Background: A 2-, 4-, and 12-month schedule of a novel 13-valent-pneumococcal conjugate vaccine (PCV13), containing serotype 1, 3, 4, 5, 6A, 6B 7F, 9V, 14, 18C, 19A, 19F, and 23F polysaccharides individually conjugated to CRM197 was evaluated in a randomized, double-blind, controlled infant study. Methods: Two hundred eighty-six healthy infants received PCV13 or the 7-valent-pneumococcal conjugate vaccine (PCV7) at 2, 4, and 12 months of age, alongside a serogroup C meningococcal (MenC) vaccine (2 and 4 months of age), DTaP-IPV-Hib (2, 3, and 4 months), and a Hib-MenC vaccine (12 months). Specific antibody responses were assessed at age 5, 12, and 13 months. Results: At 13 months of age, >97% of PCV13 recipients had pneumococcal serotype-specific serum IgG concentrations ≥0.35 μg/mL for each vaccine serotype except serotype 3 (88.2%), and at least 93% of PCV13 recipients had OPA titers ≥1:8 for each serotype. At 5 months, 110/114 (96.5%) of PCV13 recipients and 100/102 (98.0%) of PCV7 recipients had serum anti-PRP (Hib) IgG concentration ≥0.15 μg/mL (difference, 1.5%; CI, −7.1%–3.7%), while 119/120 (99.2%) and 117/118 (99.2%), respectively, had MenC serum bactericidal assay titers of ≥1:8. All PCV13 recipients and 110/113 (97.3%) of PCV7 recipients had IgG concentrations against fimbrial agglutinogens of ≥2.2 EU/mL; IgG concentrations for the remaining pertussis antigens were ≥5 EU/mL for all participants. Local reactions and systemic events were similar in the PCV13 and PCV7 groups. Conclusions: A 2-, 4-, and 12-month course of PCV13 was immunogenic for all 13 vaccine serotypes and was well tolerated.
Increased susceptibility to malaria in pregnancy is well recognized, and has generally been assumed to be due to hormonal changes resulting in altered immunity. Based on previous work demonstrating enhanced parasite growth in young normal and thalassemic red blood cells, we hypothesized that in pregnancy increased malaria susceptibility may be due, in part, to the increase in the population of young red cells.FC27 strain of Plasmodium falciparum was cultured in the red cells and sera from healthy primigravida pregnant (n=9) and non-pregnant (n=9) women. Red cells from both pregnant and non-pregnant women were each placed in three cultures containing the sera from pregnant, non-pregnant and pooled control samples. Cultures were set up in triplicate and incubated for 144 hours. Parasite development and growth were assessed by slide microscopy.At 96 hours the median parasite growth in cells from pregnant samples (5.7%) was significantly better than that in the non-pregnant cells (4.8%) (p=0.01). There was no significant difference in parasite growth in cultures with pregnant and non-pregnant sera. As expected, there were significant differences in parameters measuring red cell age between the cells from pregnant and nonpregnant samples: median red cell creatine (11.09 mg/dl) versus (6.90 mg/dl) (p=0.004) and median reticulocyte count (2.3%) versus (1.4%) (p=0.0006).These preliminary results are consistent with the hypothesis that an increased population of young red cells may contribute to increased malaria susceptibility during pregnancy.
Interventions to support people with hypertension in attending clinics and taking their medication have potential to improve outcomes, but delivery on a wide scale and at low cost is challenging. Some trials evaluating clinical interventions using short message service (SMS) text-messaging systems have shown important outcomes, although evidence is limited. We have developed a novel SMS system integrated with clinical care for use by people with hypertension in a low-resource setting. We aim to test the efficacy of the system in improving blood pressure control and treatment adherence compared to usual care. The SMS Text-message Adherence suppoRt trial (StAR) is a pragmatic individually randomised three-arm parallel group trial in adults treated for hypertension at a single primary care centre in Cape Town, South Africa. The intervention is a structured programme of clinic appointment, medication pick-up reminders, medication adherence support and hypertension-related education delivered remotely using an automated system with either informational or interactive SMS text-messages. Usual care is supplemented by infrequent non-hypertension related SMS text-messages. Participants are 1:1:1 individually randomised, to usual care or to one of the two active interventions using minimisation to dynamically adjust for gender, age, baseline systolic blood pressure, years with hypertension, and previous clinic attendance. The primary outcome is the change in mean systolic blood pressure at 12-month follow-up from baseline measured with research staff blinded to trial allocation. Secondary outcomes include the proportion of patients with 80% or more of days medication available, proportion of participants achieving a systolic blood pressure less than 140 mmHg and a diastolic blood pressure less than 90 mmHg, hospital admissions, health status, retention in clinical care, satisfaction with treatment and care, and patient related quality of life. Anonymised demographic data are collected on non-participants. The StAR trial uses a novel, low cost system based on widely available mobile phone technology to deliver the SMS-based intervention, manage communication with patients, and measure clinically relevant outcomes. The results will inform implementation and wider use of mobile phone based interventions for health care delivery in a low-resource setting. NCT02019823
Insomnia is a prevalent sleep disorder that negatively affects quality of life. Multicomponent cognitive-behavioural therapy (CBT) is the recommended treatment but access remains limited, particularly in primary care. Sleep restriction therapy (SRT) is one of the principal active components of CBT and could be delivered by generalist staff in primary care. The aim of this randomised controlled trial is to establish whether nurse-delivered SRT for insomnia disorder is clinically and cost-effective compared with sleep hygiene advice.
1501 Background: Delays in cancer diagnosis can lead to increased mortality, leading to specialized diagnostic pathways for symptomatic patients when cancer is suspected. Identification of circulating tumour DNA can stratify individuals into those more or less likely to have cancer and predict the cancer origin. This could both expedite cancer diagnosis and reduce harm and inefficient investigation in those who do not have cancer. We evaluated the performance of a next-generation sequencing MCED test (GRAIL, LLC) using cell-free DNA (cfDNA) isolated from whole blood in symptomatic patients referred to cancer diagnostic clinics by their primary care physician. Methods: Patients referred for urgent imaging, endoscopy or other diagnostic modalities to investigate symptoms suspicious for cancer were invited to take part. Participants with non-specific symptoms or being tested for lung, gynaecological, upper gastrointestinal (GI) or lower GI cancers gave a blood sample on the day they attended for urgent standard of care investigations. cfDNA was isolated from blood samples and stored until the MCED test was performed in batches, blinded to clinical outcome. The test’s predictions (cancer signal detected yes/no; predicted signal origin) were compared with the diagnosis obtained by standard care to establish the positive and negative predictive value (PPV & NPV), sensitivity and specificity across the whole study population, by referral pathway, and by presenting symptom. In addition, sensitivity was analysed by cancer site and stage. Results: 6238 participants were recruited over 5 months from the 5 clinical pathways at 44 hospital sites in England and Wales. 5461 individuals had an MCED test result and diagnostic outcome and were evaluable. Mean age was 62.1 years (SD, 13.8), 3609 (66.1%) female, 2533 (46.4%) current or former smokers. 368 (6.7%) evaluable patients had a cancer diagnosed. The MCED test detected a cancer signal in 323 cases, 244 in whom cancer was diagnosed and 79 where it was not, yielding a PPV of 75.5% (95% CI 70.5-80.1%), NPV 97.6% (97.1-98.0%), sensitivity 66.3% (61.2-71.1%), and specificity 98.4% (98.1-98.8%). Sensitivity increased with increasing age and cancer stage, from 24.2% (16.0-34.1%) in Stage I to 95.3% (88.5-98.7%) in Stage IV. Sensitivity 80.4% (66.1-90.6%) and NPV 99.1% (98.2-99.6%) were highest for patients referred with symptoms qualifying for the upper GI pathway. Conclusions: This is the first large-scale prospective evaluation of an MCED test in a symptomatic population. These data provide the basis for a prospective, interventional study in patients presenting to primary care with non-specific signs and symptoms with low, but higher than background, probability of being due to cancer. Study data are also being used to enhance the negative predictive value of the current MCED classifier for a symptomatic population. Clinical trial information: ISRCTN10226380 .
The multicomponent serogroup B meningococcal (4CMenB) vaccine was recently licensed for use in Europe. There are currently no data on the persistence of bactericidal antibodies induced by use of this vaccine in infants. Our objective was to evaluate serogroup B–specific bactericidal antibodies in children aged 40–44 months previously vaccinated at 2, 4, 6 and 12 months of age.
Methods:
Participants given 4 doses of 4CMenB as infants received a fifth dose of the vaccine at 40–44 months of age. Age-matched participants who were MenB vaccine–naive received 4CMenB and formed the control group. We evaluated human complement serum bactericidal activity (hSBA) titres at baseline and 1 month after each dose of 4CMenB.
Results:
Before a booster dose at enrolment, 41%–76% of 17 participants previously vaccinated with 4CMenB in infancy had hSBA titres of 4 or greater against 4 reference strains. Before vaccination in the control group (n = 40) these proportions were similar for strains 44/76-SL (63%) and M10713 (68%) but low for strains NZ98/254 (0%) and 5/99 (3%). A booster dose in the 4CMenB-primed participants generated greater increases in hSBA titres than in controls.
Interpretation:
As has been observed with other meningococcal vaccines, bactericidal antibodies waned after vaccination with 4CMenB administered according to an approved infant vaccination schedule of 2, 4, 6 and 12 months of age, but there was an anamnestic response to a booster dose at 40–44 months of age. If 4CMenB were introduced into routine vaccination schedules, assessment of the need for a booster dose would require data on the impact of these declining titres on vaccine effectiveness. ClinicalTrials.gov, no. NCT01027351
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