Robin Dowie

HPV testing in combination with liquid-based cytology in primary cervical screening (ARTISTIC): a randomised controlled trial.

BACKGROUND Testing for human papillomavirus (HPV) DNA is reportedly more sensitive than cytology for the detection of high-grade cervical intraepithelial neoplasia (CIN). The effectiveness of HPV testing in primary cervical screening was assessed in the ARTISTIC trial, which was done over two screening rounds approximately 3 years apart (2001-03 and 2004-07) by comparing liquid-based cytology (LBC) combined with HPV testing against LBC alone. METHODS Women aged 20-64 years who were undergoing routine screening as part of the English National Health Service Cervical Screening Programme in Greater Manchester were randomly assigned (between July, 2001, and September, 2003) in a ratio of 3:1 to either combined LBC and HPV testing in which the results were revealed and acted on, or to combined LBC and HPV testing where the HPV result was concealed from the patient and investigator. The primary outcome was the detection rate of cervical intraepithelial neoplasia grade 3 or worse (CIN3+) in the second screening round, analysed by intention to treat. This trial is registered with the International Standard Randomised Controlled Trial Number ISRCTN25417821. FINDINGS There were 24 510 eligible women at entry (18 386 in the revealed group, 6124 in the concealed group). In the first round of screening 233 women (1.27%) in the revealed group had CIN3+, compared with 80 (1.31%) women in the concealed group (odds ratio [OR] 0.97, 95% CI 0.75-1.25; p>0.2). There was an unexpectedly large drop in the proportion of women with CIN3+ between the first and second rounds of screening in both groups, at 0.25% (29 of 11 676) in the revealed group and 0.47% (18 of 3866 women) in the concealed group (OR 0.53, 95% CI 0.30-0.96; p=0.042). For both rounds combined, the proportion of women with CIN3+ were 1.51% (revealed) and 1.77% (concealed) (OR 0.85, 95% CI 0.67-1.08; p>0.2). INTERPRETATION LBC combined with HPV testing resulted in a significantly lower detection rate of CIN3+ in the second round of screening compared with LBC screening alone, but the effect was small. Over the two screening rounds combined, co-testing did not detect a higher rate of CIN3+ or CIN2+ than LBC alone. Potential changes in screening methodology should be assessed over at least two screening rounds. FUNDING National Institute of Health Research Health Technology Assessment Programme.

ARTISTIC: A randomised trial of human papillomavirus (HPV) testing in primary cervical screening

OBJECTIVES Primary cervical screening uses cytology to detect cancer precursor lesions [cervical intraepithelial neoplasia stage 3 or beyond (CIN3+)]. Human papillomavirus (HPV) testing could add sensitivity as an adjunct to cytology or as a first test, reserving cytology for HPV-positive women. This study addresses the questions: Does the combination of cytology and HPV testing achieve a reduction in incident CIN3+?; Is HPV testing cost-effective in primary cervical screening?; Is its use associated with adverse psychosocial or psychosexual effects?; and How would it perform as an initial screening test followed by cytology for HPV positivity? DESIGN ARTISTIC was a randomised trial of cervical cytology versus cervical cytology plus HPV testing, evaluated over two screening rounds, 3 years apart. Round 1 would detect prevalent disease and round 2 a combination of incident and undetected disease from round 1. SETTING Women undergoing routine cervical screening in the NHS programme in Greater Manchester. PARTICIPANTS In total 24,510 women aged 20-64 years were enrolled between July 2001 and September 2003. INTERVENTIONS HPV testing was performed on the liquid-based cytology (LBC) sample obtained at screening. Women were randomised in a ratio of 3:1 to have the HPV test result revealed and acted upon if persistently positive in cytology-negative cases or concealed. A detailed health economic evaluation and a psychosocial and psychosexual assessment were also performed. MAIN OUTCOME MEASURES The primary outcome was CIN3+ in round 2. Secondary outcomes included an economic assessment and psychosocial effects. A large HPV genotyping study was also conducted. RESULTS In round 1 there were 313 CIN3+ lesions, representing a prevalence in the revealed and concealed arms of 1.27% and 1.31% respectively (p = 0.81). Round 2 (30-48 months) involved 14,230 (58.1%) of the women screened in round 1 and only 31 CIN3+ were detected; the CIN3 rate was not significantly different between the revealed and concealed arms. A less restrictive definition of round 2 (26-54 months) increased CIN3+ to 45 and CIN3+ incidence in the arms was significantly different (p = 0.05). There was no difference in CIN3+ between the arms when rounds 1 and 2 were combined. Prevalence of high-risk HPV types was age-dependent. Overall prevalence of HPV16/18 increased with severity of dyskaryosis. Mean costs per woman in round 1 were 72 pounds and 56 pounds for the revealed and concealed arms (p < 0.001); an age-adjustment reduced these mean costs to 65 pounds and 52 pounds. Incremental cost-effectiveness ratio for detecting additional CIN3+ by adding HPV testing to LBC screening in round 1 was 38,771 pounds. Age-adjusted mean cost for LBC primary screening with HPV triage was 39 pounds compared with 48 pounds for HPV primary screening with LBC triage. HPV testing did not appear to cause significant psychosocial distress. CONCLUSIONS Routine HPV testing did not add significantly to the effectiveness of LBC in this study. No significant adverse psychosocial effects were detected. It would not be cost-effective to screen with cytology and HPV combined but HPV testing, as either triage or initial test triaged by cytology, would be cheaper than cytology without HPV testing. LBC would not benefit from combination with HPV; it is highly effective as primary screening but HPV testing has twin advantages of high negative predictive value and automated platforms enabling high throughput. HPV primary screening would require major contraction and reconfiguration of laboratory services. Follow-up continues in ARTISTIC while maintaining concealment for a further 3-year round of screening, which will help in screening protocol development for the post-vaccination era.

An assessment of parental satisfaction with mode of delivery of specialist advice for paediatric cardiology: Face-to-face versus videoconference

Comparisons of parental satisfaction were made after specialist paediatric cardiology consultations were conducted either by conventional face-to-face delivery or telemedicine. Satisfaction statements were rated by 100 parents: 20 who experienced telemedicine; 56 with new children seen in the outreach clinics; 24 with children on review whose next appointment was at the specialist centre. There was general satisfaction with both types of consultations, but significant differences were noted. Those who had videoconferences felt that they had received an explanation about how the specialist advice would be obtained, and that they could see the pictures being discussed clearly. Those who had experienced telemedicine believed that teleconsultations could save them travelling time and money and they found the technical aspects of sound and picture quality acceptable. They were not discomforted by the technology and felt reassured by the consultation with the specialist. However, there was some ambivalence towards the statements suggesting that teleconsultations could take the place of conventional face-to-face consultations.

Telemedicine in pediatric and perinatal cardiology: Economic evaluation of a service in English hospitals

OBJECTIVES Pediatric cardiology has an expanding role in fetal and pediatric screening. The aims of this study were to observe how district hospitals use a pediatric telecardiology service, and to compare the costs and outcomes of patients referred to specialists by means of this service or conventionally. METHODS A telemedicine service was set up between a pediatric cardiac center in London and four district hospitals for referrals of second trimester women, newborn babies, and older children. Clinicians in each hospital decided on the role for their service. Clinical events were audited prospectively and costed, and patient surveys were conducted. RESULTS The hospitals differed in their selection of patient groups for the service. In all, 117 telemedicine patients were compared with 387 patients seen in London or in outreach clinics. Patients selected for telemedicine were generally healthier. For all patients, the mean cost for the initial consultation was 411 UK pounds for tele-referrals and 277 UK pounds for conventional referrals, a nonsignificant difference. Teleconsultations for women and children were significantly more expensive because of technology costs, whereas for babies, ambulance transfers were much more costly. After 6-months follow-up, the difference between referral methods for all patients was nonsignificant (telemedicine, 3,350 UK pounds; conventional referrals, 2,172 UK pounds), and nonsignificant within the patient groups. CONCLUSIONS Telemedicine was perceived by cardiologists, district clinicians, and families as reliable and efficient. The equivocal 6-month cost results indicate that investment in the technology is warranted to enhance pediatric and perinatal cardiology services.

Cost implications of introducing a telecardiology service to support fetal ultrasound screening

A district hospital in south-east England used a telecardiology service for fetal cardiac diagnosis alongside an existing arrangement for referring pregnant women directly to perinatal cardiologists in London for detailed fetal echocardiography. Women were identified for referral according to local protocols when having a second trimester anomaly scan. For the telemedicine referrals, the sonographers video-recorded images from the anomaly scans for transmission during monthly videoconferences. The cost of the womens antenatal care was calculated from the specialist assessment until delivery, while family costs were collected in a postal survey. Over 15 months, telemedicine was used in 52 cases, while 24 women were seen in London. The London women were more likely to have had an ultrasound abnormality (29% v 10%, P = 0.047). A telemedicine assessment of 5 min duration was more costly than an examination in London (mean cost per referral of £206 v £74, P < 0.001). However, the telecardiology service was cost neutral after 14 days and for the extended period until delivery. Travel costs for London women averaged £37 compared with £5.50 for the telemedicine referrals. Telemedicine may be useful to support perinatal cardiologists in the UK whose workloads are expanding in response to improved standards in antenatal ultrasound screening.

Liquid-based cytology can improve efficiency of cervical smear readers: evidence from timing surveys in two NHS cytology laboratories

Objective:  Cervical screening programmes in England and Wales were advised by the National Institute for Clinical Excellence in 2003 to adopt liquid‐based cytology (LBC) in place of conventional Papanicolaou (Pap) cytology to facilitate laboratory efficiency. Pilot evaluations in England and Scotland monitored daily or weekly workloads of smear readers and concluded that LBC could increase hourly throughput rates. This study, instead, used timing surveys to determine screening rates.

A paediatric telecardiology service for district hospitals in south-east England: an observational study.

Objectives: To compare caseloads of new patients assessed by paediatric cardiologists face-to-face or during teleconferences, and assess NHS costs for the alternative referral arrangements. Design: Prospective cohort study over 15 months. Setting: Four district hospitals in south-east England and a London paediatric cardiology centre. Patients: Babies and children. Intervention: A telecardiology service introduced alongside outreach clinics. Measurements: Clinical outcomes and mean NHS costs per patient. Results: 266 new patients were studied: 75 had teleconsultations (19 of 42 newborns and 56 of 224 infants and children). Teleconsultation patients generally were younger (49% being under 1 year compared with 32% seen personally (p = 0.025)) and their symptoms were not as severe. A cardiac intervention was undertaken immediately or planned for five telemedicine patients (7%) and 30 conventional patients (16%). However, similar proportions of patients were discharged after being assessed (32% telemedicine and 39% conventional). During scheduled teleconferences the mean duration of time per patient in sessions involving real-time echocardiography was 14.4 min, and 8.5 min in sessions where pre-recorded videos were transmitted. Mean cost comparisons for telemedicine and face-to-face patients over 14-day and 6-month follow-up showed the telecardiology service to be cost neutral for the three hospitals with infrequently-held outreach clinics (£1519 vs £1724 respectively after 14 days). Conclusion: Paediatric cardiology centres with small cadres of specialists are under pressure to cope with ever-expanding caseloads of new patients with suspected anomalies. Innovative use of telecardiology alongside conventional outreach services should suitably, and economically, enhance access to these specialists.

Costs of neonatal care for low-birthweight babies in English hospitals

Aim:  To estimate mean costs of neonatal care for babies with birthweights ≤1800 g in a regional Level 3 unit and three Level 2 units providing short‐term intensive care.

Costs of NHS maternity care for women with multiple pregnancy compared with high-risk and low-risk singleton pregnancy.

Objective  To compare antenatal and obstetric costs for multiple pregnancy versus singleton pregnancy risk groups and to identify factors driving cost differentials.

A decision analytic approach to commissioning ambulance cardiac services

The paper discusses how a decision analytic framework has been used by an English health authority in relation to the commissioning of ambulance cardiac services. Strategies for the management by ambulance personnel of victims of cardiac arrest and persons with acute chest pain of cardiac origin were modelled in a decision-event tree, and a bibliographic database established. The international research literature prior to 1997 was searched in order to derive probability values for the tree. However, after checking whether the subgroupings of results in the papers were in accordance with the variables in the tree, the number of useful papers on acute chest pain was found to be only two. In the almost complete absence of information--even from small observational studies--on the management of the great majority of patients with cardiac symptoms transported by ambulance, the local ambulance service and the main providers of hospital services in the district are now collaborating in field studies of cardiac care in order to improve the inputs into the model.