Tracing teachers' perceptions of entanglement of digitally-mediated educational activities and learning environments: a practice-oriented method.

School spaces, technologies, and educational activities shape each other reciprocally. This mixed-methods study (i) developed a methodological framework for tracing the interdependence between school spaces, digital instruments, and teachers' practices in their use, and (ii) created practice-based knowledge about the relations of teachers' perceptions of educational activities to school spaces in order to acknowledge architects and educational practitioners in designing learning environments that support educational renewal. We participated in the construction process of a new general upper-secondary school building in Finland, taking into consideration the school's operating culture and teachers' pedagogic needs (social aspects), as well as the mediation of school spaces by digitalization and national curriculum reformation (material aspects). The data were collected through a teacher survey (n = 31), teacher interviews (n = 10), and the analysis of group notes that teachers (n = 39) generated in a participatory workshop. The results revealed that teachers consider it critical in the design of new learning environments to foster a collaborative and multidisciplinary school culture that emphasizes learners' wellbeing and inclusion, as well as utilizing readily-available digital instruments with basic-level functionality. The developed methodological framework appeared suitable for visualizing (with radar charts) the sociomaterial interdependence of school spaces, digital instruments, and teachers' personal and collective pedagogical activities. We argue that teachers' perceptions of school spaces, digital instruments, and pedagogic practices entanglement consolidates learning environments design from an educational point of view and should be taken into consideration when constructing new school buildings.

Immunogenicity and Safety of a Measles-Mumps-Rubella Vaccine Administered as a First Dose to Children Aged 12 to 15 Months: A Phase III, Randomized, Noninferiority, Lot-to-Lot Consistency Study.

BACKGROUND: MMR II (M-M-R II [Merck & Co, Inc.]) is currently the only measles, mumps, and rubella (MMR) vaccine licensed in the United States. A second MMR vaccine would mitigate the potential risk of vaccine supply shortage or delay. In this study, we assessed the immunogenicity and safety of another MMR vaccine (MMR-RIT [Priorix, GlaxoSmithKline]) compared with those of the MMR II in 12- to 15-month-old children who received it as a first dose. METHODS: In this phase III, observer-blinded, noninferiority, lot-to-lot consistency clinical trial (ClinicalTrials.gov identifier NCT01702428), 5003 healthy children were randomly assigned to receive 1 dose of MMR-RIT (1 of 3 production lots) or MMR II along with other age-recommended routine vaccines. We evaluated the immunogenicity of all vaccines in terms of antibody concentrations (by using an enzyme-linked immunosorbent assay or electrochemiluminescence assay) and/or seroresponse rates 43 days after vaccination. We also assessed the reactogenicity and safety of the vaccines. RESULTS: Immunoresponses after vaccination with MMR-RIT were robust and noninferior to those after vaccination with the MMR II. Immunogenicity of the 3 production lots of MMR-RIT was consistent; more than 97% of the children had a seroresponse to MMR components. The coadministered vaccines elicited similar immunoresponses in the MMR-RIT and MMR II groups. Both MMR vaccines resulted in comparable reactogenicity profiles, and no safety concerns were detected. CONCLUSIONS: If licensed, the MMR-RIT could provide a valid option for the prevention of measles, mumps, and rubella in children in the United States and would reduce potential risks of a vaccine shortage.

Quality of Life Impact of an Adjuvanted Recombinant Zoster Vaccine in Adults Aged 50 Years and Older.

BACKGROUND: To determine the efficacy of an adjuvanted recombinant zoster vaccine in reducing the herpes zoster (HZ) burden of illness, HZ burden of interference with activities of daily living, and HZ impact on quality of life. METHODS: The assessments were integrated in two Phase III trials, ZOE-50 (NCT01165177) and ZOE-70 (NCT01165229). HZ burden of illness and HZ burden of interference with activities of daily living were assessed by the Zoster Brief Pain Inventory (ZBPI) instrument and quality of life by the EuroQol-5 Dimension (EQ-5D) utility index and the SF-36 health survey. We report the ZOE-50 results and a pooled analysis of patients aged 70 years and older from the trials combined. RESULTS: The estimated vaccine efficacy in reducing HZ burden of illness and HZ burden of interference was greater than 90% in both the ZOE-50 and the pooled ZOE-70 analysis. In confirmed HZ cases, adjuvanted recombinant zoster vaccine reduced the maximal ZBPI worst-pain score in the pooled ZOE-70 analysis (p = .032) and the maximal ZBPI average-pain scores in both the ZOE-50 (p = .049) and the pooled ZOE-70 analysis (p = .043). In breakthrough HZ cases, trends for diminished loss of quality of life compared with placebo-recipient HZ cases were observed, with differences up to 0.14 on the EQ-5D index at time points during the 4 weeks following HZ onset. CONCLUSIONS: Adjuvanted recombinant zoster vaccine reduced the HZ burden of illness significantly, particularly due to its very high vaccine efficacy in preventing HZ. For breakthrough HZ cases, the results suggest that the adjuvanted recombinant zoster vaccine mitigated severity of HZ-related pain, burden of interference with activities of daily living, and recipients' utility loss.

Immunogenicity and safety of primary and booster vaccination with 2 investigational formulations of diphtheria, tetanus and Haemophilus influenzae type b antigens in a hexavalent DTPa-HBV-IPV/Hib combination vaccine in comparison with the licensed Infanrix hexa.

Safety and immunogenicity of 2 investigational formulations of diphtheria, tetanus and Haemophilus influenzae type b antigens of the combined diphtheria-tetanus-acellular pertussis-hepatitis B-inactivated poliomyelitis-Hib vaccine (DTPa-HBV-IPV/Hib) were evaluated in a Primary (NCT01248884) and a Booster vaccination (NCT01453998) study. In the Primary study, 721 healthy infants (randomized 1:1:1) received 3 doses of DTPa-HBV-IPV/Hib formulation A (DATAPa-HBV-IPV/Hib), or B (DBTBPa-HBV-IPV/Hib) or the licensed DTPa-HBV-IPV/Hib vaccine (Infanrix hexa, GSK; control group) at 2, 3, 4 months of age. Infants were planned to receive a booster dose at 12-15 months of age with the same formulation received in the Primary study; however, following high incidence of fever associated with the investigational formulations in the Primary study, the Booster study protocol was amended and all infants yet to receive a booster dose (N = 385) received the licensed vaccine. In the Primary study, non-inferiority of 3-dose vaccination with investigational formulations compared with the licensed vaccine was not demonstrated due to anti-pertactin failing to meet the non-inferiority criterion. Post-primary vaccination, most infants had seroprotective levels of anti-diphtheria (100% of infants), anti-tetanus antigens (100%), against hepatitis B (≥ 97.5% across groups), polyribosyl-ribitol-phosphate (≥ 88.0%) and poliovirus types 1-3 (≥ 90.5%). Seropositivity rates for each pertussis antigen were 100% in all groups. Higher incidence of fever (> 38°C) was reported in infants receiving the investigational formulations (Primary study: 75.0% [A] and 72.1% [B] vs 58.8% [control]; Booster study, before amendment: 49.4% and 46.6% vs 37.4%, respectively). The development of the investigational formulations was not further pursued.

Efficacy of the Herpes Zoster Subunit Vaccine in Adults 70 Years of Age or Older.

BACKGROUND: A trial involving adults 50 years of age or older (ZOE-50) showed that the herpes zoster subunit vaccine (HZ/su) containing recombinant varicella-zoster virus glycoprotein E and the AS01B adjuvant system was associated with a risk of herpes zoster that was 97.2% lower than that associated with placebo. A second trial was performed concurrently at the same sites and examined the safety and efficacy of HZ/su in adults 70 years of age or older (ZOE-70). METHODS: This randomized, placebo-controlled, phase 3 trial was conducted in 18 countries and involved adults 70 years of age or older. Participants received two doses of HZ/su or placebo (assigned in a 1:1 ratio) administered intramuscularly 2 months apart. Vaccine efficacy against herpes zoster and postherpetic neuralgia was assessed in participants from ZOE-70 and in participants pooled from ZOE-70 and ZOE-50. RESULTS: In ZOE-70, 13,900 participants who could be evaluated (mean age, 75.6 years) received either HZ/su (6950 participants) or placebo (6950 participants). During a mean follow-up period of 3.7 years, herpes zoster occurred in 23 HZ/su recipients and in 223 placebo recipients (0.9 vs. 9.2 per 1000 person-years). Vaccine efficacy against herpes zoster was 89.8% (95% confidence interval [CI], 84.2 to 93.7; P<0.001) and was similar in participants 70 to 79 years of age (90.0%) and participants 80 years of age or older (89.1%). In pooled analyses of data from participants 70 years of age or older in ZOE-50 and ZOE-70 (16,596 participants), vaccine efficacy against herpes zoster was 91.3% (95% CI, 86.8 to 94.5; P<0.001), and vaccine efficacy against postherpetic neuralgia was 88.8% (95% CI, 68.7 to 97.1; P<0.001). Solicited reports of injection-site and systemic reactions within 7 days after injection were more frequent among HZ/su recipients than among placebo recipients (79.0% vs. 29.5%). Serious adverse events, potential immune-mediated diseases, and deaths occurred with similar frequencies in the two study groups. CONCLUSIONS: In our trial, HZ/su was found to reduce the risks of herpes zoster and postherpetic neuralgia among adults 70 years of age or older. (Funded by GlaxoSmithKline Biologicals; ZOE-50 and ZOE-70 ClinicalTrials.gov numbers, NCT01165177 and NCT01165229 .).

Safety and immunogenicity of an intramuscular quadrivalent influenza vaccine in children 3 to 8 y of age: A phase III randomized controlled study.

A quadrivalent, inactivated, split-virion influenza vaccine containing a strain from both B lineages (IIV4) has been developed, but its safety and immunogenicity in young children has not been described. This was a phase III, randomized, double-blind, active-controlled, multi-center study to examine the immunogenicity and safety of IIV4 in children 3-8 y of age (EudraCT no. 2011-005374-33). Participants were randomized 5:1:1 to receive the 2013/2014 Northern Hemisphere formulation of IIV4, an investigational trivalent comparator (IIV3) containing the B/Victoria lineage strain, or the licensed Northern Hemisphere IIV3 containing the B/Yamagata lineage strain. Participants who had not previously received a full influenza vaccination schedule received 2 doses of vaccine 28 d apart; all others received a single dose. 1242 children were included. For all 4 strains, IIV4 induced geometric mean haemagglutination inhibition titres non-inferior to those induced by the IIV3 comparators. For both B strains, geometric mean antibody titres induced by IIV4 were superior to those induced by the IIV3 with the alternative lineage strain. Similar proportions of participants vaccinated with IIV4 and IIV3 reported solicited injection-site reactions, solicited systemic reactions, and vaccine-related adverse events. A single vaccine-related serious adverse event, thrombocytopenia, was reported 9 d after vaccination with IIV4 and resolved without sequelae. In conclusion, in children aged 3-8 y who received one dose or 2 doses 28 d apart, IIV4 had an acceptable safety profile, was as immunogenic as IIV3 for the shared strains, and had superior immunogenicity for the additional B strain.

Immunogenicity and Safety of a Trivalent Inactivated Influenza Vaccine in Children 6 Months to 17 Years of Age, Previously Vaccinated with an AS03-Adjuvanted A(H1N1)Pdm09 Vaccine: Two Open-label, Randomized Trials.

BACKGROUND: During the influenza pandemic 2009-2010, an AS03-adjuvanted A(H1N1)pdm09 vaccine was used extensively in children 6 months of age and older, and during the 2010-2011 influenza season, the A(H1N1)pdm09 strain was included in the seasonal trivalent inactivated influenza vaccine (TIV) without adjuvant. We evaluated the immunogenicity and safety of TIV in children previously vaccinated with the AS03-adjuvanted A(H1N1)pdm09 vaccine. METHODS: Healthy children were randomized (1:1) to receive TIV or a control vaccine. Children were aged 6 months to 9 years (n = 154) and adolescents 10-17 years (n = 77) when they received AS03-adjuvanted A(H1N1)pdm09 vaccine at least 6 months before study enrolment. Hemagglutination inhibition (HI) and neutralizing antibody responses against the A(H1N1)pdm09 strain were evaluated before (day 0) and at day 28 and month 6 after study vaccination. Reactogenicity was assessed during the 7 day postvaccination period, and safety was assessed for 6 months. RESULTS: At day 0, >93.9% of all children had HI titers ≥1:40 for the A(H1N1)pdm09 strain, which increased to 100% at both day 28 and month 6 in the TIV group. Between days 0 and 28, HI antibody geometric mean titers against A(H1N1)pdm09 increased by 9-fold and 4-fold in children 6 months to 9 years of age and 10-17 years of age, respectively. CONCLUSION: AS03-adjuvanted A(H1N1)pdm09 vaccine-induced robust immune responses in children that persisted into the next season, yet were still boosted by TIV containing A(H1N1)pdm09. The reactogenicity and safety profile of TIV did not appear compromised by prior receipt of AS03-adjuvanted A(H1N1)pdm09 vaccine.

Immunogenicity of 10-valent pneumococcal nontypeable Haemophilus Influenzae Protein D Conjugate Vaccine when administered as catch-up vaccination to children 7 months to 5 years of age.

BACKGROUND: We evaluated catch-up vaccination schedules with 10-valent pneumococcal nontypeable Haemophilus influenzae Protein D Conjugate Vaccine (PHiD-CV). METHODS: In this open, controlled study, children stratified into 4 age groups (N = 150 each) were vaccinated with PHiD-CV: (a) <6 months reference group: 3 primary doses with booster at 12 to 15 months, (b) 7 to 11 months: 2 doses and booster at 12 to 15 months, (c) 12 to 23 months: 2 doses, and (d) 2 to 5 years: 1 dose. Serotype-specific pneumococcal responses were measured by 22F-inhibition enzyme-linked immunosorbent assay (ELISA) and opsonophagocytic activity (OPA) assay. RESULTS: In the 7 to 11 months group postbooster antibody geometric mean concentrations (except for 2 serotypes) and OPA geometric mean titers (GMTs) were in the same ranges or higher relative to postbooster values in the <6 months reference group. Following 2 doses in the 12 to 23 months group, the percentages reaching threshold levels for ELISA (except for serotypes 6B and 23F) and OPA (except for serotype 1) were comparable or higher than <6 months reference postbooster values. Antibody geometric mean concentrations and OPA GMTs, while comparable or higher than reference postprimary values, were for some serotypes lower than reference postbooster values. Following 1 dose in the 2 to 5 years group ELISA responses were lower than the reference group for several serotypes. CONCLUSIONS: A catch-up PHiD-CV schedule of 2 doses and booster for children 7 to 11 months of age was acceptable. For children 12 to 23 months of age, 2 doses seem to provide adequate priming although a booster dose might confer further benefit. Responses following 1 dose in children 2 to 5 years of age suggest that 2 doses may be preferable.

Safety and immunogenicity of a booster dose of the 10-valent pneumococcal nontypeable Haemophilus influenzae protein D conjugate vaccine coadministered with measles-mumps-rubella-varicella vaccine in children aged 12 to 16 months.

BACKGROUND: A booster dose of pneumococcal conjugate vaccine may be administered at the same age as measles-mumps-rubella-varicella (MMRV) vaccination. This study examined the safety, reactogenicity, and immunogenicity of a booster dose of the 10-valent pneumococcal nontypeable Haemophilus influenzae protein D conjugate vaccine (PHiD-CV) when coadministered with MMRV vaccine. METHODS: In this open, controlled study, 325 healthy children aged 12 to 14 months were randomized to 1 of 3 groups: the first group (N = 110) received PHiD-CV and MMRV vaccine followed 6 to 8 weeks later by MMRV and DTPa-HBV-IPV/Hib vaccines; the second group (N = 101) received DTPa-HBV-IPV/Hib and MMRV vaccines followed 6 to 8 weeks later by PHiD-CV and MMRV vaccine; the third group (N = 114) received PHiD-CV and DTPa-HBV-IPV/Hib vaccine during 1 vaccination visit. Immune responses were assessed with GlaxoSmithKline's 22F-inhibition enzyme-linked immunosorbent assay (for PHiD-CV), commercial enzyme-linked immunosorbent assay (for MMR), or indirect immunofluorescence assay (for varicella). Adverse events were recorded by the parents/guardians. RESULTS: After the first vaccination, 2 peaks in fever (rectal temperature > or =38 degrees C) were observed; at days 0 to 2, related to PHiD-CV and DTPa-HBV-IPV/Hib vaccination, and at days 4 to 12, related to MMRV vaccination. Booster responses to pneumococcal antigens and protein D and seroconversion rates for all MMRV vaccine components were high. CONCLUSIONS: PHiD-CV and MMRV vaccine can be coadministered without compromising the safety and immunogenicity profiles of either vaccine.

RotaTeq, a pentavalent rotavirus vaccine: efficacy and safety among infants in Europe.

A pentavalent human-bovine reassortant oral rotavirus vaccine, RotaTeq, was evaluated among nearly 70,000 infants in the Rotavirus Efficacy and Safety Trial (REST), of which 30,523 were from Europe. All infants were followed for serious adverse events as well as hospitalizations and emergency department (ED) visits. All adverse events, health care utilization, and RVGE regardless of severity were evaluated in the clinical efficacy cohort (N=2686) in Finland. RotaTeq was 98.3% (95% CI, 90.2-100%) and 68.0% (95% CI 60.3-74.4%) efficacious against severe rotavirus gastroenteritis (RVGE) and all RVGE due to any serotype for two rotavirus seasons post-vaccination. The combined rate of hospitalizations and ED visits due to RVGE of any serotype was reduced by 94.5% (95% CI, 91.3-96.8%) for up to 2 years after vaccination. There were no statistically significant differences between RotaTeq and placebo for any of the safety outcomes. In Europe, RotaTeq was highly efficacious and well tolerated.

A randomized, double-blind study of the safety, transmissibility and phenotypic and genotypic stability of cold-adapted influenza virus vaccine.

BACKGROUND: Live attenuated influenza vaccine (LAIV; FluMist) is a trivalent vaccine containing cold-adapted influenza vaccine viruses that infect and replicate in cells lining the nasopharynx to induce immunity. Recovery of viruses (shedding) is measured by culture of nasal specimens. Shedding of vaccine viruses is not equated with transmission because transmission requires more virus than is detected in many nasal swabs. Previous studies with LAIV did not detect transmission to close contacts. The primary objective of this study was to estimate the probability of transmission to placebo contacts in a day care setting. METHODS: One hundred ninety-seven healthy children aged 9 to 36 months attending day care were randomized to receive vaccine or placebo. Postvaccination viral shedding, safety, genotype and phenotype of shed viruses and probability of transmission were assessed. RESULTS: Eighty percent of 98 vaccine recipients shed at least one vaccine strain. No clinically significant differences in solicited adverse events attributable to vaccine occurred; safety profiles were similar in both groups. Vaccine virus isolates retained their phenotypic characteristics (cold adaptation and temperature sensitivity) and did not revert at nucleotides known to confer an attenuating phenotype. There was one confirmed transmission of a vaccine strain to a single placebo recipient. According to the Reed-Frost model, the calculated probability of transmission to a child after contact with a single vaccinated child was 0.58% (95% confidence interval, 0-1.7%). There was no increased reactogenicity or other safety concerns in the recipient child. CONCLUSIONS: Young children in a day care setting had a high rate of shedding and a low rate of transmission. No clinically significant illness occurred among children who received vaccine or placebo or in the child to whom the vaccine virus was transmitted.