Managing attention deficit/hyperactivity disorder: unmet needs and future directions

The management of attention deficit/hyperactivity disorder (ADHD) requires a multimodal approach. Although shared-care protocols are suggested, uptake by general practice has been tentative. Behavioural management, both on its own and in combination with pharmacotherapy, reduces core symptoms and associated behaviours, such as oppositional defiant disorder (ODD). Links with education and social support are also important for helping children and their families. Psychostimulants have shown to be effective in the treatment of ADHD, however, their short duration of action highlights potential limitations. Other drugs used in the management of ADHD and comorbid disorders include antidepressants, clonidine and its analogues, newer atypical neuroleptics, and atomoxetine, a novel, non-stimulant therapy that has potential to fulfil some unmet treatment needs. Further research is needed in preschool children, girls, those with epilepsy, young adults, and in those with associated sleep disturbance. Selected rating scales and careful history taking, allied to close links with schools, are vital for the initial and ongoing assessment of ADHD and its comorbidities.     

Content-specificity of dysfunctional cognitions for patients with bipolar mania versus unipolar depression: a preliminary study

OBJECTIVE: Dysfunctional beliefs or cognitions are considered to be fundamental to both the phenomenology and pathogenesis of depression. However, the cognitive aspects of mania have not been as thoroughly investigated. We sought to compare the maladaptive beliefs and cognitions of 23 bipolar manic or hypomanic patients, 28 patients with unipolar major depression, and 24 normal adults. METHOD: The Cognition Checklist for Mania (CCL-M) was used to assess the beliefs. This 61-item self-report instrument is scored for seven subscales measuring (a) self-importance, (b) interpersonal grandiosity, (c) inappropriate spending, (d) excitement and risk-taking, (e) interpersonal frustrations, (f) goal-driven activity, and (g) past or future outlooks on life, and also yields a total score. RESULTS: The mean CCL-M total score of the bipolar-manic patients was significantly higher than the mean CCL-M total score of the unipolar-depressed patients, and the patients' mean CCL-M total score was also higher than that of the normal adults. The mean scores of the subscales measuring excitement and past and future memories and expectations were also significantly higher for the bipolar-manic than unipolar-depressed patients. CONCLUSIONS: Bipolar-manic patients endorse with maladaptive beliefs and cognitions that are associated with mania more than do unipolar-depressed patients and normal adults. The implications for the early identification of cognitions associated with prodromal states of mania, and for psychotherapeutic interventions, are discussed.     

The internal struggle between the wish to die and the wish to live: a risk factor for suicide

OBJECTIVE: This study attempted to assess whether an index of the difference between the wish to die and the wish to live constitutes a risk factor for suicide. METHOD: A study group of 5,814 patients, including 44 who committed suicide (0.8%), were recruited from a psychiatric outpatient clinic. Structured diagnostic interviews and clinician ratings of the wish to live and wish to die were conducted. The outcome variable was the occurrence of suicide, as indicated on death certificates. RESULTS: A dichotomized index score of the difference between the wish to live and the wish to die yielded a hazard ratio of 6.51 for suicide. This index contributed a unique risk for suicide after the authors controlled for age, psychiatric hospitalization, suicide attempts, bipolar disorder, major depressive disorder, and unemployment status. CONCLUSIONS: The difference between the wish to die versus the wish to live is a unique risk factor for suicide.     

Tinzaparin sodium for thrombosis treatment and prevention during pregnancy

OBJECTIVE: This study was undertaken to assess the pharmacodynamic profile, safety, and efficacy of tinzaparin during pregnancy. STUDY DESIGN: Fifty-four pregnant women, 12 for treatment of thrombosis and 42 for thromboprophylaxis, received tinzaparin by once daily injection. Four-hour postdose anti-Xa results were analyzed by use of repeated measures statistical methods. RESULTS: One woman (3.4%) on the 175 anti-Xa U/kg dose and three women (20%) on the 50 anti-Xa U/kg dose required a dose increase during the initial dose titration phase to achieve target anti-Xa activity. No thrombotic events occurred. CONCLUSION: The 175 anti-Xa U/kg dose is appropriate for treatment and for high-risk thromboprophylaxis throughout pregnancy. In pregnant women at moderate risk of thrombosis, a higher tinzaparin dose is required than in the nonpregnant state and 75 anti-Xa U/kg appears to be appropriate. The majority of women do not need a dose increase with advancing gestation.     

Low molecular weight heparin (tinzaparin) therapy for moderate risk thromboprophylaxis during pregnancy. A pharmacokinetic study

Low molecular weight heparin (LMWH) is used increasingly for prophylaxis and treatment of venous thromboembolism during pregnancy. However, the prophylactic dose for patients at moderate risk varies between centers, and the recommended LMWH dose for the non pregnant patient is frequently used in pregnant women. The aim of this study was to investigate the effects of pregnancy on the pharmacokinetics of anti-Xa levels during moderate risk thromboprophylaxis with the LMWH, tinzaparin. In 24 pregnant women, one of three doses of tinzaparin (50, 75 or 100 IU/kg) were given according to the treating physician's assessment of their risk profile. Four-hour peak anti-Xa levels were measured throughout pregnancy and 24-hour profiles were measured at 28 and 36 weeks gestation. Doses were adjusted when peak anti-Xa levels fell below 0.1 IU/ml and, in some cases, when levels at 10 and 18 hours post injection were undetectable (<0.05 IU/ml). Our results showed that women receiving tinzaparin (50 IU/kg) frequently had peak (4 hour) anti-Xa levels below 0.1IU/ml and that 46% of these patients required dose adjustment. Similarly anti-Xa levels were also found to be low over the 24-hour period. A starting dose of 75 IU/kg, once daily, gave greater anti-Xa cover over the 24-hour period and may avoid the need for dose adjustment. The results suggest that the pharmacokinetics of tinzaparin are affected by pregnancy. Larger studies are required to determine whether an increased tinzaparin dose (75 IU/kg) would be more effective in the prevention of thrombosis during pregnancy than 50 IU/kg.     

A multisite, randomized controlled trial for children with sexual abuse-related PTSD symptoms

OBJECTIVE: To examine the differential efficacy of trauma-focused cognitive-behavioral therapy (TF-CBT) and child-centered therapy for treating posttraumatic stress disorder (PTSD) and related emotional and behavioral problems in children who have suffered sexual abuse. METHOD: Two hundred twenty-nine 8- to 14-year-old children and their primary caretakers were randomly assigned to the above alternative treatments. These children had significant symptoms of PTSD, with 89% meeting full DSM-IV PTSD diagnostic criteria. More than 90% of these children had experienced traumatic events in addition to sexual abuse. RESULTS: A series analyses of covariance indicated that children assigned to TF-CBT, compared to those assigned to child-centered therapy, demonstrated significantly more improvement with regard to PTSD, depression, behavior problems, shame, and abuse-related attributions. Similarly, parents assigned to TF-CBT showed greater improvement with respect to their own self-reported levels of depression, abuse-specific distress, support of the child, and effective parenting practices. CONCLUSIONS: This study adds to the growing evidence supporting the efficacy of TF-CBT with children suffering PTSD as a result of sexual abuse and suggests the efficacy of this treatment for children who have experienced multiple traumas.     

Does gestation vary by ethnic group? A London-based study of over 122,000 pregnancies with spontaneous onset of labour

BACKGROUND: Evidence exists that normal gestational length varies with ethnicity. This UK-based study compares gestational length amongst a cohort of white European, Black and Asian women. METHODS: The cohort comprised 122 415 nulliparous women with singleton live fetuses at the time of spontaneous labour, giving birth in the former North West Thames Health Region, London, UK. RESULTS: The median gestational age at delivery was 39 weeks in Blacks and Asians and 40 weeks in white Europeans. Black women with normal body mass index (BMI) (18.5-24.9 kg/m(2)) had increased odds of preterm delivery (odds ratio [OR] = 1.33, 95% CI: 1.15, 1.56, adjusted for deprivation and BMI) compared with white Europeans. The OR of preterm delivery was also increased in Asians compared with white Europeans (OR = 1.45, 95% CI: 1.33, 1.56, adjusted for single unsupported status and smoking). Meconium stained amniotic fluid, which is a sign of fetal maturity, was statistically significantly more frequent in preterm Black and Asian infants and term Black infants compared with white European infants. CONCLUSIONS: This research suggests that normal gestational length is shorter in Black and Asian women compared with white European women and that fetal maturation may occur earlier.     

The role and regulation of COX-2 during viral infection

Prostaglandins are lipid mediators, generated by cyclooxygenase (COX), that have been shown to participate in the regulation of virus replication and the modulation of inflammatory responses following infection. A number of studies support a role for PGE2 in the modulation of virus replication and virulence in a cell type and virus selective manner. Virus infection also stimulates the expression of a number of proinflammatory gene products, including COX-2, inducible nitric oxide synthase (iNOS) as well as proinflammatory cytokines. This review will focus on the mechanisms by which proinflammatory prostaglandin production regulates virus replication and virulence. In addition, the signaling pathways that are activated during a virus infection, and that regulate proinflammatory gene expression in macrophages will be reviewed. Specific attention will be placed on the ability of virus infection to activate multiple signaling cascades (such as PKR, MAPK, iPLA2, NF-kappaB) and how these pathways are integrated in the regulation of individual target gene expression.     

A comparison of the prevalence of respiratory illness and non-specific health symptoms in two Victorian cities

OBJECTIVE: To compare the prevalence of respiratory illness and non-specific health symptoms among adults and children aged 4-15 years living in Portland and Warrnambool, Victoria. METHODS: A postal survey of 3,903 adults in Portland and Warrnambool systematically selected from the electoral roll was undertaken. Both an adults and children's questionnaire were enclosed in the mailing to each adult. If there were children aged 4-15 years in the household, an adult was asked to complete a questionnaire for the child who would next celebrate a birthday. Questionnaires were returned by 2,111 adults (54%) and for 585 children. RESULTS: No significant differences in the prevalence of self-reported asthma or wheeze were observed among adults or children residing in Portland and Warrnambool. The likelihood of itchy eyes, skin rash and stuffy nose was significantly higher in Portland adults and children compared with those in Warrnambool. Dry cough at night was increased among Portland children, but not significantly so. CONCLUSIONS: Higher rates of non-specific symptoms were observed in Portland but from a cross-sectional survey such as this, it is not possible to identify the cause of these higher rates. They may be related to environmental factors such as pollens or emissions from aluminium production, fertiliser production or bulk handling activities on the wharf, or they may be attributable to other factors such as response or recall bias.