A study protocol for a double-blind randomised placebo-controlled trial evaluating the efficacy of carrageenan nasal and throat spray for COVID-19 prophylaxis-ICE-COVID.

INTRODUCTION: At present, vaccines form the only mode of prophylaxis against COVID-19. The time needed to achieve mass global vaccination and the emergence of new variants warrants continued research into other COVID-19 prevention strategies. The severity of COVID-19 infection is thought to be associated with the initial viral load, and for infection to occur, viruses including SARS-CoV-2 must first penetrate the respiratory mucus and attach to the host cell surface receptors. Carrageenan, a sulphated polysaccharide extracted from red edible seaweed, has shown efficacy against a wide range of viruses in clinical trials through the prevention of viral entry into respiratory host cells. Carrageenan has also demonstrated in vitro activity against SARS-CoV-2. METHODS AND ANALYSIS: A single-centre, randomised, double-blinded, placebo-controlled phase III trial was designed. Participants randomised in a 1:1 allocation to either the treatment arm, verum Coldamaris plus (1.2 mg iota-carrageenan (Carragelose®), 0.4 mg kappa-carrageenan, 0.5% sodium chloride and purified water), or placebo arm, Coldamaris sine (0.5% sodium chloride) spray applied daily to their nose and throat for 8 weeks, while completing a daily symptom tracker questionnaire for a total of 10 weeks. PRIMARY OUTCOME: Acquisition of COVID-19 infection as confirmed by a positive PCR swab taken at symptom onset or seroconversion during the study. Secondary outcomes include symptom type, severity and duration, subsequent familial/household COVID-19 infection and infection with non-COVID-19 upper respiratory tract infections. A within-trial economic evaluation will be undertaken, with effects expressed as quality-adjusted life years. DISCUSSION: This is a single-centre, phase III, double-blind, randomised placebo-controlled clinical trial to assess whether carrageenan nasal and throat spray reduces the risk of development and severity of COVID-19. If proven effective, the self-administered prophylactic spray would have wider utility for key workers and the general population. TRIAL REGISTRATION: NCT04590365; ClinicalTrials.gov NCT04590365. Registered on 19 October 2020.

Differential rates of group B streptococcus (GBS) colonisation in pregnant women in a racially diverse area of London, UK: a cross-sectional study.

OBJECTIVE: To describe the epidemiology of maternal group B streptococcus (GBS) colonisation by racial group. DESIGN: Cross-sectional study. SETTING: Antenatal clinics in London North West University Healthcare NHS Trust. POPULATION: Pregnant women. METHODS: Group B streptococcus (GBS) colonisation status was recorded during a screening programme for the prevention of invasive early-onset GBS infection. Information regarding age, address, ethnicity, parity, mode of delivery, body mass index (BMI), and diabetes was routinely collected. Data were analysed by multivariable analysis. MAIN OUTCOME MEASURES: Association between GBS colonisation and putative risk factors. RESULTS: Overall, 29.1% (1836/6309) of the women were colonized with GBS. Multivariable analysis showed significantly higher colonisation among women of black African origin (39.5%; OR = 1.57) compared with white British women (27.4%), and lowest colonisation in women of South Asian origin (23.3%; OR = 0.8). Higher parity (≥2) was associated with higher colonisation (35.3%), with the odds of colonisation over 40% higher than for nulliparous women. Increasing BMI was associated with an incremental rise in colonisation from 23 to 35%. Colonisation was not associated with age, season or mode of testing. CONCLUSION: This study identified high maternal GBS colonisation rates in a racially and socially diverse population. The highest rates were seen in women of black African origin and also with higher parity and BMI. Further research is needed to understand the relationship between these factors and rectovaginal colonisation. TWEETABLE ABSTRACT: Study of group B streptococcus colonisation in pregnant women in London shows highest rates in black African women and those with high BMI and parity.

Working while unwell: Workplace impairment in people with severe asthma.

BACKGROUND: Severe asthma affects quality of life; however, its impact on workplace productivity is poorly understood. OBJECTIVE: To compare workplace productivity-absenteeism and presenteeism-and impairment in daily activities in severe and non-severe asthma over time and identify characteristics associated with presenteeism in severe asthma. METHODS: The Severe Asthma Web-based Database is an ongoing observational registry from Australia, New Zealand and Singapore. At April 2017, 434 patients with severe asthma and 102 with non-severe asthma were enrolled (18-88 years; 59% female). Participants provided comprehensive clinical and questionnaire data at baseline and were followed-up every 6 months for 24 months. Absenteeism (percentage of time not at work), presenteeism (self-reported impairment at work) and impairment in daily activities outside work due to health problems in the last week were calculated. RESULTS: At baseline, 61.4% of participants with severe asthma and 66.2% with non-severe asthma under 65 years were employed. At younger ages (30-50 years), fewer severe asthma participants were employed (69% vs 100%). Presenteeism and impairment in daily activity were more frequently reported in severe asthma and in participants with poorer asthma control, poorer lung function and more past-year exacerbations (P < .01). Over time, deteriorating asthma control was associated with increasing presenteeism. Although absenteeism was not different between severe and non-severe asthma, worse asthma control was associated with absenteeism (P < .001). In participants with severe asthma, presenteeism was reported more frequently in those with poorer asthma control, poorer asthma-related quality of life and symptoms of depression or anxiety (P < .01). CONCLUSION AND CLINICAL RELEVANCE: Severe asthma was associated with impairment at work and outside the workplace. Improving asthma control and mental health may be important targets for optimizing workplace productivity in severe asthma. Presenteeism and absenteeism may represent key metrics for assessing intervention efficacy in people with severe asthma of working age.

The reciprocal relationship between physical activity and depression: Does age matter?

BACKGROUND: The level of physical activity (PA) and the prevalence of depression both change across the lifespan. We examined whether the association between PA and depression is moderated by age. As sense of mastery and functional limitations have been previously associated with low PA and depression in older adults, we also examined whether these are determinants of the differential effect of age on PA and depression. METHODS: 1079 patients with major depressive disorder (aged 18-88 years) were followed-up after two-years; depression diagnosis and severity as well as PA were re-assessed. Linear and logistic regression analyses were used to test reciprocal prospective associations between PA and depression outcomes. In all models the interaction with age was tested. RESULTS: PA at baseline predicted remission of depressive disorder at follow-up (OR = 1.43 [95% CI: 1.07-1.93], p = .018). This effect was not moderated by age. PA predicted improvement of depression symptom severity in younger (B = -2.03; SE = .88; p = .022), but not in older adults (B = 2.24; SE = 1.48; p = .128) (p = .015 for the interaction PA by age in the whole sample). The level of PA was relatively stable over time. Depression, sense of mastery and functional limitation were for all ages not associated with PA at follow-up. CONCLUSIONS: Age did not moderate the impact of PA on depressive disorder remission. Only in younger adults, sufficient PA independently predicts improvement of depressive symptom severity after two-year follow-up. Level of PA rarely changed over time, and none of the determinants tested predicted change in PA, independent of age.

Outcome of a screening programme for the prevention of neonatal invasive early-onset group B Streptococcus infection in a UK maternity unit: an observational study.

BACKGROUND: Against a background of failure to prevent neonatal invasive early-onset group B Streptococcus infections (GBS) in our maternity unit using risk-based approach for intrapartum antibiotic prophylaxis, we introduced an antenatal GBS carriage screening programme to identify additional women to target for prophylaxis. OBJECTIVES: To describe the implementation and outcome of an antepartum screening programme for prevention of invasive early-onset GBS infection in a UK maternity unit. DESIGN: Observational study of outcome of screening programme (intervention) with comparison to historical controls (preintervention). SETTING: Hospital and community-based maternity services provided by Northwick Park and Central Middlesex Hospitals in North West London. PARTICIPANTS: Women who gave birth between March 2014 and December 2015 at Northwick Park Hospital. METHODS: Women were screened for GBS at 35-37 weeks and carriers offered intrapartum antibiotic prophylaxis. Screening programme was first introduced in hospital (March 2014) and then in community (August 2014). Compliance was audited by review of randomly selected case records. Invasive early-onset GBS infections were defined through GBS being cultured from neonatal blood, cerebrospinal fluid or sterile fluids within 0-6 days of birth. MAIN OUTCOME: Incidence of early-onset GBS infections. RESULTS: 6309 (69%) of the 9098 eligible women were tested. Screening rate improved progressively from 42% in 2014 to 75% in 2015. Audit showed that 98% of women accepted the offer of screening. Recto-vaginal GBS carriage rate was 29.4% (1822/6193). All strains were susceptible to penicillin but 11.3% (206/1822) were resistant to clindamycin. Early onset GBS rate fell from 0.99/1000 live births (25/25276) in the prescreening period to 0.33/1000 in the screening period (Rate Ratio=0.33; p=0.08). In the subset of mothers actually screened, the rate was 0.16/1000 live births (1/6309), (Rate Ratio=0.16; p<0.05). CONCLUSIONS: Our findings confirm that an antenatal screening programme for prevention of early-onset GBS infection can be implemented in a UK maternity setting and is associated with a fall in infection rates.

Sit, step, sweat: longitudinal associations between physical activity patterns, anxiety and depression.

BACKGROUND: Physical inactivity has been identified as a risk factor for depression and, less often, as a long-term consequence of depression. Underexplored is whether similar bi-directional longitudinal relationships are observed for anxiety disorders, particularly in relation to three distinct indicators of activity levels - sports participation, general physical activity and sedentary behavior. METHOD: Participants were from the Netherlands Study of Depression and Anxiety (NESDA; N = 2932, 18-65 years old; 57% current anxiety or depressive disorder, 21% remitted disorder, 22% healthy controls). At baseline, 2, 4, and 6 years, participants completed a diagnostic interview and self-report questionnaires assessing psychopathology symptom severity, physical activity indicators, and sociodemographic and health covariates. RESULTS: Consistently across assessment waves, people with anxiety and/or depressive disorders had lower sports participation and general physical activity compared to healthy controls. Greater anxiety or depressive symptoms were associated with lower activity according to all three indicators. Over time, a diagnosis or greater symptom severity at one assessment was associated with poorer sports participation and general physical activity 2 years later. In the opposite direction, only low sports participation was associated with greater symptom severity and increased odds of disorder onset 2 years later. Stronger effects were observed for chronicity, with lower activity according to all indicators increasing the odds of disorder chronicity after 2 years. CONCLUSIONS: Over time, there seems to a mutually reinforcing, bidirectional relationship between psychopathology and lower physical activity, particularly low sports participation. People with anxiety are as adversely affected as those with depression.

Morphology of muscle attachment sites in the modern human hand does not reflect muscle architecture.

Muscle attachment sites (entheses) on dry bones are regularly used by paleontologists to infer soft tissue anatomy and to reconstruct behaviors of extinct organisms. This method is commonly applied to fossil hominin hand bones to assess their abilities to participate in Paleolithic stone tool behaviors. Little is known, however, about how or even whether muscle anatomy and activity regimes influence the morphologies of their entheses, especially in the hand. Using the opponens muscles from a sample of modern humans, we tested the hypothesis that aspects of hand muscle architecture that are known to be influenced by behavior correlate with the size and shape of their associated entheses. Results show no consistent relationships between these behaviorally-influenced aspects of muscle architecture and entheseal morphology. Consequently, it is likely premature to infer patterns of behavior, such as stone tool making in fossil hominins, from these same entheses.

A systematic review of psychological interventions for excessive alcohol consumption among people with psychotic disorders.

OBJECTIVE: Excessive alcohol consumption is common among people with psychotic disorders. While there is an extensive literature on the efficacy of psychological treatments for excessive drinking, few studies have examined interventions addressing this issue among people with psychotic disorders. METHOD: Systematic searches in PubMed and PsycINFO were conducted to identify randomized controlled trials comparing manual-guided psychological interventions for excessive alcohol consumption among individuals with psychotic disorders. Of the 429 articles identified, seven met inclusion criteria. Data were extracted from each study regarding study sample characteristics, design, results, clinical significance of alcohol consumption results, and methodological limitations. RESULTS: Assessment interviews, brief motivational interventions, and lengthier cognitive behavior therapy have been associated with reductions in alcohol consumption among people with psychosis. While brief interventions (i.e. 1-2 sessions) were generally as effective as longer duration psychological interventions (i.e. 10 sessions) for reducing alcohol consumption, longer interventions provided additional benefits for depression, functioning, and other alcohol outcomes. CONCLUSION: Excessive alcohol consumption among people with psychotic disorders is responsive to psychological interventions. It is imperative that such approaches are integrated within standard care for people with psychosis.

Interleukin-6, C-reactive protein and interleukin-10 after antidepressant treatment in people with depression: a meta-analysis.

BACKGROUND: Cross-sectional studies support an association between depression and inflammatory markers. However, little is known of their relationship in the context of antidepressant treatment. Our aim was to explore via meta-analysis whether antidepressant treatment is associated with a reduction in three inflammatory markers associated with depression. METHOD: A computerized search of EMBASE, Medline, PsycINFO and Cochrane Library databases was completed using subject headings for depression and either interleukin-6, C-reactive protein or interleukin-10, selecting studies which reported circulating levels of inflammatory markers before and after antidepressant treatment for people with depression. Outcome and moderator variables were coded for analysis, including inflammatory marker change, depression severity change, age, gender ratio, assay brand, treatment response and weight change. RESULTS: Pooled effect sizes showed a significant decrease in interleukin-6 (n=14, d=-0.42, p=0.02), marginally significant decrease in C-reactive protein (n=8, d=-0.57, p=0.05) and a non-significant decrease in interleukin-10 (n=3, d=-0.45, p=0.14) after treatment. High levels of heterogeneity were observed, which may be associated with clinical variations between the studies such as weight gain, anxiety, incomplete remission and other individual differences and co-morbidities. CONCLUSIONS: The findings of this meta-analysis indicate that there may be a normalization of overactive inflammatory processes following antidepressant treatment.

Detection of impaired glucose regulation and/or type 2 diabetes mellitus, using primary care electronic data, in a multiethnic UK community setting.

AIMS/HYPOTHESIS: The aim of this study was to develop and validate a score for detecting the glycaemic categories of impaired glucose regulation (IGR) and type 2 diabetes using the WHO 2011 diagnostic criteria. METHODS: We used data from 6,390 individuals aged 40-75 years from a multiethnic population based screening study. We developed a logistic regression model for predicting IGR and type 2 diabetes (diagnosed using OGTT or HbA(1c) ≥ 6.5% [48 mmol/mol]) from data which are routinely stored in primary care. We developed the score by summing the ß coefficients. We externally validated the score using data from 3,225 participants aged 40-75 years screened as part of another study. RESULTS: The score includes age, ethnicity, sex, family history of diabetes, antihypertensive therapy and BMI. Fifty per cent of a population would need to be invited for testing to detect type 2 diabetes mellitus on OGTT with 80% sensitivity; this is slightly raised to 54% that need to be invited if using HbA(1c). Inviting the top 10% for testing, 9% of these would have type 2 diabetes mellitus using an OGTT (positive predictive value [PPV] 8.9% [95% CI 5.8%,12.8%]), 26% would have IGR (PPV 25.9% [95% CI 20.9%, 31.4%]). Using HbA(1c) increases the PPV to 19% for type 2 diabetes mellitus (PPV 18.6% [95% CI 14.2%, 23.7%]) and 28% for an HbA(1c) between 6.0% and 6.4% (PPV 28.3% [95% CI 23.1%, 34.0%]). CONCLUSIONS: The score can be used to reliably identify those with undiagnosed IGR and type 2 diabetes in multiethnic populations. This is the first score developed taking into account HbA(1c) in the diagnosis of type 2 diabetes.

The Leicester Risk Assessment score for detecting undiagnosed Type 2 diabetes and impaired glucose regulation for use in a multiethnic UK setting.

AIMS: Risk assessment scores identify those at high risk of impaired glucose regulation and Type 2 diabetes mellitus. To date no risk assessment scores that can be completed by a lay person have been developed and validated specifically for multiethnic populations in the UK. METHODS: We used data on 6186 subjects aged 40-75 years from a multiethnic UK screening study (73% white European, 22% South Asian). All participants were given a 75 g oral glucose tolerance test. We developed logistic regression models for predicting current impaired glucose regulation (impaired fasting glycaemia/impaired glucose tolerance) or Type 2 diabetes mellitus using data from anthropometric measurements and self-reported questionnaires. Using the best-fitting model, we developed the Leicester Risk Assessment score. We externally validated the score using data from 3171 subjects aged 40-75 years from a separate screening study. RESULTS: The components of the final model are age, ethnicity [white European vs. other (predominantly South Asian)], sex, first degree family history of diabetes, antihypertensive therapy or history of hypertension, waist circumference and body mass index. The score ranges from 0 to 47. Validating this model using the data from the second screening study gave an area under the receiver operator characteristic curve of 72% (95% confidence interval, 69-74%). A cut point of 16 had a sensitivity of 81% and a specificity of 45%. CONCLUSIONS: The Leicester Risk Assessment score can be used to identify those at high risk of impaired glucose regulation and Type 2 diabetes mellitus in UK multiethnic populations. The score is simple (seven questions) and non-invasive.

Rationale and design of the ADDITION-Leicester study, a systematic screening programme and randomised controlled trial of multi-factorial cardiovascular risk intervention in people with type 2 diabetes mellitus detected by screening.

BACKGROUND: Earlier diagnosis followed by multi-factorial cardiovascular risk intervention may improve outcomes in type 2 diabetes mellitus (T2DM). Latent phase identification through screening requires structured, appropriately targeted population-based approaches. Providers responsible for implementing screening policy await evidence of clinical and cost effectiveness from randomised intervention trials in screen-detected T2DM cases. UK South Asians are at particularly high risk of abnormal glucose tolerance and T2DM. To be effective national screening programmes must achieve good coverage across the population by identifying barriers to the detection of disease and adapting to the delivery of earlier care. Here we describe the rationale and methods of a systematic community screening programme and randomised controlled trial of cardiovascular risk management within a UK multiethnic setting (ADDITION-Leicester). DESIGN: A single-blind cluster randomised, parallel group trial among people with screen-detected T2DM comparing a protocol driven intensive multi-factorial treatment with conventional care. METHODS: ADDITION-Leicester consists of community-based screening and intervention phases within 20 general practices coordinated from a single academic research centre. Screening adopts a universal diagnostic approach via repeated 75g-oral glucose tolerance tests within an eligible non-diabetic population of 66,320 individuals aged 40-75 years (25-75 years South Asian). Volunteers also provide detailed medical and family histories; complete health questionnaires, undergo anthropometric measures, lipid profiling and a proteinuria assessment. Primary outcome is reduction in modelled Coronary Heart Disease (UKPDS CHD) risk at five years. Seven thousand (30% of South Asian ethnic origin) volunteers over three years will be recruited to identify a screen-detected T2DM cohort (n = 285) powered to detected a 6% relative difference (80% power, alpha 0.05) between treatment groups at one year. Randomisation will occur at practice-level with newly diagnosed T2DM cases receiving either conventional (according to current national guidelines) or intensive (algorithmic target-driven multi-factorial cardiovascular risk intervention) treatments. DISCUSSION: ADDITION-Leicester is the largest multiethnic (targeting >30% South Asian recruitment) community T2DM and vascular risk screening programme in the UK. By assessing feasibility and efficacy of T2DM screening, it will inform national disease prevention policy and contribute significantly to our understanding of the health care needs of UK South Asians. TRIAL REGISTRATION: Clinicaltrial.gov (NCT00318032).

Growth patterns of highland children and some possible implications for assessment of nutritional status.

Cross-sectional height and weight data from children under 5 years of age at three locations in the highlands of Papua New Guinea are analysed. The proportion of children under 90% height for age increases rapidly with age. The proportion of children under 80% weight for height is much lower at ages and peaks in the second year of life. Thus, the increase with age in the proportion of children below 80% weight for age is primarily due to a progressive increase in the height deficit. The implications of this growth pattern for monitoring nutritional status will not be clear until the relative health significance of a deficit in height as compared to a deficit in weight for height has been determined.