A school-based educational on-site vaccination intervention for adolescents in an urban area in Germany: feasibility and psychometric properties of instruments in a pilot study

Background Vaccination rates for measles, mumps, and rubella (MMR) and diphtheria, tetanus, pertussis, and polio (Tdap-IPV) are not optimal among German adolescents. Education in combination with easy access to vaccination may be a promising approach to improve vaccination rates. The present paper describes a pilot study of a planned cluster randomized controlled trial (cRCT) in which we aim to improve MMR and Tdap-IPV vaccination rates together with knowledge and self-efficacy in a school setting. Methods The study covered 863 students from 41 classes of four schools. The optimization and feasibility of access to schools, recruitment strategies, intervention, and assessment procedures were examined. The course and content of the educational unit were evaluated with a mixed-methods approach. A pre-post measurement design was tested for the vaccination rate in all schools. Additionally, at two schools, improvement in vaccination-related knowledge and perceived self-efficacy were measured by questionnaire pre-educational unit (n=287) and post-educational unit (n=293). The remaining two schools provided only postintervention data. Finally, we evaluated the psychometric properties (i.e., reliability, retest reliability, and change rates) of the questionnaire, applying Cronbach’s alpha, factor analyses, generalized estimating equations and linear mixed models. Results The findings of the pilot study indicated good feasibility. Of the total sample, 437 students (50.9%) brought their vaccination cards to school, 68 students received Tdap-IPV vaccinations, and 11 received MMR vaccinations. Out of six knowledge questions, on average, the students had M=2.84 (95% CI [2.69, 3.10]) correct answers before and M=4.45 (95% CI [4.26, 4.64]) after the class. Ranging from 1 to 4, the self-efficacy scale changed by 0.3 points (p <.001); Cronbach’s alpha was 0.67 and 0.76 pre- and post-educational unit, respectively, and a one-factor solution was found. Content analysis of the five semistructured group interviews (n=12, 58.3% female) showed that all students found the length of the intervention to be appropriate. The teaching methods, including interactive and social media components, were perceived as very good. Conclusions A school-based educational and on-site vaccination intervention appears to be feasible in terms of procedures and the adequacy of the instruments for the adolescent target group. Trial registration ISRCTN, ISRCTN18026662. Pilot study for main trial registered 8 December 2017.

PENGEMBANGAN MEDIA KOMIK DALAM MENINGKATKAN MINAT BELAJAR KESEHATAN REPRODUKSI KADER GEMPI KESPRO (GENERASI MUDA PEDULI KESEHATAN REPRODUKSI)

Health material is material that requires caution in distributing so that students do not get it wrong. For this reason, teacher expertise is needed in packaging elements in the learning process. One way that can be used in responding to these learning challenges is to develop learning media. Comic is one of the visual media that has several functions in learning, namely the function of attention, affective function, cognitive function and compensatory function. This illustrated media contains learning materials that are packaged to suit the daily lives of students. This type of research is a development research that aims to develop comic media in order to increase interest in learning reproductive health in Gempi Kespro cadres. The development research model used is a modification of the procedural model from Borg and Gall which consists of a preliminary study, determining the goals to be achieved at each stage, developing the initial product form, initial testing, initial revision, main trial, 2nd revision, validation test expert and final revision. Product reviews use modifications of criteria based on quality, namely design, breadth of material, ease of understanding, coherence of images and text as well as image and text writing. The data is presented descriptively. The results of the initial trial, main trial and expert validation showed a positive value for all aspects of the assessment. The conclusion of this study is that the learning media for reproductive health comics is appropriate to be used in increasing student interest in learning in the field of reproductive health ABSTRAKMateri kesehatan reproduksi merupakan materi yang memerlukan kehati-hatian dalam penyampaian agar siswa tidak keliru dalam menerimanya. Untuk itu diperlukan kepiawaian pengajar dalam mengemas unsur dalam proses pembelajarannya. Salah satu cara yang dapat digunakan dalam menjawab tantangan pembelajaran tersebut adalah dengan mengembangkan media belajar. Komik merupakan salah satu media visual memiliki beberapa fungsi dalam pembelajaran yaitu fungsi atensi, fungsi afektif, fungsi kognitif dan fungsi kompensatoris. Media bergambar ini berisi materi pembelajaran yang dikemas menyesuaikan kehidupan siswa sehari-hari. Jenis penelitian ini merupakan penelitian pengembangan yang bertujuan mengembangkan media komik guna meningkatkan minat belajar kesehatan reproduksi pada kader gempi kespro. Model penelitian pengembangan yang digunakan adalah modifikasi model procedural dari Borg and Gall yang terdiri dari studi pendahuluan, menentukan tujuan yang akan dicapai disetiap tahapan, mengembangkan bentuk produk awal, uji coba awal, revisi awal, uji coba utama, revisi ke-2, uji validasi ahli dan revisi akhir. Review penilaian produk menggunakan modifikasi dari criteria berdasarkan kualitas yaitu desain, keluasan materi, kemudahan materi dipahami, keruntutan gambar dan tulisan serta kejelasan gambar dan tulisan. Data disajikan secara deskriptif. Hasil dari uji coba awal, uji coba utama dan validasi ahli menunjukkan nilai positif dari keseluruan aspek penilaian. Kesimpulan dari penelitian ini adalah bahwa media pembelajaran komik kesehatan reproduksi ini layak digunakan dalam meningkatkan minat belajar siswa di bidang kesehatan reproduksi

Family Caregivers’ Experiences with Tele-Rehabilitation for Older Adults with Hip Fracture

Background: There is a knowledge gap for implementing tele-rehabilitation (telerehab) after hip fracture. We recently conducted a clinical trial (ClinicalTrials.gov Identifier: NCT02968589) to test a novel online family caregiver-supported rehabilitation program for older adults with hip fracture, called @ctivehip. In this qualitative substudy, our objective was to use semi-structured interviews to explore family caregivers experience with the telerehab program. Methods: Twenty-one family caregivers were interviewed between three and six months after the older adults completed @ctivehip. One occupational therapist with research and clinical experience, but not involved in the main trial, conducted and transcribed the interviews. We conducted a multi-step content analysis, and two authors completed one coding cycle and two recoding cycles. Results: Family caregivers who enrolled in @ctivehip were satisfied with the program, stated it was manageable to use, and perceived benefits for older adults’ functional recovery after hip fracture. They also suggested improvements for the program content, such as more variety with exercises, and increased monitoring by health professionals. Conclusions: This work extends existing literature and generates research hypotheses for future studies to test telerehab content and program implementation.

P-OGC97 Development and piloting of surgical quality assurance methods for randomised controlled trials (RCTs): an example from a trial comparing laparoscopically assisted oesophagectomy vs. open oesophagectomy

Background RCTs in surgery are frequently criticised because the standard to which operations are performed (quality assurance - QA) is not considered during study design and delivery, risking performance bias. Lack of clarity about surgical QA may also influence the successful implementation of RCT results into routine practice, because it is unclear how procedures were undertaken. We developed QA measures for an RCT comparing laparoscopically assisted and open oesophagectomy (LAO and OO). Methods Five QA categories were developed during the pilot and applied to the main trial, using data from patients receiving their randomized allocation in each group: i) entry criteria for centres; ii) entry criteria for surgeons; surgical protocols for key components of LAO and OO with mandated, prohibited and flexible components, monitored using iii) case report forms (CRFs) to record protocol adherence; and iv) intra-operative photographs to demonstrate protocol adherence (using the visible anatomical structures to determine if the component had been fully completed); and v) lymph node count and length of oesophagus. Results 8 centres and 39 surgeons participated and met entry criteria. 145 (LAO) and 149 (OO) patients underwent their randomized surgical procedure. Key procedural components were reported as complete in CRFs at similar rates in both groups, with &gt;70% undergoing mandated components. However, adherence assessed using photographs was consistently lower than the CRFs. For example, left gastric artery lymphadenectomies were reported as complete in &gt; 98% CRFs (LAO and OO) whereas photographs found this to be complete in 42% (OO) and 54% (LAO). Median nodal count was similar in both groups (145 LAO=24.7, SD = 10.6 and 149 OO = 26.4, SD = 10.2) as was length of resected oesophagus. Conclusions Assessing surgical QA in a multi-centre trial is logistically challenging but feasible. Whilst video data from laparoscopic cases could be collected and assessed, it was not possible with open surgery. Understanding adherence to the study protocol using photographs in addition to CRFs was important because of marked differences between what surgeons reported had been undertaken and images of what had been achieved. It is recommended that surgical trials include QA processes to understand protocol adherence and examine performance bias between groups.

OP135 Impact Of Updated Trial Data On The Cost-effectiveness Of Health Technologies: A Case Study On Percutaneous Mitral Repair

IntroductionExtrapolation methods are commonly used to model the cost-effectiveness of health technologies beyond observed data. Reassessing cost-effectiveness estimates using updated clinical trial data has the potential to reduce uncertainty and optimize decision-making. We present a case study based on percutaneous repair (PR) with the Mitraclip system, a technology to treat severe secondary mitral regurgitation (MR). For the study purpose, we considered the COAPT trial that evaluated the effectiveness of adding PR to medical treatment versus medical treatment alone.MethodsWe developed a time-varying Markov model to assess the cost-effectiveness of PR. Clinical inputs were based on reconstructed individual patient data from the COAPT trial results reported at 2 years, and at 3 years.We developed parametric modeling for overall survival (OS) and heart failure hospitalizations (HFH) to obtain clinically plausible extrapolations beyond observed data. We adopted the French perspective and used a 30-year time horizon. We expressed incremental cost-effectiveness ratios (ICERs) as cost per quality-adjusted life year (QALY).ResultsBased on 2 year-data, preferred parametric models for OS and HFH were exponential and log-logistic respectively, yielding an ICER of EUR21,918/QALY and >0.5 probability of PR being cost-effective (EUR50,000/QALY threshold).Updated analyses at 3 years showed a change of OS trajectory for PR that justified the use of piecewise modelling, yielding an updated ICER that went up to EUR77,904/QALY (base-case), and to a minimum of EUR58,175/QALY (scenario analysis). Using data at 3 years, PR had <0.5 probability of being cost-effective.ConclusionsIn this case study, the availability of updated survival analyses of the main trial is likely to have some impact on decision-making and/or pricing discussion as part of health-technology assessment (HTA). We aim to provide further updated analyses as 4 years results of the COAPT study become available.More broadly, original technology appraisals are frequently undertaken when mid/long-term follow-up trial data may be lacking. Our example suggests the need for continuous HTA review as new clinical data are released.

Clinical trial to analyze the effects of oral intake of Phellinus linteus (sanghuang) extract on immune function: a study protocol for a randomized, double-blind controlled trial

Background As the population of Korea ages, interest in healthcare has increased. In particular, there is an increasing demand for immune-function improvement to prevent infectious diseases. Phellinus linteus (PL) has previously been shown to exert immune-enhancing and anticancer effects. We aim to evaluate whether PL mycelium extract, cultured from the PL KCTC0399BP strain, can increase immune function, as measured using blood-test indicators. This clinical trial protocol is designed as the main trial and is based on the results of a pilot study. Methods This clinical trial is a randomized, double-blinded, placebo-controlled trial. Ninety-eight participants are enrolled and randomly divided into two groups: the experimental group (PL 1000 mg) and the control group (placebo). Participants are administered with experimental food or placebo for eight weeks. Blood tests are performed before trial initiation and 8 weeks later, at trial completion. Laboratory evaluation items are as follows: natural killer cell activity, tumor necrosis factor-α, interferon-γ, interleukin (IL)-1β, IL-2, IL-6, IL-12, immunoglobulin (Ig)G1, IgG2, and IgM. We will mainly use the full analysis dataset to statistically analyze the effectiveness of the treatment. Discussion This study evaluates the effects of PL extract on immune function and will contribute to knowledge on the value of PL as an immune-function–boosting functional food. Trial registration Clinical Research Information Service (CRIS) of Korea CRIS-KCT0005460. Registered on 12 October 2020

Protocol: Pentoxifylline optimal dose finding trial in preterm neonates with suspected late onset sepsis (PTX-trial)

Background Late onset sepsis is a leading cause of death and morbidity in preterm infants. Despite optimal antibiotic treatment, sepsis related mortality and morbidity is still high. Pentoxifylline (PTX) is a methylxanthine with promising immunomodulatory properties, which can be used as an additional therapy next to antibiotics in preterm infants. PTX is increasingly used off-label in neonatal intensive care units, however up till now no dose finding study has been done for PTX in this specific population. The aim of this study (PTX-trial) is to determine the optimal dose of PTX in preterm infants (gestational age < 30 weeks) with (suspected) late onset sepsis. Dose finding in this particular population is unique, since for most drugs used in neonates the optimal dosage has not been investigated in phase II dose-seeking studies. Methods The PTX-trial is a prospective open label sequential dose-optimization study with an adapted continual reassessment method. An up-and-down dose-response design will be used, with dose step-up and step-down titration after every 3 patients. The PTX starting dosage will be 30 mg/kg/day in 6 hours as described in most previous neonatal studies. Efficacy is defined by means of biochemical and clinical parameters. Toxicity in these vulnerable patients is unwarranted. The optimal dose is defined as the ED75 (i.e., clinically and chemically effective dose for 75% of patients) in preterm neonates with late onset sepsis. We plan to include 30 neonates to determine the optimal dose using this study design. Subsequently, the optimal dose will be validated in 10 additional preterm neonates. In parallel, pharmacokinetics of PTX and its metabolites will be described as well as longitudinal evaluation of metabolomics and proteomics. Discussion The study has been approved by the Regional Medical Ethics Board of Erasmus Medical Center University Rotterdam (MEC 2019-0477) and registered at Clinicaltrials.gov (NCT04152980). Results of the main trial and each of the secondary endpoints will be submitted for publications in peer-reviewed journals. Trial registration Clinicaltrials.gov, NCT04152980, Registered November 6th, 2019

Duration of third stage labour and postpartum blood loss: a secondary analysis of the WHO CHAMPION trial data

Background Obstetric haemorrhage continues to be a leading cause of maternal mortality, contributing to more than a quarter of the 2,443,000 maternal deaths reported between 2003 and 2009. During this period, about 70% of the haemorrhagic deaths occurred postpartum. In addition to other identifiable risk factors for greater postpartum blood loss, the duration of the third stage of labour (TSL) seems to be important, as literature shows that a longer TSL can be associated with more blood loss. To better describe the association between the duration of TSL and postpartum blood loss in women receiving active management of third stage of labour (AMTSL), this secondary analysis of the WHO CHAMPION trial data has been conducted. Methods This was a secondary analysis of the WHO CHAMPION trial conducted in twenty-three sites in ten countries. We studied the association between the TSL duration and blood loss in the sub cohort of women from the CHAMPION trial (all of whom received AMTSL), with TSL upto 60 min and no interventions for postpartum haemorrhage. We used a general linear model to fit blood loss as a function of TSL duration on the log scale, arm and center, using a normal distribution and the log link function. We showed this association separately for oxytocin and for Heat stable (HS) carbetocin. Results For the 10,040 women analysed, blood loss rose steeply with third stage duration in the first 10 min, but more slowly after 10 min. This trend was observed for both Oxytocin and HS carbetocin and the difference in the trends for both drugs was not statistically significant (p-value = 0.2070). Conclusions There was a positive association between postpartum blood loss and TSL duration with either uterotonic. Blood loss rose steeply with TSL duration until 10 min, and more slowly after 10 min. Study registration The main trial was registered with Australian New Zealand Clinical Trials Registry ACTRN12614000870651 and Clinical Trial Registry of India CTRI/2016/05/006969

The economic impact of two diagnostic strategies in the management of restorations in primary teeth: a health economic analysis plan for a trial-based economic evaluation

Background Different approaches have been used by dentists to base their decision. Among them, there are the aesthetical issues that may lead to more interventionist approaches. Indeed, using a more interventionist strategy (the World Dental Federation - FDI), more replacements tend to be indicated than using a minimally invasive one (based on the Caries Around Restorations and Sealants—CARS). Since the resources related to the long-term health effects of these strategies have not been explored, the economic impact of using the less-invasive strategy is still uncertain. Thus, this health economic analysis plan aims to describe methodologic approaches for conducting a trial-based economic evaluation that aims to assess whether a minimally invasive strategy is more efficient in allocating resources than the conventional strategy for managing restorations in primary teeth and extrapolating these findings to a longer time horizon. Methods A trial-based economic evaluation will be conducted, including three cost-effectiveness analyses (CEA) and one cost-utility analysis (CUA). These analyses will be based on the main trial (CARDEC-03/NCT03520309), in which children aged 3 to 10 were included and randomized to one of the diagnostic strategies (based on FDI or CARS). An examiner will assess children’s restorations using the randomized strategy, and treatment will be recommended according to the same criteria. The time horizon for this study is 2 years, and we will adopt the societal perspective. The average costs per child for 24 months will be calculated. Three different cost-effectiveness analyses (CEA) will be performed. For CEAs, the effects will be the number of operative interventions (primary CEA analysis), the time to these new interventions, the percentage of patients who did not need new interventions in the follow-up, and changes in children’s oral health-related quality of life (secondary analyses). For CUA, the effect will be tooth-related quality-adjusted life years (QALYs). Intention-to-treat analyses will be conducted. Finally, we will assess the difference when using the minimally invasive strategy for each health effect (∆effect) compared to the conventional strategy (based on FDI) as the reference strategy. The same will be calculated for related costs (∆cost). The discount rate of 5% will be applied for costs and effects. We will perform deterministic and probabilistic sensitivity analyses to handle uncertainties. The net benefit will be calculated, and acceptability curves plotted using different willingness-to-pay thresholds. Using Markov models, a longer-term economic evaluation will be carried out with trial results extrapolated over a primary tooth lifetime horizon. Discussion The main trial is ongoing, and data collection is still not finished. Therefore, economic evaluation has not commenced. We hypothesize that conventional strategy will be associated with more need for replacements of restorations in primary molars. These replacements may lead to more reinterventions, leading to higher costs after 2 years. The health effects will be a crucial aspect to take into account when deciding whether the minimally invasive strategy will be more efficient in allocating resources than the conventional strategy when considering the management of restorations in primary teeth. Finally, patients/parents preferences and consequent utility values may also influence this final conclusion about the economic aspects of implementing the minimally invasive approach for managing restorations in clinical practice. Therefore, these trial-based economic evaluations may bring actual evidence of the economic impact of such interventions. Trial registration NCT03520309. Registered May 9, 2018. Economic evaluations (the focus of this plan) are not initiated at the moment.

Caregivers Perspective Towards Use of Enteral Lactoferrin Supplementation In Newborn Infants; Formative Research Findings

Background: Infection is the second most leading cause of neonatal deaths in Pakistan. Lactoferrin is a naturally occurring protein found in human milk which can prevent neonatal infections and improve the survival of high-risk, low birth weight newborns. Bovine lactoferrin (bLF) has been recognized as a safe nutrient with no adverse effects. The aim of this study was to explore routine newborn care practices, care seeking attitudes, and assess the acceptability and the optimal method of administering bLF at the household level.Method: Exploratory qualitative research design was adopted. Thirty in-depth interviews with mothers, grandmothers and fathers of low birthweight (LBW) infants were conducted at postnatal wards and the neonatal intensive care unit (NICU) of the Aga Khan University Hospital. Eleven of these families were also recruited for a trial of improved practices (TIPs) to assess the feasibility and the method of administration of bLF prior to the main trial. Interviews were recorded and analyzed using thematic analysis.Result: Most study participants consider birthweight as a predictor of neonatal health outcomes. Caring of LBW newborns was identified as a physically and emotionally overwhelming experience. Majority of mothers believed that LBW babies are prone to infections, gastrointestinal, respiratory and developmental problems. Fathers and grandmothers were major decision makers in the family and supported the use of bLF in LBW newborns. Parents, who used bLF were satisfied with feeding method and frequency of bLF. Conclusion: Our formative study found that participants were willing to use bLF for feeding LBW babies. However, educating mothers, fathers and grandmothers is crucial for successful uptake of the intervention. Bovine lactoferrin is a safe and easy to administer according caregivers of LBWs babies. It also has potential to be translated into a safe and effective intervention for LBW babies to prevent sepsis.Trial registration: ClinicalTrials.gov identifier: NCT03431558.