaron diferencias en la detección de neoplasia avanzada (NA) entre los programas variando entre 15,1‰ y 35,8‰ participantes. La participación se relacionó con las tasas de detección (OR: 1,25 en 40-60% de participación). El test inmunoquímico cualitativo obtuvo una OR de 4,79 y el cuantitativo de 7,30 sobre guayaco. Los hombres tuvieron una OR de 2,73 sobre las mujeres, observándose en el 2012 una tasa de detección de neoplasia avanzada en hombres y mujeres de 33,1 y 14,2 x 1.000 respectivamente. CONCLUSIONES: El tipo de test resultó el factor más determinante en la detección de lesiones. Las tendencias temporales mostraron un aumento de la tasa de detección por el cambio de test a partir del 2010.

Implementation of colorectal cancer screening in Spain: main results 2006-2011.

The Spanish Cancer Screening Network involves the participation of all regional programmes and has been working for over 20 years to co-ordinate strategies and implement quality assurance in current and new regional programmes. In colorectal cancer, the target population is the group aged 50-69 years, who are offered biennial testing using the faecal occult blood test in all programmes, with follow-up colonoscopy if the faecal occult blood test is positive. This article presents the main trends, indicators and differences by sex. The main indicators from 2006 to 2011 were analysed: coverage, participation rate, positivity rate, colonoscopy uptake and lesions detected. Annual trends were adjusted by sex and region. In 2011, coverage was 9.74% of the Spanish target population. A total of 1 001 669 first invitations were registered from 2006 to 2011 and 596 649 individuals participated in the programmes (43.83% participation rate). Results were positive in 30 544 individuals (5.47%), with the lowest positivity rate occurring in 2007 (3.06%) and the highest in 2011 (6.30%) (P<0.001). In all, 27 568 colonoscopies were registered, with a high compliance rate (90.00% in 2011 and 95.59% in 2007) (P=0.381). The adenoma and colorectal cancer detection rates increased over the period, reaching 32.25/1000 and 3.42/1000 participants in 2011, respectively (P<0.001 and P=0.001). Comparison of differences by sex showed that detection rates were significantly higher in men than in women (P<0.001). Participation increased over time and has now reached an acceptable rate. Men show low participation but higher detection rates, indicating the need for further intervention. The Spanish Cancer Screening Network provides common evaluation, performance and organizational benchmarking.

Evaluation of a multicomponent programme for the management of musculoskeletal pain and depression in primary care: a cluster-randomised clinical trial (the DROP study).

BACKGROUND: Chronic musculoskeletal pain and depression are very common in primary care patients. Furthermore, they often appear as comorbid conditions, resulting in additive effect on adverse health outcomes. On the basis of previous studies, we hypothesise that depression and chronic musculoskeletal pain may benefit from an integrated management programme at primary care level. We expect positive effects on both physical and psychological distress of patients. OBJECTIVE: To determine whether a new programme for an integrated approach to chronic musculoskeletal pain and depression leads to better outcomes than usual care. DESIGN: Cluster-randomised controlled trial involving two arms: a) control arm (usual care); and b) intervention arm, where patients participate in a programme for an integrated approach to the pain-depression dyad. SETTINGS: Primary care centres in the province of Tarragona, Catalonia, Spain, Participants: We will recruit 330 patients aged 18-80 with moderate or severe musculoskeletal pain (Brief Pain Inventory, average pain subscale ≥5) for at least 3 months, and with criteria for major depression (DSM-IV). INTERVENTION: A multicomponent programme according to the chronic care model. The main components are care management, optimised antidepressant treatment, and a psychoeducational group action. Blind measurements: The patients will be monitored through blind telephone interviews held at 0, 3, 6 and 12 months. OUTCOMES: Severity of pain and depressive symptoms, pain and depression treatment response rates, and depression remission rates. ANALYSIS: The outcomes will be analysed on an intent-to-treat basis and the analysis units will be the individual patients. This analysis will consider the effect of the study design on any potential lack of independence between observations made within the same cluster. ETHICS: The protocol was approved by the Research Ethics Committee of the Jordi Gol Primary Care Research Institute (IDIAP), Barcelona, (P14/142). DISCUSSION: This project strengthens and improves treatment approaches for a major comorbidity in primary care. The design of the intervention takes into account its applicability under typical primary care conditions, so that if the programme is found to be effective it will be feasible to apply it in a generalised manner. TRIAL REGISTRATION: ClinicalTrials.gov: NCT02605278 ; Registered 28 September, 2015.

Understanding trophic interactions of Orius spp. (Hemiptera: Anthocoridae) in lettuce crops by molecular methods.

BACKGROUND: The aphid Nasonovia ribisnigri (Mosley) (Hemiptera: Aphididae) and the thrips Frankliniella occidentalis (Pergande) (Thysanoptera: Thripidae) are common pests in Mediterranean lettuce crops, where Orius spp. are common generalist predators. Predation by Orius spp. was studied in a lettuce plot by conventional polymerase chain reaction (PCR) and real-time PCR analyses using specific primers of both main pests. Also, high-throughput sequencing was used to have a wider approach of the diet of these predators in natural field conditions. RESULTS: Molecular analyses indicated a higher predation on N. ribisnigri in spring and on F. occidentalis in summer. Predation on alternative prey, like Collembola, was also found in both seasons. Real-time PCR was more sensitive than conventional PCR in showing the target trophic links, whereas high-throughput sequencing revealed predation on other natural enemies - intraguild predation (IGP), showing other trophic interactions of Orius majusculus within the studied ecosystem. CONCLUSIONS: This study gives important information about the trophic relationships present in Mediterranean lettuce crops in different periods of the year. The detected predation by Orius spp. on alternative prey, as well as on other natural enemies, should be further investigated to clarify whether it adds or detracts to the biological control of N. ribisnigri and F. occidentalis.

Molecular assessment of predation by hoverflies (Diptera: Syrphidae) in Mediterranean lettuce crops.

BACKGROUND: Hoverflies (Diptera: Syrphidae) are generalist predators of a great variety of pests. Nasonovia ribisnigri (Hemiptera: Aphididae) and Frankliniella occidentalis (Thysanoptera: Thripidae) are two common pests in Mediterranean lettuce crops, where they occur alongside alternative prey (e.g., Collembola). A semi-field experiment was conducted in an experimental lettuce plot where hoverfly predation on N. ribisnigri, F. occidentalis and Collembola was studied by conventional PCR and qPCR using specific primers, as well as by next-generation sequencing (NGS) in order to reveal other potential trophic interactions. RESULTS: Trophic linkages between hoverflies and N. ribisnigri were the strongest both in spring and summer. F. occidentalis and Collembolans were also detected in both seasons, but with less frequency. qPCR detected a higher frequency of consumption than conventional PCR when both tests were run at optimal conditions. NGS analyses showed intraguild predation on other hoverfly species, as well as on anthocorids, spiders and even aphid parasitoids. CONCLUSIONS: Conventional PCR and qPCR provided important insights into Mediterranean hoverfly species predation on target pest and non-pest prey. NGS gave a complementary approach revealing a broader diet of these predators within the studied ecosystem.

Persistence in the long term of the effects of a collaborative care programme for depression in primary care.

BACKGROUND: A collaborative care programme for depression in primary care has proven clinical effectiveness over a 12-months period. Because depression tends to relapse and to chronic course, our aim was to determine whether the effectiveness observed in the first year persists during 3 years of monitoring. METHODS: Randomised controlled trial with twenty primary care centres were allocated to intervention group or usual care group. The intervention consisted of a collaborative care programme with clinical, educational and organisational procedures. Outcomes were monitored by a blinded interviewer at baseline, 12 and 36 months. Clinical outcomes were response to treatment and remission rates, depression severity and health-related quality of life. TRIAL REGISTRATION: ISRCTN16384353. RESULTS: A total of 338 adult patients with major depression (DSM-IV) were assessed at baseline. At 36 months, 137 patients in the intervention group and 97 in the control group were assessed (attrition 31%). The severity of depression (mean Patient Health Questionnaire-9 score) was 0.95 points lower in the intervention group [6.31 versus 7.25; p=0.324]. The treatment response rate was 5.6% higher in the intervention group than in the control group [66.4% versus 60.8%; p=0.379] and the remission rate was 9.2% higher [57.7% versus 48.5%; p=0.164]. No difference reached statistical significance. LIMITATIONS: The number of patients lost (31%) before follow-up may have introduced a bias. CONCLUSIONS: Clinical benefits shown in the first year were not maintained beyond: at 36 months the differences between the control group and the intervention group reduced in all the analysed variables.

Cost-effectiveness analysis of a collaborative care programme for depression in primary care.

BACKGROUND: Collaborative care programmes lead to better outcomes in the management of depression. A programme of this nature has demonstrated its effectiveness in primary care in Spain. Our objective was to evaluate the cost-effectiveness of this programme compared to usual care. METHODS: A bottom-up cost-effectiveness analysis was conducted within a randomized controlled trial (2007-2010). The intervention consisted of a collaborative care programme with clinical, educational and organizational procedures. Outcomes were monitored over a 12 months period. Primary outcomes were incremental cost-effectiveness ratios (ICER): mean differences in costs divided by quality-adjusted life years (QALY) and mean differences in costs divided by depression-free days (DFD). Analyses were performed from a healthcare system perspective (considering healthcare costs) and from a society perspective (including healthcare costs plus loss of productivity costs). RESULTS: Three hundred and thirty-eight adult patients with major depression were assessed at baseline. Only patients with complete data were included in the primary analysis (166 in the intervention group and 126 in the control group). From a healthcare perspective, the average incremental cost of the programme compared to usual care was €182.53 (p<0.001). Incremental effectiveness was 0.045 QALY (p=0.017) and 40.09 DFD (p=0.011). ICERs were €4,056/QALY and €4.55/DFD. These estimates and their uncertainty are graphically represented in the cost-effectiveness plane. LIMITATIONS: The amount of 13.6% of patients with incomplete data may have introduced a bias. Available data about non-healthcare costs were limited, although they may represent most of the total cost of depression. CONCLUSIONS: The intervention yields better outcomes than usual care with a modest increase in costs, resulting in favourable ICERs. This supports the recommendation for its implementation.

Shifting from glucose diagnosis to the new HbA1c diagnosis reduces the capability of the Finnish Diabetes Risk Score (FINDRISC) to screen for glucose abnormalities within a real-life primary healthcare preventive strategy.

BACKGROUND: To investigate differences in the performance of the Finnish Diabetes Risk Score (FINDRISC) as a screening tool for glucose abnormalities after shifting from glucose-based diagnostic criteria to the proposed new hemoglobin (Hb)A1c-based criteria. METHODS: A cross-sectional primary-care study was conducted as the first part of an active real-life lifestyle intervention to prevent type 2 diabetes within a high-risk Spanish Mediterranean population. Individuals without diabetes aged 45-75 years (n = 3,120) were screened using the FINDRISC. Where feasible, a subsequent 2-hour oral glucose tolerance test and HbA1c test were also carried out (n = 1,712). The performance of the risk score was calculated by applying the area under the curve (AUC) for the receiver operating characteristic, using three sets of criteria (2-hour glucose, fasting glucose, HbA1c) and three diagnostic categories (normal, pre-diabetes, diabetes). RESULTS: Defining diabetes by a single HbA1c measurement resulted in a significantly lower diabetes prevalence (3.6%) compared with diabetes defined by 2-hour plasma glucose (9.2%), but was not significantly lower than that obtained using fasting plasma glucose (3.1%). The FINDRISC at a cut-off of 14 had a reasonably high ability to predict diabetes using the diagnostic criteria of 2-hour or fasting glucose (AUC = 0.71) or all glucose abnormalities (AUC = 0.67 and 0.69, respectively). When HbA1c was used as the primary diagnostic criterion, the AUC for diabetes detection dropped to 0.67 (5.6% reduction in comparison with either 2-hour or fasting glucose) and fell to 0.55 for detection of all glucose abnormalities (17.9% and 20.3% reduction, respectively), with a relevant decrease in sensitivity of the risk score. CONCLUSIONS: A shift from glucose-based diagnosis to HbA1c-based diagnosis substantially reduces the ability of the FINDRISC to screen for glucose abnormalities when applied in this real-life primary-care preventive strategy.

Registered prevalence of borderline personality disorder in primary care databases.

OBJECTIVE: Borderline personality disorder (BPD) is a common personality disorder, with a population prevalence of 1.4-5.9%, although the epidemiology of this disorder in primary care is insufficiently known. Our objective was to determine the registered prevalence of BPD in primary care databases and to study the demographic and clinical characteristics of these patients. METHODS: We performed a cross-sectional study of the computerized databases of primary care clinical records. The target population consisted of all adults (≥ 16 years old) registered in the Catalan Health Institute (n = 4,764,729). RESULTS: The prevalence of recorded BPD was 0.017%, and was higher in patients with other mental disorders, particularly substance-abuse disorders (0.161%). These patients had twice as many appointments with the general practitioner as the general population (8.1 vs. 4.4). CONCLUSION: The number of diagnoses of BPD recorded in primary care is extremely low, which contrasts with the available population-based data.

Effectiveness of a multi-component programme for managing depression in primary care: a cluster randomized trial. The INDI project.

BACKGROUND: There are significant shortcomings in the management and clinical outcomes of depressed patients. The objective is to assess the effectiveness of a multi-component programme to improve the management of depression in primary care. METHODS: This is a cluster-randomized controlled trial, conducted between June 2007 and June 2010. Twenty primary care centres were allocated to intervention group or usual care group. The intervention consisted of a multi-component programme with clinical, educational and organizational procedures including primary care nurses working as case-managers. Outcomes were monitored by a blinded interviewer at 0, 3, 6 and 12 months. TRIAL REGISTRATION: ISRCTN16384353, at http://isrctn.org. RESULTS: In total, 338 adult patients with major depression (DSM-IV) were assessed at baseline. At 12 months, 302 patients were assessed, 172 in the intervention group and 130 in the control group. The severity of depression (mean Patient Health Questionnaire-9 score) was 1.76 points lower in the intervention group [7.15 vs. 8.78, 95% CI=-3.53 to 0.02, p=0.053]. The treatment response rate was 15.4% higher in the intervention group than in the controls [66.9% vs. 51.5%, odds ratio 1.9, 95% CI=1.2 to 3.1, p=0.011)], and the remission rate was 13.4% higher [48.8% vs. 35.4%, odds ratio 1.8, 95% CI=1.1 to 2.9, p=0.026)]. LIMITATIONS: Unblinded physicians diagnosed depression in their patients and decided whether to include them in the study, so we cannot discount a hidden selection bias. CONCLUSIONS: The programme for managing depression leads to better clinical outcomes in patients with major depression in primary care settings.

Unraveling the life history of successful invaders.

Despite considerable current interest in biological invasions, the common life-history characteristics of successful invaders remain elusive. The widely held hypothesis that successful invaders have high reproductive rates has received little empirical support; however, alternative possibilities are seldom considered. Combining a global comparative analysis of avian introductions (>2700 events) with demographic models and phylogenetic comparative methods, we show that although rapid population growth may be advantageous during invasions under certain circumstances, more generally successful invaders are characterized by life-history strategies in which they give priority to future rather than current reproduction. High future breeding expectations reduce the costs of reproductive failure under uncertain conditions and increase opportunities to explore the environment and respond to novel ecological pressures.