Rhiannon Whitaker

Antenatal betamethasone and incidence of neonatal respiratory distress after elective caesarean section: pragmatic randomised trial

Abstract Objective To test whether steroids reduce respiratory distress in babies born by elective caesarean section at term. Design Multicentre pragmatic randomised trial. Setting 10 maternity units. Participants 998 consenting women randomised at decision to deliver by elective caesarean section; 503 randomised to treatment group. Interventions The treatment group received two intramuscular doses of 12 mg betamethasone in the 48 hours before delivery. The control group received treatment as usual. Outcome measures The primary outcome was admission to special care baby unit with respiratory distress. Secondary outcomes were severity of respiratory distress and level of care in response. Results Sex, birth weight, and gestation were not different between the two groups. Of the 35 babies admitted to special baby units with respiratory distress, 24 were in the control group and 11 in the intervention group (P = 0.02). The incidence of admission with respiratory distress was 0.051 in the control group and 0.024 in the treatment group (relative risk 0.46, 95% confidence interval 0.23 to 0.93). The incidence of transient tachypnoea of the newborn was 0.040 in the control group and 0.021 in the treatment group (0.54, 0.26 to 1.12). The incidence of respiratory distress syndrome was 0.011 in the control group and 0.002 in the treatment group (0.21, 0.03 to 1.32). Conclusions Antenatal betamethasone and delaying delivery until 39 weeks both reduce admissions to special care baby units with respiratory distress after elective caesarean section at term.

Goal-Oriented Cognitive Rehabilitation for People With Early-Stage Alzheimer Disease: A Single-Blind Randomized Controlled Trial of Clinical Efficacy

OBJECTIVES To provide evidence regarding the clinical efficacy of cognitive rehabilitation (CR) in early-stage Alzheimer disease (AD). DESIGN Single-blind randomized controlled trial comparing CR with relaxation therapy and no treatment. SETTING Outpatient, community-based setting. PARTICIPANTS Sixty-nine individuals (41 women, 28 men; mean age 77.78 years, standard deviation 6.32, range = 56-89) with a diagnosis of AD or mixed AD and vascular dementia and a Mini-Mental State Examination score of 18 or above, and receiving a stable dose of acetylcholinesterase-inhibiting medication. Forty-four family carers also contributed. INTERVENTION Eight weekly individual sessions of CR consisting of personalized interventions to address individually relevant goals supported by components addressing practical aids and strategies, techniques for learning new information, practice in maintaining attention and concentration, and techniques for stress management. MEASUREMENTS The primary outcomes were goal performance and satisfaction, assessed using the Canadian Occupational Performance Measure. Questionnaires assessing mood, quality of life and career strain, and a brief neuropsychological test battery were also administered. A subset of participants underwent functional magnetic resonance imaging (fMRI). RESULTS CR produced significant improvement in ratings of goal performance and satisfaction, whereas scores in the other two groups did not change. Behavioral changes in the CR group were supported by fMRI data for a subset of participants. CONCLUSIONS The findings support the clinical efficacy of CR in early-stage AD. CR offers a means of assisting people with early-stage AD and their families in managing the effects of the condition.

Generalized method for adaptive randomization in clinical trials

A flexible, generalized method of treatment allocation is proposed. The method uses a set of controlling parameters that enables the generic algorithm to produce a family of possible outcomes ranging from simple randomization to deterministic allocation. The method controls balance at stratum level, stratification level and overall without detriment to the predictability of the method. The paper lists the desirable characteristics of allocation methods and shows that the proposed method fulfils the majority and is easy to use in the clinical context, once the coding has been established. An explanation of the method for 2, 3 and 4 treatment group allocations is given. Simulations demonstrate the flexibility of the method.

Behavioural, educational and respiratory outcomes of antenatal betamethasone for term caesarean section (ASTECS trial)

Objectives To determine whether antenatal betamethasone prior to elective term caesarean section (CS) affects long term behavioural, cognitive or developmental outcome, and whether the risk of asthma or atopic disease is reduced. Design A questionnaire based follow-up of a multicentre randomised controlled trial (Antenatal Steroids for Term Elective Caesarean Section, BMJ 2005). Setting Four UK study centres from the original trial. Participants 862 participants from the four largest recruiting centres, 92% of the original study. 824 (96%) were traced and 799 (93%) were successfully contacted. Fifty-one percent (407/799) completed and returned the questionnaire. The children were aged 8–15 years (median 12.2 years, 52% girls). 386 gave consent to contact schools with 352 (91%) reports received. Main outcome measures Questionnaires including a strengths and difficulties questionnaire, International Study of Asthma and Allergies in Childhood, general health and school performance. Results There were no significant differences between children whose mothers received betamethasone and controls for the mean total strengths and difficulties questionnaire scores and subscores for hyperactivity, emotional symptoms, prosocial behaviour, conduct or peer problems. 25 (12%) children whose mothers received betamethasone had reported learning difficulties compared with 27 (14%) control children. The proportion of children who achieved standard assessment tests KS2 exams level 4 or above for mathematics, English or science was similar as were the rates of ever reported wheeze (30% vs 30%), asthma (24% vs 21%), eczema (34% vs 37%) and hay fever (25% vs 27%). Conclusions Antenatal betamethasone did not result in any adverse outcomes or reduction in asthma or atopy. It should be considered for elective CS at 37–38 weeks of gestation. Trial registration: Original trial was preregistration, the trial publication is BMJ. 2005 Sep 24;331(7518):662.

Serum C-reactive protein as a prognostic indicator in patients with oral squamous cell carcinoma.

Preoperative elevation of serum C-reactive protein (CRP) has been demonstrated as a prognostic indicator in oesophageal, gastric and colorectal cancer. This study was designed to establish if elevated preoperative levels of serum CRP could predict the prognosis of patients treated with primary surgery for oral squamous cell carcinoma (SCC). Sixty patients with oral SCC who were treated by primary surgery and microvascular free flap reconstruction, were included in the study. The relation between preoperative levels of serum CRP, clinicopathological features and patient prognosis was determined. This study showed using bivariate analysis (p=0.003) and multivariate analysis (p<0.001) that a raised preoperative CRP was associated with worse overall survival. Tumour size and stage when combined with CRP levels increases the predictive power of this indicator.

Goal-oriented cognitive rehabilitation in early-stage dementia: Study protocol for a multi-centre single-blind randomised controlled trial (GREAT)

BackgroundPreliminary evidence suggests that goal-oriented cognitive rehabilitation (CR) may be a clinically effective intervention for people with early-stage Alzheimer’s disease, vascular or mixed dementia and their carers. This study aims to establish whether CR is a clinically effective and cost-effective intervention for people with early-stage dementia and their carers.Methods/designIn this multi-centre, single-blind randomised controlled trial, 480 people with early-stage dementia, each with a carer, will be randomised to receive either treatment as usual or cognitive rehabilitation (10 therapy sessions over 3 months, followed by 4 maintenance sessions over 6 months). We will compare the effectiveness of cognitive rehabilitation with that of treatment as usual with regard to improving self-reported and carer-rated goal performance in areas identified as causing concern by people with early-stage dementia; improving quality of life, self-efficacy, mood and cognition of people with early-stage dementia; and reducing stress levels and ameliorating quality of life for carers of participants with early-stage dementia. The incremental cost-effectiveness of goal-oriented cognitive rehabilitation compared to treatment as usual will also be examined.DiscussionIf the study confirms the benefits and cost-effectiveness of cognitive rehabilitation, it will be important to examine how the goal-oriented cognitive rehabilitation approach can most effectively be integrated into routine health-care provision. Our aim is to provide training and develop materials to support the implementation of this approach following trial completion.Trial registrationCurrent Controlled Trials ISRCTN21027481

Impact of primary Sjögren's syndrome on smell and taste: effect on quality of life

OBJECTIVES To assess the prevalence of abnormal smell and taste perception in people with primary SS and the effect on quality of life (QoL). METHODS Twenty-eight participants with SS and 37 controls were enrolled in a cohort-matched, prospective, cross-sectional study. Smell and taste thresholds were measured using standardized, validated tests. QoL was assessed by the Short Form 12 (SF-12). RESULTS Smell threshold was reduced by 1 point (P = 0.002; 95% CI 0.35, 1.54) and taste threshold was reduced by 3.5 points (P < 0.001; 95% CI 1.80, 5.22) in the SS group compared with controls. The physical and mental components of SF-12 were reduced by 14.2 points (P < 0.001; 95% CI 9.47, 19.02) and 7.5 points (P = 0.002; 95% CI 2.97, 12.02), respectively, in the SS group compared with controls. Taste threshold was significantly correlated with both the physical (r = 0.48; P < 0.001) and the mental (r = 0.30; P = 0.015) components of SF-12. Smell threshold correlated with the physical (r = 0.457; P < 0.001), but not the mental component (r = 0.154; P = 0.222) of SF-12. CONCLUSIONS Clinically important impairment of chemosensory perception occurred in the SS group compared with age- and gender-matched controls. Assessment using SF-12 suggests that this impairment contributed to the reduced health-related QoL that characterized these individuals.

Intervention Now To Eliminate Repeat Unintended Pregnancy in Teenagers (INTERUPT): a systematic review of intervention effectiveness and cost-effectiveness, qualitative and realist synthesis of implementation factors and user engagement

Background The UK has the highest rate of teenage pregnancies in Western Europe, a fifth are repeat pregnancies. Unintended conceptions can result in emotional, psychological and educational harm to teenage girls, often with enduring implications for their life chances. Babies of teenage mothers have increased mortality in their first year and increased risk of poverty, educational underachievement and unemployment later in life, with associated societal costs. Methods and analysis We will conduct a streamed, mixed-methods systematic review to find and evaluate interventions designed to reduce repeat unintended teen pregnancies. Our aims are to identify Who is at greater risk of repeat unintended pregnancies? Which interventions are effective, cost-effective, how they work, in what setting and for whom? What are the barriers and facilitators to intervention uptake? Traditional electronic database searches will be augmented by targeted searches for evidence ‘clusters’ and guided by an advisory group of experts and stakeholders. To address the topics inherent complexities, we will use a highly structured, innovative and iterative approach combining methodological techniques tailored to each stream of evidence. Quantitative data will be synthesised with reference to Cochrane guidelines for public health interventions. Qualitative evidence addressing facilitators and barriers to the uptake of interventions, experience and acceptability of interventions will be synthesised thematically. We will apply the principles of realist synthesis to uncover theories and mechanisms underpinning interventions. We will conduct an integration and overarching narrative of findings authenticated by client group feedback. Ethics and dissemination We will publish the complete review in ‘Health Technology Assessment’ and sections in specialist peer-reviewed journals. We will present at national and international conferences in the fields of public health, reproductive medicine and review methodology. Findings will be fed back to service users and practitioners via workshops run by the partner collaborators. Trail registration number PROSPERO CRD42012003168. Cochrane registration number i=fertility/0068.

Gynaecological cancer follow-up: national survey of current practice in the UK

Objective To establish a baseline of national practice for follow-up after treatment for gynaecological cancer. Design Questionnaire survey. Setting Gynaecological cancer centres and units. Geographical location UK. Participants Members of the British Gynaecological Cancer Society and the National Forum of Gynaecological Oncology Nurses. Interventions A questionnaire survey. Outcome measures To determine schedules of follow-up, who provides it and what routine testing is used for patients who have had previous gynaecological cancer. Results A total of 117 responses were obtained; 115 (98%) reported hospital scheduled regular follow-up appointments. Two involved general practitioners. Follow-up was augmented or replaced by telephone follow-up in 29 responses (25%) and patient-initiated appointments in 38 responses (32%). A total of 80 (68%) cancer specialists also offered combined follow-up clinics with other specialties. Clinical examinations for hospital-based follow-up were mainly performed by doctors (67% for scheduled regular appointments and 63% for patient-initiated appointments) while telephone follow-up was provided in the majority by nurses (76%). Most respondents (76/117 (65%)) provided routine tests, of which 66/76 (87%) reported carrying out surveillance tests for ovarian cancer, 35/76 (46%) for cervical cancer, 8/76 (11%) for vulval cancer and 7/76 (9%) for endometrial cancer. Patients were usually discharged after 5 years (82/117 (70%)), whereas three (3%) were discharged after 4 years, nine (8%) after three years and one (1%) after 2 years. Conclusions Practice varied but most used a standard hospital-based protocol of appointments for 5 years and routine tests were performed usually for women with ovarian cancer. A minority utilised nurse-led or telephone follow-up. General practitioners were rarely involved in routine care. A randomised study comparing various models of follow-up could be considered.

A stepped wedge cluster randomized control trial of dried blood spot testing to improve the uptake of hepatitis C antibody testing within UK prisons

Background: The prevalence of hepatitis C (HCV) is elevated within prison populations, yet diagnosis in prisons remains low. Dried blood spot testing (DBST) is a simple procedure for the detection of HCV antibodies; its impact on testing in the prison context is unknown. Methods: We carried out a stepped-wedge cluster-randomized control trial of DBST for HCV among prisoners within five male prisons and one female prison. Each prison was a separate cluster. The order in which the intervention (training in use of DBST for HCV testing and logistic support) was introduced was randomized across clusters. The outcome measure was the HCV testing rate by prison. Imputation analysis was carried out to account for missing data. Planned and actual intervention times differed in some prisons; data were thus analysed by intention to treat (ITT) and by observed step times. Results: There was insufficient evidence of an effect of the intervention on testing rate using either the ITT intervention time (OR: 0.84; 95% CI: 0.68–1.03; P = 0.088) or using the actual intervention time (OR: 0.86; 95% CI: 0.71–1.06; P = 0.153). This was confirmed by the pooled results of five imputed data sets. Conclusions: DBST as a stand-alone intervention was insufficient to increase HCV diagnosis within the UK prison setting. Factors such as staff training and allocation of staff time for regular clinics are key to improving service delivery. We demonstrate that prisons can conduct rigorous studies of new interventions, but data collection can be problematic. Trial registration: International Standard Randomized Controlled Trial Number Register (ISRCTN number ISRCTN05628482).