Ethnicity as a predictor of outcomes of psychological therapies for anxiety and depression: a retrospective cohort analysis.

BACKGROUND: Studies on predictors of outcomes of treatment for common mental health disorders (CMDs) in community mental health settings are scarce, and sample sizes are often small. Research on the impact of identifying as a member of an ethnic minority group on treatment outcomes is limited. AIMS: To ascertain whether ethnicity is an independent predictor of outcome and the extent to which any association is mediated by other sociodemographic factors. METHOD: Retrospective observational study of anonymised treatment data collected for routine clinical purposes. Data were analysed from nine Improving Access to Psychological Therapy (IAPT) services from 2009 to 2016. Social functioning, ethnic group, age, gender, occupation and baseline severity of the mental health disorder were analysed as predictors of outcome. RESULTS: Outcomes varied with ethnic group. Levels of occupation, social deprivation, initial morbidity and social functioning varied between ethnic groups at baseline. After adjustment for these factors the impact of ethnicity was attenuated and only some ethnic groups remained as significant independent predictors of treatment outcome. CONCLUSIONS: Ethnic minority status is a marker for multiple disadvantages. Some of the differences in outcome seen between ethnic groups may be the result of more general factors present in all ethnic groups but at greater intensity in some ethnic minority groups.

Paediatric lymphoedema: A retrospective chart review of 86 cases.

AIM: To define the clinical characteristics, investigations, management and outcomes of lymphoedema in a paediatric cohort. METHODS: A retrospective chart review of children with lymphoedema seen at two tertiary paediatric hospitals since 1998. Telephone interviews with parents were performed when information was missing. Information recorded included demographic data, features of diagnosis and clinical presentation, symptoms, complications and treatment. RESULTS: A total of 86 patients with lymphoedema were identified. Eighty cases (93%) were primary and six cases (7%) were secondary. Most were female (60%). Location of swelling was most commonly the lower limbs (94%). There were 13 cases (15%) of genital involvement. Swelling presented in the first 12 months of life in 60% of primary lymphoedema patients. Complications of lymphoedema occurred in 73% of patients. Lymphoscintigraphy was the most common investigation used (65%), followed by ultrasound (57%) and magnetic resonance imaging (MRI) (35%). Eight of the 48 (17%) lymphoscintigraphs produced a false negative result or were inconclusive with a correct diagnosis subsequently made clinically and using MRI. Average time to diagnosis was 9 months. Lymphoedema was managed with compression garments (99%), manual lymph drainage (97%) and multilayered bandaging (68%). Eight patients had an operative procedure as a part of management. CONCLUSIONS: Primary lymphoedema is more common than secondary lymphoedema in children. Onset tends to be during infancy for both males and females, and the lower limb is typically involved. Causes of secondary lymphoedema are diverse and rare. Diagnosis in children is often delayed but is possible based on history and physical examination alone and when further investigation is necessary MRI is effective.

Recommending Oral Probiotics to Reduce Winter Antibiotic Prescriptions in People With Asthma: A Pragmatic Randomized Controlled Trial.

PURPOSE: Evidence from studies mainly in children has shown that orally administered probiotics may prevent respiratory tract infections and associated antibiotic use. We evaluated whether advice to take daily probiotics can reduce antibiotic prescribing for winter respiratory tract infections in people with asthma. METHODS: We conducted a randomized controlled, parallel-group pragmatic study for participants aged 5 years and older with asthma in a UK primary care setting. The intervention was a postal leaflet with advice to take daily probiotics from October 2013 to March 2014, compared with a standard winter advice leaflet. Primary outcome was the proportion of participants prescribed antibiotics for respiratory tract infections. RESULTS: There were 1,302 participants randomly assigned to a control group (n = 650) or intervention group (n = 652). There was no significant difference in the primary outcome measure, with 27.7% receiving antibiotics in the intervention group and 26.9% receiving antibiotics in the control group (odds ratio = 1.04; 95% CI, 0.82-1.34). Uptake of probiotics was low, but outcomes were similar in those who accessed probiotics (adjusted odds ratio = 1.08; 95% CI, 0.69-1.69, compared with controls). We also found no evidence of an effect on respiratory tract infections or asthma exacerbations. CONCLUSIONS: In this pragmatic community-based trial in people with asthma, we found no evidence that advising use of winter probiotics reduces antibiotic prescribing.

Use and abuse of statistics in tobacco industry-funded research on standardised packaging.

In this commentary we consider the validity of tobacco industry-funded research on the effects of standardised packaging in Australia. As the first country to introduce standardised packs, Australia is closely watched, and Philip Morris International has recently funded two studies into the impact of the measure on smoking prevalence. Both of these papers are flawed in conception as well as design but have nonetheless been widely publicised as cautionary tales against standardised pack legislation. Specifically, we focus on the low statistical significance of the analytical methods used and the assumption that standardised packaging should have an immediate large impact on smoking prevalence.

Plasma melatonin is reduced in Huntington's disease.

This study was undertaken to determine whether the production of melatonin, a hormone regulating sleep in relation to the light/dark cycle, is altered in Huntington's disease. We analyzed the circadian rhythm of melatonin in a 24-hour study of cohorts of control, premanifest, and stage II/III Huntington's disease subjects. The mean and acrophase melatonin concentrations were significantly reduced in stage II/III Huntington's disease subjects compared with controls. We also observed a nonsignificant trend toward reduced mean and acrophase melatonin in premanifest Huntington's disease subjects. Onset of melatonin rise was significantly more temporally spread in both premanifest and stage II/III Huntington's disease subjects compared with controls. A nonsignificant trend also was seen for reduced pulsatile secretion of melatonin. Melatonin concentrations are reduced in Huntington's disease. Altered melatonin patterns may provide an explanation for disrupted sleep and circadian behavior in Huntington's disease, and represent a biomarker for disease state. Melatonin therapy may help the sleep disorders seen in Huntington's disease.

Noradrenergic Add-on Therapy with Extended-Release Guanfacine in Alzheimer's Disease (NorAD): study protocol for a randomised clinical trial and COVID-19 amendments.

BACKGROUND: Guanfacine is a α2A adrenergic receptor agonist approved for treating attention deficit hyperactivity disorder (ADHD). It is thought to act via postsynaptic receptors in the prefrontal cortex, modulating executive functions including the regulation of attention. Attention is affected early in Alzheimer's disease (AD), and this may relate to pathological changes within the locus coeruleus, the main source of noradrenergic pathways within the brain. Given that cholinergic pathways, also involved in attention, are disrupted in AD, the combination of noradrenergic and cholinergic treatments may have a synergistic effect on symptomatic AD. The primary objective of the NorAD trial is to evaluate the change in cognition with 12 weeks of treatment of extended-release guanfacine (GXR) against a placebo as a combination therapy with cholinesterase inhibitors in participants with mild to moderate Alzheimer's disease. METHODS/DESIGN: NorAD is a 3-month, single-centre, randomised, double-blind, placebo-controlled, phase III trial of extended-release guanfacine (GXR) in participants with mild to moderate Alzheimer's disease. A total of 160 participants will be randomised to receive either daily guanfacine or placebo in combination with approved cholinesterase treatment for 12 weeks. The primary outcome is the change in cognition, as measured by the Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog), from baseline to follow-up in the treatment group compared to the placebo group. Secondary outcomes include the change in additional cognitive measures of attention (Tests of Attention: Trails A and B, digit-symbol substitution, Test of Everyday Attention and CANTAB-RVP), neuropsychiatric symptoms (Neuropsychiatric Inventory), caregiver burden (Zarit Burden Interview) and activities of daily living (Alzheimer's Disease Co-operative Study - Activities of Daily Living Inventory). From July 2020, observation of change following cessation of treatment is also being assessed. DISCUSSION: There is strong evidence for early noradrenergic dysfunction in Alzheimer's disease. The NorAD trial aims to determine whether guanfacine, a noradrenergic alpha-2 agonist, improves attention and cognition when used in addition to standard cholinergic treatment. TRIAL REGISTRATION: ClinicalTrials.gov NCT03116126 . Registered on 14 April 2017 EudraCT: 2016-002598-36.

Reflection on modern methods: Statistics education beyond 'significance': novel plain English interpretations to deepen understanding of statistics and to steer away from misinterpretations.

Concerns have been expressed over standards of statistical interpretation. Results with P <0.05 are often referred to as 'significant' which, in plain English, implies important. This leads some people directly into the misconception that this provides proof that associations are clinically relevant. There are calls for statistics educators to respond to these concerns. This article provides novel plain English interpretations that are designed to deepen understanding. Experience teaching postgraduates at Imperial College is discussed. A key issue with focusing on 'significance' is the common inappropriate practice of implying no association exists, simply because P >0.05. Referring to strengths of association in 'study participants' gives them gravitas, which may help to avoid this. This contrasts with the common practice of focusing on imprecision, by referring to the 'sample' and to 'point estimates'. Unlike formal statistical definitions, interpretations developed and presented here are rooted in the application of statistics. They are based on one set of study participants (not many random samples). Precision of strengths of association are based on using strengths in study participants to estimate strengths of association in the population (from which participants were selected by probability random sampling). Reference to 'compatibility with study data, dependent on statistical modelling assumptions' reminds us of the importance of data quality and modelling assumptions. A straightforward graph shows the relationship between P-values and test statistics. This figure and associated interpretations were developed to illuminate the continuous nature of P-values. This is designed to discourage focus on whether P <0.05, and encourage interpretation of exact P-values.

Evaluating cognitive profiles of patients undergoing clinical amyloid-PET imaging.

Episodic memory impairment and brain amyloid-beta are two of the main hallmarks of Alzheimer's Disease. In the clinical setting, these are often evaluated through neuropsychological testing and amyloid PET imaging, respectively. The use of amyloid PET in clinical practice is only indicated in patients with substantial diagnostic uncertainty due to atypical clinical presentation, multiple comorbidities and/or early age of onset. The relationship between amyloid-beta and cognition has been previously investigated, but no study has examined how neuropsychological features relate to the presence of amyloid pathology in the clinical population that meets the appropriate use criteria for amyloid PET imaging. In this study, we evaluated a clinical cohort of patients (n = 107) who presented at the Imperial Memory Clinic and were referred for clinical amyloid PET and neuropsychological assessment as part of their diagnostic workup. We compared the cognitive performance of amyloid-positive patients (Aß-pos, n = 47) with that of stable amyloid-negative (stableAß-neg, n = 26) and progressive amyloid-negative (progAß-neg, n = 34) patients. The amyloid-positive group performed significantly worse than both amyloid-negative groups in the visuospatial and working memory domains. Episodic memory performance, however, effectively differentiated the amyloid-positive group from the stable but not the progressive amyloid-negative group. On affective questionnaires, the stable amyloid-negative group reported significantly higher levels of depression than the amyloid-positive group. In our clinical cohort, visuospatial dysfunction and working memory impairment were better indicators of amyloid positivity than episodic memory dysfunction. These findings highlight the limited value of isolated cognitive scores in patients with atypical clinical presentation, comorbidities and/or early age of onset.

A video-feedback parenting intervention to prevent enduring behaviour problems in at-risk children aged 12-36 months: the Healthy Start, Happy Start RCT.

BACKGROUND: Behaviour problems emerge early in childhood and place children at risk for later psychopathology. OBJECTIVES: To evaluate the clinical effectiveness and cost-effectiveness of a parenting intervention to prevent enduring behaviour problems in young children. DESIGN: A pragmatic, assessor-blinded, multisite, two-arm, parallel-group randomised controlled trial. SETTING: Health visiting services in six NHS trusts in England. PARTICIPANTS: A total of 300 at-risk children aged 12-36 months and their parents/caregivers. INTERVENTIONS: Families were allocated in a 1 : 1 ratio to six sessions of Video-feedback Intervention to promote Positive Parenting and Sensitive Discipline (VIPP-SD) plus usual care or usual care alone. MAIN OUTCOME MEASURES: The primary outcome was the Preschool Parental Account of Children's Symptoms, which is a structured interview of behaviour symptoms. Secondary outcomes included caregiver-reported total problems on the Child Behaviour Checklist and the Strengths and Difficulties Questionnaire. The intervention effect was estimated using linear regression. Health and social care service use was recorded using the Child and Adolescent Service Use Schedule and cost-effectiveness was explored using the Preschool Parental Account of Children's Symptoms. RESULTS: In total, 300 families were randomised: 151 to VIPP-SD plus usual care and 149 to usual care alone. Follow-up data were available for 286 (VIPP-SD, n = 140; usual care, n = 146) participants and 282 (VIPP-SD, n = 140; usual care, n = 142) participants at 5 and 24 months, respectively. At the post-treatment (primary outcome) follow-up, a group difference of 2.03 on Preschool Parental Account of Children's Symptoms (95% confidence interval 0.06 to 4.01; p = 0.04) indicated a positive treatment effect on behaviour problems (Cohen's d = 0.20, 95% confidence interval 0.01 to 0.40). The effect was strongest for children's conduct [1.61, 95% confidence interval 0.44 to 2.78; p = 0.007 (d = 0.30, 95% confidence interval 0.08 to 0.51)] versus attention deficit hyperactivity disorder symptoms [0.29, 95% confidence interval -1.06 to 1.65; p = 0.67 (d = 0.05, 95% confidence interval -0.17 to 0.27)]. The Child Behaviour Checklist [3.24, 95% confidence interval -0.06 to 6.54; p = 0.05 (d = 0.15, 95% confidence interval 0.00 to 0.31)] and the Strengths and Difficulties Questionnaire [0.93, 95% confidence interval -0.03 to 1.9; p = 0.06 (d = 0.18, 95% confidence interval -0.01 to 0.36)] demonstrated similar positive treatment effects to those found for the Preschool Parental Account of Children's Symptoms. At 24 months, the group difference on the Preschool Parental Account of Children's Symptoms was 1.73 [95% confidence interval -0.24 to 3.71; p = 0.08 (d = 0.17, 95% confidence interval -0.02 to 0.37)]; the effect remained strongest for conduct [1.07, 95% confidence interval -0.06 to 2.20; p = 0.06 (d = 0.20, 95% confidence interval -0.01 to 0.42)] versus attention deficit hyperactivity disorder symptoms [0.62, 95% confidence interval -0.60 to 1.84; p = 0.32 (d = 0.10, 95% confidence interval -0.10 to 0.30)], with little evidence of an effect on the Child Behaviour Checklist and the Strengths and Difficulties Questionnaire. The primary economic analysis showed better outcomes in the VIPP-SD group at 24 months, but also higher costs than the usual-care group (adjusted mean difference £1450, 95% confidence interval £619 to £2281). No treatment- or trial-related adverse events were reported. The probability of VIPP-SD being cost-effective compared with usual care at the 24-month follow-up increased as willingness to pay for improvements on the Preschool Parental Account of Children's Symptoms increased, with VIPP-SD having the higher probability of being cost-effective at willingness-to-pay values above £800 per 1-point improvement on the Preschool Parental Account of Children's Symptoms. LIMITATIONS: The proportion of participants with graduate-level qualifications was higher than among the general public. CONCLUSIONS: VIPP-SD is effective in reducing behaviour problems in young children when delivered by health visiting teams. Most of the effect of VIPP-SD appears to be retained over 24 months. However, we can be less certain about its value for money. TRIAL REGISTRATION: Current Controlled Trials ISRCTN58327365. FUNDING: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 25, No. 29. See the NIHR Journals Library website for further project information.

Behaviour problems in young children are common and are linked to mental and physical health problems, and educational and social difficulties. An important factor that influences the development of behaviour problems is the quality of care that children receive from their caregivers. This study aimed to test if a six-session parenting programme [called Video-feedback Intervention to promote Positive Parenting and Sensitive Discipline (VIPP-SD)] reduced behaviour problems in children aged 1 or 2 years who were showing early signs of behaviour problems (e.g. restlessness, impulsivity, tantrums and aggression). VIPP-SD supports caregivers in responding to their child's communication and behaviour. A total of 300 families participated. All families continued to access usual health-care services (e.g. health visitors and general practitioners), but half of the families were randomly allocated to also receive the VIPP-SD programme. We visited all families when the study started, and at 5 and 24 months to see if the children whose families received VIPP-SD showed fewer behaviour problems. We measured the children's behaviour by completing interviews and questionnaires with their caregivers. We also analysed whether or not VIPP-SD was good value for money compared with existing services. We did this by comparing the cost of all of the standard health and community services that families accessed during their time in the study, taking account of the impact that VIPP-SD had on children's behaviour. The children in the VIPP-SD group had lower levels of behaviour problems following the programme than children whose parents did not receive the programme. On average, VIPP-SD children scored 2 points lower on the main measure of behaviour; an example difference would be tantrums being rated as mild rather than severe. By the 2-year visit, the VIPP-SD children continued to show lower levels of behaviour problems. It is less clear whether or not VIPP-SD is good value for money, as this depends on how much money policy-makers are willing to invest for reductions in behaviour problems. Overall, there is strong evidence that the VIPP-SD programme is effective in reducing behaviour problems in the short term. Most of this benefit appears to be maintained for the following 2 years. However, we are less certain about the long-term effect and the VIPP-SD's value for money.

A Brief Home-Based Parenting Intervention to Reduce Behavior Problems in Young Children: A Pragmatic Randomized Clinical Trial.

Importance: Behavior problems are one of the most common mental health disorders in childhood and can undermine children's health, education, and employment outcomes into adulthood. There are few effective interventions for early childhood. Objective: To test the clinical effectiveness of a brief parenting intervention, the Video-feedback Intervention to promote Positive Parenting and Sensitive Discipline (VIPP-SD), in reducing behavior problems in children aged 12 to 36 months. Design, Setting, and Participants: The Healthy Start, Happy Start study was a 2-group, parallel-group, researcher-blind, multisite randomized clinical trial conducted via health visiting services in 6 National Health Service trusts in England. Baseline and 5-month follow-up data were collected between July 30, 2015, and April 27, 2018. Of 818 eligible families, 227 declined to participate, and 300 were randomized into the trial. Target participants were caregivers of children who scored in the top 20% for behavior problems on the Strengths and Difficulties Questionnaire. Participants were randomly allocated on a 1:1 basis to receive either VIPP-SD (n = 151) or usual care (n = 149), stratified by site and number of participating caregivers. Analysis was performed on an intention-to-treat basis. Statistical analysis was performed from September 5, 2019, to January 17, 2020. Interventions: All families continued to access usual care. Families allocated to VIPP-SD were offered 6 home-based video-feedback sessions of 1 to 2 hours' duration every 2 weeks. Main Outcomes and Measures: The primary outcome was the score on an early childhood version of the Preschool Parental Account of Children's Symptoms, a semistructured interview of behavior symptoms, at 5 months after randomization. Secondary outcomes included caregiver-reported behavior problems on the Child Behavior Checklist and the Strengths and Difficulties Questionnaire. Results: Among 300 participating children (163 boys [54%]; mean [SD] age, 23.0 [6.7] months), primary outcome data were available for 140 of 151 VIPP-SD participants (93%) and 146 of 149 usual care participants (98%). There was a mean difference in the total Preschool Parental Account of Children's Symptoms score of 2.03 (95% CI, 0.06-4.01; P = .04; Cohen d = 0.20 [95% CI, 0.01-0.40]) between trial groups, with fewer behavior problems in the VIPP-SD group, particularly conduct symptoms (mean difference, 1.61 [95% CI, 0.44-2.78]; P = .007; d = 0.30 [95% CI, 0.08-0.51]). Other child behavior outcomes showed similar evidence favoring VIPP-SD. No treatment or trial-related adverse events were reported. Conclusions and Relevance: This study found that VIPP-SD was effective in reducing symptoms of early behavior problems in young children when delivered in a routine health service context. Trial Registration: isrctn.org Identifier: ISRCTN58327365.

The association between orthostatic hypotension and medication use in the British Women's Heart and Health Study.

OBJECTIVE: to determine the prevalence of orthostatic hypotension (OH) and associations with medication use in community-dwelling older women. DESIGN: cross-sectional analysis using data from the British Women's Heart and Health Study. SETTING: general practices in 23 towns in the UK. PARTICIPANTS: 3,775 women aged 60-80 years from 1999 to 2001. MAIN OUTCOME MEASURE: orthostatic hypotension-drop of > or =20 mmHg in systolic and/or a drop of > or =10 mmHg in diastolic blood pressure on standing. RESULTS: prevalence of OH was 28% (95% confidence interval [CI] 26.6, 29.4), which increased with age and hypertension. Regardless of treatment status or diagnosed hypertension, raised blood pressure was strongly associated with OH (P < 0.001). OH was strongly associated with number of antihypertensives taken (none vs three or more: odds ratio [OR] 2.24, 95% CI 1.47-3.40, P < 0.001); the association was slightly attenuated after allowing for age and co-morbidities (OR 1.99; 95% CI 1.30, 3.05; P = 0.003). Women with multiple co-morbidities had markedly increased odds of OH independent of age, number and type of medications taken (none vs four or more diagnoses: OR 2.28, 95% CI 1.58-3.30, P = 0.005). CONCLUSION: uncontrolled hypertension, use of three or more antihypertensives and multiple co-morbidities are predictors of OH in older women. Detection or monitoring of OH in these groups may prevent women from suffering its adverse consequences.

Influence of life course socioeconomic position on older women's health behaviors: findings from the British Women's Heart and Health Study.

OBJECTIVES: We examined the association between health behaviors and socioeconomic status (SES) in childhood and adult life. METHODS: Self-reported diet, smoking, and physical activity were determined among 3523 women aged 60 to 79 years recruited from general practices in 23 British towns from 1999 through 2001. RESULTS: The most affluent women reported eating more fruit, vegetables, chicken, and fish and less red or processed meat than did less affluent women. Affluent women were less likely to smoke and more likely to exercise. Life course SES did not influence the types of fat, bread, and milk consumed. Adult SES predicted consumption of all foods considered and predicted smoking and physical activity habits independently of childhood SES. Childhood SES predicted fruit and vegetable consumption independently of adult SES and, to a lesser extent, predicted physical activity. Downward social mobility over the life course was associated with poorer diets and reduced physical activity. CONCLUSIONS: Among older women, healthful eating and physical activity were associated with both current and childhood SES. Interventions designed to improve social inequalities in health behaviors should be applied during both childhood and adult life.

Influence of area and individual lifecourse deprivation on health behaviours: findings from the British Women's Heart and Health Study.

BACKGROUND: Variable findings have been reported on the contribution of census-based measures of area deprivation over and above that of individual socioeconomic position (SEP) on health outcomes. This study aims to examine the association between residence in a deprived area and health behaviours (diet, smoking and physical inactivity), and how this association is influenced by lifecourse SEP of individuals. DESIGN: A population-based longitudinal study of women aged 60-79 years in 1999-2001 recruited from one general practice in each of 23 British towns. METHODS: Three thousand five hundred twenty-two women were included in the analyses. Area deprivation scores were derived from postcode for residence and lifecourse SEP scores were calculated using 10 individual level indicators of childhood and adult circumstances. To allow direct comparisons of effect of area deprivation and individual SEP, we standardized both measures by generating relative indices of inequality. RESULTS: Both area deprivation and lifecourse SEP were independent predictors of eating fruit and vegetables [odds ratio (OR): 2.87, 95% confidence interval (CI): 2.22-3.72; comparing highest with lowest area Index of Multiple Deprivation of inequality (OR: 3.07, 95% CI: 2.33-4.06) for lifecourse SEP index of inequality] and exercise habits (OR: 2.39, 95% CI: 1.86-3.06 area deprivation; OR: 2.7, 95% CI: 2.07-3.51 individual SEP). Area deprivation was a stronger predictor of smoking behaviour (OR: 2.34, 95% CI: 1.91-3.08) than individual lifecourse SEP (OR: 1.51, 95% CI: 1.17-1.95). CONCLUSION: Most health behaviours among older women were independently associated with both living in deprived areas and individual lifecourse SEP. This suggests that additional health promotion approaches focusing on improving environments would have potential to improve health behaviour.

Inter-rater reliability of malaria parasite counts and comparison of methods.

BACKGROUND: The introduction of artemesinin-based treatment for falciparum malaria has led to a shift away from symptom-based diagnosis. Diagnosis may be achieved by using rapid non-microscopic diagnostic tests (RDTs), of which there are many available. Light microscopy, however, has a central role in parasite identification and quantification and remains the main method of parasite-based diagnosis in clinic and hospital settings and is necessary for monitoring the accuracy of RDTs. The World Health Organization has prepared a proficiency testing panel containing a range of malaria-positive blood samples of known parasitaemia, to be used for the assessment of commercially available malaria RDTs. Different blood film and counting methods may be used for this purpose, which raises questions regarding accuracy and reproducibility. A comparison was made of the established methods for parasitaemia estimation to determine which would give the least inter-rater and inter-method variation METHODS: Experienced malaria microscopists counted asexual parasitaemia on different slides using three methods; the thin film method using the total erythrocyte count, the thick film method using the total white cell count and the Earle and Perez method. All the slides were stained using Giemsa pH 7.2. Analysis of variance (ANOVA) models were used to find the inter-rater reliability for the different methods. The paired t-test was used to assess any systematic bias between the two methods, and a regression analysis was used to see if there was a changing bias with parasite count level. RESULTS: The thin blood film gave parasite counts around 30% higher than those obtained by the thick film and Earle and Perez methods, but exhibited a loss of sensitivity with low parasitaemia. The thick film and Earle and Perez methods showed little or no bias in counts between the two methods, however, estimated inter-rater reliability was slightly better for the thick film method. CONCLUSION: The thin film method gave results closer to the true parasite count but is not feasible at a parasitaemia below 500 parasites per microlitre. The thick film method was both reproducible and practical for this project. The determination of malarial parasitaemia must be applied by skilled operators using standardized techniques.

An observational study to examine how cumulative impact zones influence alcohol availability from different types of licensed outlets in an inner London Borough.

OBJECTIVES: Cumulative impact zones (CIZs) are a widely implemented local policy intended to restrict alcohol availability in areas proliferated with licensed outlets. Limited previous research has questioned their effectiveness and suggested they may play a more nuanced role in shaping local alcohol environments. This study evaluates the association between CIZ implementation and the number of licence applications made, and the number issued, relative to a control region. DESIGN: A quantitative observational study. SETTING: The inner London Borough of Southwark, which currently enforces three CIZs. POPULATION: Licence applications received by Southwark Council's Licensing Authority between 1 April 2006 and 31 March 2017 (n=1254). INTERVENTIONS: CIZ implementation. PRIMARY OUTCOME MEASURES: Five outlet types were categorised and evaluated: drinking establishments, eateries, takeaways, off sales and other outlets. Primary outcome measures were the number of applications received and the number of licences issued. These were analysed using Poisson regression of counts over time. RESULTS: Across all CIZs, implementation was associated with greater increases in the number of eateries in CIZ regions (incidence rate ratio (IRR)=1.58, 95% CI: 1.02-2.45, p=0.04) and number of takeaway venues (IRR=3.89, 95% CI: 1.32-11.49, p=0.01), relative to the control area. No discernible association was found for the remaining outlet types. Disaggregating by area indicated a 10-fold relative increase in the number of new eateries in Peckham CIZ (IRR=10.38, 95% CI: 1.39-77.66, p=0.02) and a fourfold relative increase in the number of newly licensed takeaways in Bankside CIZ (IRR=4.38, 95% CI: 1.20-15.91, p=0.03). CONCLUSIONS: CIZs may be useful as policy levers to shape local alcohol environments to support the licensing goals of specific geographical areas and diversify the night-time economy.

Prescribing trends of gabapentin, pregabalin, and oxycodone: a secondary analysis of primary care prescribing patterns in England.

BACKGROUND: The risk of iatrogenic harm from the use and misuse of prescription drugs such as gabapentin, pregabalin, and oxycodone is substantial. In recent years, deaths associated with these drugs in England have increased. AIM: To characterise general practice prescribing trends for gabapentin, pregabalin, and oxycodone - termed dependence forming medicines (DFM) - in England and describe potential drivers of unwarranted variation (that is, very high prescribing). DESIGN & SETTING: This study is a retrospective secondary analysis of open source, publicly available government data from various sources pertaining to primary care demographics and prescriptions. METHOD: This study used 5 consecutive years (April 2013-March 2018) of aggregate data to investigate longitudinal trends of prescribing and variation in prescribing trends at practice and clinical commissioning group (CCG) level. RESULTS: Annual prescriptions of gabapentin, pregabalin, and oxycodone increased each year over the period. Variation in prescribing trends was associated with GP practice deprivation quintile, where the most deprived GP practices prescribed 313% (P<0.001) and 238% (P<0.001) greater volumes of gabapentin and pregabalin per person respectively, than practices in the least deprived quintile. The highest prescribing CCGs of each of these drugs were predominantly in northern and eastern regions of England. CONCLUSION: Substantial increases in gabapentin, pregabalin, and oxycodone prescriptions are concerning and will increase iatrogenic harm from drug-related morbidity and mortality. More research is needed to understand the large variation in prescribing between general practices, and to develop and implement interventions to reduce unwarranted variation and increase the appropriateness of prescribing of these drugs.

Mobile telephone use effects on peripheral audiovestibular function: a case-control study.

Low level radio-frequency (RF) signals may produce disorientation, headache and nausea. This double blind study tested nine case-subjects, who complained of various symptoms after prolonged mobile telephone use and 21 control subjects. Each subject underwent a series of trials, in which a dummy mobile telephone exposure system was held to each ear for 30 min in (a) pulsed, (b) continuous RF emission or, (c) no emission test modes. In the active pulsed and continuous modes the same mean power as the output of a typical handset was delivered at a carrier frequency of 882 MHz and at a maximum specific absorption rate (SAR) value of 1.3 W kg(-1) (+/- 30%). In Experiment I (auditory), transient evoked otoacoustic emissions (TEOAE), which assess the outer hair cells in the inner ear, were conducted. In Experiment II (vestibular) the vestibulo-ocular reflex was recorded by video-oculography (VOG), at baseline and immediately post exposure. There were no significant TEOAE changes from baseline to post-exposure recording for any of the exposures and no significant differences in the TEOAEs' change from baseline to post exposure between cases and controls. The VOG did not identify any effect of the exposure on the vestibular end organ in either cases or controls. In conclusion, 30 min exposure to mobile phone RF did not show any immediate effects on vestibulocochlear function as measured by TEOAE and the VOR.

Sustained Socioeconomic Inequalities in Hospital Admissions for Cardiovascular Events Among People with Diabetes in England.

PURPOSE: This study aimed to determine changes in absolute and relative socioeconomic inequalities in hospital admissions for major cardiovascular causes among patients with diabetes in England. METHODS: We identified all patients with diabetes aged ≥45 years admitted to the hospital in England between 2004-2005 and 2014-2015 for acute myocardial infarction, stroke, percutaneous coronary intervention, or coronary artery bypass graft. We measured socioeconomic status using the Index of Multiple Deprivation. Diabetes-specific admission rates were calculated for each year by deprivation quintile. We assessed temporal changes using negative binomial regression models. RESULTS: Most admissions occurred among patients aged ≥65 years (71%) and men (63.3%). The number of admissions increased steadily from the least quintile to the most deprived quintile. Patients in the most deprived quintile had a 1.94-fold increased risk of acute myocardial infarction (95% confidence interval [CI], 1.79-2.10), 1.92-fold increased risk of stroke (95% CI, 1.78-2.07), 1.66-fold increased risk of coronary artery bypass graft (95% CI, 1.50-1.74), and 1.76-fold increased risk of percutaneous coronary intervention (95% CI, 1.64-1.89) compared with the least deprived group. Absolute differences in rates between the least and most deprived quintiles did not change significantly for acute myocardial infarction (P = .29) and were reduced for stroke, coronary artery bypass graft, and percutaneous coronary intervention (by 17.5, 15, and 11.8 per 100,000 patients with diabetes, respectively, P ≤ .01 for all). CONCLUSIONS: Socioeconomic inequalities persist in diabetes-related hospital admissions for major cardiovascular events in England. Besides improved risk stratification strategies that consider socioeconomically defined needs, wide-reaching population-based policy interventions are required to reduce inequalities in diabetes outcomes.

Natural immunity against capsular group X N. meningitidis following an outbreak in Togo, 2007.

BACKGROUND: Capsular group X N. meningitidis (MenX) has emerged as a cause of localized disease outbreaks in sub-Saharan Africa, but the human immune response following exposure to MenX antigens is poorly described. We therefore assessed the natural immunity against MenX in individuals who were living in an area affected by a MenX outbreak during 2007 in Togo, West Africa. During 2009, 300 healthy individuals (100 aged 3-5 years, 100 aged 13-19 years and 100 aged 20-25 years) were included in the study, and serum responses were compared with sera from age-matched controls from the U.K. and Burkina Faso. METHODS: MenX serum bactericidal antibody (SBA) was measured using rabbit complement, and antibodies against MenX polysaccharide (XPS) and outer membrane vesicles (XOMVs) were quantified by ELISA. RESULTS: The proportion of Togolese individuals with an SBA titer of ≥8 against the MenX strain was 29% (95% confidence interval (CI) 18-41) among those aged 3-5 years, 34% (95% CI 9-60) among those aged 13-19 years and 32% (95% CI 24-40) among those aged 20-25 years. These were significantly higher than observed in the control populations from the U.K (range 13-16%) and Burkina Faso (range 2-6%). CONCLUSION: In Togolese individuals, the concentration of serum IgG against XPS was higher among the two older age groups as compared to the youngest age group. Antibody concentrations against MenX PS correlated significantly with SBA titers. This supports further development of a MenX PS based conjugate vaccine. Further studies are needed to verify the ability of MenX PS to induce SBA in humans.