Queen Charlotte's Hospital Research Articles

The 1996 Continuous Negative Extrathoracic Pressure (CNEP) Trial: Were Parents' Allegations of Research Fraud Fraudulent?

Pediatricians in Britain have been watching with increasing incredulity the convoluted and dysfunctional way that their regulatory authorities have investigated allegations that fraud occurred during the conduct of a randomized, controlled trial reported in Pediatrics in December 1996.1 The study under scrutiny took place at Queen Charlotte's Hospital (London, United Kingdom) and the North Staffordshire Hospital (Stoke on Trent, United Kingdom). It was designed to determine whether the use of continuous negative extrathoracic pressure (CNEP) reduced the number of preterm infants with respiratory failure needing tracheal intubation, the length of time they needed intubation, and the time it took for them to be weaned from supplementary oxygen. It reported a marginal but statistically significant improvement in early respiratory outcomes and an even more marginal, nonsignificant increase in the number of infants in the CNEP group who did not survive to discharge. However, at least 1 family lodged a formal complaint over the way the trial had been conducted 5 months after the research article appeared, and even today, 9 years later, the issues raised by that complaint still remain unresolved. The proper conduct of clinical research, and the proper conduct of investigations into allegations of research misconduct, are rightly issues of concern to clinicians everywhere. It is worth recounting, therefore, what went wrong with the investigation of those allegations by the United Kingdom's various regulatory authorities. The initial complaint was widely reported. Indeed, 1 early headline in a national Sunday article read “Parents say ‘guinea pig’ trial killed their babies,”2 and headlines like this soon attracted the attention of a small but very active and well-organized pressure group3 that was already extremely hostile to the work of Professor David Southall, one of the principal instigators of the CNEP trial. The hostility stemmed from his use of covert … Address correspondence to Edmund Hey, DM. E-mail: shey{at}easynet.co.uk

A History of Britain's Hospitals and the Background to the Medical, Nursing and Allied Professions

A History of Britain's Hospitals and the Background to the Medical, Nursing and Allied Professions

Editor's Choice

Editor's Choice

A prospective randomised controlled trial of the Kiwi Omnicup versus conventional ventouse cups for vacuum‐assisted vaginal delivery

To evaluate the performance and safety of the Kiwi Omnicup and compare it to conventional vacuum cups in routine clinical practice. A randomised controlled trial of the Kiwi Omnicup versus conventional vacuum cups. Queen Charlotte's and Chelsea Hospital, a tertiary referral hospital in London from April 2001 to March 2004. Women requiring assisted vaginal delivery by ventouse. Women were randomised to the Kiwi Omnicup (n=206) or conventional vacuum cups (n=198). Data regarding maternal demographics, labour, mode of delivery and maternal and neonatal outcome were collected. Failure of delivery with instrument of first choice. The Kiwi Omnicup was less successful at delivery with instrument of first choice than the conventional ventouse, failure rate 30.1 versus 19.2% (RR 1.58; 95% CI 1.10-2.24). It was associated with a greater number of cup detachments (mean 0.68 compared with 0.28, with 44% compared with 18% having at least one detachment [P<0.0001]). There was no difference in the incidence of severe maternal trauma, and there were no cases of serious neonatal injury. The Kiwi Omnicup is less successful than conventional ventouse in achieving vaginal delivery, but its safety profile is comparable.

News

Research focus: Itai Nyamatore (left), Barbara Featherstone (centre) and Denise Henry each received a research bursary worth £6,250 last month as winners of the RCN's Mary Seacole leadership development award. Ms Nyamatore, strategic nurse manager at Northampton Primary Care Trust will look at supporting named nurses and care co-ordinators; Ms Featherstone, a modern matron at Northamptonshire Healthcare NHS Trust, will try to improve mental health promotion among people from black and minority ethnic backgrounds with chronic physical conditions; and Ms Henry, a practice development midwife at Queen Charlotte's and Chelsea Hospital, London, will look at setting up and co-ordinating an integrated care pathway for women with female genital mutilation.

TOCOX—A randomised, double‐blind, placebo‐controlled trial of rofecoxib (a COX‐2‐specific prostaglandin inhibitor) for the prevention of preterm delivery in women at high risk

To assess the safety and efficacy of the long term prophylactic use of rofecoxib (a COX-2-specific inhibitor) in women at high risk of preterm delivery. A randomised, double-blind, placebo-controlled trial. Queen Charlotte's and Chelsea Hospital, London and Guys and St Thomas' Hospitals, London. Ninety-eight singleton pregnancies at high risk of preterm labour. Treatment from 16 to 32 weeks. Weekly ultrasound surveillance. Fetal renal function and ductus arteriosus blood flow changes. Preterm delivery rates and neonatal outcome. Rofecoxib caused a reduction in hourly fetal urine production rates (-34%, 95% CI -13 to -50%, P = 0.004) and amniotic fluid index (-2.2, 95% CI -3.2 to -1.2, P < 0.001). This effect did not increase with time on treatment and reversed in all cases on discontinuation of treatment. Rofecoxib had an effect on the ductus arteriosus, increasing maximum systolic velocity (0.1 m/s, 95% CI 0.03-0.16, P = 0.02) and minimum diastolic velocity (0.007 m/s, 95% CI 0.0007-0.013, P= 0.03). This effect increased with time on treatment but was reversed with discontinuation of treatment and had no long term clinical sequelae. There was no difference in preterm delivery rates <30 weeks (28% on placebo vs 33% on rofecoxib, Mantel-Haensel [M-H]-adjusted risk 1.11, 95% CI 0.67-1.87). There were more deliveries <37 weeks in those on rofecoxib (40%vs 67%, M-H-adjusted risk 1.59, 95% CI 1.09-2.32). Rates of preterm prelabour rupture of membranes (PPROM) were higher in those on rofecoxib (RR 2.5, 95% CI 1.3-4.7). Rofecoxib has a significant but reversible effect on fetal renal function and the ductus arteriosus. It does not reduce the incidence of early preterm delivery <30 weeks and is associated with an increased risk of delivery before 37 weeks in women at high risk.

Preconception transabdominal cervicoisthmic cerclage

Objective The purpose of this study was to report pregnancy outcome and complication rates for women with recurrent late pregnancy loss who were treated with preconception transabdominal cervicoisthmic cerclage. Study design This was a case note review of 19 women at high risk for second trimester loss and early preterm delivery who were treated with preconception transabdominal cervicoisthmic cerclage at Queen Charlotte's and Chelsea Hospital from 1994 to 2003. Results Preconception transabdominal cervicoisthmic cerclage was associated with a postoperative fetal survival rate of 100% for pregnancies that reached >12 weeks of gestation, compared with a preoperative fetal survival rate of 12%. There were no significant intraoperative, antenatal, intrapartum or neonatal complications. Conclusion Within this case series, preconception transabdominal cervicoisthmic cerclage was a safe alternative to transabdominal cervicoisthmic cerclage that was performed in pregnancy with no risk to a fetus. It should be considered in appropriate cases in women seen for prepregnancy counseling.

Acute increase in femoral artery resistance in response to direct physical stimuli in the human fetus

Objective To determine whether fetal response to needling resembles the fetal ‘brain sparing’ response seen with hypoxaemia.Design Prospective observational study.Setting Centre for Fetal Care, Queen Charlotte's and Chelsea Hospital, London.Population Eighty‐five pregnant women undergoing invasive procedures associated with fetal prenatal diagnosis and/or management.Methods The femoral artery and the middle cerebral artery pulsatility index were measured by Doppler ultrasonography before and after 89 invasive procedures (fetal blood sampling, transfusion, bladder or cyst aspiration, shunt insertion and amniocentesis, between 17 and 36 weeks). Cases in which the fetal body was transgressed were compared with ‘control’ fetuses undergoing invasive procedures which did not directly involve needling the fetus (amniocentesis and placental cord insertion procedures).Main outcome measures Femoral artery and middle cerebral artery pulsatility index.Results The femoral artery pulsatility index rose after transgression [median change (Δ) 0.73; 95% confidence interval (CI) 0.51 to 0.98]. In contrast, there was no significant change in femoral artery pulsatility index after non‐transgression procedures (mean Δ 0.28; 95% CI −0.20 to 0.76). Analysis confirmed the fall in middle cerebral artery pulsatility index after transgression procedures (median Δ−0.19; 95% CI −0.07 to −0.35), but there was also a significant fall in middle cerebral artery pulsatility index after non‐transgression procedures (mean Δ−0.47; 95% CI −0.23 to −0.71).Conclusions The human fetus mounts a peripheral haemodynamic response to invasive procedures involving transgression of the fetal body, which is consistent with the brain sparing effect. However, the change in middle cerebral artery pulsatility index in both transgression and control procedures suggests that the changes and mechanisms may be more complex than previously thought.

Acute increase in femoral artery resistance in response to direct physical stimuli in the human fetus

Objective To determine whether fetal response to needling resembles the fetal ‘brain sparing’ response seen with hypoxaemia. Design Prospective observational study. Setting Centre for Fetal Care, Queen Charlotte's and Chelsea Hospital, London. Population Eighty-five pregnant women undergoing invasive procedures associated with fetal prenatal diagnosis and/or management. Methods The femoral artery and the middle cerebral artery pulsatility index were measured by Doppler ultrasonography before and after 89 invasive procedures (fetal blood sampling, transfusion, bladder or cyst aspiration, shunt insertion and amniocentesis, between 17 and 36 weeks). Cases in which the fetal body was transgressed were compared with ‘control’ fetuses undergoing invasive procedures which did not directly involve needling the fetus (amniocentesis and placental cord insertion procedures). Main outcome measures Femoral artery and middle cerebral artery pulsatility index. Results The femoral artery pulsatility index rose after transgression [median change (Δ) 0.73; 95% confidence interval (CI) 0.51 to 0.98]. In contrast, there was no significant change in femoral artery pulsatility index after non-transgression procedures (mean Δ 0.28; 95% CI −0.20 to 0.76). Analysis confirmed the fall in middle cerebral artery pulsatility index after transgression procedures (median Δ −0.19; 95% CI −0.07 to −0.35), but there was also a significant fall in middle cerebral artery pulsatility index after non-transgression procedures (mean Δ −0.47; 95% CI −0.23 to −0.71). Conclusions The human fetus mounts a peripheral haemodynamic response to invasive procedures involving transgression of the fetal body, which is consistent with the brain sparing effect. However, the change in middle cerebral artery pulsatility index in both transgression and control procedures suggests that the changes and mechanisms may be more complex than previously thought.

Transcervical resection of the endometrium and myometrium: a review of 111 patients after 6 years

Objective To determine the medium- to long-term amenorrhoea rate and patient satisfaction following transcervical resection of both the endometrium and inner myometrium (TCREM). Design A prospective audit of 111 patients. Subjects 111 patients referred with menorrhagia, and concomitant dysmenorrhoea in 74% of cases. Setting Queen Charlotte's and Chelsea Hospital for Women, London. Methods Data relating to patient history, operational details, subsequent bleeding and pain, satisfaction and complications, were obtained from a pro forma, case notes and an annual questionnaire with a menstrual calendar. The patients were followed up for six full years. Results 103 women (93%) completed the audit. By the sixth year of follow up 78% of the women were satisfied with the result of their TCREM, 64% being amenorrhoeic. Conclusion Resection of both the endometrium and inner myometrium appears to offer an improved amenorrhoea rate compared with resection of the endometrium alone. Patient satisfaction is high and there was no apparent increase in morbidity. This applied to women with both menorrhagia and dysmenorrhoea.

Ultrasound-guided umbilical cord occlusion using bipolar diathermy for Stage III/IV twin-twin transfusion syndrome.

To evaluate bipolar diathermy as a technique for selective fetocide in the treatment of advanced (Stage III/IV) twin-twin transfusion syndrome (TTTS). A prospective observational study in two tertiary referral fetal medicine centres: Queen Charlotte's Hospital, London, UK and Haemek Hospital, Afula, Israel. Fifteen cases of TTTS (14 twins and one triplet pregnancy) were treated by selective occlusion of either the donor (n=8) or recipient's (n=7) umbilical cord using ultrasound-guided bipolar diathermy. Following each procedure, patients were scanned serially for fetal growth, liquor volume and umbilical Doppler measurements. Procedural complications and obstetric outcome were recorded. Postnatal placental injection studies were performed. Overall co-twin survival in Stage III/IV TTTS was 13/14 (93%). There were no treatment failures. The incidence of preterm prelabour rupture of membranes (PPROM) within 3 weeks of the procedure was 3/15 (20%). In those cases where pre-procedure umbilical artery Dopplers were abnormal, the Doppler findings normalised post-procedure in all non-cord-occluded fetuses. Growth velocities of surviving donors were similar to those of surviving recipients. Bipolar diathermy appears an effective technique for the selective reduction of monochorionic twins complicated by severe as well as preterminal TTTS, with recipient and donor fetuses being equally appropriate choices for fetocide. We suggest that for advanced-stage disease where the parents can contemplate this option, cord occlusion as a single preemptive procedure maximises the opportunity for intact survival of a single survivor.

Pregnancy and the erythrocyte sedimentation rate

Objectives To determine the range of erythrocyte sedimentation rate values obtained in healthy pregnant women. To examine the effect of gestational age and haemoglobin concentration on erythrocyte sedimentation rate. Setting Queen Charlotte's Hospital, London, UK. Design Cross sectional descriptive study. Population Healthy pregnant women attending for routine outpatient antenatal visits at Queen Charlotte's Hospital in London. Methods Erythrocyte sedimentation rate was determined by the Westergren method, haemoglobin concentration by automated cell counter and gestational age by ultrasonography. The median and 95% reference range was determined for erythrocyte sedimentation rate values obtained. Linear regression analysis was used to determine the influence of haemoglobin concentration and gestational age on erythrocyte sedimentation rate. Results For 1019 women examined, the range of erythrocyte sedimentation rate values obtained was 4–112 mm/h. Gestational age and haemoglobin concentration both significantly influenced erythrocyte sedimentation rate. ( P<0.0001). For non-anaemic women the 95% reference range rose from 18–48 mm/h in the first half of pregnancy to 30–70 mm/h in the second half of pregnancy. For anaemic women the corresponding reference ranges were 21–62 mm/h and 40–95 mm/h, respectively. Conclusion For the correct interpretation of erythrocyte sedimentation rate values obtained during pregnancy gestational age and haemoglobin concentration must be taken into account.

Pregnancy and the erythrocyte sedimentation rate

To determine the range of erythrocyte sedimentation rate values obtained in healthy pregnant women. To examine the effect of gestational age and haemoglobin concentration on erythrocyte sedimentation rate. Queen Charlotte's Hospital, London, UK. Cross sectional descriptive study. Population Healthy pregnant women attending for routine outpatient antenatal visits at Queen Charlotte's Hospital in London. Erythrocyte sedimentation rate was determined by the Westergren method, haemoglobin concentration by automated cell counter and gestational age by ultrasonography. The median and 95% reference range was determined for erythrocyte sedimentation rate values obtained. Linear regression analysis was used to determine the influence of haemoglobin concentration and gestational age on erythrocyte sedimentation rate. For 1,019 women examined, the range of erythrocyte sedimentation rate values obtained was 4-112 mm/ h. Gestational age and haemoglobin concentration both significantly influenced erythrocyte sedimentation rate. (P < 0.0001). For non-anaemic women the 95% reference range rose from 18-48 mm/h in the first half of pregnancy to 30-70 mm/h in the second half of pregnancy. For anaemic women the corresponding reference ranges were 21-62 mm/h and 40-95 mm/h, respectively. For the correct interpretation of erythrocyte sedimentation rate values obtained during pregnancy gestational age and haemoglobin concentration must be taken into account.

Celebrating midwifery

Recently I have spent some time practising in the Queen Charlotte's Hospital delivery suite as part of a personal professional development programme.

Prevalence of heart disease diagnosed de novo in pregnancy in a West London population.

To determine the prevalence of heart disease diagnosed de novo in pregnancy in a West London population and to re-examine the current role of routine cardiovascular examination in antenatal care in the UK. Retrospective study. Obstetric medical clinics at Queen Charlotte's and Chelsea Hospital, University College Hospital and Northwick Park Hospital. Three hundred and twenty women referred for cardiac evaluation during pregnancy. The majority of the 139 women referred specifically for evaluation of murmurs during pregnancy were found to have physiological murmurs (97%). Only four women (3%) were found to have significant cardiac lesions de novo in their pregnancy. Three of these four women were immigrants who had no previous history of heart disease. The only woman from the UK was already known to have a murmur from childhood. Our study shows that heart disease diagnosed de novo in pregnancy in a West London population is an uncommon problem with low prevalence. It also appears to be a problem seen mainly in the immigrant population. The results emphasise the importance of taking a thorough medical history in all pregnant women. However, our results if they are confirmed, would suggest that only immigrants and those with significant symptoms or a known history of heart murmur or heart disease need undergo cardiovascular examination during pregnancy. These findings need to be confirmed in a larger group in other parts of the UK before further recommendations on selective cardiovascular examination can be made. This will have significant implications for midwifery-led care.

Low-molecular-weight heparin for obstetric thromboprophylaxis: Experience of sixty-nine pregnancies in sixty-one women at high risk

OBJECTIVE: Our purpose was to investigate the use of low-molecular-weight heparin (enoxaparin, Clexane) for thromboprophylaxis in pregnancy. STUDY DESIGN: A prospective consecutive cohort of 61 pregnant women at high risk of thromboembolism receiving antenatal thromboprophylaxis with enoxaparin (usually 40 mg, subcutaneously daily) in a total of 69 pregnancies was identified from the obstetric medicine clinic at Queen Charlotte's Hospital. Bone density measurements of the hip and lumbar spine were taken in 26 women after 28 pregnancies within 16 months post partum. Nonparametric statistics were used for comparisons. RESULTS: There were no episodes of antenatal thromboembolism. One woman (1.6%) (receiving 20 mg of enoxaparin) had a pulmonary embolus post partum. Heparin levels (anti-Xa assay) were greater with the 40 mg dose (median 0.09 U/ml) than with the 20 mg dose (median 0.03 U/ml) ( p = 0.0006) but were not affected by gestational age ( r = –0.1, p = 0.14). Enoxaparin had no effect on platelet count or on in vitro coagulation tests. Nine (32%) women had bone density in the spine or hip >1 SD below the mean for age- and sex-matched controls. CONCLUSION: This, the largest study to date of low-molecular-weight heparin use in pregnancy, confirms previous reports that it is a safe and effective alternative to unfractionated heparin for obstetric thromboprophylaxis in high-risk women. Effects on bone demineralization require further investigation. (Am J Obstet Gynecol 1997;176:1062-8.)

Blood pressure and fetal heart rate changes with patient-controlled combined spinal epidural analgesia while ambulating in labour.

To determine the effect of patient-controlled combined spinal epidural analgesia (PCEA) on maternal pulse and blood pressure, and fetal heart rate in primigravid women, when adapting different positions in labour. A prospective study. Queen Charlotte's and Chelsea hospital, London. Fifty-five primigravid women in labour at > or = 37 weeks of gestation; 40 women had supervised standing top-ups given by an anaesthetist. A further 15 women had PCEA top-ups given in each of standing, sitting and lying positions. Maternal pulse rate, blood pressure and fetal heart rate changes following epidural top-ups. In the first 40 women there was no clinically significant fall in their blood pressure (< 5 mmHg). The subsequent 15 women who had PCEA top-ups had no fall in blood pressure in the standing and sitting positions, though the average blood pressure fell significantly when a top-up was given in the lying position. Maternal heart rate increased significantly at 12 min post top-up when the women were in the standing position (P = 0.0018). In the 15 women who had PCEA top-ups, the CTG showed improvement in decelerations when women were in the standing position but deterioration when in the lying position (P < 0.01). Patient-controlled epidural analgesia top-ups with maternal mobility may be beneficial to the fetus possibly by reducing the hypotension normally associated with top-ups in the lying position.

Multiple pregnancy and reproductive choice R v. Queen Charlotte Hospital, Professor Phillip Bennett, North Thames Regional Health Authority and Social Services of Brentford and Hounslaw LBC, ex parte SPUC, ex parte Philys Bowman

Multiple pregnancy and reproductive choice R v. Queen Charlotte Hospital, Professor Phillip Bennett, North Thames Regional Health Authority and Social Services of Brentford and Hounslaw LBC, ex parte SPUC, ex parte Philys Bowman

Fetal telemedicine: six month pilot of real-time ultrasound and video consultation between the Isle of Wight and London.

Prospective audit of first six months. Referral from a district general hospital on the Isle of Wight to a comprehensive tertiary referral service, the Centre for Fetal Care at Queen Charlotte's Hospital 120 km away in London. Women whose pregnancy was suspected, or at risk, of fetal abnormality. Remote consultation by transmitting ultrasound and video in real-time over ISDN 30 telephone lines. Contemporaneous questionnaire to referring practitioner and patient. Frequency, indication, technical success and duration of consultation. Qualitative and semi-quantitative image quality. Effect of teleconsultation on need for physical referral. Twenty-nine women underwent 39 teleconsultations, and image quality was sufficient for diagnosis in all but one. Fetal abnormalities were present in 76%. Referral in person was required for only four women, significantly fewer than the 13 the referring hospital indicated would have been physically referred in the absence of this service (P < 0.001). Most mothers were counselled by the specialist "face-to-face' over the link, and 80% felt teleconsultation reduced their anxiety. A fetal telemedicine service is technically and clinically feasible. This demonstration suggests that such a service reduces the need for physical referral while increasing the rate of consultation, allowing better selection of patients who might benefit from referral. Further evaluation in a variety of clinical settings is now indicated, along with cost-benefit analysis.

Light the blue touchpaper and stand well clear

The issue of selective abortion exploded into the British media last week, propelled by two exclusive tabloid newspaper stories. A week that started with a professor of gynaecology talking about the abortion of a healthy twin ended with news of a woman expecting octuplets and a sponsorship deal of £1m. Both cases raised as many questions about media ethics as about medical ethics. The difference was that the woman patient employed a publicist to handle her story, while the professor dealt with the media unaided. For Phillip Bennett it was a week to forget. A professor of obstetrics and gynaecology at London's Queen Charlotte's Hospital, he unwittingly catapulted himself from relative obscurity into the full glare of media limelight by speaking publicly about the abortion of a healthy twin. What appeared to be a genuine attempt to air an important moral dilemma in the press turned into an uncontrollable cascade of publicity. The story first appeared in the Sunday Express, where Professor Bennett revealed that his patient, 26 weeks pregnant, was carrying healthy twins. She was in socially straitened circumstances …