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This study has two main objectives: to describe the prevalence of undetected chronic obstructive pulmonary disease (COPD) in a clinical sample of smokers with severe mental illness (SMI), and to assess the value of the Tobacco Intensive Motivational Estimated Risk tool, which informs smokers of their respiratory risk and uses brief text messages to reinforce intervention.
A multicenter, randomized, open-label, and active-controlled clinical trial, with a 12-month follow-up. Outpatients with schizophrenia (SZ) and bipolar disorder were randomized either to the experimental group—studied by spirometry and informed of their calculated lung age and degree of obstruction (if any)—or to the active control group, who followed the 5 A’s intervention.
The study sample consisted of 160 patients (71.9% SZ), 78.1% of whom completed the 12-month follow-up. Of the patients who completed the spirometry test, 23.9% showed evidence of COPD (77.8% in moderate or severe stages). TIMER was associated with a significant reduction in tobacco use at week 12 and in the long term, 21.9% of patients reduced consumption and 14.6% at least halved it. At week 48, six patients (7.3%) allocated to the experimental group achieved the seven-day smoking abstinence confirmed by CO (primary outcome in terms of efficacy), compared to three (3.8%) in the control group.
In this clinical pilot trial, one in four outpatients with an SMI who smoked had undiagnosed COPD. An intensive intervention tool favors the early detection of COPD and maintains its efficacy to quit smoking, compared with the standard 5 A’s intervention.
DNA dynamics can only be understood by taking into account its complex mechanical behavior at different length scales. At the micrometer level, the mechanical properties of single DNA molecules have been well-characterized by polymer models and are commonly quantified by a persistence length of 50 nm (~150 bp). However, at the base pair level (~3.4 Å), the dynamics of DNA involves complex molecular mechanisms that are still being deciphered. Here, we review recent single-molecule experiments and molecular dynamics simulations that are providing novel insights into DNA mechanics from such a molecular perspective. We first discuss recent findings on sequence-dependent DNA mechanical properties, including sequences that resist mechanical stress and sequences that can accommodate strong deformations. We then comment on the intricate effects of cytosine methylation and DNA mismatches on DNA mechanics. Finally, we review recently reported differences in the mechanical properties of DNA and double-stranded RNA, the other double-helical carrier of genetic information. A thorough examination of the recent single-molecule literature permits establishing a set of general ‘rules’ that reasonably explain the mechanics of nucleic acids at the base pair level. These simple rules offer an improved description of certain biological systems and might serve as valuable guidelines for future design of DNA and RNA nanostructures.
The main objective of this study was to develop a dynamic energy balance model for dairy goats to describe and quantify energy partitioning between energy used for work (milk) and that lost to the environment. Increasing worldwide concerns regarding livestock contribution to global warming underscore the importance of improving energy efficiency utilization in dairy goats by reducing energy losses in feces, urine and methane (CH4). A dynamic model of CH4 emissions from experimental energy balance data in goats is proposed and parameterized (n = 48 individual animal observations). The model includes DM intake, NDF and lipid content of the diet as explanatory variables for CH4 emissions. An additional data set (n = 122 individual animals) from eight energy balance experiments was used to evaluate the model. The model adequately (root MS prediction error, RMSPE) represented energy in milk (E-milk; RMSPE = 5.6%), heat production (HP; RMSPE = 4.3%) and CH4 emissions (E-CH4; RMSPE = 11.9%). Residual analysis indicated that most of the prediction errors were due to unexplained variations with small mean and slope bias. Some mean bias was detected for HP (1.12%) and E-CH4 (1.27%) but was around zero for E-milk (0.14%). The slope bias was zero for HP (0.01%) and close to zero for E-milk (0.10%) and E-CH4 (0.22%). Random bias was >98% for E-CH4, HP and E-milk, indicating non-systematic errors and that mechanisms in the model are properly represented. As predicted energy increased, the model tended to underpredict E-CH4 and E-milk. The model is a first step toward a mechanistic description of nutrient use by goats and is useful as a research tool for investigating energy partitioning during lactation. The model described in this study could be used as a tool for making enteric CH4 emission inventories for goats.
Landscape evolution studies enable us to understand site formation processes affecting past hunter-gatherer settlements. This work presents a landscape reconstruction of Roca dels Bous site (RB), which is a reference site for the Late Mousterian occupation of the incised valleys of the southeastern Pyrenees. For this purpose, we combined geomorphological studies, stratigraphic descriptions, new single-grain optically stimulated luminescence datasets, statistical methods, and geophysical surveys. RB formed by gravitational processes induced by fluvial undermining of the Segre River during changing late Pleistocene climatic conditions. Geomorphological and chronological data combined with fluvial age-incision models suggest that, during Late Mousterian occupation, RB was located very near the Segre floodplain level and closer to water and raw material natural resources than at present. The accumulation of gravitational deposits associated with the archaeological levels occurred at rates of 0.16–0.44 m ka-1, between 55 and 47 ka, coinciding with Marine Oxygen Isotope Stage 3 (MIS3). More detailed comparison with available climatic curves suggests that the dated RB layers were potentially deposited during cold phases within MIS3. This work provides new landscape-based evidence to examine the paleoenvironmental context of Neanderthal presence in the southeastern Pre-Pyrenees, an important region in the debate regarding Neanderthal demise in Western Europe around 40 ka.
Previous literature supports antipsychotics’ (AP) efficacy in acute first-episode psychosis (FEP) in terms of symptomatology and functioning but also a cognitive detrimental effect. However, regarding functional recovery in stabilised patients, these effects are not clear. Therefore, the main aim of this study is to investigate dopaminergic/anticholinergic burden of (AP) on psychosocial functioning in FEP. We also examined whether cognitive impairment may mediate these effects on functioning.
A total of 157 FEP participants were assessed at study entry, and at 2 months and 2 years after remission of the acute episode. The primary outcomes were social functioning as measured by the functioning assessment short test (FAST). Cognitive domains were assessed as potential mediators. Dopaminergic and anticholinergic AP burden on 2-year psychosocial functioning [measured with chlorpromazine (CPZ) and drug burden index] were independent variables. Secondary outcomes were clinical and socio-demographic variables.
Mediation analysis found a statistical but not meaningful contribution of dopaminergic receptor blockade burden to worse functioning mediated by cognition (for every 600 CPZ equivalent points, 2-year FAST score increased 1.38 points). Regarding verbal memory and attention, there was an indirect effect of CPZ burden on FAST (b = 0.0045, 95% CI 0.0011–0.0091) and (b = 0.0026, 95% CI 0.0001–0.0006) respectively. However, only verbal memory post hoc analyses showed a significant indirect effect (b = 0.009, 95% CI 0.033–0.0151) adding premorbid IQ as covariate. We did not find significant results for anticholinergic burden.
CPZ dose effect over functioning is mediated by verbal memory but this association appears barely relevant.
To determine the association between functional impairment, as reported in a lay-administered structured interview (CIDI), and severity of depression, depressive symptoms and risk factors for depression.
We undertook a cross-sectional study of 5442 consecutive attendees at general practices in seven Spanish provinces participating in the PredictD-Spain study on predictors of depression. Participants were administered the depression section of the Composite International Diagnostic Interview (WHO-CIDI 2.1), allowing diagnoses by the ICD-10 and DSM-IV classifications for depressive episodes. Impairment was measured using the CIDI question about whether symptoms seriously interfered with important areas of functioning, such as work or looking after the house and family. We measured a set of 39 known risk factors for depression.
Firstly, the 6-month prevalence of a depressive episode according to ICD-10 was 28.7% (1563) and of major depression according to DSM-IV it was 13.6% (742). Secondly, out of the 1563 patients with a depressive episode according to ICD-10, nearly half (47.9%; n=749) had no impairment in important areas of functioning.
As the ICD-10 criteria for depressive diagnoses do not include the criteria that symptoms cause impairment in social, occupational or other important areas of functioning, a large number of false positive cases are included in reported prevalence rates; and secondly, the measurement of functional impairment, at least operationalized using a lay-administered structured interview such as CIDI, is not enough, in epidemiological research studies, to assess the clinical importance of depressive symptoms.
The predictD study is a pioneering international study whose main objective was to develop a risk index for the onset of major depression in general practice attendees.
The aim of this exploratory study was to determine the opinion of primary care attendees and their general practitioners about how to implement primary prevention of major depression. The intervention consisted of informing primary care attendees about their risk level and risk profile for the onset of major depression.
The study participants were primary care attendees and general practitioners in urban health centres of 7 Spanish provinces. The methodology used was qualitative: there were 14 in-depth interviews (two from each province), 7 DAFO groups and 7 focus groups.
The results showed that attendees generally welcomed this precautionary measure. Some even proposed potential changes in their lifestyles to prevent depression, such as improving social relationships, taking things more calmly or doing more leisure activities, while others asked their GP for advice. The GPs were more resistant about informing primary care attendees, raising doubts about the validity-reliability of the instrument, their lack of education about what they should or should not advise their attendees, the danger of creating excessive fear in their attendees, or the barrier of lack of time in the office to do these activities.
Primary care attendees welcome this preventive measure more than their general practitioners.
We analyzed the association of age at onset of psychosis(AOP) with having a history of cannabis use in patients with a first episode of non-affective psychosis(FENAP) and investigated the impact on the AOP of exposure to cannabis in adolescence, compared with young adulthood, and of the additional exposure to cocaine.
We recruited 112 consecutive patients with a FENAP. CIDI was used to assess drug use and to define the age at onset of heaviest use(AOHU) of a drug, as the age when drug was used the most for each patient. The effect of cannabis and cocaine AOHU on AOP was explored through Kruskal-Wallis and Mann-Whitney tests, and logistic regression. Sex-adjusted cumulative hazard curves and Cox regression models were used to compare the AOP of patients with and without a history of cannabis use, or associated cocaine use.
AOP was significantly associated with the use of cannabis, independently of sex, use of cocaine, tobacco smoking or excessive alcohol consumption. There was a dose-response relationship between cannabis AOHU and AOP: the earlier the AOHU the earlier the AOP. Hazard curves showed that patients with a history of cannabis use had a higher hazard of having a first episode psychosis than the rest of the patients (sex-adjusted log rank χ2=23.43,df=1, p< 0.001). Their respective median AOP (25th, 75th percentiles) were 23.5 (21,28) and 33.5 years (27,45) (for log-transformed AOP, t=5.6, df=110, p< 0.001).
Our results are in favor of a catalytic role for cannabis use in onset of psychosis.
One of the most important prognostic factors in patients diagnosed with schizophrenia is the number of hospitalizations they need during their life. In this work we describe risk factors which determinate psychotic relapse.
Retrospective review of the clinical histories of patients diagnosed with schizophrenia who needed hospitalization during the year 2008 using Hospital Ramon Cajal's history software. Data were analyzed using the SPSS software 15.0 version.
- Socio-demographic: We collected a total of 57 patients, 60% were men and 77,2% were single who lived with their families. 52,8% only had Primary education and 14% had been to University. 38,6% were pensioner and 12,3% workers.
- Risk factors: 54,4% had abandoned their medication, 7% had had recent modifications in their medication, and 35,1% received long acting antipsychotic. 42,1% were identified as substance users.
- 40,4% had been diagnosed with schizophrenia more than three years ago; 57,9% had had less than 3 previous hospitalizations, and 54,4% need hospitalization the previous year.
Male under 30 years old have more risk of needing more hospitalizations. The main risk factor for suffering new psychotic episodes is the medication nonadherence, modifying medication only causes new episodes in few patients. Patients receiving long-acting antipsychotic agents suffer less psychotic relapse. Substance abuse among schizophrenia patients is a major complicating factor since almost half of the hospitalizations are related to it.
Personality dimensions have been associated with symptoms dimensions in schizophrenic patients (SP). In this paper we study the relationships between symptoms of functional psychoses and personality dimensions in SP and their first-degree relatives (SR), in other psychotic patients (PP) and their first-degree relatives (PR), and in healthy controls in order to evaluate the possible clinical dimensionality of these disorders. Twenty-nine SP, 29 SR, 18 PP, 18 PR and 188 controls were assessed using the temperament and character inventory (TCI-R). Current symptoms were evaluated with positive and negative syndrome scale (PANSS) using the five-factor model described previously (positive [PF], negative [NF], disorganized [DF], excitement [EF] and anxiety/depression [ADF]). Our TCI-R results showed that patients had different personality dimensions from the control group, but in relatives, these scores were not different from controls. With regard to symptomatology, we highlight the relations observed between harm avoidance (HA) and PANSS NF, and between self-transcendence (ST) and PANSS PF. From a personality traits-genetic factors point of view, schizophrenia and other psychosis may be initially differentiated by temperamental traits such as HA. The so-called characterial traits like ST would be associated with the appearance of psychotic symptoms.
To compare patterns of temperament and character and the prevalence of Obsessive-Compulsive Personality Disorder (OCPD) and OCPD traits in parents of children with OCD and parents of healthy controls.
TCI and SCID-II were administered to 63 parents of 32 children with OCD and 63 parents of age- and sex-matched controls with no psychiatric diagnosis. Interviewers were not blind to proband status. Personality dimension scores and frequencies of OCPD criteria in both groups were compared after excluding parents with a diagnosis of OCD. Relationships between TCI dimensions and OCPD symptoms in parents and the clinical characteristics of OCD children were also studied.
Parents of OCD children presented significantly higher scores in harm avoidance and lower scores in self-directedness, cooperativeness and reward dependence than parents of healthy children. A higher incidence of OCPD was found in parents of probands (p < 0.02). Hoarding, perfectionism and preoccupation with details were significantly more frequent in parents of OCD children. Counting, ordering and cleaning compulsions in OCD children predicted elevated odds of perfectionism and rigidity in their parents.
The existence of the dimensional personality profile associated with OCD in parents of children with OCD and the higher number of OCPD criteria in these parents in comparison to parents of healthy children highlight the importance of the role of personality factors in familial OCD.
Impaired sustained and selective attention have been seen as vulnerability factors to psychotic disorders. Relatives of psychotic patients are a risk population for psychosis, and previous studies have shown that they displayed more attentional deficits compared with healthy controls. Additionally, relatives have more pathological personality and schizotypy, the least considered also to be the expression of the genetic vulnerability to schizophrenia. There are few studies that relate attention to personality factors in relatives of psychotic patients.
To compare attentional performance of siblings of psychotic patients with those of healthy controls, taking into account their pathological and schizotypal personality.
The Spanish version of the SPQ and the DAPP-BQ were administered to a sample of 51 subjects that were divided into four groups by a hierarchical cluster analysis: siblings with high pathological personality (SHPP), siblings with low pathological personality (SLPP), controls with high pathological personality (CHPP), and controls with low pathological personality (CLPP). In all the subjects we assessed a sustained attention index (SUA) and a selective attention index (SEA). We compared the performance of the four groups on these attentional indexes.
We found that SHPP had worse performance on sustained attention compared with CLPP. Specifically this difference was in the reaction time item of the SUA.
The high schizotypy and pathological personality had an influence on sustained attentional performance in the siblings of patients with psychosis, but not in the healthy controls.
Bipolar spectrum disorders often go unrecognised and undiagnosed. One of the underlying reasons is the poor recognition of bipolar disorder among patients presenting depressive episodes. Our goal was to estimate the MDQ rate of positive screens for bipolar disorder in a Spanish sample of outpatients with a current major depressive episode and compare it with their psychiatric diagnosis.
971 consecutively outpatients with a current DSM-IV TR diagnosis of major depressive episode were included. Study measures included socio-demographic and clinical data, Clinical Global Impressions–Severity of Illness Scale (CGI-S), Hamilton Depression Scale (HAMD) and MDQ.
905 patients fulfilled criteria to be included in the analysis. All suffered a current depressive episode. 74.3% (n= 671) of the patients had received previously a diagnosis of unipolar depression and 25.7% (n= 232) of bipolar disorder by a psychiatrist. Using a MDQ of 7-or-more-item threshold, the global positive screen rate for bipolar disorder was 41,3% (n=373). From the 671 patients with previous unipolar depression diagnosis, 161 (24%) screened positive for bipolar disorder with MDQ, whereas in 232 patients diagnosed of bipolar disorder, 212 (91.4%) screened positive.
MDQ showed a positive screen rate for bipolar disorder in 24% of patients with a previous diagnosis of unipolar disorder and a current depressive episode. Screening tools like MDQ could contribute to increased detection of bipolar disorder in patients with depression. Early diagnosis of bipolar disorder may have, therefore, important clinical and therapeutic implications in order to improve the illness course and the long-term functional prognosis.
Recent studies have suggested that functional impairment in bipolar disorder may be strongly associated with residual depressive symptoms. However, there is a notable disparity between functional recovery and symptomatic recovery. This study was carried out to investigate clinical factors as potential predictors on functional impairment in a well defined euthymic bipolar sample.
Seventy-one patients were recruited from the Bipolar Disorder Program at the Clinic Hospital of Barcelona. A Structured Clinical Interview for DSM-IV-TR, HAM-D and YMRS were used to diagnostic assessment and euthymia criteria. The Functioning Assessment Short Test (FAST) was employed to assess functional impairment. The FAST is a reliable and valid, interview-administered scale, rapid and easy to apply (3-6 min). It consists of 24 items which allow to assess six specific areas of functioning such as autonomy, occupational functioning, cognitive functioning, financial issues, interpersonal relationships, and leisure time.
The sample comprised 36 (51%) men, aged 48±13.56 years. Several clinical variables were associated with poor functioning on a linear regression model, such as age, depressive symptoms, number of previous mixed episodes and number of previous hospitalizations. This model explained 44% of the variance (F=12.54, df=58, p< 0.001).
In this study, specific clinical and socio-demographic characteristics were identified as predictors of functional impairment in remitted bipolar patients. Poor functioning was identified in patients with older age and more severe illness course.
Natural polyamines (putrescine, spermidine and spermine) are low molecular weight highly protonated aliphatic molecules that physiologically modulate NMDA, AMPA/kainate glutamatergic receptors and limbic dopaminergic neurotransmission. Previous studies had demonstrated that polyamine metabolism might be disrupted in schizophrenia, what could potentially be linked to glutamatergic dysfunction. In particular, polyamine levels in blood and fibroblast cultures from patients with schizophrenia had previously been found to be higher than in healthy controls. Indeed, a significant positive correlation between blood polyamine levels and severity of illness may exist.
In order to test potential differences in blood polyamine levels between drug-free schizophrenia in-patients (n = 12), and healthy controls (n = 26, blood donors), spermidine (spd), spermine (spm), and spermidine/spermine index (spd/spm) were determined using HPLC after dansylation.
No significant differences were found between groups (t = 0,974; df = 36; P = 0,337 for spd, t = l0, 52; df = 36; P = 0,959 for Spm, and, t = 0, 662; df = 36; P = 0,512 for spd/spm).
Though we couldn’t replicate previous findings suggesting disturbances in blood polyamine levels in schizophrenia, this issue may be a promising target. Future research should take into account possible factors such as sex, nutritional state, and stress.
Suicide is a major and preventable public health problem. Risk factors may vary with age, gender, or ethnic group, being substance abuse one of the most frequent.
To investigate the relation of substance related disorder and suicide attempt.
Review of the suicidal attempts of patients with personal history of substance related disorder attended during the year 2010.
We identified 85 cases.
Alcohol (64″3%) and cocaine (47″7%) were the two most identified substances. Cannabis (17″2%) and heroin (23″06%) were less consumed. Benzodiacepines abuse was very frequent among the patients attended (38″2%).
Previous attempts were found in 43″8% of the patients.
Drug overdose was the most commonly method used (98″4%), especially with benzodiacepines and antidepressants, but non psychiatric drugs were also frequent. Substance overdosage or intoxication was the second most frequent method used (23%), and poisoning the third (9%). Most of times these methods were presented with concomitant drug overdose.
Defenestration threats were very rare (2″34%), and always associated with hospitalization request by the patient.
We did find significant differences when studying triggers (family, partnership, economical or others) compared with non substance abusers suicidal attempts.
- Chronic substance misuse and acute substance abuse is associated with a higher risk of suicide, what may be explained by the disinhibiting effects of psychoactive substances.
- As benzodiazepine misuse is associated with suicide, special care must be taken when prescribing to at risk patients such as substance abusers
Antidepressants are recommended to be withdrawn during a manic episode. This analysis explored the characteristics of patients receiving antidepressants during an acute manic episode in the context of a large, observational study.
EMBLEM (European Mania in Bipolar Longitudinal Evaluation of Medication) is a 2-year prospective observational study of acute mania/mixed mania. Of 2416 patients, 345 (14%) were taking an antidepressant (AD) and 2071 (86%) were not (NAD) during acute mania. Demographic and clinical variables were collected at baseline and at outpatient visits up to 2 years. Illness severity was measured using Clinical Global Impressions–Bipolar Disorder (CGI-BP), 5-item Hamilton Depression Rating Scale (HAM-D-5), and Young Mania Rating Scale (YMRS). Logistic regression analysis was used to identify variables associated with AD use.
AD use varied across countries (p<0.05), more use with mixed episodes (p<0.001), rapid cyclers (p=0.02), more previous depressive episodes (p<0.001) and higher HAM-D-5 severity at baseline (p<0.001) but less use with higher education (p=0.029), YMRS (p=0.022), CGI-BP overall (p=0.006) severity and inpatients at baseline (p<0.001). There were no differences in alcohol abuse or suicide attempts. Depression recurrence rates were significantly higher with AD (p<0.001).
The EMBLEM study suggests that patients with mania receiving antidepressants are more likely to be outpatients with mixed mania or rapid cycling, and have a higher risk of depressive recurrence during follow-up. Clinicians seem to maintain antidepressants in manic patients to address depressive features during mania and prevent further depressive episodes.
Schizophrenia requires new antipsychotic that can relieve suffering and improve the prognosis of schizophrenic patients.
To study efficacy and safety of Ariprazole in patients with acute schizophrenia.
We studied 16 patients with acute episode of schizophrenia, 6 were first episodes and 10 acute reactivations. We used ARIPRAZOLE for 6 months to evaluate its effectiveness and tolerance. All patients were hospitalised and received Ariprazole in progressively larger doses, beginning with 10 mg/day and increasing to 30 mg at 10 days. Evaluation measures were PANSS, initial and 6 months, and CGI, initial (severity) and 6 months (evolution-improvement). Side effects were evaluated.
Mean PANSS in first episodes: 85 at onset and 36 at 6 months; in reactivations: 75 at onset and 32 at 6 months. ICG showed a mean severity of 4.6 in the first episodes and 4.2 in reactivations; at 6 months the mean improvement was 2.3 in the first episodes and 2.3 in reactivations. The transitory side effects were found, which did not require discontinuation of the drug: insomnia in 15% of first episodes and in 22% of reactivations; nausea in 16% vs. 22%; a certain disinhibition (not manic) in 83% of first episodes and in 77% of reactivations.
ARIPRAZOLE is an effective antipsychotic in the first and successive episodes of schizophrenia. It improved insight and the subjective feeling of well-being and made the psychotic condition easier to bear. This definitely made it a drug of first choice for acute or reactivated schizophrenia.