Determinants of diagnostic discordance for non-diabetic hyperglycaemia and Type 2 diabetes using paired glycated haemoglobin measurements in a large English primary care population: cross-sectional study.

AIM: To investigate factors influencing diagnostic discordance for non-diabetic hyperglycaemia and Type 2 diabetes. METHODS: Some 10 000 adults at increased risk of diabetes were screened with HbA1c and fasting plasma glucose (FPG). The 2208 participants with initial HbA1c ≥ 42 mmol/mol (≥ 6.0%) or FPG ≥ 6.1 mmol/l were retested after a median 40 days. We compared the first and second HbA1c results, and consequent diagnoses of non-diabetic hyperglycaemia and Type 2 diabetes, and investigated predictors of discordant diagnoses. RESULTS: Of 1463 participants with non-diabetic hyperglycaemia and 394 with Type 2 diabetes on first testing, 28.4% and 21.1% respectively had discordant diagnoses on repeated testing. Initial diagnosis of non-diabetic hyperglycaemia and/or impaired fasting glucose according to both HbA1c and FPG criteria, or to FPG only, made reclassification as Type 2 diabetes more likely than initial classification according to HbA1c alone. Initial diagnosis of Type 2 diabetes according to both HbA1c and FPG criteria made reclassification much less likely than initial classification according to HbA1c alone. Age, and anthropometric and biological measurements independently but inconsistently predicted discordant diagnoses and changes in HbA1c . CONCLUSIONS: Diagnosis of non-diabetic hyperglycaemia or Type 2 diabetes with a single measurement of HbA1c in a screening programme for entry to diabetes prevention trials is unreliable. Diagnosis of non-diabetic hyperglycaemia and Type 2 diabetes should be confirmed by repeat testing. FPG results could help prioritise retesting. These findings do not apply to people classified as normal on a single test, who were not retested.

Socioeconomic position and depression in South African adults with long-term health conditions: a longitudinal study of causal pathways.

AIMS: There is convincing evidence that lower socioeconomic position is associated with increased risk of mental disorders. However, the mechanisms involved are not well understood. This study aims to elucidate the causal pathways between socioeconomic position and depression symptoms in South African adults. Two possible causal theories are examined: social causation, which suggests that poor socioeconomic conditions cause mental ill health; and social drift, which suggests that those with poor mental health are more likely to drift into poor socioeconomic circumstances. METHODS: The study used longitudinal and cross-sectional observational data on 3904 adults, from a randomised trial carried out in 38 primary health care clinics between 2011 and 2012. Structural equation models and counterfactual mediation analyses were used to examine causal pathways in two directions. First, we examined social causation pathways, with language (a proxy for racial or ethnic category) being treated as an exposure, while education, unemployment, income and depression were treated as sequential mediators and outcomes. Second, social drift was explored with depression treated as a potential influence on health-related quality of life, job loss and, finally, income. RESULTS: The results suggest that the effects of language on depression at baseline, and on changes in depression during follow-up, were mediated through education and income but not through unemployment. Adverse effects of unemployment and job loss on depression appeared to be mostly mediated through income. The effect of depression on decreasing income appeared to be mediated by job loss. CONCLUSIONS: These results suggest that both social causation and social selection processes operate concurrently. This raises the possibility that people could get trapped in a vicious cycle in which poor socioeconomic conditions lead to depression, which, in turn, can cause further damage to their economic prospects. This study also suggests that modifiable factors such as income, employment and treatable depression are suitable targets for intervention in the short to medium term, while in the longer term reducing inequalities in education will be necessary to address the deeply entrenched inequalities in South Africa.

Socioeconomic and modifiable predictors of blood pressure control for hypertension in primary care attenders in the Western Cape, South Africa.

BACKGROUND: Low socioeconomic status is associated with the risk of hypertension. There are few reports of the effect of socioeconomic and potentially modifiable factors on the control of hypertension in South Africa (SA). OBJECTIVES: To investigate associations between patients' socio-economic status and characteristics of primary healthcare facilities, and control and treatment of blood pressure in hypertensive patients. METHODS: We enrolled hypertensive patients attending 38 public sector primary care clinics in the Western Cape, SA, in 2011, and followed them up 14 months later as part of a randomised controlled trial. Blood pressure was measured and prescriptions for antihypertension medications were recorded at baseline and follow-up. Logistic regression models assessed associations between patients' socioeconomic status, characteristics of primary healthcare facilities, and control and treatment of blood pressure. RESULTS: Blood pressure was uncontrolled in 60% (1 917/3 220) of patients at baseline, which was less likely in patients with a higher level of education (p=0.001) and in English compared with Afrikaans respondents (p=0.033). Treatment was intensified in 48% (892/1 872) of patients with uncontrolled blood pressure at baseline, which was more likely in patients with higher blood pressure at baseline (p<0.001), concurrent diabetes (p=0.013), more education (p=0.020), and those who attended clinics offering off-site drug supply (p=0.009), with a doctor every day (p=0.004), or with more nurses (p<0.001). CONCLUSION: Patient and clinic factors influence blood pressure control and treatment in primary care clinics in SA. Potential modifiable factors include ensuring effective communication of health messages, providing convenient access to medications, and addressing staff shortages in primary care clinics.

Lifestyle interventions for weight loss in adults with severe obesity: a systematic review.

Severe obesity is an increasingly prevalent condition and is often associated with long-term comorbidities, reduced survival and higher healthcare costs. Non-surgical methods avoid the side effects, complications and costs of surgery, but it is unclear which non-surgical method is most effective. The objective of this article was to systematically review the effectiveness of lifestyle interventions compared to standard or minimal care for weight loss in adults with severe obesity. MEDLINE, EMBASE, CENTRAL, databases of on-going studies, reference lists of any relevant systematic reviews and the Cochrane Library database were searched from inception to February 2016 for relevant randomized controlled trials (RCTs). Inclusion criteria were participants with severe obesity (body mass index [BMI] > 40 kg/m2 or BMI > 35 kg/m2 with comorbidity) and interventions with a minimal duration of 12 weeks that were multi-component combinations of diet, exercise and behavioural therapy. Risk of bias was evaluated using the Cochrane risk of bias criteria. Meta-analysis was not possible because of methodological heterogeneity. Seventeen RCTs met the inclusion criteria. Weight change in kilograms of participants from baseline to follow-up was reported for 14 studies. Participants receiving the lifestyle intervention had a greater decrease in weight than participants in the control group for all studies (1.0-11.5 kg). Lifestyle interventions varied greatly between the studies. Overall lifestyle interventions with combined diet and exercise components achieved the greatest weight loss. Lifestyle interventions for weight loss in adults with severe obesity were found to result in increased weight loss when compared to minimal or standard care, especially those with combined diet and exercise components.

Risk of diabetic retinopathy at first screen in children at 12 and 13 years of age.

AIMS: To investigate the relationships between age at diagnosis of diabetes, age at diabetic eye screening and severity of diabetic retinopathy at first and subsequent screenings in children aged 12 or 13 years. METHODS: Data were extracted from four English screening programmes and from the Scottish, Welsh and Northern Irish programmes on all children with diabetes invited for their first and subsequent screening episodes from the age of 12 years. Retinopathy levels at first and subsequent screens, time from diagnosis of diabetes to first screening and age at diagnosis in years were calculated. RESULTS: Data were available for 2125 children with diabetes screened for the first time at age 12 or 13 years. In those diagnosed with diabetes at 2 years of age or less, the proportion with retinopathy in one or both eyes was 20% and 11%, respectively, decreasing to 8% and 2% in those diagnosed between 2 and 12 years (P < 0.0001). Only three children (aged 8, 10 and 11 years at diagnosis of diabetes) had images graded with referable retinopathy and, of these, two had non-referable diabetic retinopathy at all subsequent screenings. Of 1703 children with subsequent images, 25 were graded with referable diabetic retinopathy over a mean follow-up of 3.1 years, an incidence rate of 4.7 (95% confidence interval, 3.1-7.0) per 1000 per year. CONCLUSIONS: In this large cohort of children, the low prevalence and incidence rates of referable diabetic retinopathy suggest that screening earlier than age 12 is not necessary.

Screening attendance, age group and diabetic retinopathy level at first screen.

AIMS: To report on the relationships between age at diagnosis of diabetes, time from registration with the screening programme to first diabetic eye screening and severity of diabetic retinopathy. METHODS: Data were extracted from four English screening programmes and from the Scottish, Welsh and Northern Irish programmes. Time from diagnosis of diabetes to first screening and age at diagnosis were calculated. RESULTS: Time from registration with the screening programme to first screening episode is strongly related to age at registration. Within 18 months of registration 89% of 3958 young people under 18 years of age and 81% of 391 293 people over 35 years of age were seen. In 19 058 people between 18 and 34 years of age, 80% coverage was not reached until 2 years and 9 months. The time from diagnosis of diabetes to first screening is positively associated with severity of disease (P < 0.0001). CONCLUSIONS: This report is the first that to demonstrate that those in the 18-34 year age group are least likely to attend promptly for screening after registration with a higher risk of referable diabetic retinopathy being present at the time of first screen. Date of diagnosis should be recorded and prodigious efforts made to screen all people promptly after diagnosis. Screening programmes should collect data on those who have not attended within one year of registration.

The SOAR stroke score predicts hospital length of stay in acute stroke: an external validation study.

AIMS: The objective of this study is to externally validate the SOAR stroke score (Stroke subtype, Oxfordshire Community Stroke Project Classification, Age and prestroke modified Rankin score) in predicting hospital length of stay (LOS) following an admission for acute stroke. METHODS: We conducted a multi-centre observational study in eight National Health Service hospital trusts in the Anglia Stroke & Heart Clinical Network between September 2008 and April 2011. The usefulness of the SOAR stroke score in predicting hospital LOS in the acute settings was examined for all stroke and then stratified by discharge status (discharged alive or died during the admission). RESULTS: A total of 3596 patients (mean age 77 years) with first-ever or recurrent stroke (92% ischaemic) were included. Increasing LOS was observed with increasing SOAR stroke score (p < 0.001 for both mean and median) and the SOAR stroke score of 0 had the shortest mean LOS (12 ± 20 days) while the SOAR stroke score of 6 had the longest mean LOS (26 ± 28 days). Among patients who were discharged alive, increasing SOAR stroke score had a significantly higher mean and median LOS (p < 0.001 for both mean and median) and the LOS peaked among patients with score value of 6 [mean (SD) 35 ± 31 days, median (IQR) 23 (14-48) days]. For patients who died as in-patient, there was no significant difference in mean or median LOS with increasing SOAR stroke score (p = 0.68 and p = 0.79, respectively). CONCLUSION: This external validation study confirms the usefulness of the SOAR stroke score in predicting LOS in patients with acute stroke especially in those who are likely to survive to discharge. This provides a simple prognostic score useful for clinicians, patients and service providers.

Patient characteristics predicting failure to receive indicated care for type 2 diabetes.

AIMS: To determine which patient characteristics were associated with failure to receive indicated care for diabetes over time. METHODS: English Longitudinal Study of Ageing participants aged 50 or older with diabetes reported receipt of care described by four diabetes quality indicators (QIs) in 2008-9 and 2010-11. Annual checks for glycated haemoglobin (HbA1c), proteinuria and foot examination were assessed as a care bundle (n=907). A further QI (n=759) assessed whether participants with cardiac risk factors were offered ACE inhibitors or angiotensin II receptor blockers (ARBs). Logistic regression modelled associations between failure to receive indicated care in 2010-11 and participants' socio-demographic, lifestyle and health characteristics, diabetes self-management knowledge, health literacy, and previous QI achievement in 2008-9. RESULTS: A third of participants (2008-9=32.8%; 2010-11=32.2%) did not receive all annual checks in the care bundle. Nearly half of those eligible were not offered ACE inhibitors/ARBs (2008-9=44.6%; 2010-11=44.5%). Failure to receive a complete care bundle was associated with lower diabetes self-management knowledge (odds ratio (OR) 2.05), poorer cognitive performance (1.78), or having previously received incomplete care (3.32). Participants who were single (OR=2.16), had low health literacy (1.50) or had received incomplete care previously (6.94) were more likely to not be offered ACE inhibitors/ARBs. Increasing age (OR=0.76) or body mass index (OR=0.70) was associated with lower odds of failing to receive this aspect of care. CONCLUSIONS: Quality improvement initiatives for diabetes might usefully target patients with previous receipt of incomplete care, poor knowledge of annual diabetes care processes, and poorer cognition and health literacy.

Economic inequalities in burden of illness, diagnosis and treatment of five long-term conditions in England: panel study.

OBJECTIVE: We compared the distribution by wealth of self-reported illness burden (estimated from validated scales, biomarker and reported symptoms) for angina, cataract, depression, diabetes and osteoarthritis, with the distribution of self-reported medical diagnosis and treatment. We aimed to determine if the greater illness burden borne by poorer participants was matched by appropriately higher levels of diagnosis and treatment. DESIGN: The English Longitudinal Study of Ageing, a panel study of 12,765 participants aged 50 years and older in four waves from 2004 to 2011, selected using a stratified random sample of households in England. Distribution of illness burden, diagnosis and treatment by wealth was estimated using regression analysis. OUTCOME MEASURES: The main outcome measures were ORs for the illness burden, diagnosis and treatment, respectively, adjusted for age, sex and wealth. We estimated the illness burden for angina with the Rose Angina scale, diabetes with fasting glycosylated haemoglobin, depression with the Centre for Epidemiologic Studies Depression Scale, osteoarthritis with self-reported pain and disability and cataract with self-reported poor vision. Medical diagnoses were self-reported for all conditions. Treatment was defined as ß-blocker prescription for angina, surgery for osteoarthritis and cataract, and receipt of predefined effective interventions for diabetes and depression. RESULTS: Compared with the wealthiest, the least wealthy participant had substantially higher odds for illness burden from any of the five conditions at all four time points, with ORs ranging from 4.2 (95% CI 2.6 to 6.8) for diabetes to 15.1 (11.4 to 20.0) for osteoarthritis. The ORs for diagnosis and treatment were smaller in all five conditions, and ranged from 0.9 (0.5 to 1.4) for diabetes treatment to 4.5 (3.3 to 6.0) for angina diagnosis. CONCLUSIONS: The substantially higher illness burden in less wealthy participants was not matched by appropriately higher levels of diagnosis and treatment.

Effectiveness of directly observed treatment of tuberculosis: a systematic review of controlled studies.

BACKGROUND: There is controversy about the effectiveness of directly observed treatment (DOT) for anti-tuberculosis treatment. This systematic review aimed to synthesise evidence from studies that compared DOT and self-administered treatment (SAT) or different types of DOT for anti-tuberculosis treatment. METHODS: Multiple databases were searched by two independent reviewers to identify relevant randomised (RCTs) and non-randomised studies. The risk of bias was independently assessed by two reviewers, and studies at high risk of bias were excluded. Data extraction was conducted by one reviewer and checked by a second reviewer. Primary outcome measures were cure and treatment success. RESULTS: We included eight RCTs and 15 non-randomised studies that were predominantly conducted in low- and middle-income countries. There was no convincing evidence that clinic DOT was more effective than SAT. Evidence from both RCTs and non-randomised studies suggested that community DOT was more effective than SAT. Community DOT was as effective as, or more effective than, clinic DOT. There was no statistically significant difference in results between family and non-family community DOT. CONCLUSIONS: Community DOT by non-family members might be the best option if it is more convenient to patients and less costly to health services than clinic DOT.

Evaluation of a multidisciplinary Tier 3 weight management service for adults with morbid obesity, or obesity and comorbidities, based in primary care.

A multidisciplinary Tier 3 weight management service in primary care recruited patients with a body mass index ≥40 kg·m(-2) , or 30 kg·m(-2) with obesity-related co-morbidity to a 1-year programme. A cohort of 230 participants was recruited and evaluated using the National Obesity Observatory Standard Evaluation Framework. The primary outcome was weight loss of at least 5% of baseline weight at 12 months. Diet was assessed using the two-item food frequency questionnaire, activity using the General Practice Physical Activity questionnaire and quality of life using the EuroQol-5D-5L questionnaire. A focus group explored the participants' experiences. Baseline mean weight was 124.4 kg and mean body mass index was 44.1 kg·m(-2) . A total of 102 participants achieved 5% weight loss at 12 months. The mean weight loss was 10.2 kg among the 117 participants who completed the 12-month programme. Baseline observation carried forward analysis gave a mean weight loss of 5.9 kg at 12 months. Fruit and vegetable intake, activity level and quality of life all improved. The dropout rate was 14.3% at 6 months and 45.1% at 1 year. Focus group participants described high levels of satisfaction. It was possible to deliver a Tier 3 weight management service for obese patients with complex co-morbidity in a primary care setting with a full multidisciplinary team, which obtained good health outcomes compared with existing services.

Use of haemoglobin A1c to detect impaired fasting glucose or Type 2 diabetes in a United Kingdom community based population.

AIMS: To evaluate the diagnostic accuracy of haemoglobin A1c (HbA1c) in screening for impaired fasting glucose and Type 2 diabetes (T2DM). METHODS: We screened 3904 adults aged 45-70 (mean age 58.6 [standard deviation (SD) 6.9] years, mean body mass index (BMI) 29.9 [SD 4.7]kg/m(2)), with fasting plasma glucose (FPG) and HbA1c as part of a large diabetes prevention programme. We assessed the diagnostic accuracy of HbA1c for predicting impaired fasting glucose (IFG), (defined either as FPG 5.6-6.9 mmol/l, or 6.1-6.9 mmol/l), and T2DM (FPG ≥ 7.0 mmol/l). RESULTS: The prevalences of IFG were 13.8% (FPG 5.6-6.9 mmol/l) and 4.5% (FPG 6.1-6.9 mmol/l) and of T2DM was 2.1%. Using FPG 5.6-6.9 mmol/l as the IFG reference standard, HbA1c of 39-47 mmol/mol (5.7-6.4%) was 63% sensitive and 81% specific, and HbA1c 43-47 mmol/mol (6.1-6.4%) was 21% sensitive and 98% specific, in diagnosing IFG. HbA1c ≥ 48 mmol/mol (6.5%) was 61% sensitive and 99% specific in diagnosing T2DM. Having HbA1c 39-47 mmol/mol (5.7-6.4%), male sex, and body mass index >29.5 together increased the odds of IFG 6.5-fold (95% confidence interval (CI) 5.5-7.8) compared to the pre-test odds. CONCLUSION: Defining 'pre-diabetes' at a lower HbA1c threshold of 39 mmol/mol (5.7%) instead of 47 mmol/mol (6.1%) increases its sensitivity in diagnosing IFG, but current American Diabetes Association definitions of 'pre-diabetes' based on HbA1c would fail to detect almost 40% of people currently classified as IFG. This has implications for current and future diabetes prevention programmes, for vascular risk management, and for clinical advice given to people with 'pre-diabetes' based on fasting glucose data.

Effect on tuberculosis outcomes of educational outreach to South African clinics during two randomised trials.

SETTING: Public sector primary care clinics in Free State Province, South Africa. OBJECTIVES: To investigate the effects of on-site in-service clinical skills training for nurse practitioners on tuberculosis (TB) treatment outcomes in the same clinics. DESIGN: Analysis of TB programme data from clinics taking part in two consecutive randomised trials of educational outreach aimed at improving respiratory and human immunodeficiency virus/acquired immune-deficiency syndrome care based on the Practical Approach to Lung Health. We compared treatment outcomes between control and intervention clinics among all patients diagnosed with TB during either trial. RESULTS: During the two trials, participating clinics treated 4187 and 2333 TB patients, respectively. Neither intervention was associated with better outcomes overall. However, among retreatment patients, cure or completion rates in intervention clinics were significantly higher during the second trial (OR 1.78, 95%CI 1.13-2.76). Patients in clinics that had received both interventions had higher cure or completion rates (OR 1.99, 95%CI 1.53-2.58) and lower default rates (OR 0.25, 95%CI 0.097-0.63) than patients in clinics that had received neither intervention. CONCLUSION: Although not primarily focused on TB treatment, the interventions appeared to improve successful treatment completion rates among TB retreatment cases. Integrated care programmes support attainment of important TB programme goals.

Trends in yield and effects of screening intervals during 17 years of a large UK community-based diabetic retinopathy screening programme.

AIMS: To describe changes in risk profiles and yield in a screening programme and to investigate relationships between retinopathy prevalence, screening interval and risk factors. METHODS: We analysed a population of predominantly Type 2 diabetic patients, managed in general practice, and screened between 1990 and 2006, with up to 17 years' follow-up and up to 14 screening episodes each. We investigated associations between referable or sight-threatening diabetic retinopathy (STDR), screening interval and frequency of repeated screening, whilst adjusting for age, duration and treatment of diabetes, hypertension treatment and period. RESULTS: Of 63 622 screening episodes among 20 788 people, 16 094 (25%) identified any retinopathy, 3136 (4.9%) identified referable retinopathy and 384 (0.60%) identified STDR. The prevalence of screening-detected STDR decreased by 91%, from 1.7% in 1991-1993 to 0.16% in 2006. The prevalence of referable retinopathy increased from 2.0% in 1991-1993 to 6.7% in 1998-2001, then decreased to 4.7% in 2006. Compared with screening intervals of 12-18 months, screening intervals of 19-24 months were not associated with increased risk of referable retinopathy [adjusted odds ratio 0.93, 94% confidence interval (CI) 0.82-1.05], but screening intervals of more than 24 months were associated with increased risk (odds ratio 1.56, 95% CI 1.41-1.75). Screening intervals of < 12 months were associated with high risks of referable retinopathy and STDR. CONCLUSIONS: Over time the risk of late diagnosis of STDR decreased, possibly attributable to earlier diagnosis of less severe retinopathy, decreasing risk factors and systematic screening. Screening intervals of up to 24 months should be considered for lower risk patients.

Integrating children's services in England: national evaluation of children's trusts.

BACKGROUND: Poor co-ordination of services can have severe consequences for disadvantaged children with complex needs. Since 2003 national and local governments in England embarked on sweeping reforms aimed at improving and integrating local health, education and social services for children. These were to be organized locally by children's trusts and piloted by 35 children's trust pathfinders. METHODS: This study described and compared the experience of integrating children's services in all 35 children's trust pathfinders, covering 20% of children in England. It had a prospective mixed-methods design. Over 3 years we interviewed 147 managers and professionals working in the children's trusts, including 172 semi-structured interviews, carried out two questionnaire surveys of the 35 children's trusts and analysed official documents. RESULTS: In most areas different agencies jointly commissioned children's services, especially for mental health, disabilities and multi-purpose children's centres, and increasingly pooled finances. Provision of multi-agency and multi-professional services was increasing. Professionals generally supported these changes but found them stressful. All children's trusts appointed directors of children's services and established boards representing multiple agencies. Systems for sharing information about individual children were mostly in place but were still underused. Health services were generally less involved in joint work than were local authorities' education and social care services, with notable exceptions. Areas where local authorities and health authorities shared geographical boundaries made most progress. Some children's trusts made few changes beyond their statutory obligations. CONCLUSION: Children's trusts enabled major changes to services in areas where local actors and organizations were motivated and empowered. In other areas the remit of children's trusts was often too broad and vague to overcome entrenched organizational and professional divisions and interests. Policymakers need to balance facilitation of change in areas with dynamic change agents with methods for ensuring that dormant areas and agencies are not left behind.

Diabetic retinopathy and socioeconomic deprivation in Gloucestershire.

OBJECTIVES: To investigate socioeconomic variations in diabetes prevalence, uptake of screening for diabetic retinopathy, and prevalence of diabetic retinopathy. METHODS: The County of Gloucestershire formed the setting of the study. A cross-sectional study of people with diabetes was done on a countywide retinopathy-screening database. Diabetes prevalence with odds ratios, uptake of screening, prevalence of any retinopathy and prevalence of sight-threatening retinopathy at screening were compared for different area deprivation quintiles. Logistic regression was used to adjust for confounding. RESULTS: With each increasing quintile of deprivation, diabetes prevalence increased (odds ratio 0.84), the probability of having been screened for diabetic retinopathy decreased (odds ratio 1.11), and the prevalence of sight-threatening diabetic retinopathy among screened patients increased (odds ratio of 0.98), while the prevalence of non-sight-threatening diabetic retinopathy remained unchanged with each increasing quintile of deprivation. CONCLUSION: Sight-threatening diabetic retinopathy was associated with socioeconomic deprivation, but non-sight-threatening diabetic retinopathy was not. Uptake of screening was inversely related to socioeconomic deprivation.

Contamination in trials of educational interventions.

OBJECTIVES: To consider the effects of contamination on the magnitude and statistical significance (or precision) of the estimated effect of an educational intervention, to investigate the mechanisms of contamination, and to consider how contamination can be avoided. DATA SOURCES: Major electronic databases were searched up to May 2005. METHODS: An exploratory literature search was conducted. The results of trials included in previous relevant systematic reviews were then analysed to see whether studies that avoided contamination resulted in larger effect estimates than those that did not. Experts' opinions were elicited about factors more or less likely to lead to contamination. We simulated contamination processes to compare contamination biases between cluster and individually randomised trials. Statistical adjustment was made for contamination using Complier Average Causal Effect analytic methods, using published and simulated data. The bias and power of cluster and individually randomised trials were compared, as were Complier Average Causal Effect, intention-to-treat and per protocol methods of analysis. RESULTS: Few relevant studies quantified contamination. Experts largely agreed on where contamination was more or less likely. Simulation of contamination processes showed that, with various combinations of timing, intensity and baseline dependence of contamination, cluster randomised trials might produce biases greater than or similar to those of individually randomised trials. Complier Average Causal Effect analyses produced results that were less biased than intention-to-treat or per protocol analyses. They also showed that individually randomised trials would in most situations be more powerful than cluster randomised trials despite contamination. CONCLUSIONS: The probability, nature and process of contamination should be considered when designing and analysing controlled trials of educational interventions in health. Cluster randomisation may or may not be appropriate and should not be uncritically assumed always to be a solution. Complier Average Causal Effect models are an appropriate way to adjust for contamination if it can be measured. When conducting such trials in future, it is a priority to report the extent, nature and effects of contamination.

To freeze or not to freeze: a cost-effectiveness analysis of wart treatment.

BACKGROUND: Several general practitioner (GP)-prescribed and over-the-counter therapies for warts and verrucae are available. However, the cost-effectiveness of these treatments is unknown. OBJECTIVES: To compare the cost-effectiveness of different treatments for cutaneous warts. METHODS: We designed a decision-analytic Markov simulation model based on systematic review evidence to estimate the cost-effectiveness of various treatments. The outcome measures studied are percentage of patients cured, cost of treatment and incremental cost-effectiveness ratio for each treatment, compared with no treatment, after 18 weeks. RESULTS: Duct tape was most cost-effective but published evidence of its effectiveness is sparse. Salicylic acid was the most cost-effective over-the-counter treatment commonly used. Cryotherapy administered by a GP was less cost-effective than GP-prescribed salicylic acid and less cost-effective than cryotherapy administered by a nurse. CONCLUSIONS: Duct tape could be adopted as the primary treatment for cutaneous warts if its effectiveness is verified by further rigorous trials. Nurse-administered cryotherapy is likely to be more cost-effective than GP-administered cryotherapy.

Effectiveness and cost-effectiveness of salicylic acid and cryotherapy for cutaneous warts. An economic decision model.

OBJECTIVES: To estimate the costs of commonly used treatments for cutaneous warts, as well as their health benefits and risk. To create an economic decision model to evaluate the cost-effectiveness of these treatments, and, as a result, assess whether a randomised controlled trial (RCT) would be feasible and cost-effective. DATA SOURCES: Focus groups, structured interviews and observation of practice. Postal survey sent to 723 patients. A recently updated Cochrane systematic review and published cost and prescribing data. REVIEW METHODS: Primary and secondary data collection methods were used to inform the development of an economic decision model. Data from the postal survey provided estimates of the effectiveness of wart treatments in a primary care setting. These estimates were compared with outcomes reported in the Cochrane review of wart treatment, which were largely obtained from RCTs conducted in secondary care. A decision model was developed including a variety of over-the-counter (OTC) and GP-prescribed treatments. The model simulated 10,000 patients and adopted a societal perspective. RESULTS: OTC treatments were used by a substantial number of patients (57%) before attending the GP surgery. By far the most commonly used OTC preparation was salicylic acid (SA). The results of the economic model suggested that of the treatments prescribed by a GP, the most cost-effective treatment was SA, with an incremental cost-effectiveness ratio (ICER) of 2.20 pound/% cured. The ICERs for cryotherapy varied widely (from 1.95 to 7.06 pound/% cured) depending on the frequency of applications and the mode of delivery. The most cost-effective mode of delivery was through nurse-led cryotherapy clinics (ICER = 1.95 pound/% cured) and this could be a cost-effective alternative to GP-prescribed SA. Overall, the OTC therapies were the most cost-effective treatment options. ICERs ranged from 0.22 pound/% cured for OTC duct tape and 0.76 pound/% cured for OTC cryotherapy to 1.12 pound/% cured for OTC SA. However, evidence in support of OTC duct tape and OTC cryotherapy is very limited. Side-effects were commonly reported for both SA and cryotherapy, particularly a burning sensation, pain and blistering. CONCLUSIONS: Cryotherapy delivered by a doctor is an expensive option for the treatment of warts in primary care. Alternative options such as GP-prescribed SA and nurse-led cryotherapy clinics provide more cost-effective alternatives, but are still expensive compared with self-treatment. Given the minor nature of most cutaneous warts, coupled with the fact that the majority spontaneously resolve in time, it may be concluded that a shift towards self-treatment is warranted. Although both duct tape and OTC cryotherapy appear promising new self-treatment options from both a cost and an effectiveness perspective, more research is required to confirm the efficacy of these two methods of wart treatment. If these treatments are shown to be as cost-effective as or more cost-effective than conventional treatments, then a shift in service delivery away from primary care towards more OTC treatment is likely. A public awareness campaign would be useful to educate patients about the self-limiting nature of warts and the possible alternative OTC treatment options available. Two future RCTs are recommended for consideration: a trial of SA compared with nurse-led cryotherapy in primary care, and a trial of home treatments. Greater understanding of the efficacy of these home treatments will give doctors a wider choice of treatment options, and may help to reduce the overall demand for cryotherapy in primary care.

Effectiveness and cost effectiveness of syndromic sexually transmitted infection packages in South African primary care: cluster randomised trial.

OBJECTIVES: To evaluate the effectiveness and cost effectiveness of syndromic sexually transmitted infection (STI) packages on appropriate treatment and preventive management during primary care consultations. METHODS: Cluster randomised trial of 37 Durban primary care clinics randomised to use syndromic packages (containing antibiotics, condoms, partner notification cards, and written information) or not. We assessed outcomes using simulated patients who reported STI symptoms and recorded how they were managed, before and after implementation (269 and 256 simulated patient consultations). We adjusted for baseline values and intra-clinic correlation of outcomes statistically. We used health department information to estimate the extra resources needed to provide the packages to 20 clinics for 1 year and their costs. RESULTS: Simulated patients in intervention clinics were more likely to receive appropriate syndromic STI management (correct treatment plus condoms offered plus partner notification cards offered; prevalence rate ratio 2.3; 95% confidence intervals (CI) 1.6 to 3.0) and to receive more STI advice and information (odds ratio 1.5; 95% CI 1.01 to 2.1). Women were less likely to receive appropriate syndromic STI management. The intervention increased STI information provision in women more than in men. The extra cost per extra patient appropriately managed was $1.51. CONCLUSIONS: Syndromic packages improved syndromic STI management at a reasonable cost and should be used more widely.