Does research into sensitive areas do harm? Experiences of research participation after a child's diagnosis with Ewing's sarcoma

Objective: To investigate family members' experiences of involvement in a previous study (conducted August 1995 to June 1997) following their child's diagnosis with Ewing's sarcoma. Design: Retrospective survey, conducted between 1 November and 30 November 1997, using a postal questionnaire. Participants: Eighty-one of 97 families who had previously completed an in-depth interview as part of a national case-control study of Ewing's sarcoma. Main outcome measures: Participants' views on how participation in the previous study had affected them and what motivated them to participate. Results: Most study participants indicated that taking part in the previous study had been a positive experience. Most (n = 79 [97.5%]) believed their involvement would benefit others and were glad to have participated, despite expecting and finding some parts of the interview to be painful. Parents whose child was still alive at the time of the interview recalled participation as more painful than those whose child had died before the interview. Parents who had completed the interview less than a year before our study recalled it as being more painful than those who had completed it more than a year before. Conclusions: That people suffering bereavement are generally eager to participate in research and may indeed find it a positive experience is useful information for members of ethics review boards and other gatekeepers, who frequently need to determine whether studies into sensitive areas should be approved. Such information may also help members of the community to make an informed decision regarding participation in such research.

Assault-related admissions to hospital in Central Australia

Objective: To determine the number of assault-related admissions to hospital in the Central Australia region of the Northern Territory over a six-year period. Design and setting: Retrospective analysis of all patients admitted to Alice Springs Hospital (ASH) and Tennant Creek Hospital (TCH) from July 1995 to June 2001, where the primary cause of injury was assault. Main outcome measures: Frequency of assault-related admission to hospital; demographic characteristics of the victims. Results: in the six years, there were 2449 assault-related admissions to ASH and 545 to TCH. Adults aged 25-34 years were most frequently hospitalised for assault, in a proportion greater than their proportion in the NT population, Females represented 59.7% of people admitted to ASH and 54.7% to TCH, greater than their proportion in the NT population. Aboriginals comprised 95.2% of ASH and 89.0% of TCH admissions, and were admitted in a significantly greater proportion than their proportion in the NT population (P < 0.001). The age-adjusted hospital admission rate resulting from assault has increased (P = 0.002) at an average rate of 1.6 (SE, 0.2) per 10 000 people per year. The proportion of assault-related admissions associated with alcohol has also increased significantly (P < 0.001). Conclusion: The frequency of assault-related admissions to hospital, especially among the Aboriginal population, suggests that this major public health issue is escalating.

Should we debrief and counsel people who have had psychological shock?

Design: Randomised controlled trial of psychological debriefing. Setting: A British teaching hospital (the Radcliffe Hospital, Oxford). Patients: 66 men and 40 women, aged 17–69 years, admitted to hospital after a motor vehicle accident. Most had been the driver of a car. Median admission duration was four days for the 52 control patients and eight days for the 54 who underwent the intervention. Interventions: A debriefing of about one hour on Day 2 of admission, encouraging patients to describe the accident and express their emotions, followed by a cognitive appraisal which included describing common reactions to traumatic experiences and suggesting a range of people who might be able to assist in the future, including the patient's general practitioner. 91 patients were assessed at four months and 61 were assessed at three years. Control patients had no debriefing or counselling. Main outcome measures: Impact of Event Scale (IES, which focuses on intrusive thoughts and avoidance of similar situations to the event); Brief Symptom Inventory (BSI, a measure of 53 symptoms); and other questions related to physical pain and functional activities. Main results: At four months there was still considerable psychological morbidity among the patients who were followed up. There was a significant difference (P < 0.05) in changes of IES between the 42 who received the intervention, in whom it increased from 15 (standard deviation [SD], 15) to 16 (SD, 15), and the 49 controls, in whom it fell from 15 (SD, 12) to 13 (SD, 14). Similarly, two subscales of the BSI score changed significantly between the intervention group, among whom it deteriorated from 0.5 (SD, 0.5) to 0.6 (SD, 0.8), and the control s, in whom it hardly changed from 0.4 (SD, 0.3) to 0.4 (SD, 0.4). Among the 61 patients followed for three years, the 30 randomised to receive the intervention were significantly worse, by self-report, both psychologically and physically. Their mean IES score deteriorated from a baseline of 15 (SD, 14) to 16 (SD, 18). In comparison, scores for the 31 control patients improved from 16 (SD, 12) to 13 (SD, 17). The difference in change was significant (P < 0.05). Among all patients with high initial scores, these decreased among the controls but not among those receiving the intervention. Conclusion: Psychological counselling should only be used in the context of trials rather than routine care.

General practitioner attitudes to case conferences: how can we increase participation and effectiveness?

Objectives: To identify general practitioners' views on the barriers to using case conferencing (as outlined in the Medical Benefits Schedule (MBS) Enhanced Primary Care package) and to develop a set of principles to encourage greater GP participation in case conferences. Design: Qualitative study, involving semistructured questions administered to focus groups of GPs, conducted between April and July 2001 as part of a broader study of case coordination in palliative care. Participants: 29 GPs from urban, regional, and rural areas of Queensland. Principal findings: Many of the GPs' work practices militated against participation in traditionally structured case conferences. GPs thought the range of MBS item numbers should be expanded to cover alternative methods of liaison (eg, phone consultations with other service providers). The onerous bureaucratic processes required to claim reimbursement were an additional disincentive. Conclusions: GPs would probably be more likely to participate in case conferences if they were initiated by specialist services and arranged more flexibly to suit GP work schedules.

Randomisation in clinical trials

Randomisation is the process of assigning clinical trial participants to treatment groups. Randomisation gives each participant a known (usually equal) chance of being assigned to any of the groups. Successful randomisation requires that group assignment cannot be predicted in advance.

Benefits, harms and costs of screening mammography in women 70 years and over: a systematic review

Objective: To assess the (i) benefits, (ii) harms and (iii) costs of continuing mammographic screening for women 70 years and over. Data sources and synthesis: (i) We conducted a MEDLINE search (1966 - July 2000) for decision-analytic models estimating life-expectancy gains from screening in older women. The five studies meeting the inclusion criteria were critically appraised using standard criteria. We estimated relative benefit from each model's estimate of effectiveness of screening in older women relative to that in women aged 50-69 years using the same model. (ii) With data from BreastScreen Queensland, we constructed balance sheets of the consequences of screening for women in 10-year age groups (40-49 to 80-89 years), and (iii) we used a validated model to estimate the marginal cost-effectiveness of extending screening to women 70 years and over. Results: For women aged 70-79 years, the relative benefit was estimated as 40%-72%, and 18%-62% with adjustment for the impact of screening on quality of life. For women over 80 years the relative benefit was about a third, and with quality-of-life adjustment only 14%, that in women aged 50-69 years. (ii) Of 10 000 Australian women participating in ongoing screening, about 400 are recalled for further testing, and, depending on age, about 70-112 undergo biopsy and about 19-80 cancers are detected. (iii) Cost-effectiveness estimates for extending the upper age limit for mammographic screening from 69 to 79 years range from $8119 to $27 751 per quality-adjusted life-year saved, which compares favourably with extending screening to women aged 40-49 years (estimated at between $24 000 and $65 000 per life-year saved). Conclusions: Women 70 years and over, in consultation with their healthcare providers, may want to decide for themselves whether to continue mammographic screening. Decision-support materials are needed for women in this age group.

Cholesterol-lowering therapy with pravastatin in patients with average cholesterol levels and established ischaemic heart disease: is it cost-effective?

Objective: To measure the cost-effectiveness of cholesterol-lowering therapy with pravastatin in patients with established ischaemic heart disease and average baseline cholesterol levels. Design: Prospective economic evaluation within a double-blind randomised trial (Long-Term Intervention with Pravastatin in Ischaemic Disease [LIPID]), in which patients with a history of unstable angina or previous myocardial infarction were randomised to receive 40 mg of pravastatin daily or matching placebo. Patients and setting: 9014 patients aged 35-75 years from 85 centres in Australia and New Zealand, recruited from June 1990 to December 1992. Main outcome measures: Cost per death averted, cost per life-year gained, and cost per quality-adjusted life-year gained, calculated from measures of hospitalisations, medication use, outpatient visits, and quality of life. Results: The LIPID trial showed a 22% relative reduction in all-cause mortality (P < 0.001). Over a mean follow-up of 6 years, hospital admissions for coronary heart disease and coronary revascularisation were reduced by about 20%. Over this period, pravastatin cost $A4913 per patient, but reduced total hospitalisation costs by $A1385 per patient and other long-term medication costs by $A360 per patient. In a subsample of patients, average quality of life was 0.98 (where 0 = dead and 1 = normal good health); the treatment groups were not significantly different. The absolute reduction in all-cause mortality was 3.0% (95% CI, 1.6%-4.4%), and the incremental cost was $3246 per patient, resulting in a cost per life saved of $107730 (95% Cl, $68626-$209881) within the study period. Extrapolating long-term survival from the placebo group, the undiscounted cost per life-year saved was $7695 (and $10 938 with costs and life-years discounted at an annual rate of 5%). Conclusions: Pravastatin therapy for patients with a history of myocardial infarction or unstable angina and average cholesterol levels reduces all-cause mortality and appears cost effective compared with accepted treatments in high-income countries.

Ross River virus disease in tropical Queensland: evolution of rheumatic manifestations in an inception cohort followed for six months

Objective: To describe the natural history of rheumatic manifestations of Ross River virus (RRV) disease. Design: Prospective longitudinal clinical review. Setting: North Queensland local government areas of Cairns, Douglas, Mareeba and Atherton during January to May 1998. Participants: General practice patients diagnosed with RRV disease on the basis of symptoms and a positive RRV IgM result. Main outcome measures: Rheumatic symptoms and signs assessed as soon as possible after disease onset and on two subsequent occasions (up to 6.5 months after onset). Results: 57 patients were recruited, 47 of whom were reviewed three times (at means of 1.1, 2.4 and 3.6 months after disease onset). Results are reported for these 47: 46 (98%) complained of joint pain at first review, with the ankles, wrists, fingers, knees and metacarpophalangeal joints (II-IV) most commonly involved. Prevalence of joint pain decreased progressively on second and third reviews, both overall (92% and 68% of patients, respectively), and in the five joints most commonly affected. The prevalence of other common rheumatic symptoms and signs, and use of non-steroidal anti-inflammatory drugs, also progressively declined over the three reviews. Conclusions: Earlier studies may have overestimated the prevalence and duration of symptoms in RRV disease. Progressive resolution over 3-6 months appears usual.

Control of Aedes vectors of dengue in three provinces of Vietnam by use of Mesocyclops (Copepoda) and community-based methods validated by entomologic, clinical, and serological surveillance

We describe remarkable success in controlling dengue vectors, Aedes aegypti (L.) and Aedes albopictus (Skuse), in 6 communes with 11,675 households and 49,647 people in the northern provinces of Haiphong, Hung Yen, and Nam Dinh in Vietnam. The communes were selected for high-frequency use of large outdoor concrete tanks and wells. These were found to be the source of 49.6-98.4% of Ae. aegypti larvae, which were amenable to treatment with local Mesocyclops, mainly M. woutersi Van der Velde, M. aspericornis (Daday) and M. thermocyclopoides Harada. Knowledge, attitude, and practice surveys were performed to determine whether the communities viewed dengue and dengue hemorrhagic fever as a serious health threat; to determine their knowledge of the etiology, attitudes, and practices regarding control methods including Mesocyclops; and to determine their receptivity to various information methods. On the basis of the knowledge, attitude, and practice data, the community-based dengue control program comprised a system of local leaders, health volunteer teachers, and schoolchildren, supported by health professionals. Recycling of discards for economic gain was enhanced, where appropriate, and this, plus 37 clean-up campaigns, removed small containers unsuitable for Mesocyclops treatment. A previously successful eradication at Phan Boi village (Hung Yen province) was extended to 7 other villages forming Di Su commune (1,750 households) in the current study. Complete control was also achieved in Nghia Hiep (Hung Yen province) and in Xuan Phong (Nam Dinh province); control efficacy was greater than or equal to 99.7% in the other 3 communes (Lac Vien in Haiphong, Nghia Dong, and Xuan Kien in Nam Dinh). Although tanks and wells were the key container types of Ae. aegypti productivity, discarded materials were the source of 51% of the standing crop of Ae. albopictus. Aedes albopictus larvae were eliminated from the 3 Nam Dinh communes, and 86-98% control was achieved in the other 3 communes. Variable dengue attack rates made the clinical and serological comparison of control and untreated communes problematic, but these data indicate that clinical surveillance by itself is inadequate to monitor dengue transmission.

The role of putative phosphorylation sites in the targeting and shuttling of the aquaporin-2 water channel

In renal collecting ducts, a vasopressin-induced cAMP increase results in the phosphorylation of aquaporin-2 (AQP2) water channels at Ser-256 and its redistribution from intracellular vesicles to the apical membrane. Hormones that activate protein kinase C (PKC) proteins counteract this process. To determine the role of the putative kinase sites in the trafficking and hormonal regulation of human AQP2, three putative casein kinase II (Ser-148, Ser-229, Thr-244), one PKC (Ser-231), and one protein kinase A (Ser-256) site were altered to mimic a constitutively non-phosphorylated/phosphorylated state and were expressed in Madin-Darby canine kidney cells. Except for Ser-256 mutants, seven correctly folded AQP2 kinase mutants trafficked as wild-type AQP2 to the apical membrane via forskolin-sensitive intracellular vesicles. With or without forskolin, AQP2-Ser-256A was localized in intracellular vesicles, whereas AQP2-S256D was localized in the apical membrane. Phorbol 12-myristate 13-acetate-induced PKC activation following forskolin treatment resulted in vesicular distribution of all AQP2 kinase mutants, while all were still phosphorylated at Ser-256. Our data indicate that in collecting duct cells, AQP2 trafficking to vasopressin-sensitive vesicles is phosphorylation-independent, that phosphorylation of Ser-256 is necessary and sufficient for expression of AQP2 in the apical membrane, and that PMA-induced PKC-mediated endocytosis of AQP2 is independent of the AQP2 phosphorylation state.