Prospective randomised controlled trial of methods of call and recall for cervical cytology screening.

OBJECTIVE--To discover whether systematic methods of call and recall are more effective than a non-systematic method and to see which of the two systematic methods was more effective. DESIGN--Prospective randomised controlled trial over a year. SETTING--One group general practice. PATIENTS--416 Women over 35 eligible for a smear test who had never had a cervical smear test or in whom a smear test was overdue (previous test more than five years before). INTERVENTIONS--One group received written invitations to have a smear taken. The second group had their notes tagged so that the doctor would remind them (when they attended for another reason) to have a smear test. No special intervention was made in the third group. MAIN OUTCOME MEASURE--Performance of a cervical smear test during the year of the study. RESULTS--32% (45/140) of the screened group, 27% (39/142) of the tagged group, and 15% (20/134) of the control group had a smear test during the year. The percentage of women having a smear test in the screened group was not significantly different from that in the tagged group, but the percentages in the two groups were significantly different from that in the control group. Whether a woman had had a previous smear test significantly affected the uptake of the invitation to have a smear test independently of the method of invitation. CONCLUSIONS--The systematic methods of call and recall were more effective than a non-systematic method. There was no significant difference between the two systematic methods (sending letters or tagging the notes) at one year.     

Evaluation of a stroke family care worker: results of a randomised controlled trial.

OBJECTIVE: To examine the effect of contact with a stroke family care worker on the physical, social, and psychological status of stroke patients and their carers. DESIGN: Randomised controlled trial with broad entry criteria and blinded outcome assessment six months after randomisation. SETTING: A well organised stroke service in an Edinburgh teaching hospital. SUBJECTS: 417 patients with an acute stroke in the previous 30 days randomly allocated to be contacted by a stroke family care worker (210) or to receive standard care (207). The patients represented 67% of all stroke patients assessed at the hospital during the study period. MAIN OUTCOME MEASURES: Patient completed Barthel index, Frenchay activities index, general health questionnaire, hospital anxiety and depression scale, social adjustment scale, mental adjustment to stroke scale, and patient satisfaction questionnaire; carer completed Frenchay activities index, general health questionnaire, hospital anxiety and depression scale, social adjustment scale, caregiving bassles scale, and carer satisfaction questionnaire. RESULTS: The groups were balanced for all important baseline variables. There were no significant differences in physical outcomes in patients or carers, though patients in the treatment group were possibly more helpless less well adjusted socially, and more depressed, whereas carers in the treatment group were possibly less hassled and anxious. However, both patients and carers in the group contacted by the stroke family care worker expressed significantly greater satisfaction with certain aspects of their care, in particular those related to communication and support. CONCLUSIONS: The introduction of a stroke family care worker improved patients'' and their carers'' satisfaction with services and may have had some effect on psychological and social outcomes but did not improve measures of patients'' physical wellbeing.     

Antenatal screening for carriers of cystic fibrosis: randomised trial of stepwise v couple screening.

OBJECTIVE--To perform a rigorous comparative evaluation of stepwise and couple approaches to antenatal carrier screening for cystic fibrosis. DESIGN--Pragmatic randomised trial. SETTING--Hospital antenatal clinic serving a regional population. SUBJECTS--2002 women (couples) attending for booking antenatal visit at less than 17 weeks'' gestation with no family history of cystic fibrosis. INTERVENTIONS--Offering counselling and carrier testing for cystic fibrosis, either to women in the first instance (stepwise) or to couples (couple screening). MAIN OUTCOME MEASURES--Uptake rates; anxiety; knowledge of cystic fibrosis and carrier status (both partners); attitudes to health, pregnancy, the baby, and screening (both partners); and uptake of carrier testing by relatives. RESULTS--Uptake of screening was the same for both approaches (90%). After delivery most women remembered test results and their meaning, but 53/253 (21%) of those with negative results of couple testing had forgotten that repeat testing would be advisable if they had a pregnancy with a new partner. With stepwise screening women identified as carriers had high levels of anxiety when results were received (mean anxiety score 52.3). This dissipated with a reassuring partner''s result (carriers'' mean anxiety score 36.1) to levels similar to those receiving negative results from couple screening. Of those receiving negative results, women who had stepwise screening were significantly less anxious than those who had couple screening (mean score with result 32.1 v 35.4, 95% confidence interval for difference -4.7 to -2.1). CONCLUSIONS--Couple screening allows carriers to avoid transient high levels of anxiety, but is associated with more anxiety and false reassurance among most screenees who will test negative. Stepwise screening gives carriers and their relatives genetic information and is, in our opinion, the better method.     

O-9Uncommon subtypes of borderline nuclear changes: cytological features and predictive value

Introduction:  To establish the significance of cytological features which could predict clinically significant endometrial pathology, and therefore guide reporting practice in cervical samples.
Methods:  A retrospective review of SurePath liquid-based cytology (LBC) cervical samples between 2002 and 2006, obtained at screening and colposcopy. These smears contained normal endometrial cells present at inappropriate times of the menstrual cycle, endometrial cells with atypia (borderline change) and with features suspicious / diagnostic of endometrial carcinoma (glandular neoplasia). False negative and false positive cases detected on subsequent histology were also included. The control group comprised negative samples and a few abnormal smears. All smears were randomly assigned and blinded to menopausal status, age, use of oral contraceptive pill and hormone replacement therapy and presence of intrauterine device. Each smear was reviewed for 16 cytologic criteria and a cytological diagnosis was given for each.
Results:  A total of 219 smears were available for review; 137 were negative, out of which 85 contained normal endometrial cells, 41 contained endometrial cells with atypia, 10 contained endometrial cells with features suggestive of adenocarcinoma and 31 contained endometrial cells with features diagnostic of adenocarcinoma. The feature most associated with benign endometrial cells is top hat with central cell condensation. In contrast, the features associated with malignant endometrial cells are smooth nuclear membrane, pale chromatin, small nucleoli and scalloped borders.
Discussion:  The criteria identified in this study do not definitively define a neoplastic process, but appear to be helpful in individual cases. This study emphasises that endometrial changes should be always interpreted with the relevant clinical information, which would otherwise lead to overdiagnosis in premenopausal women.     

Adequacy of cervical cytology sampling with the Cervex brush and the Aylesbury spatula: a population based randomised controlled trial.

OBJECTIVE: To compare the adequacy of cervical cytology sampling with two sampling instruments commonly used in primary care-namely, the Aylesbury spatula and the Cervex brush. DESIGN: Pair matched, population based randomised controlled trial. SETTING: 86 general practices and family planning clinics in Greater Manchester. SUBJECTS: 15 882 cervical smears taken from women aged 20-64 years as part of the national cervical screening programme. INTERVENTIONS: Participating centres were allocated to sample with either the Cervex brush or the Aylesbury spatula. MAIN OUTCOME MEASURE: Inadequate smear rate. RESULTS: 5.4% and 5.5% (433/8086 and 426/7796) of smears taken with the Cervex brush and the Aylesbury spatula respectively were reported as inadequate (odds ratio 0.95; 95% confidence interval 0.74 to 1.22). CONCLUSION: The Cervex brush offers no advantage over the Aylesbury spatula in reducing inadequate smear rates in the primary care setting.     

Improving adherence to medication in stroke survivors (IAMSS): a randomised controlled trial: study protocol

Background  

Adherence to therapies is a primary determinant of treatment success, yet the World Health Organisation estimate that only 50% of patients who suffer from chronic diseases adhere to treatment recommendations. In a previous project, we found that 30% of stroke patients reported sub-optimal medication adherence, and this was associated with younger age, greater cognitive impairment, lower perceptions of medication benefits and higher specific concerns about medication. We now wish to pilot a brief intervention aimed at (a) helping patients establish a better medication-taking routine, and (b) eliciting and modifying any erroneous beliefs regarding their medication and their stroke.     

Improving uptake of breast screening in multiethnic populations: a randomised controlled trial using practice reception staff to contact non-attenders.

OBJECTIVES: To determine whether a two hour training programme for general practice reception staff could improve uptake in patients who had failed to attend for breast screening, and whether women from different ethnic groups benefited equally. DESIGN: Controlled trial, randomised by general practice. SETTING: Inner London borough of Newham. SUBJECTS: 2064 women aged 50-64 years who had failed to attend for breast screening. Women came from 26 of 37 eligible practices, 31% were white, 17% were Indian, 10% Pakistani, 14% black, 6% Bangladeshi, 1% Chinese, 4% were from other ethnic groups, and in 16% the ethnic group was not reported. MAIN OUTCOME MEASURES: Attendance for breast screening in relation to ethnic group in women who had not taken up their original invitation. RESULTS: Attendance in the intervention group was significantly better than in the control group (9% v 4%). The response was best in Indian women--it was 19% in the intervention group and 5% in the control group. CONCLUSIONS: This simple, low cost intervention improved breast screening rates modestly. Improvement was greatest in Indian women--probably because many practice staff shared their cultural and linguistic background. This intervention could be effective as part of a multifaceted strategy to improve uptake in areas with low rates.     

An intervention to improve teacher well-being support and training to support students in UK high schools (the WISE study): A cluster randomised controlled trial

BackgroundTeachers are at heightened risk of poor mental health and well-being, which is likely to impact on the support they provide to students, and student outcomes. We conducted a cluster randomised controlled trial, to test whether an intervention to improve mental health support and training for high school teachers led to improved mental health and well-being for teachers and students, compared to usual practice. We also conducted a cost evaluation of the intervention.Methods and findingsThe intervention comprised (i) Mental Health First Aid training for teachers to support students; (ii) a mental health awareness session; and (iii) a confidential staff peer support service. In total 25 mainstream, non-fee-paying secondary schools stratified by geographical area and free school meal entitlement were randomly allocated to intervention (n = 12) or control group (n = 13) after collection of baseline measures. We analysed data using mixed-effects repeated measures models in the intention-to-treat population, adjusted for stratification variables, sex, and years of experience. The primary outcome was teacher well-being (Warwick-Edinburgh Mental Well-being Scale). Secondary outcomes were teacher depression, absence, and presenteeism, and student well-being, mental health difficulties, attendance, and attainment. Follow-up was at months 12 (T1) and 24 (T2). We collected process data to test the logic model underpinning the intervention, to aid interpretation of the findings. A total of 1,722 teachers were included in the primary analysis. Teacher well-being did not differ between groups at T2 (intervention mean well-being score 47.5, control group mean well-being score 48.4, adjusted mean difference −0.90, 95% CI –2.07 to 0.27, p = 0.130). The only effect on secondary outcomes was higher teacher-reported absence among the intervention group at T2 (intervention group median number of days absent 0, control group median number of days absent 0, ratio of geometric means 1.04, 95% CI 1.00 to 1.09, p = 0.042). Process measures indicated little change in perceived mental health support, quality of relationships, and work-related stress. The average cost of the intervention was £9,103 per school. The study’s main limitations were a lack of blinding of research participants and the self-report nature of the outcome measures.ConclusionsIn this study, we observed no improvements to teacher or student mental health following the intervention, possibly due to a lack of impact on key drivers of poor mental health within the school environment. Future research should focus on structural and cultural changes to the school environment, which may be more effective at improving teacher and student mental health and well-being.Trial registrationwww.isrctn.com ISRCTN95909211.

Using a cluster randomized study, Judi Kidger and colleagues study an intervention to improve teacher wellbeing support and training to support students in UK high schools (the WISE study).     

Adjuvant treatment with polyadenylic-polyuridylic acid in operable breast cancer: updated results of a randomised trial.

The results of a randomised trial of polyadenylic-polyuridylic acid given as adjuvant treatment for operable breast cancer were reviewed after a mean follow up period of 87 months. Of the 300 patients included in the original trial, 145 had been allocated to conventional treatment alone and served as controls. At the time of review the overall survival of the group given polyadenylic-polyuridylic acid was significantly improved (p less than 0.05) as compared with that of the controls given conventional treatment alone. Significant benefit (p less than 0.02) was also observed among patients with evidence of disease in lymph nodes, the best results occurring in those with up to three invaded nodes, who showed a significant increase in both overall and relapse free survival. No evidence of toxicity was recorded. These findings confirm the value of polyadenylic-polyuridylic acid as adjuvant treatment for operable breast cancer. Results in an experimental model and in patients receiving the adjuvant suggested a possible role of interferon and natural killer (NK) cells in the mechanism of action.     

O-12The use of control samples in the PAPANICOLAOU technical external quality assessment scheme

Technical external quality assessment (TEQA) in Wales is based on NHSCSP publication 19, which sets out policy and procedures for the scheme. The purpose of EQA is to sustain and improve the quality of patient care by promoting a high standard of performance. Following the introduction of liquid base cytology (LBC) technical limitations, particularly in assessing counterstaining, have been noted. LBC provides the means to address these limitations - As part of a development plan for TEQA in Wales, a control sample procedure was introduced to the scheme. A pooled control sample was composed, containing residual material from six 'matched' negative samples, re-suspended in collection fluid. Aliquots of this sample were distributed for processing and staining, to the 13 laboratories registered with the scheme. The slides produced were assessed at a scheduled TEQA assessment in accordance with the standard criteria. Initial overall scoring for these control samples produced acceptable levels of staining for 12 of the laboratories - one laboratory produced a marginal score. Repeat distributions have shown maintained or improved results. This method provides a prospective quality assessment tool, which counters the emphasis on slide selection and eliminates potential selection bias, whilst introducing consistency and improving comparability across participant laboratories. The method may also prove helpful in identifying technical inconsistencies such as equipment or handling errors that may occur during sample processing prior to or during staining. The control process, which is now used routinely in the Welsh TEQA scheme; is considered complimentary to, and not a replacement for, the selection process established in NHSCSP #19. However, we feel that this development could be considered as a new initiative in the National TEQA scheme. The control process is applicable to all LBC systems in current use.     

Chemotherapy in pancreatic cancer: results of a controlled,prospective, randomised,multicentre trial.

Forty patients with inoperable pancreatic cancer were included in a prospective, randomised, controlled trial of multiple chemotherapy. The survival of 19 untreated control patients was compared with that of 21 patients who received an initiation course of intravenous fluorouracil, cyclophosphamide, methotrexate, and vincristine given over five days followed by intravenous fluorouracil and mitomycin given over three or five days at six-week intervals thereafter. Median survival in treated patients was 44 weeks, which was significantly longer than the nine weeks seen in controls. In patients without metastases median survival was 48 weeks in the treated group and 12 weeks in controls. In patients with metastases it was 30 weeks in treated patients and seven weeks in controls. The treatment was well tolerated and seemed to confer a significant prolongation of survival, comparing favourably with previous reports of chemotherapy with or without radiotherapy. If the results are confirmed this regimen may be useful in district general hospital practice.     

Intermittent screening and treatment versus intermittent preventive treatment of malaria in pregnancy: a randomised controlled non-inferiority trial

Background

The effectiveness of intermittent preventive treatment of malaria in pregnancy (IPTp) may be compromised by the spread of resistance to sulphadoxine/pyrimethamine (SP) across Africa. But little informtion exists on alternative drugs for IPTp or alternative strategies for the prevention of malaria in pregnancy. Therefore, we have investigated whether screening with a rapid diagnostic test and treatment of those who are positive (IST) at routine antenatal clinic attendances is as effective and as safe as SP-IPTp in pregnant women.

Methods and Findings

During antenatal clinic sessions in six health facilities in Ghana held between March 2007 and September 2007, 3333 pregnant women who satisfied inclusion criteria were randomised into three intervention arms (1) standard SP-IPTp, (2) IST and treatment with SP or (3) IST and treatment with amodiaquine+artesunate (AQ+AS). All women received a long-lasting insecticide treated net. Study women had a maximum of three scheduled follow-up visits following enrolment. Haemoglobin concentration and peripheral parasitaemia were assessed between 36 and 40 weeks of gestation. Birth weight was measured at delivery or within 72 hours for babies delivered at home. Parasite prevalence at enrolment in primigravidae and in multigravidae was 29.6% and 10.2% respectively. At 36–40 weeks of gestation the prevalence of asymptomatic parasitaemia was 12.1% in study women overall and was very similar in all treatment groups. The risk of third trimester severe anaemia or low birth weight did not differ significantly between the three treatment groups regardless of gravidity. IST with AQ+AS or SP was not inferior to SP-IPTp in reducing the risk of low birth weight (RD = -1.17[95%CI; -4.39-1.02] for IST-SP vs. SP-IPTp and RD = 0.78[95%CI; -2.11-3.68] for IST-AQAS vs. SP-IPTp); third trimester severe anaemia (RD = 0.29[95%CI; -0.69-1.30] for IST-SP vs. SP-IPTp and RD = -0.36[95%CI;-1.12-0.44] for IST-AQAS vs. SP-IPTp).

Conclusion

The results of this study suggest that in an area of moderately high malaria transmission, IST with SP or AS+AQ may be a safe and effective strategy for the control of malaria in pregnancy. However, it is important that these encouraging findings are confirmed in other geographical areas and that the impact of IST on placental malaria is investigated.

Trial Registration

ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT00432367","term_id":"NCT00432367"}}NCT00432367 [{"type":"clinical-trial","attrs":{"text":"NCT00432367","term_id":"NCT00432367"}}NCT00432367]     

Cost effectiveness of day and inpatient psychiatric treatment: results of a randomised controlled trial.

OBJECTIVE: To compare direct and indirect costs of day and inpatient treatment of acute psychiatric illness. DESIGN: Randomised controlled trial with outcome and costs assessed over 12 months after the date of admission. SETTING: Teaching hospital in an inner city area. SUBJECTS: 179 patients with acute psychiatric illness referred for admission who were suitable for random allocation to day hospital or inpatient treatment. 77 (43%) patients had schizophrenia. INTERVENTIONS: Routine inpatient or day hospital treatment. MAIN OUTCOME MEASURES: Direct and indirect costs over 12 months, clinical symptoms, social functioning, and burden on relatives over the follow up period. RESULTS: Clinical and social outcomes were similar at 12 months, except that inpatients improved significantly faster than day patients and burden on relatives was significantly less in the day hospital group at one year. Median direct costs to the hospital were 1923 pounds (95% confidence interval 750 pounds to 3174 pounds) per patient less for day hospital treatment than inpatient treatment. Indirect costs were greater for day patients; when these were included, overall day hospital treatment was 2165 pounds cheaper than inpatient treatment (95% confidence interval of median difference 737 pounds to 3593 pounds). Including costs to informants when appropriate meant that day hospital treatment was 1994 pounds per patient cheaper (95% confidence interval 600 pounds to 3543 pounds). CONCLUSIONS: Day patient treatment is cheaper for the 30-40% of potential admissions that can be treated in this way. Carers of day hospital patients may bear additional costs. Carers of all patients with acute psychiatric illness are often themselves severely distressed at the time of admission, but day hospital treatment leads to less burden on carers in the long term.     

Towards a rational screening strategy for albuminuria: results from the unreferred renal insufficiency trial

Background

There remains debate about the screening strategies for albuminuria. This study evaluated whether a screening strategy in an apparently healthy population based on basic clinical and biochemical parameters could be more effective than a strategy where screening for albuminuria is performed unselectively.

Methodology/Principal Findings

The Unreferred Renal Insufficiency (URI) Study is a cross-sectional study on the prevalence of metabolic risk factors in Belgian workers, volunteering to be screened during a routine yearly occupational check-up. Subjects (n = 295) with treated hypertension, known diabetes, treated dyslipidaemia, cardiovascular and renal disease were excluded. Among 1,191 apparently healthy subjects, 23% had unknown hypertension, 13% had impaired glucose tolerance, 15.4% had normoalbuminuria, 4.2% had microalbuminuria and 0.4% had macroalbuminuria. Subjects with resting heart rate ≥85 bpm, plasma glucose ≥5.6 mmol/L and blood pressure ≥140/90 mmHg were associated with albuminuria of any degree. A strategy where only subjects with at least one of these risk factors (n = 431) were screened for albuminuria, would identify all subjects with macroalbuminuria (5/5), 64% of those with microalbuminuria (32/50), and less than half of those with normoalbuminuria (81/183). An alternative strategy whereby subjects were first screened for presence of albuminuria, and additional cardiovascular risk factors were only measured in subjects positive for albuminuria (n = 238), would identify only 27% (118/431) of the subjects with additional and potentially modifiable cardiovascular risk factors. On the other hand, half of the subjects in this study with albuminuria (120/238, of which 102 had normoalbuminuria), had no additional cardiovascular risk factor at all.

Conclusions

Screening an apparently healthy population directly for albuminuria will result in a high percentage of false positives, mostly measured in the normal range. Screening for microalbuminuria and macroalbuminuria based on presence of additional, potentially modifiable risk factors appears to be more beneficial. Trial registration 2006 {"type":"clinical-trial","attrs":{"text":"NCT00365911","term_id":"NCT00365911"}}NCT00365911     

Testing approaches to sharing trial results with participants: The Show RESPECT cluster randomised,factorial, mixed methods trial

BackgroundSharing trial results with participants is an ethical imperative but often does not happen. We tested an Enhanced Webpage versus a Basic Webpage, Mailed Printed Summary versus no Mailed Printed Summary, and Email List Invitation versus no Email List Invitation to see which approach resulted in the highest patient satisfaction with how the results were communicated.Methods and findingsWe carried out a cluster randomised, 2 by 2 by 2 factorial, nonblinded study within a trial, with semistructured qualitative interviews with some patients (ISRCTN96189403). Each cluster was a UK hospital participating in the ICON8 ovarian cancer trial. Interventions were shared with 384 ICON8 participants who were alive and considered well enough to be contacted, at 43 hospitals. Hospitals were allocated to share results with participants through one of the 8 intervention combinations based on random permutation within blocks of 8, stratified by number of participants. All interventions contained a written plain English summary of the results. The Enhanced Webpage also contained a short video. Both the Enhanced Webpage and Email contained links to further information and support. The Mailed Printed Summary was opt-out.Follow-up questionnaires were sent 1 month after patients had been offered the interventions. Patients’ reported satisfaction was measured using a 5-point scale, analysed by ordinal logistic regression estimating main effects for all 3 interventions, with random effects for site, restricted to those who reported receiving the results and assuming no interaction. Data collection took place in 2018 to 2019.Questionnaires were sent to 275/384 randomly selected participants and returned by 180: 90/142 allocated Basic Webpage, 90/133 Enhanced Webpage; 91/141 no Mailed Printed Summary, 89/134 Mailed Printed Summary; 82/129 no Email List Invitation, 98/146 Email List Invitation. Only 3 patients opted out of receiving the Mailed Printed Summary; no patients signed up to the email list. Patients’ satisfaction was greater at sites allocated the Mailed Printed Summary, where 65/81 (80%) were quite or very satisfied compared to sites with no Mailed Printed Summary 39/64 (61%), ordinal odds ratio (OR) = 3.15 (1.66 to 5.98, p < 0.001). We found no effect on patient satisfaction from the Enhanced Webpage, OR = 1.47 (0.78 to 2.76, p = 0.235) or Email List Invitation, OR = 1.38 (0.72 to 2.63, p = 0.327). Interviewees described the results as interesting, important, and disappointing (the ICON8 trial found no benefit). Finding out the results made some feel their trial participation had been more worthwhile. Regardless of allocated group, patients who received results generally reported that the information was easy to understand and find, were glad and did not regret finding out the results. The main limitation of our study is the 65% response rate.ConclusionsNearly all respondents wanted to know the results and were glad to receive them. Adding an opt-out Mailed Printed Summary alongside a webpage yielded the highest reported satisfaction. This study provides evidence on how to share results with other similar trial populations. Further research is needed to look at different results scenarios and patient populations.Trial registrationISRCTN: ISRCTN96189403.

In this mixed methods trial, Annabelle South and colleagues investigate different approaches to sharing the results of a clinical trial with its participants.