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Sexuality is a crucial area of human life. A proper examination to assess and detect problems in this field, it seems imperative to intervene when transsexual patients. Therefore accurately known, the sexual practices of these patients, allows us to work directly on possible alterations in the functioning of sexual life during the therapeutic process.
Describe patterns of sexual behavior in patients diagnosed with transsexualism
Gender and Identity Disorder Unit (GIDU)
Selected by consecutive sampling, 200 transsexuals treated at GIDU Malaga, aged between 20 and 40 years and who agreed to participate in the study. Comprising 142 transgender male-to-woman (MtW) and 58 women-to-man (WtM).
Was conducted through a heterocompleted questionnaire that included questions about sexuality, personality traits and demographic characteristics. These were filled in the consultation and were anonymous.
11.6% of MtW transsexuals have never had sex. 26.8% of the MtW and 29% of WtM are more than 3 months without masturbating. 54.1% of the MtW avoid having sex due to the rejection of his genitals, lack of sexual desire and previous traumatic experience. Transgender respondents had secondary education, stable jobs and they were single.
It is vital that we explore the sex lives of transsexual patients. This information must be integrated in a systematic and rigorous evaluation process. According to the results presented, the hyposexuality would be the most significant feature that describes sexuality for this population.
Folie á deux is a rare mental syndrome, firstly described by Falret in France on 1997, and renamed in the DSM-IV as shared psychotic disorder, and in the ICD-10 as induced delusional disorder; in which a paranoid or delusional belief is shared by two people with a very close relationship, and usually belonging to the same family. Social withdrawal is a common characteristic of both persons during the initial stage of the disorder.
A 16 years-old adolescent boy, born in Russia, and having this syndrome is presented in this study. After his arrival to Spain, he lived with his father with important social isolation for six months, and he begun to report delusional ideas with mystical-religious and ufological content. His father was diagnosed as having a delusional disorder with the same contents. Both patients received behavioural-cognitive therapy (CBT) with the aim of modifying their delusional beliefs, even that they went on living together. No antipsychotic medication was needed.
Clear changes were observed in their delusional system, particularly in the degree of conviction, as well as in distress, thought interference, and anxiety, and also an improvement was observed in the understanding of their beliefs, and in their social relationship with peers.
Social withdrawal as well as cultural differences associated to their immigrant condition played a critical role in the establishment of the induced delusional disorder, and CBT modified the delusional system, even father and son continued living together.
Serotonin Syndrome (SS) is an adverse drug reaction that drives mental-status changes, autonomic hyperactivity and neuromuscular abnormalities.
Neuroleptic Malignant Syndrome (NMS) is an idiopathic reaction to dopamine-antagonist that consists of extra-pyramidal symptoms, autonomic dysfunction, hyperthermia, diaphoresis and fluctuating consciousness.
Differential diagnosis is sometimes difficult for their overlapping clinical features. Potentially lethal, both require heightened clinical awareness for prevention, recognition and prompt treatment.
Caucasian 59 years-old woman with Catatonic profile (Scored: severity-17points/ 5 screening in Bush-Francis Catatonia-Rating-Scale).
Past Medical History
- Bipolar Disorder type-2 (25 years of evolution)
15 days before hospitalization, anafranil and fluoxetine treatment was replaced by Trazodone 200 mg/day and venlafaxine 150mg/day. She was also on valpromida and lorazepam 15 mg/day.
Mutism, negativism. No reaction to painful stimuli, stuporous. Diaphoresis, pallor, tremor, axial rigidity without pyramidalism (>lower limbs), high fever (40°C), tachycardia (>100lpm), rhabdomyolysis (CPK reached 17.000, 48 hours after the admission), leukocytosis, upper transaminasas, hiponatremia with hiperpotasemia.
-NMS: Intensity, duration and high CPK are suggestive (Sternbach). This syndrome has been described due to Venlafaxine.
-SS: Combination of Venlafaxine and Trazodone favors but she doesn't have acatisia, hiperreflexia, diarrhea and it wasn't resolved after 96 hours.
Drugs were removed and Lorazepam on high doses (5mg/day) was prescribed. One month later the patient was totally recovered of the episode.
If unsure diagnoses it's priority to remove the causing drugs and supportive care. Afterwards, it can be used benzodiacepines, also dantroleno in SNM.
Recovery from a psychotic episode is a dynamic process after the devastating effects of being diagnosed with a serious mental illness, or the trauma of being hospitalized, rather than a cure or the absence of symptoms. Psychological recovery implies finding and maintaining hope, the reestablishment of a positive identity, finding meaning in life, and taking responsibility for one's life.
The stages of the subjective psychological process of recovery after the first psychotic episode were explored; since psychological functioning, as well as symptoms and social functioning in the critical period probably are the most important long-term outcome predictor variables.
The RSQ (Drayton, et al., 1998) and the STORI (Andresen, et al., 2006) were used to assess 30 patients (72.4% males) recovering from the first episode of a non-affective psychosis, 3 to 9 months after their clinical discharge. The mean age was 24.34 (SD=4.5, range=17-34).
The RSQ stages of recovery were: Tendency toward sealing-over (7.7%), Mixed, sealing-over predominates (42.3%), Mixed, integration predominates (38.5%), and Tendency toward integration (11.5%). The STORI stages of recovery were: Moratorium (11.5%), Awareness (31.0%), Preparation (27.0%), Rebuilding (11.5%), and Growth (19.0%). Significant correlations were found between better recovery stages and patient's adherence to treatment (X2 = 9.579, p = 0.008). Correlations between recovery stages and symptoms, neuropsychological functioning, and other variables were also explored.
Recovery styles of Integration and Growth significantly correlate with treatment adherence, a better symptomatic (less negative and general symptoms) and functional recovery, but not with DUP, stigma, or neuropsychological variables.
To estimate the prevalence of depression and anxiety in caregivers of dependent grade II and III of a health center. Calculate the perceived social support for caregivers. Estimating the degree of caregiver stress. Assess the socio-demographic factors associated.
Descriptive and transversal.
Primary Health Care.
We selected 55 dependent caregivers grade II and III consecutive sample, according to the law of dependence, belonging to the health center Algeciras-North and were registered in the database of the Center on January 31, 2009. Exclude those who would not participate in the study, did not understand the Spanish language or could not contact with them.
We conducted through a questionnaire that contained heteroadministrated Hamilton scales for depression and anxiety, social support scale of the Duke, caregiver overload of Zarit and sociodemographic variables. The accomplishment was held at the home of the caregiver.
We detected the presence of depressive disorders in 47.3% (95% 14,6-39%) respondents and anxiety disorders in 25.5% (95% 23-6-61,1%). 36.4% (CI 95% 23,8-50,4%) of caregivers had low social support and overhead was 57.1% (CI 95% 43,2-70,9%).
Caregivers of Dependent grade II and III in our area are at risk of depressive disorders and anxiety. At the same time, they feel helpless, so we think it would be interesting to be given greater attention from health centers in order to identify them early.
The close anatomical and functional connection between the orbitofrontal cortex and olfactory processing suggests that emotion regulation and olfactory identification could be associated. Smell identification deficit (SID) is common in adult schizophrenia, but it has been less studied in bipolar patients, who also show a significant degree of social disadvantage.
A sample of 27 euthymic bipolar patients were recluted. Euthymia was defined as YMRS < 6 and HDRS < 8, during a 3-month period. Patients were assessed with the University of Pennsylvania Smell Identification Test (UPSIT), Face Recognition Test and a verbal Theory of Mind test (Faux Pas Test), in order to examine the association between olfactory identification ability and social cognition domains.
According to the hypothesis, olfactory identification was positively correlated with Face Emotion Recognition (Pearson, p = 0.007) and verbal Theory of Mind (Pearson, p=0.030). Smell identification was similar in smoker (15/27) and non-smoker subgroup of the sample (U Mann Whitney; p = n.s). No differences were neither found between male (14/27) and female subgroup (U; p = n.s).
Olfactory identification and social cognition (specially, face emotion recognition) appear to represent two correlated traits in bipolar disorder, suggesting a possible common neural substrate.
Bipolar patients show a significant degree of psychosocial disfunction even in euthymia. Recent studies have reported deficits in Theory of Mind and emotion recognition in BD. Our hypothesis is that social cognition deficit could be associated with a poor general functioning and psychosocial disadvantage in BD.
A sample of 27 euthymic bipolar patients were recluted. Based on Global Assessment of Functioning, they were divided into two groups: good or low general functioning. Euthymia was defined as YMRS < 6 and HDRS < 8, during a 3-month period. Patients with high (n 18) and low (n 9) functioning were compared on several clinical variables and on social / general cognitive measures. Both verbal and non verbal Theory of Mind capacities were assesed (faux pas test and face emotion recognition test). Finally, sustained attention and executive functions were evaluated (Asarnow Test and WSCT).
High- and low-functioning groups did not differ with respect to demographic and clinical variables (age, sex, age at onset, years of evolution of illness, history of prior psychotic symptoms; p = n.s.). However, low-functioning group showed poorer performance than high-functioning group both in faux pas test (U Mann Whitney; p=0.035) and face emotion recognition (U; p = 0.021). In addition, low-functioning group also showed a significant impairment in general cognitive funtions such as sustained attention (U, p = 0.007) and executive funtions (U, p = 0.046).
Social cognition deficit is associated with a poorer general functioning and psychosocial disadvantage.
Calcineurin inhibitors can cause neurological and psychiatric side effects. Mild symptoms to severe complications can be found.
We report a 49 year old man who received an orthotopic liver transplantation in May 2010. He received tacrolimus. Ten days later, while he was still in Hospital, he suffered behavioural disorders, being psychotic with delusions of persecution; he called the police thinking that he was being poisened by the staff of the Hospital. Although his Tacrolimus blood concentration had been kept in the normal range, his symptoms improved dramatically when the Tacrolimus was changed into Cyclosporine and Haloperidol was introduced at high doses (7 mg/day) for 10 days when the dose was reduced to 4 mg/day.
Chronic hepatitis VHC 1a in 1994. Received treatment with Interferon alfa in 1997 with no antiviral answer. In 2001 new treatment with pegylated Interferon and Ribavirine with positive virological answer but had to be stopped because of psychoses secondary to treatment. New treatment in March 2006 to March 2007 with Pegasys+Ribavirine with rapid virologycal answer with prophylactic Olanzapine 5 mg during a year with no psychotic symptons. In May 2009, Child Pugh C10, in list for liver transplantation.
We discuss the implications of these findings and the relevance for future clinical care in these patients.
Metabolic syndrome is a frequent, severe, undiagnosed physical comorbidity in patients with severe mental disorders.
To develop a predictive model of metabolic syndrome for patients with schizophrenic or bipolar disorders, useful for both clinical practice and research.
Naturalistic, one-year follow-up study conducted in Asturias, Spain. A total of 172 patients with schizophrenic (Sch-P) or bipolar (BD-P) disorders (ICD-10 criteria), under maintenance treatment, who gave written informed consent were included. Metabolic syndrome was defined according to the modified NCEP ATP-III criteria. Multivariate Adaptive Regression Splines (MARS), Genetic Algorithms (GA), and Support Vector Machine (SVM) analysis were performed.
Starting from a large set of demographic and clinical variables, and by means of intermediate MARS and GA models, an SVM model able to classify if a patient with schizophrenia or bipolar disorder suffers from metabolic syndrome with an accuracy of 98.68% (sensitivity 100%, specifity 94.4%) was obtained. The final model only needs 6 variables: Sch-P:
(1) Low HDL-cholesterol,
(2) Fasting glucose level,
(3) Family history of obesity,
(4) Triglyceride level,
(5) Family history of dyslipidemia, and
(6) Use of antidepressants; BD-P: (1), (2), (3),
(7) Use of lipid-lowering medication,
(8) Use of antipsychotics, and
(9) Use of mood stabilizers.
We developed a simple and easy to use predictive model to identify metabolic syndrome in patients with schizophrenic or bipolar disorders.
Pregabalin is indicated for the treatment of GAD in adults in Europe. The efficacy and safety of pregabalin for the treatment of adults and elderly patients with GAD has been demonstrated in 6 of 7 short-term clinical trials of 4 to 8 weeks.
To characterise the long-term efficacy and safety of pregabalin in subjects with GAD.
Subjects were randomised to double-blind treatment with either high-dose pregabalin (450-600 mg/d), low-dose pregabalin (150-300 mg/d), or lorazepam (3-4 mg/d) for 3 months. Treatment was extended with drug or blinded placebo for a further 3 months.
At 3 months, mean change from baseline Hamilton Anxiety Rating Scale (HAM-A) for pregabalin high- and low-dose, and for lorazepam ranged from -16.0 to -17.4. Mean change from baseline Clinical Global Impression-Severity (CGI-S) scores ranged from -2.1 to -2.3 and mean CGI-Improvement (CGI-I) scores were 1.9 for each active treatment group. At 6 months, improvement was retained for all 3 active drug groups, even when switched to placebo. HAM-A and CGI-S change from baseline scores ranged from -14.9 to -19.0 and -2.0 to -2.5, respectively. Mean CGI-I scores ranged from 1.5 to 2.3. The most frequently reported adverse events were insomnia, fatigue, dizziness, headache, and somnolence.
Efficacy was observed at 3 months, with maintained improvement in anxiety symptoms over 6 months of treatment. These results are consistent with previously reported efficacy and safety trials of shorter duration with pregabalin and lorazepam in subjects with GAD.
Normal Pressure Hydrocephalus(Hakim-Adams Syndrome)is a dilation of the ventricles without an increase of intracranial pressure.It corresponds to he classic triade of are gait disturbance, memory/cognitive problems,and urinary incontinence. Manic and depressive symptoms can be related to hydrocephalus occlusus even in the absence of neurological symptoms.These symptoms disappear after neurosurgery or pharmacological treatment.
A 26 year old-male,from Cabo Verde,is interviewed in the Emergency Department in June 2011 presenting disturbance of general behaviour.He is being aggressive and presents flight of ideas.The diagnosis: “Hypomanic state” treated with lorazepam 6 mg/day and Olanzapine 5 mg/day. August 2011, the patient is reevaluated because of his behaviour:soliloquies,laughs,expansive mood, abnormal irritability, easily excited to enthusiasm and irritable humor. He also presents psychomotor agitation associated to delusion of persecution.He has not been taking his medication. No other neurological symptoms are detected.
In Hospital he receives Risperidone 6 mg/day, Clorazepate Dipotassium45mg/day and Lormetazepam 2 mg /day disappearing most of the symptoms.
A MRI was done, presenting triventricular hydrocephalus with absence of intraparenchymal damage.After monitoring the intracranial pressure, Neurosurgery decides not to perform surgery.
In the case of not responding to Risperidone, studies have been published that Aripiprazole (atypical antipsychotic with a unique partial agonistic effect at D2receptors)is effective and safe in the treatment of manic episode. Some publications about the reduction of D2receptors demonstrated that the binding of striatal was reduced in NPH.
Sometimes imaging tests are needed in patients with behavioural disturbance as manic symptoms in order to avoid misdiagnosis and it is crucial for the correct medical and chirurgical treatment.
Pregabalin is indicated for the treatment of generalised anxiety disorder (GAD) in adults in Europe. When pregabalin is discontinued, a 1-week (minimum) taper is recommended to prevent potential discontinuation symptoms.
To evaluate whether a 1-week pregabalin taper, after 3 or 6 months of treatment, is associated with the development of discontinuation symptoms (including rebound anxiety) in subjects with GAD.
Subjects were randomised to double-blind treatment with low- (150-300 mg/d) or high-dose pregabalin (450-600 mg/d) or lorazepam (3-4 mg/d) for 3 months. After 3 months ~25% of subjects in each group (per the original randomisation) underwent a double-blind, 1-week taper, with substitution of placebo. The remaining subjects continued on active treatment for another 3 months and underwent the 1-week taper at 6 months.
Discontinuation after 3 months was associated with low mean changes in Physician Withdrawal Checklist (PWC) scores (range: +1.4 to +2.3) and Hamilton Anxiety Rating Scale (HAM A) scores (range: +0.9 to +2.3) for each pregabalin dose and lorazepam. Discontinuation after 6 months was associated with low mean changes in PWC scores (range: -1.0 to +3.0) and HAM A scores (range: -0.8 to +3.0) for all active drugs and placebo. Incidence of rebound anxiety during pregabalin taper was low and did not appear related to treatment dose or duration.
A 1-week taper following 3 or 6 months of pregabalin treatment was not associated with clinically meaningful discontinuation symptoms as evaluated by changes in the PWC and HAM A rating scales.
The concept of schizophrenia as a systemic disease includes, not only psychosis, but an increase in somatic comorbidity and cardiovascular risk . Furthermore, it is known the implication of inflammation in the pathogenesis of schizophrenia .
To determinate potential inflammatory/metabolic biomarkers of schizophrenia's dimensions.
Sample: 36 outpatients with schizophrenia for less than 11 years, under stable maintenance treatment (mean age [32.25], males [63.9%]) and their 36 matched controls (age [32.53 ± 6.63]; males [72.2%]).
PANSS, Clinical Assessment Interview for Negative Symptoms(CAINS), Calgary Scale(CDS), CGI, Personal and Social Performance Scale(PSP). Biomarkers: C-reactive protein (CRP), homocysteine, glucose, insulin, HOMA-IR (insulin resistance), cholesterol, HDL, LDL, triglycerides.
Biomarkers differences between groups are shown in Table 1. Table 2 shows the correlations found after controlling for Body Mass Index [patients(28.61 ± 5.69);controls(24.64 ± 3.80);p = 0.001] and Smoking [patients(52.8%-yes);controls(5.6%-yes);p = 0.000].
1. CRP, a potential inflammatory biomarker in schizophrenia, is related to depression severity. Homocysteine, representing an oxidative stress, is related to positive, negative, cognitive and depressive symptoms severity, and worse functioning. 2. Patients with schizophrenia have lower HDL–related to negative and cognitive symptoms severity and worse functioning–and insulin resistance – related to worse cognition –.
Disclosure of interest
The authors have not supplied their declaration of competing interest.
To use a Machine Learning (ML) approach to compare Neuropsychiatric Symptoms (NPS) in participants of a longitudinal study who developed dementia and those who did not.
Mann-Whitney U and ML analysis. Nine ML algorithms were evaluated using a 10-fold stratified validation procedure. Performance metrics (accuracy, recall, F-1 score, and Cohen’s kappa) were computed for each algorithm, and graphic metrics (ROC and precision-recall curves) and features analysis were computed for the best-performing algorithm.
Primary care health centers.
128 participants: 78 cognitively unimpaired and 50 with MCI.
Diagnosis at baseline, months from the baseline assessment until the 3rd follow-up or development of dementia, gender, age, Charlson Comorbidity Index, Neuropsychiatric Inventory-Questionnaire (NPI-Q) individual items, NPI-Q total severity, and total stress score and Geriatric Depression Scale-15 items (GDS-15) total score.
30 participants developed dementia, while 98 did not. Most of the participants who developed dementia were diagnosed at baseline with amnestic multidomain MCI. The Random Forest Plot model provided the metrics that best predicted conversion to dementia (e.g. accuracy=.88, F1=.67, and Cohen’s kappa=.63). The algorithm indicated the importance of the metrics, in the following (decreasing) order: months from first assessment, age, the diagnostic group at baseline, total NPI-Q severity score, total NPI-Q stress score, and GDS-15 total score.
ML is a valuable technique for detecting the risk of conversion to dementia in MCI patients. Some NPS proxies, including NPI-Q total severity score, NPI-Q total stress score, and GDS-15 total score, were deemed as the most important variables for predicting conversion, adding further support to the hypothesis that some NPS are associated with a higher risk of dementia in MCI.
Human trafficking is a crime and a human rights violation that involves various and simultaneous traumatic events (sexual and physical violence, coercion). Yet, it is unknown how the patterning of violence and coercion affects the mental health of female and male trafficking survivors.
We conducted a cross-sectional study using a sample of 1015 female and male survivors of trafficking who received post-trafficking assistance services in Cambodia, Thailand or Vietnam. We assessed symptoms of anxiety and depression with the Hopkins Symptoms Checklist and symptoms of post-traumatic stress disorder (PTSD) with the Harvard Trauma Questionnaire. Violence was measured with questions from the World Health Organization International Study on Women's Health. Latent class analysis (LCA) was used to identify distinct patterns of violence and coercion in females and males. Novel multi-step mixture modelling techniques were employed to assess the association of the emergent classes with anxiety, depression and PTSD in females and males.
LCA identified two distinct classes of violence and coercion experiences in females (class I: severe sexual and physical violence and coercion (20%); class II: sexual violence and coercion (80%)) and males (class I: severe physical violence and coercion (41%); class II: personal coercion (59%)). Females in class I had a two-fold increase in the odds of anxiety (OR = 2.10; 95% CI: 1.57–2.81) and PTSD (OR = 2.07; 95% CI: 1.03–4.17) compared with females in class II, but differences in the prevalence of anxiety, depression and PTSD were not significant when comparing males in class I to class II.
Specific patterns of violence and coercion provide a more in-depth understanding of the role of gender in the experience of violence and coercion and its association with mental health in survivors of trafficking. This information could be useful to target comprehensive mental health services for female and male trafficking survivors.
Aliphatic and polycyclic aromatic hydrocarbons (AHs and PAHs) were investigated in soil and meltwater stream sediments near the Uruguayan Artigas Research Station (BCAA). Gas chromatography with flame ionization detection and gas chromatography mass spectrometry were used to determine the composition of AHs and PAHs, respectively. Total AH concentrations were in the range 0.57–2333 µg g-1, while total PAH concentrations were in the range 1.36–51 650 ng g-1. Based on AH and PAH concentrations, sites in the service area and next to the boat storeroom are highly contaminated, while the other sites sampled have moderate to low contamination levels or are not impacted. High unresolved complex mixture concentrations indicate the occurrence of previous petrogenic contamination, but the dominance of low molecular weight and alkyl PAHs indicate recent oil introductions. Anthropogenic hydrocarbons dominate and are related to diesel fuel and organic residue combustion, fuel storage and boat traffic. Petrogenic contamination is relatively high, as at other Antarctic stations, but is restricted to the boat storeroom and the service area where the incinerator, the generator room and fuel tanks are located. Improvements made in fuel management procedures and the dismantling of the old fuel tanks will reduce the risk of diesel leaks and their impact on the environment near the BCAA. This study provides reference information for future environmental monitoring.
Accurate models of X-ray absorption and re-emission in partly stripped ions are necessary to calculate the structure of stars, the performance of hohlraums for inertial confinement fusion and many other systems in high-energy-density plasma physics. Despite theoretical progress, a persistent discrepancy exists with recent experiments at the Sandia Z facility studying iron in conditions characteristic of the solar radiative–convective transition region. The increased iron opacity measured at Z could help resolve a longstanding issue with the standard solar model, but requires a radical departure for opacity theory. To replicate the Z measurements, an opacity experiment has been designed for the National Facility (NIF). The design uses established techniques scaled to NIF. A laser-heated hohlraum will produce X-ray-heated uniform iron plasmas in local thermodynamic equilibrium (LTE) at temperatures
eV and electron densities
. The iron will be probed using continuum X-rays emitted in a
diameter source from a 2 mm diameter polystyrene (CH) capsule implosion. In this design,
of the NIF beams deliver 500 kJ to the
mm diameter hohlraum, and the remaining
directly drive the CH capsule with 200 kJ. Calculations indicate this capsule backlighter should outshine the iron sample, delivering a point-projection transmission opacity measurement to a time-integrated X-ray spectrometer viewing down the hohlraum axis. Preliminary experiments to develop the backlighter and hohlraum are underway, informing simulated measurements to guide the final design.
The objective of this study was to assess the effectiveness of a catheter-related bloodstream infection (CR BSI) reduction programme and healthcare workers' compliance with recommendations. A 3-year surveillance programme of CR BSIs in all hospital settings was implemented. As part of the programme, there was a direct observation of insertion and maintenance of central venous catheters (CVCs) to determine performance. A total of 38 education courses were held over the study period and feedback reports with the results of surveillance and recommendations were delivered to healthcare workers every 6 months. A total of 6722 short-term CVCs were inserted in 4982 patients for 58 763 catheter-days. Improvements of compliance with hand hygiene was verified at the insertion (87·1–100%, P < 0·001) and maintenance (51·1–72·1%, P = 0·029) of CVCs; and the use of chlorhexidine for skin disinfection was implemented at insertion (35·7–65·4%, P < 0·001) and maintenance (33·3–45·9%, P < 0·197) of CVCs. There were 266 CR BSI incidents recorded with an annual incidence density of 5·75/1000 catheter-days in the first year, 4·38 in the second year [rate ratio (RR) 0·76, 95% confidence interval (CI) 0·57–1·01] and 3·46 in the third year (RR 0·60, 95% CI 0·44–0·81). The education programme clearly improved compliance with recommendations for CVC handling, and was effective in reducing the burden of CR BSIs.