Lifetime Course Research Articles

Cost-Utility analysis of tissue plasminogen activator therapy for acute ischaemic stroke: a Canadian healthcare perspective.

There are over 40000 ischaemic strokes annually in Canada, which result in significant morbidity, mortality and burden to the healthcare system. A recent, large clinical trial has evaluated tissue plasminogen activator (t-PA) intravenously for the treatment of acute ischaemic stroke with promising outcomes but with an increased risk of symptomatic intracranial haemorrhage. To compare clinical and economic outcomes of intravenous t-PA therapy (0.9 mg/kg, to a maximum of 90 mg, initiated within 3 hours of stroke onset) versus no t-PA for acute ischaemic stroke based on the outcomes achieved in the National Institute of Neurological Disorders and Stroke (NINDS) trial. A Markov model depicting the natural lifetime course after an initial acute ischaemic stroke. On the basis of this model, a simulated trial compared no t-PA with t-PA. A hypothetical cohort of 1000 patients with acute ischaemic stroke. Canadian healthcare system. Total acute stroke and post-stroke treatment costs and cumulative quality-adjusted life-years (QALYs). For a hypothetical cohort of 1000 patients, the estimated lifetime stroke costs were 103100000 Canadian dollars (SCan) [1999 values) in the t-PA arm ($Can103100 per patient) compared with SCan106900000 in the no t-PA arm ($Can106900 per patient), yielding a lifetime cost difference of $Can3800000 in favour of t-PA versus no t-PA (SCan3800 per patient). In the hypothetical cohort, t-PA treatment resulted in 13 130 QALYs versus 9670 QALYs with no t-PA treatment. This translated into a net benefit of 3460 additional QALYs per 1000 patients (3.46 QALYs per patient). No treatment, outcome or economic variables influenced the model outcome. From the standpoint of cost effectiveness, treatment of acute ischaemic stroke with intravenous t-PA is an economically attractive strategy.

Obsessive-complusive disorder: pharmacological treatment.

Obsessive-compulsive disorder (OCD) in children and adolescents is often a disabling condition, which demands treatment with medication. Research shows that serotonin is involved in the disorder and empirical treatment studies show that antidepressants with serotonin activity are effective. The first choice of treatment in the psychopharmacological approach to OCD in children and adolescents are the SSRI agents, which have been documented as being effective as well as well-tolerated in children and adolescents. The best-documented SSRI to this point is sertraline. However, fluoxetine and fluoxamine have also undergone systematic studies in children and adolescents. Clomipramine has been proven effective, however, side effects caused by this agent would suggest that an SSRI is a better choice. Treatment with an SSRI seems to have effect in approximately 75 % of patients with OCD. There are still no systematic studies analyzing augmenting medication for children and adolescents with OCD. Research indicates that the combination of medication and psychotherapy (cognitive behavioural therapy) is important in most cases. Based on a few long-term follow-up studies on OCD children and adolescents there is not evidence that all children and adolescents suffer a lifetime course of the disease. It is therefore recommended that discontinuation is attempted after 1-1.5 years of successful treatment.

Regional brain volume change over the life-time course of schizophrenia

The concept that schizophrenia has its antecedents in neurodevelopment has long been debated and has been at the forefront of research on this disorder over the last decade. However new recent evidence from controlled longitudinal studies indicates that some of the structural brain anomalies observed in schizophrenia may continue to progress sporadically after the onset of clinical illness. The studies vary in cohort composition, stage of illness studied, duration of follow-up interval, and specific brain regions with findings. Nevertheless, the findings as a whole suggest that the brain changes in size throughout the lifespan of an individual and to a greater extent in schizophrenia. While the detected abnormalities could be explained by various technical artifacts, or physiological epi-phenomena, that they result from an ongoing neurochemical, physiological or morphological process characteristic of the underlying basis for the disorder is an intriguing possibility that lends itself to possible future intervention.

Differential effects of olanzapine on the gene expression of superoxide dismutase and the low affinity nerve growth factor receptor.

Neuroanatomical studies of schizophrenia suggest that progressive neuropathological changes (such as neuronal atrophy and/or cell death) occur over the lifetime course of the disease. Early intervention with atypical neuroleptics has been shown to prevent progression of at least some symptoms, although the mechanisms by which neuroleptics may do this remain unknown. In this study, PC12 cells were used to determine the effects of the new atypical antipsychotic olanzapine on the gene expression of superoxide dismutase (SOD1) and the low affinity nerve growth factor receptor (p75). The results show that olanzapine increases SOD1 at concentrations of 10 and 100 microM after 48 hr of incubation in PC12 cultures. The treatment decreases p75 gene expression at concentrations 100 microM after 48 hr of incubation. Since both the upregulation of SOD1 mRNA and the antisense blockade of p75 mRNA have been associated with reduced cell death, our results suggest that olanzapine has neuroprotective potential and thus may be useful in preventing further neurodegeneration accompanying schizophrenia.

The comparative validity of eleven alcoholism typologies.

This study directly compared the clinical validity of 11 empirically defined alcoholism typologies to determine whether some typologies are clinically more valid than others. A sample of 360 hospitalized alcoholic men were extensively evaluated at entry into the study and again 1 year later. Twenty-three measures of clinical validity were employed; 15 were postdictive and 8 were predictive. Postdictive retrospective measures obtained at entry into the study included family history, age of onset and lifetime course characteristics associated with alcoholism severity, general psychopathology and psychosocial functioning. Predictive outcome measures drawn from information obtained during the 1-year follow-up included: abstinence, alcoholism severity and clinician ratings of outcome. The measures were subjected to various statistical analyses, including factor analysis. We found that all of the alcoholism typologies met at least 7 of the 23 a priori measures of clinical validity. The correlations between these conceptually and methodologically disparate typologies were often striking. Exploratory factor analysis, which explained 35% of the variance, suggested three possible underlying dimensions to account for the overlap among typologies: (1) age and its correlates, including age-of-alcoholism onset; (2) "pure" alcoholism versus psychiatrically heterogeneous alcoholism that encompassed antisocial personality disorder; and (3) current severity of psychiatric distress, impairment and dysfunction. No single method of subtyping alcoholics clearly emerged as superior. All demonstrated some degree of predictive and postdictive clinical validity. Most methods of subtyping correlated positively with each other at moderate, but typically significant, levels.

A review of bipolar disorder among adults.

This paper reviews the epidemiology, etiology, assessment, and management of bipolar disorder. Special attention is paid to factors that complicate treatment, including noncompliance, comorbid disorders, mixed mania, and rapid cycling. Advances in biopsychosocial treatments are briefly reviewed, including new health service models for providing care. A MEDLINE search was done for the period from January 1988 through October 1997 using the key terms of bipolar disorder, diagnosis, and treatment. Papers selected for further review included those published in English in peer-reviewed journals. Preference was given to articles reporting randomized, controlled trials. Bipolar disorder is a major public health problem. The etiology of the disorder appears multifactorial. Diagnosis often occurs years after onset of the disorder. Comorbid conditions are common. Management includes a lifetime course of medication and attention to psychosocial issues for patients and their families. Standardized treatment guidelines for the management of acute mania have been developed. New potential treatments are being investigated. Assessment of bipolar disorder must include careful attention to comorbid disorders and predictors of compliance. Randomized trials are needed to further evaluate the efficacy of medication, psychosocial interventions, and other health service interventions, particularly as they relate to the management of acute bipolar depression, bipolar disorder co-occurring with other disorders, and maintenance prophylactic treatment.

Schizophrenic patients and cocaine use: Antecedents to hospitalization and course of treatment

This study was designed to assess whether cocaine abuse was associated with a different set of antecedents and course for hospitalized schizophrenic patients. Forty‐three cocaine‐using and 27 non‐cocaine‐using patients with schizophrenia admitted to a dual diagnosis unit were compared with regard to antecedents to hospitalization such as prior treatment episodes, reliance on drugs for pleasure and tension reduction, and criminal history as well as course of hospital treatment. Cocaine‐using patients were more likely to have had a history of prior inpatient drug treatment and to rely on drugs to a greater extent for tension reduction and pleasure. There was a trend for cocaine users to have a history of arrests for violent crimes. Although cocaine‐using patients exhibited lower levels of global distress during the first week of hospitalization, they were no different from their counterparts who abused nonpsychostimulant drugs with regard to outcome of hospital treatment. These findings suggest that the lifetime course of illness among schizophrenic patients presenting for hospitalization who abuse cocaine may be characterized by episodes of repeated inpatient drug treatment and impaired impulse control. More rigorous discharge planning and aftercare program monitoring in the community as well as stress management interventions directed to tension reduction are therefore warranted.

Older adult controlled drinkers and abstainers.

Little is known about the lifetime course of alcohol problems, especially during late adulthood. Many individuals with a history of alcohol problems achieve remission of their symptoms through abstinence or controlled drinking. This study examined 135 older adults with a prior history of alcohol diagnoses who were symptom free for at least the past year. Two groups were identified based on their alcohol consumption within the past year: abstinent individuals (n = 92) and controlled drinkers (n = 43). The groups did not differ in age, racial composition, education, income, or years since their last alcohol-related symptom, but they did differ in gender composition, indices of alcoholism severity, history of formal and informal treatment, as well as lifetime alcohol consumption patterns. Abstinent individuals had more severe alcohol problems, consumed higher amounts of alcohol on drinking days, had more years of heavy alcohol consumption, and were more likely to have attended alcohol treatment and Alcoholics Anonymous (AA). The controlled drinkers had a longer history of moderate social drinking, and their current consumption habits appeared to be similar to symptom-free older adult drinkers. The results suggest that gender, alcoholism severity, history of formal and informal treatment, and past consumption patterns are associated with whether older adults with histories of alcoholism attain successful outcomes through abstinence or controlled drinking.

Comorbidity in the anxiety disorders: The use of a life-chart approach

Findings of comorbidity across the anxiety and depressive disorders have implications for aetiology, diagnosis and treatment. This paper describes a method to assess one aspect of the relationship between comorbid disorders: the degree to which one illness experience is believed to be caused by the earlier experience of a different illness. The life-chart method involves the use of a semi-structured interview to document the lifetime course of disorders. The method was reliable in a sample of patients treated at a specialized treatment unit for anxiety disorders. Patients fell into three major groupings: those with one disorder only (19%); those who fulfilled criteria for two or more disorders, but with one disorder primary and other disorders secondary to it (55%); and those who fulfilled criteria for two or more independent disorders (26%).

Age-Related Prognostic Factors in the Severity of Illness of Tourette's Syndrome in Monozygotic Twins

Tourette's syndrome (TS) was studied in 18 pairs of monozygotic twins where at least one member of the twin set had TS. Sixteen twin sets were concordant for motor tics and had different ages of onset of motor tics (as reported by the mothers and/or medical records). Among these pairs, the earlier motor ticquer was more likely to have a more severe course of illness as assayed by two different indices. In the 10 sets concordant for vocal tics, the earlier vocal ticquer had a more severe course as assayed by only one index. The authors conclude that an early age of onset of motor tics may be the strongest predictor of a more severe life-time course of a tic disorder.

Mania in the elderly

Mania continues to be a fascinating and important clinical entity. Its distinctive features make it amenable to systematic analysis of the genetic, environmental and biological variables that contribute to this disorder. Data from studies of the elderly may be important in helping to elucidate unanswered questions about affective disorders in younger adults. Geriatric patients offer the opportunity to study a lifetime course retrospectively and to identify familial predispositions because of prolonged exposure in first degree relatives. Finally, the nature and prevalence of heterogeneous neurological disorders, especially cerebrovascular disease, may now be clarified with modem developments in neuroimaging

Genetic aspects in chronic schizophrenia morbidity risks and contributory factors

112 schizophrenics, over 55 years old, and their relatives were studied. Aims of the study were (1) to evaluate the assumption that using an appropriate selection of probands and methods of the morbid risk estimation, one may expect to obtain a higher (and probably more realistic) value of risk to children; and (2) to assess the possible influence of patients' and relatives' characteristics on the magnitude of the morbid risk. The main results were (1) the values of risks (0.04±0.02 for spouses; 0.08±0.02 for siblings; 0.17±0.04 for offspring); (2) the risk to siblings and to children increased with the numbers of other relatives affected; (3) no clinical symptoms in probands (evaluated throughout the lifetime course of the disease) were associated with an increased/decreased value of risk to any class of relatives.

Lifetime course of chronic depression in older men.

The lifetime course of illness in older outpatient men who remained symptomatic despite adequate pharmacologic treatment for depression was examined. A bimodal distribution of age of onset of first major depression was found, with 75% having onset before age 35 years and 25% having onset after age 50 years. At all ages, episodes of chronic depression developed after episodes of major depression and appeared to be partially resolved major depression. In 88% of patients, anxiety disorders developed before age 35 years, preceded onset of other disorders, and continued throughout the patient's lifetime. Seventy percent developed alcoholism and 25% had a medical illness that impaired function to a significant degree. The importance of obtaining a lifetime course of illness in older patients is discussed.

Diel Rhythm and Lifetime Course of Oviposition in Toxorhynchites Amboinensis (Diptera: Culicidae)1

The diel rhythm and lifetime course of oviposition was studied in Toxorhynchites amboinensis. The 1st egg laid by Tx. amboinensis females was on day 4 after emergence. Many eggs were laid on day 5 and most on day 6. Thirteen females kept from emergence till death lived from 15 to 84 days and laid from 30 to 253 eggs, with a mean (±SE) of 155 ± 19. Mean daily oviposition diminished progressively throughout the adult life-span and could be fitted to the equation y = 1/(0.013x + 1/15.56). Oviposition was diurnal, with a small peak from 0600 to 1000 h and a major one from 1200 to 1500 h. Throughout the oviposition period the number of elliptical flights preceding ejection of each egg and the time required to complete these flights increased significantly.

Use of a self-report symptom scale to detect depression in a community sample

The authors gave the CES-D, a self-report depression symptom scale, to 515 people drawn from a longitudinal community survey. The subjects were also interviewed using the Schedule for Affective Disorders and Schizophrenia (SADS). From the information collected on the SADS, the subjects were given diagnoses based on Research Diagnostic Criteria. The results indicate a modest relationship between self-reported symptoms of depression and the diagnosis of a major or minor depression. However, the groups defined as "cases" by such reports also include many people with other diagnoses or with no diagnoses at all. Thus, symptom scales are useful for the screening of depressed persons in research studies but are only rough indicators of clinical depression in the community.