A prospective longitudinal investigation of the (dis)continuity of mental health difficulties between mid- to late-childhood and the predictive role of familial factors.

Understanding individual variation in the continuity of youth mental health difficulties is critical for identifying the factors that promote recovery or chronicity. This study establishes the proportion of children showing psychopathology at 9 years, whose pathology had either remitted or persisted at 13. It describes the socio-demographic and clinical profiles of these groups, and examines the factors in 9-year-olds' familial environments that predict longitudinal remission vs. persistence of psychopathology. The study utilised data from a prospective longitudinal study of 8568 Irish children. Child psychopathology was assessed using the Strengths and Difficulties Questionnaire (SDQ). Analysis established the rates of continuity of SDQ classifications between 9 and 13 years. Analysis also investigated the familial factors that predicted the remission vs. persistence of psychopathological symptoms, controlling for socio-demographic and child factors. Average SDQ scores improved between the ages of 9 and 13, F(1, 7292) = 276.52, p < 0.001, [Formula: see text] = 0.04. Of children classified Abnormal aged 9, 41.1% remained so classified at 13, 21.4% were reclassified Borderline, and 37.6% Normal. Demographic and child risk factors for persistence of pathology were maleness (ß = -1.00, p = 0.001, CI = 0.20-0.67), one-carer households (ß = -0.71, p = 0.04, CI = 0.25-0.97), poor physical health (ß = -0.64, p = 0.03, CI = 0.30-0.92), and low cognitive ability (ß = 0.61, p = 0.002, CI = 1.26-2.70). Controlling for these factors, the only familial variable at 9 years that predicted subsequent pathological persistence was caregiver depression (ß = -0.07, p = 0.03, CI = 0.87-0.99). The analysis highlights substantial rates of psychopathological discontinuity in a community sample and identifies the children most at risk of chronic mental health problems. These results will inform the targeting of early interventions and distribution of clinical resources.

SUPPORTING PRETERM INFANT ATTACHMENT AND SOCIOEMOTIONAL DEVELOPMENT IN THE NEONATAL INTENSIVE CARE UNIT: STAFF PERCEPTIONS.

The infant-parent relationship has been shown to be of particular significance to preterm infant socioemotional development. Supporting parents and infants in this process of developing their relationships is an integral part of neonatal intensive care; however, there is limited knowledge of NICU staff perceptions about this aspect of care. To explore NICU staff perceptions about attachment and socioemotional development of preterm infants, experience of training in this area and the emotional impact of their work. A cross-sectional questionnaire survey of staff perceptions of the emotional experiences of parents and the developing parent-infant relationship in an NICU was conducted in a Level III NICU, after pilot testing, revision, and ethical approval. Fifty-seven (68%) of NICU staff responded to the survey. Respondents identified parents' emotional experiences such as "anxiety," "shock," "loss of control," and "lack of feelings of competence as parents" as highly prevalent. Infant cues of "responding to parent's voice" and "quieting-alerting" were ranked most highly; "crying" and "physiological changes" were ranked lowest. Preterm infant medical risk, maternal emotional state, and mental health are perceived to impact most highly on the developing relationship, as compared with infant state or behavior and socioeconomic factors. Fifty-three (93%) respondents felt confident, and 50 (87.8%) felt competent discussing their emotional experiences with parents. Fifty-four (95%) responded that attending to these areas was an integral part of their role; however, staff had seldom received education in this area. Respondents also perceived that specific psychological support for parents was lacking both during and after the infant's discharge. While all staff surveyed perceived the nature of their work to be emotionally stressful, there were differences among NICU staff disciplines and with years of experience in the NICU in terms of their perceptions about education in this area, the place of supervision for staff, and in relation to opportunities to discuss the emotional impact of the work on staff. NICU staff perceive their role as integral to supporting the developing parent-infant relationship and preterm infant socioemotional development; however, education in this area and provision of specific psychological support are lacking. Opportunities for staff to discuss and reflect on this aspect of their work should be developed and evaluated given the essential, but emotionally challenging, nature of their work with preterm babies and their parents.

Association between autoimmune thyroiditis and depressive disorder in psychiatric outpatients.

Thyroid diseases are often associated with psychiatric disorders. The prevalence of autoimmune thyroiditis in the general population is estimated to be at about 5-14 %. A clinical study was conducted to evaluate the association between autoimmune thyroiditis and depression in psychiatric outpatients. Fifty-two patients with depression and nineteen patients with schizophrenia (serving as control group), attending a psychiatric outpatient unit, were included. In addition to the measurement of thyroid-stimulating hormone (TSH), free triiodothyronine, free thyroxine, antithyroid peroxidase (anti-TPO) antibodies, and anti-thyroglobulin antibodies, ultrasound examination of the thyroid gland was performed. The proportion of pathologically increased anti-TPO levels in patients with depression was high. Furthermore, the distribution of pathologically increased anti-TPO levels was significantly (χ (2) = 5.5; p = 0.019) different between patients with depression (32.7 %) and patients with schizophrenia (5.3 %). In a gender- and age-adjusted logistic regression, the odds ratio of uni- or bipolar patients with depression for an autoimmune thyroiditis was ten times higher (95 % CI = 1.2-85.3) when compared with schizophrenia patients. TSH basal level did not differ between patients with depression and patients with schizophrenia. Our study demonstrates a strong association between anti-TPO levels, which are considered to be of diagnostic value for autoimmune thyroiditis (in combination with a hypoechoic thyroid in ultrasonography) with uni- or bipolar depression. It should be noted that the routinely measured TSH level is not sufficient in itself to diagnose this relevant autoimmune comorbidity.

Psychostimulant prescribing trends in a paediatric population in Ireland: a national cohort study.

BACKGROUND: Psychotropic paediatric prescribing trends are increasing internationally. The aim of this study is to examine the prevalence and secular trends in psychotropic prescribing in Irish children and adolescents between 2002 and 2011. METHODS: Data was obtained from the Irish General Medical Services (GMS) scheme pharmacy claims database from the Health Service Executive Primary Care Reimbursement Services (HSE-PCRS). Prescribing rates per 1000 eligible population and associated 95% confidence intervals (CIs) were calculated across years (2002-2011), age groups (0-4, 5-11, 12-15 years) and gender. Rates of concomitant prescriptions for psycholeptics and antidepressants were also examined. The total expenditure costs were calculated and expressed as a percentage of the cost of all prescriptions for this age group (≤ 15 years). RESULTS: In 2002, 3.77/1000 GMS population (95% CI: 3.53-4.01) received at least one psychostimulant prescription and this rate increased to 8.63/1000 GMS population (95% CI: 8.34-8.92) in 2011. Methylphenidate was the most frequently prescribed psychostimulant. For both males and females the prevalence of medication use was highest among the 12-15 year old group. On average, a psycholeptic medication was prescribed to 8% of all psychostimulant users and an antidepressant was concomitantly prescribed on average to 2%. Total expenditure rose from €89,254 in 2002 to €1,532,016 in 2011. CONCLUSIONS: The rate and cost of psychostimulant prescribing among GMS children and adolescents in Ireland increased significantly between 2002 and 2011. Further research is necessary to assess the safety, efficacy and economic impact of concomitant psychotropic prescribing in this population.

Longitudinal stability of the diurnal rhythm of intraocular pressure in subjects with healthy eyes, ocular hypertension and pigment dispersion syndrome.

BACKGROUND: The diurnal fluctuation of intraocular pressure may be relevant in glaucoma. The aim of this study was to find out whether the timing of diurnal fluctuation is stable over the years. METHODS: Long-term IOP data from the Erlangen Glaucoma Registry, consisting of several annual extended diurnal IOP profiles for each patient, was retrospectively analyzed. Normal subjects, patients with ocular hypertension and with pigment dispersion syndrome were included because these subjects had not been treated with antiglaucomatous medications at the time of data acquisition. A cosine curve was fitted to the IOP data and the stability of individual rhythms over the years was tested using the Rayleigh test. To compare the peak times among groups, means were calculated only from subjects with a significant Rayleigh test. RESULTS: Of the fifty-two eligible subjects, a total of 364 extended diurnal IOP profiles measured in a sitting position had been collected over a period of 114 ± 39 months. The Rayleigh test indicated intraindividual stability of phase timing only in 19 subjects (36%). In subjects with pigment dispersions syndrome, peak IOP occurred on average two hours and seven minutes later during the day compared with subjects without this condition (p = 0.05). CONCLUSIONS: Fitting of cosine curves to the clinical IOP profiles was generally feasible, although careful interpretation is warranted due to lack of measurements in supine position and between midnight and 7 am. The interesting observation of a phase lag in eyes with pigment dispersion syndrome warrants confirmation and exploration in future prospective studies. The analysis of the IOP data showed no stable individual rhythm in the long term in a majority of patients.

Factors associated with self-cutting as a method of self-harm: findings from the Irish National Registry of Deliberate Self-Harm.

BACKGROUND: Research suggests that patients presenting to hospital with self-cutting differ from those with intentional overdose in demographic and clinical characteristics. However, large-scale national studies comparing self-cutting patients with those using other self-harm methods are lacking. We aimed to compare hospital-treated self-cutting and intentional overdose, to examine the role of gender in moderating these differences, and examine the characteristics and outcomes of those patients presenting with combined self-cutting and overdose. METHODS: Between 2003 and 2010, the Irish National Registry of Deliberate Self-Harm recorded 42,585 self-harm presentations to Irish hospital emergency departments meeting the study inclusion criteria. Data were obtained on demographic and clinical characteristics by independent data registration officers. RESULTS: Compared with overdose only, involvement of self-cutting (with or without overdose) was significantly more common in males than females, with an overrepresentation of males aged <35 years. Independent of gender, involvement of self-cutting (with or without overdose) was significantly associated with younger age, city residence, repetition within 30 days and repetition within a year (females only). Factors associated with self-cutting as the sole method were no fixed abode/living in an institution, presenting outside 9 a.m. to 5 p.m., not consuming alcohol and repetition between 31 days and 1 year (males only). CONCLUSION: The demographic and clinical differences between self-harm patients underline the presence of different subgroups with implications for service provision and prevention of repeated self-harm. Given the relationship between self-cutting and subsequent repetition, service providers need to ensure that adequate follow-up arrangements and supports are in place for the patient.

Facilitative effects of VNS on the motor threshold: implications for its antidepressive mode of action?

In the present study, the effects of vagus nerve stimulation (VNS) on the resting motor threshold (rMT) of patients treated with repetitive transcranial magnetic stimulation were evaluated. Patients showed a significant decrease in the rMT during VNS-on stimulation. VNS was the only significant factor affecting rMT changes and did not appear to be a static variable. Further studies should focus on the effect of VNS on neural neurogenesis in depressive disorders, and the effects of other treatment options for major depressive disorder on the rMT should also be determined.

Weight, body image and bullying in 9-year-old children.

AIM: To explore the association between weight and bullying; considering victims and perpetrators as two aspects of bullying, and subjective perception and objective measurement as two aspects of weight. METHODS: This study is based on the first wave of data collection from Growing Up in Ireland - the National Longitudinal Study of Children. The two-stage sample design included a sample of 910 primary schools in Ireland, from which a sample of 8568 nine-year-old children and their families was randomly selected. Analysis is based on statistically reweighted data to ensure that it is representative of all 9-year-olds in Ireland. RESULTS: Significantly (P < 0.001) more girls were overweight or obese (33.1%: 23.1% overweight and 10% obese) than boys (25.2%: 18.3% and 6.9%). Children who were body mass index (BMI) classified as overweight or obese were significantly (P < 0.001) more likely to be victimised when compared with children whose BMI was not classified as overweight or obese. BMI-classified thinness was not significantly associated with victimisation; however, the body image of being skinny or very skinny was significantly (P = 0.015) associated with being victimised. Bullying perpetration was not associated with BMI-derived weight classification but was significantly (P < 0.001) associated with the child's own self-description of weight. CONCLUSIONS: Overall body image was found to have a stronger association with victimisation and bullying perpetration than objective BMI-derived weight classification. Further research investigating the mediating role of body image in the relationship between weight, victimisation and bullying is necessary to better understand this association.

EEG alterations during treatment with olanzapine.

The aim of this naturalistic observational study was to investigate EEG alterations in patients under olanzapine treatment with a special regard to olanzapine dose and plasma concentration. Twenty-two in-patients of a psychiatric university ward with the monodiagnosis of paranoid schizophrenia (ICD-10: F20.0), who received a monotherapy of olanzapine were included in this study. All patients had a normal alpha-EEG before drug therapy, and did not suffer from brain-organic dysfunctions, as verified by clinical examination and cMRI scans. EEG and olanzapine plasma levels were determined under steady-state conditions (between 18 and 22 days after begin of treatment). In 9 patients (40.9%), pathological EEG changes (one with spike-waves) consecutive to olanzapine treatment were observed. The dose of olanzapine was significantly higher in patients with changes of the EEG than in patients without changes (24.4 mg/day (SD: 8.1) vs. 12.7 mg/day (SD: 4.8); T = -4.3, df = 21, P < 0.001). In patients with EEG changes, the blood plasma concentration of olanzapine (45.6 µg/l (SD: 30.9) vs. 26.3 µg/l (SD: 21.6) tended to be also higher. The sensitivity of olanzapine dosage to predict EEG changes was 66.7%, the specificity 100% (Youden-index: 0.67). EEG abnormalities during olanzapine treatment are common. These are significantly dose dependent. Thus, EEG control recordings should be mandatory during olanzapine treatment with special emphasis on dosages exceeding 20 mg per day, although keeping in mind that EEGs have only a limited predictive power regarding future epileptic seizures.

Palliative first-line therapy with weekly high-dose 5-fluorouracil and sodium folinic acid as a 24-hour infusion (AIO regimen) combined with weekly irinotecan in patients with metastatic adenocarcinoma of the stomach or esophagogastric junction followed by secondary metastatic resection after downsizing.

BACKGROUND: The aim of this retrospective study was to evaluate the efficacy and safety of weekly high-dose 5-fluorouracil (5-FU)/folinic acid (FA) as 24-h infusion (AIO regimen) plus irinotecan in patients with histologically proven metastatic gastroesophageal adenocarcinoma (UICC stage IV). MATERIAL/METHODS: From 08/1999 to 12/2008, 76 registered, previously untreated patients were evaluable. Treatment regimen: irinotecan (80 mg/m²) as 1-h infusion followed by 5-FU (2000 mg/m²) combined with FA (500 mg/m²) as 24-h infusion (d1, 8, 15, 22, 29, 36, qd 57). RESULTS: Median age: 59 years; male/female: 74%/26%; ECOG ≤1: 83%; response: CR: 1%, PR: 16%, SD: 61%, PD: 17%, not evaluable in terms of response: 5%; tumor control: 78%; median OS: 11.2 months; median time-to-progression: 5.3 months; 1-year survival rate: 49%; 2-year survival rate: 17%; no evidence of disease: 6.6%; higher grade toxicities (grade 3/4): anemia: 7%, leucopenia: 1%, ascites: 3%, nausea: 3%, infections: 12%, vomiting: 9%, GI bleeding of the primary tumor: 4%, diarrhea: 17%, thromboembolic events: 4%; secondary metastatic resection after downsizing: 16 patients (21%), R-classification of secondary resections: R0/R1/R2: 81%/6%/13%, median survival of the 16 patients with secondary resection: 23.7 months. CONCLUSIONS: Combined 5-FU/FA as 24-h infusion plus irinotecan may be considered as an active palliative first-line treatment accompanied by tolerable toxicity; thus offering an alternative to cisplatin-based treatment regimens. Thanks to efficient interdisciplinary teamwork, secondary metastatic resections could be performed in 16 patients. In total, the patients who had undergone secondary resection had a median survival of 23.7 months, whereas the median survival of patients without secondary resection was 10.1 months (p≤0.001).

Quantification of fatty acid ethyl esters (FAEE) and ethyl glucuronide (EtG) in meconium from newborns for detection of alcohol abuse in a maternal health evaluation study.

Fatty acid ethyl esters (FAEE) and ethyl glucuronide (EtG) were determined in 602 meconium samples in a maternal health evaluation study for detection of gestational alcohol consumption. A validated headspace solid phase microextraction method in combination with GC-MS was used for FAEE and the cumulative concentration of ethyl palmitate, ethyl linoleate, ethyl oleate, and ethyl stearate with a cut-off of 500 ng/g was applied for interpretation. A new and simple method was developed and validated for quantification of EtG from 10-20 mg meconium with D(5)-EtG as internal standard consisting of 30 min. extraction with methanol/water (1:1, v/v), evaporation of methanol, filtration of the aqueous solution through a cellulose filter and injection into LC-MS-MS. The limits of detection and quantification for EtG were 10 and 30 ng/g, the recovery 86.6 to 106.4% and the standard deviation of the concentrations ranged from 13% at 37 ng/g to 5% at 46,700 ng/g (N = 6). FAEE above the cut-off were found in 43 cases (7.1%) with cumulative concentrations between 507 and 22,580 ng/g and with one outlier of about 150,000 ng/g (EtG not detected). EtG was detected in 97 cases (16.3%) and concentrations between LOD and 10,200 ng/g with another outlier of 82,000 ng/g (FAEE 10,500 ng/g). Optimal agreement between the two markers was obtained with a cut-off for EtG of 274 ng/g and 547 cases with both FAEE- and EtG-negative, 33 cases with both FAEE- and EtG-positive, nine cases with FAEE-positive and EtG-negative, and seven cases with FAEE-negative and EtG-positive. Differences in physical, chemical, and biochemical properties and in the pharmacokinetic behavior are discussed as reasons for the deviating cases. In none of the 602 cases, serious alcohol consumption was reported by the mothers and no evidence for gestational ethanol exposure was observed in the medical investigation of the newborns. It is concluded that the combined use of FAEE and EtG in meconium as markers for fetal alcohol exposure essentially increases the accuracy of the interpretation and helps to avoid false positive and false-negative results.

Non-right-handedness and free serum testosterone levels in detoxified patients with alcohol dependence.

AIMS: The influence of testosterone on the extent of hemispheric dominance has been discussed not just during the first two trimesters of pregnancy but also later in life. An increase in free serum testosterone levels has been found during and after the detoxification phase of patients with alcohol dependence. METHODS: In 250 participants (125 men and 125 women) with alcohol dependence immediately after the direct withdrawal phase (Day 21) and in 250 healthy age- and gender-matched participants, free testosterone in the serum was determined and handedness was assessed as a peripheral marker of central hemispheric dominance. RESULTS: Patients with alcohol dependence were 2.7-fold (odds ratio, OR: 2.66; 95% confidence interval, CI: 1.62-4.38) and men 4.1-fold (OR: 4.12; 95% CI: 2.44-6.98) more likely to be non-right-handed (NRH). In addition to male gender, non-right-handedness and alcohol dependence contributed statistically significantly to higher serum testosterone levels. Testosterone values of patients with alcohol dependence differed significantly between the four different Lesch subtypes; in particular, participants with alcohol dependence classified according to Lesch subtype IV were found to have significantly higher serum testosterone levels (F = 20.5; P < 0.001) when compared to participants classified according to Lesch subtypes I-III. CONCLUSIONS: An alteration of hemispheric dominance and thus an exogenously modifiable neuronal plasticity may be demonstrated directly on a population at risk.

Use of analgesics in intentional drug overdose presentations to hospital before and after the withdrawal of distalgesic from the Irish market.

BACKGROUND: Distalgesic, the prescription-only analgesic compound of paracetamol (325 mg) and dextropropoxyphene (32.5 mg) known as co-proxamol in the UK, was withdrawn from the Irish market as of January 2006. This study aimed to evaluate the impact of the withdrawal of distalgesic in terms of intentional drug overdose (IDO) presentations to hospital emergency departments (EDs) nationally. METHODS: A total of 42,849 IDO presentations to 37 of the 40 hospitals EDs operating in Ireland in 2003-2008 were recorded according to standardised procedures. Data on sales of paracetamol-containing drugs to retail pharmacies for the period 1998-2008 were obtained from IMS Health. RESULTS: The withdrawal of distalgesic from the Irish market resulted in an immediate reduction in sales to retail pharmacies from 40 million tablets in 2005 to 500,000 tablets in 2006 while there was a 48% increase in sales of other prescription compound analgesics. The rate of IDO presentations to hospital involving distalgesic in 2006-2008 was 84% lower than in the three years before it was withdrawn (10.0 per 100,000). There was a 44% increase in the rate of IDO presentations involving other prescription compound analgesics but the magnitude of this rate increase was five times smaller than the magnitude of the decrease in distalgesic-related IDO presentations. There was a decreasing trend in the rate of presentations involving any paracetamol-containing drug that began in the years before the distalgesic withdrawal. CONCLUSIONS: The withdrawal of distalgesic has had positive benefits in terms of IDO presentations to hospital in Ireland and provides evidence supporting the restriction of availability of means as a prevention strategy for suicidal behaviour.

Neoadjuvant treatment with weekly high-dose 5-fluorouracil as a 24h-infusion, folinic acid and biweekly oxaliplatin in patients with primary resectable liver metastases of colorectal cancer: long-term results of a phase II trial.

BACKGROUND: In 2003 Wein et al. published data after a short median follow up (23 months). Here we report on the long-term results. MATERIAL/METHODS: The patients (n=20) received a neoadjuvant treatment regimen comprising biweekly 85 mg/m2 oxaliplatin (L-OHP) (2h-infusion, d 1, 15, 29 qd 57) and 500 mg/m2 calcium folinic acid (FA) (1-2h-infusion, d 1, 8, 15, 22, 29, 36 qd 57) followed by 2600 mg/m2 5-Fluorouracil (5-FU) (24h-infusion, d 1, 8, 15, 22, 29, 36 qd 57). Two cycles of chemotherapy were administered, with a third being added when the treatment was well tolerated. Thereafter, curative resection of the liver metastases was attempted. RESULTS: After neoadjuvant therapy, imaging procedures revealed complete remission in 2 patients (10%) and partial remission in 18 patients (90%). Diarrhea (Common Toxicity Criteria toxicity grade 3) was observed in 6 patients (30%) as main symptom of toxicity, followed by vomiting in 3 patients (15%). Higher grade sensomotoric neuropathy did not present. The curative resectability rate (R0) was 80%. In 9 out of 18 patients (50%) undergoing surgical intervention minor postoperative complications occurred. No postoperative mortality was observed. Over a median follow up of 45,5 months the median survival of all patients is 3.0 years and the 5-year overall survival rate is 40%. The 5-year disease-free survival rate is 25%. CONCLUSIONS: Neoadjuvant treatment with 5-FU combined with FA and L-OHP proved to be highly effective and well tolerated. Disease-free survival rates and median overall survival rates are promising.

Palliative first-line treatment with weekly high-dose 5-fluorouracil as 24h-infusion and gemcitabine in metastatic pancreatic cancer (UICC IV).

BACKGROUND: The aim of this study was to evaluate the efficacy and toxic side effects of combined gemcitabine plus weekly high-dose 5-Fluorouracil (5-FU) as 24h-infusion in patients with metastatic pancreatic cancer (UICC IV) as validation group of an earlier phase II study. Primary endpoints were to assess the response and tumour control rate. MATERIAL/METHODS: This study comprised 60 prospectively registered patients with metastatic pancreatic cancer (UICC IV). A locally advanced disease was defined as exclusion criteria. The treatment schedule was weekly gemcitabine (1.000 mg/m(2)) as a 0.5h-infusion combined with 5-FU (2.000 mg/m(2)) as a 24h-infusion on day 1, 8 and 15 every 28 days. RESULTS: Response rate (CR+PR) was achieved in 7% of the patients, tumour control rate (CR+PR+SD) was achieved in 59%. Median time-to-progression was 4 months, median overall survival was 7.3 months (95% CI 5.4-9.1). The median survival of patients with normal CEA value was 10.6 months (95% CI 7.8-13.4); with a normal CA 19-9 median survival was 10.1 months (95% CI 4.6-15.7) and with ECOG performance status 0 median survival was 10.1 months (95% CI 8.6-15.3). As higher grade toxicity (grade 3/4) leukopenia (15%), anaemia (10%) and thrombopenia (5%) were observed. Nausea and diarrhea (grade 3/4) occurred in 5% of the patients and vomiting in 2%. CONCLUSIONS: The administration of gemcitabine and 5-FU as a 24h-infusion is feasible and offers good tumour control rate accompanied by tolerable toxicity. The subgroup of patients with a good performance status (ECOG 0) and tumour markers within the normal range benefit from the gemcitabine combination therapy.

Suicide and deliberate self harm in older Irish adults.

BACKGROUND: Hospital-treated deliberate self harm and suicide among older adults have rarely been examined at a national level. METHODS: The Irish Central Statistics Office provided suicide and undetermined death data for 1980-2006. The National Registry of Deliberate Self Harm collected data relating to deliberate self harm presentations made in 2006-2008 to all 40 Irish hospital emergency departments. RESULTS: Rates of female suicide among older adults (over 55 years) were relatively stable in Ireland during 1980-2006 whereas male rates increased in the 1980s and decreased in more recent decades. Respectively, the annual male and female suicide and undetermined death rate was 22.1 and 7.6 per 100,000 in 1997-2006. Male and female deliberate self harm was 3.0 and 11.0 times higher at 67.4 and 83.4 per 100,000, respectively. Deliberate self harm and suicide decreased in incidence with increasing age. Deliberate self harm generally involved drug overdose (male: 72%; female 85%) or self-cutting (male: 15%; female 9%). The most common methods of suicide were hanging (41%) and drowning (29%) for men and drowning (39%) and drug overdose (24%) for women. City and urban district populations had the highest rates of hospital-treated self harm. The highest suicide rates were in urban districts. CONCLUSIONS: Older Irish adults have high rates of hospital-treated deliberate self harm but below average rates of suicide. Drowning was relatively common as a method of suicide. Restricting availability of specific medications may reduce both forms of suicidal behavior.

Statistical methods for detecting and comparing periodic data and their application to the nycthemeral rhythm of bodily harm: A population based study.

BACKGROUND: Animals, including humans, exhibit a variety of biological rhythms. This article describes a method for the detection and simultaneous comparison of multiple nycthemeral rhythms. METHODS: A statistical method for detecting periodic patterns in time-related data via harmonic regression is described. The method is particularly capable of detecting nycthemeral rhythms in medical data. Additionally a method for simultaneously comparing two or more periodic patterns is described, which derives from the analysis of variance (ANOVA). This method statistically confirms or rejects equality of periodic patterns. Mathematical descriptions of the detecting method and the comparing method are displayed. RESULTS: Nycthemeral rhythms of incidents of bodily harm in Middle Franconia are analyzed in order to demonstrate both methods. Every day of the week showed a significant nycthemeral rhythm of bodily harm. These seven patterns of the week were compared to each other revealing only two different nycthemeral rhythms, one for Friday and Saturday and one for the other weekdays.

N-methyl-D-aspartate 2b receptor subtype (NR2B) promoter methylation in patients during alcohol withdrawal.

NMDA receptors and especially the NR2B receptor subtype play a crucial role during chronic ethanol consumption and alcohol withdrawal. Therefore, the NR2B receptor subtype expression in peripheral blood cells of 32 male patients suffering from alcohol dependency were assessed through quantitative RT-PCR and to explore regulating epigenetic mechanisms, a methylation analysis was conducted using bisulfite sequencing of a fragment of the NR2B promoter region. The expression of the NR2B receptor increased significantly during the first 24 h of withdrawal treatment (day 1; t = 4.1, P = 0.001), and also on and day 3 (t = 2.4; P = 0.029). The severity of alcohol drinking pattern, measured by lifetime drinking and daily ethanol intake, was negatively correlated with the methylation of a defined cluster of five CPG-sites within the NR2B promoter (lifetime drinking: Spearman's rho = -0.55; P = 0.013; daily ethanol intake: rho = -0.46; P = 0.043). These findings might explain the observation of an impact of alcohol consumption patterns on the gravity of withdrawal symptoms.

Weekly high-dose 5-fluorouracil as a 24-h infusion and sodium folinic acid (AIO regimen) plus irinotecan in patients with locally advanced nonresectable and metastatic adenocarcinoma or squamous cell carcinoma of the oesophagus: a phase II trial.

In the majority of patients with oesophageal carcinoma, curative treatment proves to be impossible when diagnosis was established; therefore, most of the patients are candidates for palliative chemotherapy. The aim of this phase II study was to evaluate the efficacy and safety of 5-fluorouracil/folinic acid (AIO regimen) plus irinotecan in patients with locally advanced or metastatic carcinoma of the oesophagus. The methods used a prospective phase II trial, start: November 2002; patients: n=25; chemotherapy: irinotecan (80 mg/m2) as a 1-h infusion and 5-fluorouracil (2000 mg/m2) with sodium folinic acid (500 mg/m2) as a 24-h infusion on days 1, 8, 15, 22, 29 and 36, repeated on day 57. Last date of evaluation: 28 February 2007; n=24; adenocarcinoma: n=13, squamous cell carcinoma (SCC): n=11; UICC III/IV: 3/21; grading G1/G2/G3/G4: 0/8/12/4; median age: 58 years (range 44-75); men/women: 19/5; Eastern Cooperative Oncology Group index 0/1/2: 3/17/4; applications: 460. Higher-grade toxicity: grade 3 diarrhoea: n=2, grade 4 diarrhoea: n=1, grade 4 vomiting: n=1, grade 4 nausea: n=1, grade 3 fatigue: n=1, grade 3 hyponatraemia: n=2, grade 4 elevation of creatinine: n=1, thrombosis of the vena subclavia: n=1, ischaemic lesion of the brain stem: n=1. Three patients died after two chemotherapeutic applications because of high tumour burden. Evaluable for response: n=19. Partial response: n=8 (33%), stable disease: n=9 (38%), progressive disease: n=2 (8%), not evaluable: n=5 (21%). Time-to-progression: 6.6 months (range 1.6-24.6). Total median survival: 13.6 months (median survival of adenocarcinoma: 20.3 months, median survival of SCC: 10.0 months). Secondary resection (R0): n=3. In oesophageal carcinomas, the AIO regimen plus irinotecan is excellently manageable as an outpatient treatment and shows efficacy in adenocarcinomas and SCCs of the oesophagus.

Determination of axonal transport velocities via image cross- and autocorrelation.

On their way to the synapse and back, neuronal proteins are carried in cargo vesicles along axons and dendrites. Here, we demonstrate that the key parameters of axonal transport, i.e., particle velocities and pausing times can be read out from CCD-camera images automatically. In the present study, this is achieved via cross- and autocorrelation of kymograph columns. The applicability of the method was measured on simulated kymographs and data from axonal transport timeseries of mRFP-labeled synaptophysin. In comparing outcomes of velocity determinations via a performance parameter that is analogous to the signal-to-noise ratio (SNR) definition, we find that outcomes are dependent on sampling, particle numbers and signal to noise of the kymograph. Autocorrelation of individual columns allows exact determination of pausing time populations. In contrast to manual tracking, correlation does not require experience, a priori assumptions or disentangling of individual particle trajectories and can operate at low SNR.