72 research outputs found
Teachers’ personal experiences of sexual initiation motivating their sexuality education messages in secondary schools in Kampala, Uganda
Little is known about how teachers’ personal sexual experiences influence their motivations and practices when teaching sexuality education. Cultural schema theory was used to explore teachers’ personal experience of the onset of sexual activity and explain how sexuality education teaching is influenced by such experiences. In-depth interviews were conducted with 40 secondary school teachers in Kampala, Uganda. The interviews were transcribed verbatim and analysed using principles of grounded theory. Findings show that while teachers’ personal experience of sexual initiation did not directly align with the content of their messages, due to the centrality and evocative function of these schemas these experiences strengthened teachers’ motivation to teach sexuality education because they enabled them to empathise with students. The study concludes that teachers’ personal experiences of sexual initiation provide intrinsic motivation for teaching sexuality education. The inclusion of dialogues and activities which encourage self-reflexivity in teacher education and training may improve the delivery of sex, sexuality and relationships education
Teachers' Professional Identity in the Context of School-based Sexuality Education in Uganda - a Qualitative Study
School-based sexuality education makes teachers important gatekeepers of students’ access
to information about sexual and reproductive
health and rights. The school setting has the
potential to reach large numbers of students.
However, teachers’ professional identities may
go beyond, differ from or even conflict with the
qualities required of sexuality educators.
To gain a better understanding of the role of
professional identity in the delivery of schoolbased sexuality education, this study used
cultural schema theory to study teachers’ professional identities, and how these motivate
them to provide sexuality education. In-depth
interviews were conducted with 40 sexuality
education teachers at secondary schools in
Kampala, the capital of Uganda. Sexuality
education lessons were observed to validate the
findings from the interviews. Results identified
five cultural schemas of professional identity:
(i) upholder of ethics and regulations;
(ii) authority figure; (iii) counsellor and guide;
(iv) role model; and (v) guardian. The study
concludes that teachers’ cultural schemas of
professional identity motivate them to adhere
to moral discourses of abstinence and sexual
innocence. To support teachers in taking
more comprehensive approaches to sexuality
education, it is important that they receive
adequate teacher training and support from
the Ugandan government, the school
administration and the wider communit
Young people’s perceptions of relationships and sexual practices in the abstinence-only context of Uganda
The Ugandan government has been criticised on several grounds for its
abstinence-only policies on sexuality education directed towards young
people. These grounds include the failure to recognise the multiple
realities faced by young people, some of whom may already be sexually
active. In the study reported on this paper, students’ perceptions
of relationships and sexual practices were analysed to obtain an
understanding of how young people construct and negotiate their
sexual agency in the context of abstinence-only messages provided
in Ugandan secondary schools and at the wider community level. Ten
in-depth interviews and six focus group discussions were conducted
with students aged 15–19 years (N = 55) at an urban co-educational
secondary school. Data were transcribed verbatim and analysed using
grounded theory. Findings show that students engage in sexual activity
despite their belief that contraception is ineffective and their fears for
the consequences. Students’ age, gender, financial capital and perceived
sexual desire further increase risk and vulnerability. To improve their
effectiveness, school-based sexuality education programmes should
support students to challenge and negotiate structural factors such as
gender roles and sociocultural norms that influence sexual practices
and increase vulnerability and risk
A statistical analysis protocol for the time-differentiated target temperature management after out-of-hospital cardiac arrest (TTH48) clinical trial
Background The TTH48 trial aims to determine whether prolonged duration (48
hours) of targeted temperature management (TTM) at 33 (±1) °C results in
better neurological outcomes compared to standard duration (24 hours) after
six months in comatose out-of-hospital cardiac arrest (OHCA) patients. Methods
TTH48 is an investigator-initiated, multicentre, assessor-blinded, randomised,
controlled superiority trial of 24 and 48 hours of TTM at 33 (±1) ° C
performed in 355 comatose OHCA patients aged 18 to 80 years who were admitted
to ten intensive care units (ICUs) in six Northern European countries. The
primary outcome of the study is the Cerebral Performance Category (CPC) score
observed at six months after cardiac arrest. CPC scores of 1 and 2 are defined
as good neurological outcomes, and CPC scores of 3, 4 and 5 are defined as
poor neurological outcomes. The secondary outcomes are as follows: mortality
within six months after cardiac arrest, CPC at hospital discharge, Glasgow
Coma Scale (GCS) score on day 4, length of stay in ICU and at hospital and the
presence of any adverse events such as cerebral, circulatory, respiratory,
gastrointestinal, renal, metabolic measures, infection or bleeding. With the
planned sample size, we have 80% power to detect a 15% improvement in good
neurological outcomes at a two-sided statistical significance level of 5%.
Discussion We present a detailed statistical analysis protocol (SAP) that
specifies how primary and secondary outcomes should be evaluated. We also
predetermine covariates for adjusted analyses and pre-specify sub-groups for
sensitivity analyses. This pre-planned SAP will reduce analysis bias and add
validity to the findings of this trial on the effect of length of TTM on
important clinical outcomes after cardiac arrest. Trial registration
ClinicalTrials.gov: NCT01689077, 17 September 201
a multicentre, randomised, parallel-group, assessor-blinded clinical trial (the TTH48 trial): study protocol for a randomised controlled trial
Background The application of therapeutic hypothermia (TH) for 12 to 24 hours
following out-of-hospital cardiac arrest (OHCA) has been associated with
decreased mortality and improved neurological function. However, the optimal
duration of cooling is not known. We aimed to investigate whether targeted
temperature management (TTM) at 33 ± 1 °C for 48 hours compared to 24 hours
results in a better long-term neurological outcome. Methods The TTH48 trial is
an investigator-initiated pragmatic international trial in which patients
resuscitated from OHCA are randomised to TTM at 33 ± 1 °C for either 24 or 48
hours. Inclusion criteria are: age older than 17 and below 80 years; presumed
cardiac origin of arrest; and Glasgow Coma Score (GCS) <8, on admission. The
primary outcome is neurological outcome at 6 months using the Cerebral
Performance Category score (CPC) by an assessor blinded to treatment
allocation and dichotomised to good (CPC 1–2) or poor (CPC 3–5) outcome.
Secondary outcomes are: 6-month mortality, incidence of infection, bleeding
and organ failure and CPC at hospital discharge, at day 28 and at day 90
following OHCA. Assuming that 50 % of the patients treated for 24 hours will
have a poor outcome at 6 months, a study including 350 patients (175/arm) will
have 80 % power (with a significance level of 5 %) to detect an absolute 15 %
difference in primary outcome between treatment groups. A safety interim
analysis was performed after the inclusion of 175 patients. Discussion This is
the first randomised trial to investigate the effect of the duration of TTM at
33 ± 1 °C in adult OHCA patients. We anticipate that the results of this trial
will add significant knowledge regarding the management of cooling procedures
in OHCA patients
Continuous PEGasparaginase Dosing Reduces Hypersensitivity Reactions in Pediatric ALL:A Dutch Childhood Oncology Group ALL11 Randomized Trial
PURPOSE:The primary objective of this randomized study was to determine whether a continuous dosing schedule (without the asparaginase-free interval) would result in less hypersensitivity reactions to PEGasparaginase (PEGasp) compared with the standard noncontinuous dosing schedule.METHODS:Eight hundred eighteen patients (age 1-18 years) with ALL were enrolled in the Dutch Childhood Oncology Group-ALL11 protocol and received PEGasp. Three hundred twelve patients stratified in the medium-risk arm were randomly assigned to receive 14 individualized PEGasp doses once every two weeks in either a noncontinuous or continuous schedule after the first three doses in induction (EudraCT: 2012-000067-25). Hypersensitivity reactions were defined as allergies, allergic-like reactions, and silent inactivation. Secondary end points were other asparaginase-related toxicities, asparaginase activity and antibody levels, and outcome.RESULTS:During induction, 27 of 818 patients (3.3%) experienced hypersensitivity reactions. After random assignment, 4 of 155 (2.6%) in the continuous treatment arm versus 17 of 157 (10.8%) patients in the noncontinuous treatment arm had hypersensitivity reactions (P <.01), of which two (1.3%) versus 13 (8.3%) were inactivating reactions (P <.01). The occurrence of inactivating hypersensitivity reactions was seven times lower in the continuous arm (odds ratio, 0.15 [0.032-0.653]). In addition, antibody levels were significantly lower in the continuous arm (P <.01). With exception of a lower incidence of increased amylase in the continuous arm, there were no significant differences in total number of asparaginase-associated toxicities between arms. However, the timing of the toxicities was associated with the timing of the asparaginase administrations. No difference in 5-year cumulative incidence of relapse, death, or disease-free survival was found between both treatment arms.CONCLUSION:A continuous dosing schedule of PEGasp is an effective approach to prevent antibody formation and inactivating hypersensitivity reactions. The continuous PEGasp schedule did not increase toxicity and did not affect the efficacy of the therapy.</p
Continuous PEGasparaginase Dosing Reduces Hypersensitivity Reactions in Pediatric ALL:A Dutch Childhood Oncology Group ALL11 Randomized Trial
PURPOSE:The primary objective of this randomized study was to determine whether a continuous dosing schedule (without the asparaginase-free interval) would result in less hypersensitivity reactions to PEGasparaginase (PEGasp) compared with the standard noncontinuous dosing schedule.METHODS:Eight hundred eighteen patients (age 1-18 years) with ALL were enrolled in the Dutch Childhood Oncology Group-ALL11 protocol and received PEGasp. Three hundred twelve patients stratified in the medium-risk arm were randomly assigned to receive 14 individualized PEGasp doses once every two weeks in either a noncontinuous or continuous schedule after the first three doses in induction (EudraCT: 2012-000067-25). Hypersensitivity reactions were defined as allergies, allergic-like reactions, and silent inactivation. Secondary end points were other asparaginase-related toxicities, asparaginase activity and antibody levels, and outcome.RESULTS:During induction, 27 of 818 patients (3.3%) experienced hypersensitivity reactions. After random assignment, 4 of 155 (2.6%) in the continuous treatment arm versus 17 of 157 (10.8%) patients in the noncontinuous treatment arm had hypersensitivity reactions (P <.01), of which two (1.3%) versus 13 (8.3%) were inactivating reactions (P <.01). The occurrence of inactivating hypersensitivity reactions was seven times lower in the continuous arm (odds ratio, 0.15 [0.032-0.653]). In addition, antibody levels were significantly lower in the continuous arm (P <.01). With exception of a lower incidence of increased amylase in the continuous arm, there were no significant differences in total number of asparaginase-associated toxicities between arms. However, the timing of the toxicities was associated with the timing of the asparaginase administrations. No difference in 5-year cumulative incidence of relapse, death, or disease-free survival was found between both treatment arms.CONCLUSION:A continuous dosing schedule of PEGasp is an effective approach to prevent antibody formation and inactivating hypersensitivity reactions. The continuous PEGasp schedule did not increase toxicity and did not affect the efficacy of the therapy.</p
Human CD1c+ DCs are critical cellular mediators of immune responses induced by immunogenic cell death
Chemotherapeutics, including the platinum compounds oxaliplatin (OXP) and cisplatin (CDDP), are standard care of treatment for cancer. Although chemotherapy has long been considered immunosuppressive, evidence now suggests that certain cytotoxic agents can efficiently stimulate antitumor responses, through the induction of a form of apoptosis, called immunogenic cell death (ICD). ICD is characterized by exposure of calreticulin and heat shock proteins (HSPs), secretion of ATP and release of high-mobility group box 1 (HMGB1). Proper activation of the immune system relies on the integration of these signals by dendritic cells (DCs). Studies on the crucial role of DCs, in the context of ICD, have been performed using mouse models or human in vitro-generated monocyte-derived DCs (moDCs), which do not fully recapitulate the in vivo situation. Here, we explore the effect of platinum-induced ICD on phenotype and function of human blood circulating DCs. Tumor cells were treated with OXP or CDDP and induction of ICD was investigated. We show that both platinum drugs triggered translocation of calreticulin and HSP70, as well as the release of ATP and HMGB1. Platinum treatment increased phagocytosis of tumor fragments by human blood DCs and enhanced phenotypic maturation of blood myeloid and plasmacytoid DCs. Moreover, upon interaction with platinum-treated tumor cells, CD1c+ DCs efficiently stimulated allogeneic proliferation of T lymphocytes. Together, our observations indicate that platinum-treated tumor cells may exert an active stimulatory effect on human blood DCs. In particular, these data suggest that CD1c+ DCs are critical mediators of immune responses induced by ICD
Improved Outcome for ALL by Prolonging Therapy for IKZF1 Deletion and Decreasing Therapy for Other Risk Groups
PURPOSE: The ALL10 protocol improved outcomes for children with ALL by stratifying and adapting therapy into three minimal residual disease-defined risk groups: standard risk, medium risk (MR), and high risk. IKZF1-deleted (IKZF1del) ALL in the largest MR group still showed poor outcome, in line with protocols worldwide, accounting for a high number of overall relapses. ALL10 showed high toxicity in Down syndrome (DS) and excellent outcome in ETV6::RUNX1 ALL. Poor prednisone responders (PPRs) were treated as high risk in ALL10. In ALL11, we prolonged therapy for IKZF1del from 2 to 3 years. We reduced therapy for DS by omitting anthracyclines completely, for ETV6::RUNX1 in intensification, and for PPR by treatment as MR. METHODS:Eight hundred nineteen patients with ALL (age, 1-18 years) were enrolled on ALL11 and stratified as in ALL10. Results were compared with those in ALL10. RESULTS: The five-year overall survival (OS), event-free survival (EFS), cumulative risk of relapse (CIR), and death in complete remission on ALL11 were 94.2% (SE, 0.9%), 89.0% (1.2), 8.2% (1.1), and 2.3% (0.6), respectively. Prolonged maintenance for IKZF1del MR improved 5-year CIR by 2.2-fold (10.8% v 23.4%; P = .035) and EFS (87.1% v 72.3%; P = .019). Landmark analysis at 2 years from diagnosis showed a 2.9-fold reduction of CIR (25.6%-8.8%; P = .008) and EFS improvement (74.4%-91.2%; P = .007). Reduced therapy did not abrogate 5-year outcome for ETV6::RUNX1 (EFS, 98.3%; OS, 99.4%), DS (EFS, 87.0%; OS, 87.0%), and PPR (EFS, 81.1%; OS, 94.9%). CONCLUSION: Children with IKZF1del ALL seem to benefit from prolonged maintenance therapy. Chemotherapy was successfully reduced for patients with ETV6::RUNX1, DS, and PPR ALL. It has to be noted that these results were obtained in a nonrandomized study using a historical control group.</p
Evaluation of the pharmacokinetics of prednisolone in paediatric patients with acute lymphoblastic leukaemia treated according to Dutch Childhood Oncology Group protocols and its relation to treatment response
Glucocorticoids form the backbone of paediatric acute lymphoblastic leukaemia (ALL) treatment. Many studies have been performed on steroid resistance; however, few studies have addressed the relationship between dose, concentration and clinical response. The aim of the present study was to evaluate the pharmacokinetics of prednisolone in the treatment of paediatric ALL and the correlation with clinical parameters. A total of 1028 bound and unbound prednisolone plasma concentrations were available from 124 children (aged 0–18 years) with newly diagnosed ALL enrolled in the Dutch Childhood Oncology Group studies. A population pharmacokinetic model was developed and post hoc area under the curve (AUC) was tested against treatment outcome parameters. The pharmacokinetics of unbound prednisolone in plasma was best described with allometric scaling and saturable binding to proteins. Plasma protein binding decreased with age. The AUC of unbound prednisolone was not associated with any of the disease parameters or treatment outcomes. Unbound prednisolone plasma concentrations correlated with age. No effect of exposure on clinical treatment outcome parameters was observed and does not substantiate individualised dosing. Poor responders, high-risk and relapsed patients showed a trend towards lower exposure compared to good responders. However, the group of poor responders was small and requires further research.</p
- …