Digital messaging to support control for type 2 diabetes (StAR2D): a multicentre randomised controlled trial.

BACKGROUND: Failure to take medicines for diabetes as prescribed contributes to poor outcomes from the condition. Mobile phones are ubiquitous and short message service (SMS) texts have shown promise as a low-cost intervention. We tested the effectiveness of SMS-text messaging in improving outcomes in adults with type 2 diabetes. METHODS: StAR2D was a 12-month two-arm randomised trial of SMS-text messaging and usual care in Cape Town, South Africa and Lilongwe, Malawi. Messages used behaviour change theory and were developed with patients and staff. The intervention group received four messages each week. The primary outcome was change in HbA1c. Secondary outcomes were the proportion of patients who collected > 80% medication and changes in systolic blood pressure, lipids, cardiovascular risk, and the proportion of the participants reaching treatment goals. RESULTS: The trial took place between 1 October, 2016 and 1 October 2018, 1186 participants were randomised to intervention (593) and control (593) groups. 91% of participants completed follow-up. There was a reduction in HbA1c (DCCT) in both groups but not in mean change (95% CI) between groups (- 0.08% (- 0.31 to 0.16) (IFCC - 0.82 mmol/mol (- 3.44 to 1.79). There was a small but not significant increase in the proportions of participants likely to have collected 80% or more of medication (Relative risk 1.11 (0.84 to 1.47; P = 0.47). There was a significant difference between groups in change in systolic blood pressure from baseline of 3.46 mmHg (1.48 to 5.44, P = 0.001) in favour of the intervention group. The between group difference in change in 10-year risk of coronary heart disease was - 0.71% (- 1.46 to 0.04, P = 0.064). The proportion of participants meeting treatment goals in the intervention group was 36.0% and in the control group 26.8% (Relative risk 1.36 (1.13 to 1.63, P = 0.001). Participants reported many challenges to adherence despite finding messages acceptable and useful. CONCLUSIONS: Whilst SMS text messages do not lead to improved glycaemia in these low-resource settings there appeared to be an impact on blood pressure and achievement of treatment goals but the mechanisms for this are unclear. Text messages alone, may be unsuccessful unless accompanied by health system strengthening and other forms of self-management support for type 2 diabetes. TRIAL REGISTRATION: Trial registration: ISRCTN, ISRCTN70768808. Registered 1 July 2015, http://www.isrctn.com/I ISRCTN70768808.

[An association of ulcerative colitis with tumor necrosis factor superfamily member 15 gene polymorphisms in Chinese patients].

Objective: To explore the relationship between ulcerative colitis (UC) susceptibility and tumor necrosis factor superfamily member (TNFSF) 15 gene polymorphisms and haplotypes in Han nationality in Zhejiang province of China. Methods: A total of 408 UC patients and 574 healthy controls were recruited in this study. Three single nucleotide polymorphisms of TNFSF15 (rs3810936, rs4263839, rs4979462) were examined by improved multiple ligase detection reaction (iMLDR) technique. Analyses of linkage disequilibrium (LD) and haplotype were performed by Haploview 4.2 software in all study subjects. Results: The variant allele A and genotype (GA+AA) of rs4263839 were less frequent in UC patients than in controls (45.34% vs. 50.17%, P=0.035;68.38% vs. 76.66%, P=0.004). According to the severity and location of disease, UC patients were divided into different subgroups. After multiple comparison correction(α=0.012 5), the frequencies of variant allele A and genotype (GA+AA) of rs4263839 were lower in patients with severe UC than in the controls (37.69% vs. 50.17%, P=0.007; 60.00% vs. 76.66%, P=0.004). Similar findings were also drawn for patients with extensive colitis in contrast with the controls (42.22% vs. 50.17%, P=0.009; 63.33% vs. 76.66%, P<0.001). Furthermore, the haplotype analysis indicated that three SNPs above were in a strong LD. The frequency of haplotype TAC was lower in UC patients than in the controls(40.83% vs. 46.04%, P=0.023). Also it was less prevalent in patients with severe UC and patients with extensive colitis when compared with controls respectively (33.38% vs. 46.04%, P=0.005;37.22% vs. 46.04%, P=0.003). Conclusions: TNFSF15 (rs4263839) variation might not only reduce the risk of UC, but also affect the severity and lesion location of UC. The haplotype TAC formed by rs3810936, rs4263839 and rs4979462 might be related to a lower risk of UC, especially in patients with severe colitis or patients with extensive colitis.

[Reproductive outcomes following women with previous cesarean scar pregnancy].

Objective: To investigate the reproductive outcomes after the previous cesarean scar pregnancy (CSP). Methods: The clinical data of 138 patients with CSP in Tianjin Medical University General Hospital from January 2011 to March 2016 were collected and analyzed.Fifty-four cases underwent uterine artery embolization+ dilation & curettage (UAE+ D&C) surgery, 41 cases underwent D&C surgery, and 43 cases underwent laparoscopic surgery.Reproductive outcomes were followed up and analyzed. Results: All women were followed up for (46±17) months.It was encouraging that 37 women got 42 spontaneous pregnancies among 50 women with fertility plan, and the subsequent spontaneous pregnancy rate was 74.0%(37/50). Unfortunately, 6 women experienced recurrence of CSP (RCSP) in the subsequent pregnancies, and the RCSP rate was 14.3%(6/42). There were no significant differences with regard to spontaneous pregnancy rate and RCSP rate among the 3 groups (P>0.05). Nineteen women had led to a live delivery indeed without the presence of placenta previa, placenta accrete, uterine rupture and postpartum hemorrhage in the perinatal period. Conclusion: The reproductive outcomes following the previous CSP include the intrauterine pregnancy, spontaneous abortion and RCSP.The individualized treatments on CSP had no significant differences to the subsequent spontaneous pregnancy rate which was favorable in the future fertility plan.The incidence of RCSP was not significantly reduced by laparoscopic uterine scar repair.The risk of RCSP appeared to be increased in the subsequent pregnancies, and early diagnosis and treatment were needed to exclude the abnormal CSP.The overall perinatal outcomes were favorable.

Long-term persistence of immunity and B-cell memory following Haemophilus influenzae type B conjugate vaccination in early childhood and response to booster.

BACKGROUND: Protection against Haemophilus influenzae type b (Hib), a rapidly invading encapsulated bacteria, is dependent on maintenance of an adequate level of serum antibody through early childhood. In many countries, Hib vaccine booster doses have been implemented after infant immunization to sustain immunity. We investigated the long-term persistence of antibody and immunological memory in primary-school children following infant (with or without booster) Hib vaccination. METHODS: Anti-polyribosylribitol phosphate (PRP) immunoglobulin G (IgG) concentration and the frequency of circulating Hib-specific memory B cells were measured before a booster of a Hib-serogroup C meningococcal (MenC) conjugate vaccine and again 1 week, 1 month, and 1 year after the booster in 250 healthy children aged 6-12 years in an open-label phase 4 clinical study. RESULTS: Six to 12 years following infant priming with 3 doses of Hib conjugate vaccine, anti-PRP IgG geometric mean concentrations were 3.11 µg/mL and 0.71 µg/mL and proportions with anti-PRP IgG ≥1.0 µg/mL were 79% and 43% in children who had or had not, respectively, received a fourth Hib conjugate vaccine dose (mean age, 3.9 years). Higher baseline and post-Hib-MenC booster responses (anti-PRP IgG and memory B cells) were found in younger children and in those who had received a fourth Hib dose. CONCLUSIONS: Sustained Hib conjugate vaccine-induced immunity in children is dependent on time since infant priming and receipt of a booster. Understanding the relationship between humoral and cellular immunity following immunization with conjugate vaccines may direct vaccine design and boosting strategies to sustain individual and population immunity against encapsulated bacteria in early childhood. Clinical Trials Registration ISRCTN728588998.

Paediatric meningitis in the conjugate vaccine era and a novel clinical decision model to predict bacterial aetiology.

OBJECTIVES: The aims of this study were to assess aetiology and clinical characteristics in childhood meningitis, and develop clinical decision rules to distinguish bacterial meningitis from other similar clinical syndromes. METHODS: Children aged <16 years hospitalised with suspected meningitis/encephalitis were included, and prospectively recruited at 31 UK hospitals. Meningitis was defined as identification of bacteria/viruses from cerebrospinal fluid (CSF) and/or a raised CSF white blood cell count. New clinical decision rules were developed to distinguish bacterial from viral meningitis and those of alternative aetiology. RESULTS: The cohort included 3002 children (median age 2·4 months); 1101/3002 (36·7%) had meningitis, including 180 bacterial, 423 viral and 280 with no pathogen identified. Enterovirus was the most common pathogen in those aged <6 months and 10-16 years, with Neisseria meningitidis and/or Streptococcus pneumoniae commonest at age 6 months to 9 years. The Bacterial Meningitis Score had a negative predictive value of 95·3%. We developed two clinical decision rules, that could be used either before (sensitivity 82%, specificity 71%) or after lumbar puncture (sensitivity 84%, specificity 93%), to determine risk of bacterial meningitis. CONCLUSIONS: Bacterial meningitis comprised 6% of children with suspected meningitis/encephalitis. Our clinical decision rules provide potential novel approaches to assist with identifying children with bacterial meningitis. FUNDING: This study was funded by the Meningitis Research Foundation, Pfizer and the NIHR Programme Grants for Applied Research.

ZnO nanomaterials based surface acoustic wave ethanol gas sensor.

ZnO nanomaterials based surface acoustic wave (SAW) gas sensor has been investigated in ethanol environment at room temperature. The ZnO nanomaterials have been prepared through thermal evaporation of high-purity zinc powder. The as-prepared ZnO nanomaterials have been characterized with scanning electron microscopy (SEM), transmission electron microscopy (TEM) and X-ray Diffraction (XRD) techniques. The results indicate that the obtained ZnO nanomaterials, including many types of nanostructures such as nanobelts, nanorods, nanowires as well as nanosheets, are wurtzite with hexagonal structure and well-crystallized. The SAW sensor coated with the nanostructured ZnO materials has been tested in ethanol gas of various concentrations at room temperature. A network analyzer is used to monitor the change of the insertion loss of the SAW sensor when exposed to ethanol gas. The insertion loss of the SAW sensor varies significantly with the change of ethanol concentration. The experimental results manifest that the ZnO nanomaterials based SAW ethanol gas sensor exhibits excellent sensitivity and good short-term reproducibility at room temperature.

The impact of off-pump coronary artery bypass surgery on postoperative renal function.

OBJECTIVES: A number of risk factors have been recognised for postoperative renal dysfunction following on-pump coronary artery bypass surgery (CABG). There are, however, few studies that have evaluated the potential reno-protective effects of off-pump CABG in the presence of other confounding risk factors. The aim of this study was to determine if off-pump CABG reduces the risk of renal injury. METHODS: Serum creatinine values (preoperatively and day 1, 2 and 4 postoperatively) and other clinical data were prospectively collected on 1580 consecutive patients who underwent first-time CABG from 2002 to 2005. Creatinine clearance was calculated using the Cockcroft and Gault equation. The effect of on-pump vs. off-pump CABG on renal function was analysed, adjusting for age, gender, diabetes mellitus, left ventricular (LV) function and preoperative creatinine clearance, using multiple regression analysis. RESULTS: One thousand one hundred and forty-five (73%) patients underwent on-pump CABG and 435 (27%) underwent off-pump CABG. The two groups were similar with respect to age, gender and diabetes. Two hundred and seventy-four (17%) patients were females and 274 (17%) patients had diabetes. Multivariate analysis demonstrated significantly lower creatinine clearance postoperatively in patients with diabetes (P<0.001) and advanced age (P<0.001). The on-pump group had significantly lower postoperative creatinine clearance in comparison to the off-pump group (P= 0.01). The effect remained consistent after adjusting for potential risk factors (age, diabetes, gender, LV function and preoperative creatinine clearance) in the multivariate analysis. CONCLUSION: Off-pump surgery is associated with a reduction in postoperative renal injury.

Antibody persistence after serogroup C meningococcal conjugate immunization of United Kingdom primary-school children in 1999-2000 and response to a booster: a phase 4 clinical trial.

BACKGROUND: After immunization with serogroup C meningococcal (MenC) conjugate vaccine, antibody responses and vaccine effectiveness are sustained in adolescents, in contrast to rapid waning in young children. We investigated the persistence of serum bactericidal antibody (SBA) titers in children 6 years after immunization with MenC vaccine (primed between 2 months and 6 years of age). The response to a Haemophilus influenzae type b-MenC conjugate (Hib-MenC) booster was also measured. METHODS: A phase 4 clinical trial was conducted among 250 healthy 6-12-year-old children. SBA titers were measured before, 1 month after, and 1 year after Hib-MenC administration. The correlate of protection was an SBA titer of 8. RESULTS: An SBA titer of 8 was observed in 61 (25% [95% confidence interval {CI}, 20%-30%]) of 244 participants (mean age, 9.1 years; mean interval since MenC immunization, 6.75 years). The proportion with an SBA titer of 8 and the SBA geometric mean titer increased with age, from 12% (95% CI, 4%-23%) to 48% (95% CI, 29%-67%) and from 2.90 (95% CI, 2.11-3.99) to 17.20 (95% CI, 6.80-43.5), respectively, from a mean age of 7.0 to 12.1 years. One month after the Hib-MenC booster, all participants had an SBA titer of 8, which was sustained in 99.6% at 1 year. CONCLUSIONS: As a result of waning antibody, the majority of 6-12-year-old children in the United Kingdom have inadequate serological protection against MenC. The persistence of MenC immunity and the response to a Hib-MenC booster is dependent on age at priming. A booster was highly effective in this cohort and could sustain population immunity against MenC disease. Trial registration. Current Controlled Trials ( http://www.controlled-trials.com ) identifier: ISRCTN72858898 .

Denitrosylation of nNOS induced by cerebral ischemia-reperfusion contributes to nitrosylation of CaMKII and its inhibition of autophosphorylation in hippocampal CA1.

OBJECTIVE: The aim of this study is to investigate the relation between CaMKII S-nitrosylation and its activation, as well as the underlying mechanism, after global cerebral ischemia-reperfusion. MATERIALS AND METHODS: The rat model of cerebral ischemia-reperfusion was established by four-vessel occlusion of 15 min and reperfusion of different times. nNOS inhibitor 7-nitroindazole (7-NI), exogenous nitric oxide donor GSNO (nitrosoglutathione), or N-methyl-D-aspartate receptor (NMDAR) antagonist MK-801 were administered before ischemia. The expressions of S-nitrosylation and phosphorylation of CaMKII and nNOS were detected by biotin switch assay, immunoblotting, and immunohistochemical staining after cerebral ischemia-reperfusion. The survival of hippocampal CA1 pyramidal cells after administration of the three drugs was examined by cresyl violet staining. RESULTS: Following cerebral ischemia-reperfusion, the S-nitrosylation of CaMKII was increased, accompanied by a decrease of phosphorylation, suggesting a decrease of activity (p<0.05). Meanwhile, the phosphorylation and S-nitrosylation of nNOS were notably decreased at the same time point (p<0.05). The administration of 7-NI, GSNO, and MK-801 increased the S-nitrosylation and phosphorylation of nNOS, leading to the attenuation of increased S-nitrosylation and decreased autophosphorylation of CaMKII after cerebral ischemia-reperfusion (p<0.05). Administration of MK-801, GSNO, and 7-NI significantly decreased the neuronal damage in rat hippocampal CA1 caused by cerebral ischemia-reperfusion (p<0.05). CONCLUSIONS: After cerebral ischemia-reperfusion, the decrease of autophosphorylation of CaMKII regulated by its S-nitrosylation may be due to the denitrosylation of nNOS and subsequent NO production. Increasing the phosphorylation of CaMKII by nNOS inhibitor, exogenous NO donor or NMDA receptor antagonist exerted neuroprotective effects against cerebral ischemia-reperfusion injury.

High calpain-1 expression predicts a poor clinical outcome and contributes to tumor progression in pancreatic cancer patients.

BACKGROUND: Pancreatic cancer (PC) is a highly aggressive and metastatic disease, with an elevated mortality rate. It is, therefore, crucial to assess factors affecting the prognosis of PC patients. Meanwhile, calpain-1 is associated with malignant tumor progression and metastasis. Thus, it is meaningful to evaluate the relationship between calpain-1 and PC. MATERIALS AND METHODS: Calpain-1 protein expression was assessed by immunohistochemistry in 96 pancreatic cancer samples and paired adjacent non-cancerous specimens. In addition, calpain-1 protein levels were assessed in six PC cell lines by western blot (WB). Next, PC cells were transfected with calpain-1 siRNA, and silencing was confirmed by WB. Finally, cell proliferation, colony formation, migration and invasion assays, and cell apoptosis analysis were performed to examine the effects of calpain-1 knockdown on proliferation, growth, apoptosis, migration, and invasion in PC cells. RESULTS: The results showed that calpain-1 was overexpressed in PC tissues and cells. Meanwhile, calpain-1 overexpression was associated with tumor site (P = 0.029), metastasis (P = 0.000), and TNM stage (P = 0.000), but showed no associations with histological grade (P = 0.396), age (P = 0.809), sex (P = 1.000), and lesion size (P = 0.679). The Kaplan-Meier method demonstrated that the low calpain-1 expression group had increased overall survival (OS) compared with patients expressing high calpain-1 levels (28.7 ± 4.1 vs. 17.0 ± 2.3 months) (P = 0.005). Besides, calpain-1 in PC cells was successfully silenced by liposome-mediated RNA interference, resulting in reduced cell growth, invasion, and metastasis in PC cells, with no effect on apoptosis. CONCLUSION: The above findings suggest that calpain-1 should be considered a potential biomarker for PC prognosis and therapy.

High-sensitivity far-forward collective scattering diagnostic on HL-2A tokamak.

The multichannel formic acid (HCOOH, λ = 432.5 µm) laser interferometer and Faraday-effect polarimeter on HL-2A tokamak have been developed to measure the far-forward collective scattering from electron density fluctuations. The far-forward collective scattering system provides eight channels of line-integrated electron density fluctuations, covering the wave-number range: k⊥ < 1.6 cm-1. With the new diagnostic, the density fluctuations caused by plasma energetic particles and turbulence have been routinely observed in HL-2A experiments.

[Prospective study on the effect of BMI and waist circumference on diabetes of adults in Zhejiang province].

Objective: To explore the effect of BMI and waist circumference on diabetes of adults. Methods: After excluding participants with heart disease, stroke, cancer and diabetes at baseline study, 53 916 people aged 30-79 in the China Kadoorie Biobank (CKB) study from Tongxiang city of Zhejiang province were recruited. Cox regression model was used to estimate the hazards ratios (HR) for the associations of baseline BMI and waist circumference with incident diabetes. Results: Among 391 512 person-years of the follow-up program between 2004 and 2013 (median 7.26 years), a total of 944 men and 1 643 women were diagnosed as having diabetes. Compared to those with normal weight, after adjusting for known or potential factors, HR of both overweight and obesity in men for incident diabetes appeared as 2.72 (95%CI: 2.47-2.99) and 6.27 (95%CI: 5.33-7.36), respectively. The corresponding figures in women were 2.19 (95%CI: 2.04-2.36) and 3.78 (95%CI: 3.36-4.26). Compared to those with normal waist circumference, after adjusting for known or potential factors, HR of Ⅰgrade andⅡgrade in men for diabetes were 2.56 (95%CI: 2.22-2.95) and 4.66 (95%CI: 4.14-5.24), respectively. The corresponding figures in women were 1.99 (95%CI: 1.80-2.21) and 3.16 (95%CI: 2.90-3.44), respectively. Conclusions: Overweight, obesity and central obesity were all associated with the increased incident of diabetes. Strategies on diabetes prevention should include not only losing weight, but reducing waist circumference as well.

Evaluation of software for multiple imputation of semi-continuous data.

It is now widely accepted that multiple imputation (MI) methods properly handle the uncertainty of missing data over single imputation methods. Several standard statistical software packages, such as SAS, R and STATA, have standard procedures or user-written programs to perform MI. The performance of these packages is generally acceptable for most types of data. However, it is unclear whether these applications are appropriate for imputing data with a large proportion of zero values resulting in a semi-continuous distribution. In addition, it is not clear whether the use of these applications is suitable when the distribution of the data needs to be preserved for subsequent analysis. This article reports the findings of a simulation study carried out to evaluate the performance of the MI procedures for handling semi-continuous data within these statistical packages. Complete resource use data on 1060 participants from a large randomized clinical trial were used as the simulation population from which 500 bootstrap samples were obtained and missing data imposed. The findings of this study showed differences in the performance of the MI programs when imputing semi-continuous data. Caution should be exercised when deciding which program should perform MI on this type of data.

Assessing disease burden of respiratory disorders in Hong Kong children with hospital discharge data and linked laboratory data.

OBJECTIVES: To describe the pattern of respiratory disorders in the Hong Kong paediatric population admitted to government hospitals, and to assess the reliability of the diagnoses by linkage with laboratory data. METHODS: Discharge diagnoses for all admissions are recorded in a central computerised database, the Clinical Management System. These data were analysed for the inclusive period July 1997 to June 1999. Virology laboratory results from a single hospital were linked to the Clinical Management System diagnostic codes to examine discrepancies in coding specific viral aetiologies. RESULTS: A primary diagnosis of a respiratory disorder was noted in 37.5% (upper respiratory 30.1%, tonsillitis/pharyngitis 10.5%, croup/laryngitis 2.3%, acute otitis media 2.7%, bronchitis/chest infection 2.6%, bronchiolitis 10.2%, pneumonia 20.9%, influenza 4%, asthma and allergic rhinitis 16.5%), and a primary or secondary diagnosis in 42.5% of children younger than 15 years. The incidence rates of respiratory illness coded as bronchiolitis and influenza were respectively estimated to be 887-979 and 222-381 per 100,000 children under 5 years and 3551-3949 and 415-528 per 100,000 children under the age of 1 year. The percentage of respiratory-associated admissions varied significantly by hospital and detailed analysis of data at one hospital highlighted important discrepancies between discharge diagnosis and laboratory results. CONCLUSIONS: These passive surveillance data provide general estimates of the disease burden for respiratory disorders in Hong Kong children. Active surveillance studies are required to provide more accurate estimates of the disease burden. Consideration should be given to enhance the Clinical Management System by routinely linking all laboratory data with discharge diagnosis information, by establishing sentinel surveillance hospitals and by assessing new strategies to standardise coding.

Uptake and acceptability of influenza vaccination in day nursery children.

Preschoolers play an important role in the transmission of influenza, and suffer significant morbidity. Paediatric vaccination could prevent serious outcomes and offer broader societal benefits. This study explored parental views on influenza and paediatric vaccination and determined the uptake of a nursery-based vaccination programme for infants aged 6-23 months. Children were offered two doses of inactivated vaccine in 2004/05, and a single dose at the start of the 2005/06 season. An uptake rate of 11% (60/535) was achieved with 83% (50/60) of participants completing the programme. Semi-structured interviews were conducted with 10 parents. Thematic analysis of the data informed the development of a questionnaire. This was distributed to 650 parents, with children aged 6-30 months attending one of the 18 supporting nurseries. A response rate of 13% (83/650) was achieved. The low uptake rate achieved in the programme and findings from the interviews/questionnaire suggest parents were not convinced about the seriousness of paediatric influenza. Indeed, over two-thirds (55/81) questioned the necessity for an annual vaccination. Parents found it difficult to differentiate influenza from other respiratory illnesses, and expressed concerns about the need for annual injections and vaccine safety. Paediatric vaccination to increase herd immunity was held in balance with the notion that children should only be vaccinated if they are the main beneficiaries. Parental education on the burden of childhood influenza, on the direct benefits of influenza vaccination, and on indirect benefits to society is a necessity for a successful paediatric vaccination programme.

ImmunoglobuliN in the Treatment of Encephalitis (IgNiTE): protocol for a multicentre randomised controlled trial.

INTRODUCTION: Infectious and immune-mediated encephalitides are important but under-recognised causes of morbidity and mortality in childhood, with a 7% death rate and up to 50% morbidity after prolonged follow-up. There is a theoretical basis for ameliorating the immune response with intravenous immunoglobulin (IVIG), which is supported by empirical evidence of a beneficial response following its use in the treatment of viral and autoimmune encephalitis. In immune-mediated encephalitis, IVIG is often used after a delay (by weeks in some cases), while diagnosis is confirmed. Wider use of IVIG in infectious encephalitis and earlier use in immune-mediated encephalitis could improve outcomes for these conditions. We describe the protocol for the first ever randomised control trial of IVIG treatment for children with all-cause encephalitis. METHODS AND ANALYSIS: 308 children (6 months to 16 years) with a diagnosis of acute/subacute encephalitis will be recruited in ∼30 UK hospitals and randomised to receive 2 doses (1 g/kg/dose) of either IVIG or matching placebo, in addition to standard treatment. Recruitment will be over a 42-month period and follow-up of each participant will be for 12 months post randomisation. The primary outcome is 'good recovery' (score of 2 or lower on the Glasgow Outcome Score Extended-paediatric version), at 12 months after randomisation. Additional secondary neurological measures will be collected at 4-6 weeks after discharge from acute care and at 6 and 12 months after randomisation. Safety, radiological, other autoimmune and tertiary outcomes will also be assessed. ETHICS AND DISSEMINATION: This trial has been approved by the UK National Research Ethics committee (South Central-Oxford A; REC 14/SC/1416). Current protocol: V4.0 (10/03/2016). The findings will be presented at national and international meetings and conferences and published in peer-reviewed journals. TRIAL REGISTRATION NUMBERS: NCT02308982, EudraCT201400299735 and ISRCTN15791925; Pre-results.

Immunogenicity of a low-dose diphtheria, tetanus and acellular pertussis combination vaccine with either inactivated or oral polio vaccine compared to standard-dose diphtheria, tetanus, acellular pertussis when used as a pre-school booster in UK children: A 5-year follow-up of a randomised controlled study.

This serological follow up study assessed the kinetics of antibody response in children who previously participated in a single centre, open-label, randomised controlled trial of low-dose compared to standard-dose diphtheria booster preschool vaccinations in the United Kingdom (UK). Children had previously been randomised to receive one of three combination vaccines: either a combined adsorbed tetanus, low-dose diphtheria, 5-component acellular pertussis and inactivated polio vaccine (IPV) (Tdap-IPV, Repevax(®); Sanofi Pasteur MSD); a combined adsorbed tetanus, low-dose diphtheria and 5-component acellular pertussis vaccine (Tdap, Covaxis(®); Sanofi Pasteur MSD) given concomitantly with oral polio vaccine (OPV); or a combined adsorbed standard-dose diphtheria, tetanus, 2-component acellular pertussis and IPV (DTap-IPV, Tetravac(®); Sanofi Pasteur MSD). Blood samples for the follow-up study were taken at 1, 3 and 5 years after participation in the original trial (median, 5.07 years of age at year 1), and antibody persistence to each vaccine antigen measured against defined serological thresholds of protection. All participants had evidence of immunity to diphtheria with antitoxin concentrations greater than 0.01IU/mL five years after booster vaccination and 75%, 67% and 79% of children who received Tdap-IPV, Tdap+OPV and DTap-IPV, respectively, had protective antitoxin levels greater than 0.1IU/mL. Long lasting protective immune responses to tetanus and polio antigens were also observed in all groups, though polio responses were lower in the sera of those who received OPV. Low-dose diphtheria vaccines provided comparable protection to the standard-dose vaccine and are suitable for use for pre-school booster vaccination.

Long-term survival in patients with advanced immunodeficiency.

OBJECTIVE: To identity prognostic factors associated with survival time in HIV-infected patients with advanced immunodeficiency. DESIGN: Prospective cohort study. PARTICIPANTS: A total of 1284 HIV-infected patients with serial CD4 count measurements and at least one CD4 cell count < or = 50 x 10(6)/I (CD4 < or = 50). MAIN OUTCOME MEASURE: Survival from initial CD4 cell count < or = 50 x 10(6)/l. RESULTS: The median survival from initial CD4 < or = 50 x 10(6)/l was 17.1 months. The risk of death increased by 2% 195% confidence interval (Cl), 1-31 for each year of age, by 10% (95% Cl, 3-16) for each 10 x 10(6)/l decrease in CD4 count, and by 14% (95% Cl, 9-18) for each 1 g/dl decrease in haemoglobin level. Compared to AIDS-free patients with CD4 < or = 50 x 10(6) cells/l, the risk of dying was 1.5-fold (95% Cl, 1.2-1.9) that of patients who had an AIDS diagnosis for fewer than 3 months prior to CD4 < or = 50, 1.8-fold for patients with an AIDS diagnosis for 4-11 months prior to CD4 < or = 50, and twice that of patients with AIDS for > or = 12 months prior to CD4 < or = 50. The risk of dying for patients whose rate of CD4 cell decline was > 40 x 10(6)/l per 6 months was 1.7-fold (95% Cl, 1.3-2.3) that of patients with an average CD4 cell loss < 40 x 10(6)/l per 6 months, after adjusting for age, haemoglobin and duration of AIDS prior to CD4 < or = 50 x 10(6) cells/l. A prognostic score was developed from the final multivariate model, based on age at CD4 < or = 50, haemoglobin at CD4 < or = 50, duration of AIDS and rate of CD4 decline prior to CD4 < or = 50. CONCLUSIONS: Routinely available clinical and laboratory data including haemoglobin level, rate of CD4 decline and duration of AIDS can be readily translated into a prognostic score and then used to predict the survival experience of an HIV-infected patient with advanced immunodeficiency.