Adverse events in phase one studies: a study in 430 healthy volunteers

Summary All the clinical, laboratory and electrocardiographic adverse events detected during 24 Phase I studies in the same unit over a 5 y period are reported here. 430 healthy male volunteers were involved, corresponding to 5488 days of follow-up.The overall incidence of adverse events was 13.5%, with a significant difference between active drug (15.3%) and placebo (7.4%) treatments. There were 69 distinct types of adverse events. Headache was the most frequent symptom (2%). There were severe adverse events in 20 cases (0.36%), with an incidence of 20/430 per subject (4.6%). There were no deaths or life-threatening events.Although the main objective of Phase I studies is to determine the maximum dose tolerated, cause-effect relationships with adverse events are hard to establish, because of the frequency of adverse events with placebo, and because of the limited number of subjects included such studies.     

Screening for Depression in Patients with Chronic Illness

Why should depression screening be conducted in chronically ill populations? Depression is a disabling illness and is very common among patients who have chronic illnesses. Despite its high prevalence in this patient population, depression often goes unrecognized. Having a plan for a population-based screening program for depression can not only identify patients who are at risk of depression, but can also help to foster early treatment and enhanced care for these patients. This article provides an overview of commonly-used depression screening tools and presents an example of how this might be carried out in a healthcare organization.     

Children's understanding of cancer

Explanations of cancer need to take into account developmental changes in children's cognitive and emotional abilities to understand illness. Children below 5 years of age are usually informed by parents, and older children by medical staff. Information tends to focus on details of treatments and procedures, and less on the seriousness of the disease and length of time involved. There are indications that early and honest information is associated with better behaviour and adjustment in the child, communication within the family and compliance with treatment, although methodological inadequacies in assessment of adjustment and knowledge of cancer limit the ability to generalize these findings. Communication with children should take into account developmental changes in children's ability to understand illness information. Communicators should also provide emotional support to deal with the threatening nature of this information.     

Q-tip pap smear: Should it be done routinely in patients who have developmental disabilities?

In some patients with mental retardation, a Q-tip pap smear obtained blindly from the upper vagina may be the only cytologic smear obtainable without subjecting the patient to heavy sedation or to examination under anesthesia. The efficacy of blind Q-tip smears has not been previously determined. Of 31 Q-tip smears obtained from patients with CIN, the Q-tip smear identified the abnormality in 10 (32%) patients. For those patients who will not submit to examination without anesthesia or sedation, routine screening with multiple smears, obtained on an annual basis has the potential to identify many cases of CIN which otherwise would not be identified at all, and in certain patients, this method outweighs the risks of heavy sedation or general anesthesia. Because of the greatly reduced sensitivity of the Q-tip pap, every effort should be made to help the patient and/or her family or guardian to understand the implications and risks of this method. However, if an examination under anesthesia is performed for other indications, a complete gynecologic examination and a direct smear should be obtained at that time.     

No Worries, No Cares: An Investigation into Self-Reported "Nondistress" in College Students

An important methodological issue in depressionanalog research is whether individuals who scoreextremely low on self-report measures like the BeckDepression Inventory (BDI) should be included innondepressed control groups. Joiner, Schmidt, and Metalsky(1994) found that college students with BDI scores of 0or 1 evidenced a fake-good test taking style as measuredby the MMPI validity scales. The present study investigated whether very low BDI scores (BDI= 0 or 1; n = 21) might be associated with an elevatedpositive mood state, extreme optimism, positiveattributional style or social desirability. Resultsindicated that the very low scoring BDI subjects scoredhigher on social desirability than the low scoring group(BDI = 2 9, n = 63). Significant differences on mood,symptom and cognitive measures disappeared when social desirability was entered as a covariate.Findings support Kendall, Hollon, Beck, Hammen, andIngram's (1987) recommendation that subjects who score0 or 1 on the BDI should be excluded from a nondepressed control group.     

Randomized trial of adjuvant chemotherapy for operable breast cancer comparing i.v. CMF to an epirubicin-containing regimen [see comment]

From January 1985 to December 1987, 228 women with breast cancer smaller than 3 cm were treated by surgery +/- radiotherapy. All of them had axillary node involvement (N+) and/or lacked estrogen and progesterone steroid receptors (EPR-). They were randomized in an adjuvant chemotherapy trial comparing 9 intravenous CMF courses (cyclophosphamide, methotrexate, 5FU)--113 patients--to a polychemotherapy consisting of 3 courses of MTV (mitomycin C, thiotepa, vindesine) plus 3 courses of EVM (epirubicin, vincristine, methotrexate)--115 patients. Prognostic factors were well balanced between the two treatment groups. With a 59-month median follow-up, local breast relapses are more frequent in the CMF group, but regional and metastatic recurrences are the same in the two groups. Overall survival is identical. Toxicity is different: alopecia and neurotoxicity are more frequent in the MTV+EVM group, but general and digestive toxicities are equivalent. Haematologic toxicity is greater in the CMF group, requiring more frequent dosage reductions.     

‘You have to learn to live with it’: a qualitative and quantitative study of older people with asthma

Introduction: Asthma mortality has declined overall because of a range of public health initiatives. In western countries, the majority of asthma deaths now occur in people over the age of 50. The reasons for the poorer response of older age groups to public health asthma initiatives are not known. Objectives: We undertook a study to investigate the disease perspectives of older people with asthma and barriers which may exist and prevent optimal asthma care. Methods: Fifty‐five participants (16 male and 39 female) aged over 50 from an inner city, suburban area and a rural region were recruited. Lung function was measured, and questionnaire data on asthma symptoms, knowledge and control, medication use and respiratory health were collected. Participants were also interviewed in‐depth, and the quantitative and qualitative data were triangulated. Results: Participants with a duration of asthma for >30 years reported significantly fewer symptoms and better quality of life irrespective of asthma severity, indicating less appreciation of symptoms in those with a long asthma duration. Interviews revealed this was related to previous asthma management strategies when treatment options were limited. Participants with a recent diagnosis sought understanding of asthma and the reason for their illness. Initiatives to improve asthma care in older people need to reflect these findings. Conclusions: Self‐management strategies for older people need to be tailored according to the time of disease onset and the duration of disease. Please cite this paper as: Goeman DP, O’Hehir RE, Jenkins C, Scharf SL and Douglass JA. ‘You have to learn to live with it’: a qualitative and quantitative study of older people with asthma. The Clinical Respiratory Journal 2007; 1:99–105.