Abstract Background The randomised-controlled trial (RCT) provides the best evidence for evaluating treatment effects and is accepted as a gold standard for clinical and regulatory decision making (1;2). One of the major challenges to the conduct of RCTs is the recruitment of adequate numbers of participants. Inadequate numbers reduce the power of a study to detect statistically significant treatment effects, and may cause delays, increased costs and failure to complete trials. The need for clinical trials in children has been increasingly recognised by the scientific community, resulting in increased demands for the inclusion of children in trials. For several reasons, recruiting children to trials is more challenging than recruiting adults, as consent issues are more difficult because parents make decisions about trial participation on behalf of their child. Despite general professional and community support for paediatric clinical trials, parents and paediatricians express reluctance when their own child or patient is asked to participate. Although researchers working with children commonly experience difficulty with recruiting children to RCTs, little is known about this very important subject. The method by which potential participants are approached for trial participation, the influence of their health care provider and the attitude of potential participants (or their parents, in the case of children), are critical to the understanding of the decision making process for trial participation. This thesis is one of the first major attempts to explore the issues surrounding the recruitment of children to RCTs, and is divided into four studies which address these issues. Methods Recruitment strategies used to encourage participation in randomised controlled trials (systematic review) Eligible experimental and observational studies comparing methods of recruiting participants for RCTs were identified after a comprehensive search of Medline, Embase, the Cochrane Library and reference lists. Independent data extractions were completed by two reviewers who assessed the studies for eligibility and methodological quality. Outcome measures were consent rates, proportion enrolled by each method and cost of recruitment per participant. Summary estimators of effects were calculated using a random effects model and expressed as relative risk with 95% confidence intervals. Heterogeneity was analysed using the Q statistic. Paediatricians� attitudes to children�s participation in randomised controlled trials (focus group research) Qualitative analysis of focus group discussions involving 16 paediatricians and 5 trainees from a paediatric teaching hospital in Sydney was undertaken. Doctors varied in occupation, experience, research activity, age, gender, ethnicity and parenthood experience. A professional facilitator conducted the semi-structured group discussions. Recruitment ceased when informational redundancy was reached, after 4 focus groups involving 21 participants. The transcribed audiotapes were analysed by theme linkage using the constant comparative method. Australian paediatricians� and adult physicians� attitudes to randomised controlled trials (survey) A 44-item questionnaire was sent to 250 paediatricians and 250 adult physicians randomly selected from the membership list of the Royal Australasian College of Physicians. Questions assessing doctors� treatment philosophies and attitudes to trials were compared with demographic and practice variables. Parents� attitudes to children�s participation in randomised controlled trials (focus group research) Qualitative analysis of focus group discussions involving 33 parents from 5 different settings (representing parents of children with a life threatening, chronic or acute illness, with experience in trials and of healthy children) was undertaken. Parents varied in age, gender, ethnicity, level of education, research experience and their child�s health status. The transcribed discussions were analysed by theme linkage using the constant comparative method. Results Recruitment strategies used to encourage participation in randomised controlled trials (systematic review) Fifty papers were included (out of 8602 titles and abstracts searched) which described 8 RCTs, 2 quasi RCTs, 13 prospective cohort studies, 30 retrospective cohort studies and 2 before-after studies. These studies assessed how over 4 million people were approached for RCT participation using 87 different recruitment strategies, with 103,406 people enrolling in RCTs. Health care provider (HCP) referrals had the highest participant consent rates at the time of exposure to trial information (HCP referral versus target mailing: relative risk (RR) 1.84 (95% confidence interval (95%CI) 1.08, 3.13)). They also had the highest consent rates when potential participants respond to the recruitment material by further enquiry about the trial (HCP referral versus community presentation: RR 1.37 (1.06; 1.78); HCP referral versus worksite approach: RR 25.20 (20.19, 31.45); HCP referral versus general community approach: RR 2.53 (0.46, 14.05); HCP referral versus mailing: RR 3.29 (1.26, 8.60); HCP referral versus media: RR 2.66 (1.31, 5.41)). However, by the time potential participants attend eligibility assessment for trial participation, no difference in consent rates could be distinguished by method of recruitment. Higher proportions of study participants were recruited by methods that exposed larger numbers of potential candidates to trial information (despite their lower consent rates). The stated recruitment cost ranged from US$0 to $1108 per participant, with mailing being the most cost-effective method and community methods (such as community presentations, pamphlets and posters displayed at community sites) the least effective. Paediatricians� attitudes to children�s participation in randomised controlled trials (focus group research) From the focus group discussions, paediatricians thought parents balanced perceived gains and risks when deciding about trial participation. They also believed the child�s condition and parents� health beliefs and personal attributes influenced parents� decisions. Other factors thought to be important by paediatricians were the doctors� beliefs and their relationship with the investigators. Paediatricians perceived gains for trial participation including professional benefits for themselves, improved patient care, convenience for the families and themselves and scientific advancement. Perceived risks included inconvenience, inadequate resources and potential harms to the patient and the doctor-patient relationship. Paediatricians with previous research experience were most knowledgeable about RCTs and perceived greatest gains from trial participation. Paediatricians� personal treatment preferences hindered trial support. Australian paediatricians� and adult physicians� attitudes to randomised controlled trials (survey) Response rate from the paediatricians� and adult physicians� survey was 60% (300/500). Australian paediatricians and adult physicians are very similar in their treatment philosophies, and are clinician-oriented rather than research-oriented in their attitudes, with primary allegiance to their patients and preference for selecting treatment rather than referring for trial participation in the face of treatment uncertainty. Professional activities are clinically focused, with limited time assigned for research. Australian doctors perceive little reward for trial participation and claim that the opinions of referring doctors regarding RCTs does not influence them. Predictors of favourable attitudes to trial participation from the survey were time allocation for research, a history of referring patients to trials in the past and younger age (all p values less than 0.0001). Parents� attitudes to children�s participation in randomised controlled trials (focus group research) When parents were interviewed, they acknowledged balancing risks and benefits when deciding about trial participation for their child. Perceived benefits include the offer of hope, better care of their child, the opportunity to access new treatments, healthcare professionals and health information, meeting others in similar circumstances and helping others. Perceived risks include potential side effects, being randomised to ineffective treatments and the inconvenience of participation. The decision for trial participation is also influenced by parental factors (parents� knowledge, beliefs and emotional response), child factors (the child�s health status and preference about participation), trial factors (the use of placebos and the uncertainties of research) and doctor factors (doctor�s recommendations and communication of trial information). Conclusions There are many challenges to the successful conduct of RCTs. Ways of addressing these include: using effective methods of recruiting potential study participants (such as mailing of recruitment material to potential participants) and abandoning ineffective strategies (such as community methods): fostering greater willingness for trial participation by addressing parents� and paediatricians� concerns including enhancing communication between researchers, paediatricians and parents, and improving the gains-hazard balance (by increasing incentives while decreasing inconveniences); and reforming in the health care system to raise the priority placed on clinical research by restructuring clinical research in a clinically predominant workplace and with a clinically predominant workforce. The findings from this study have implications for researchers planning RCTs for children in the future. Careful consideration of the above will enhance RCTs participation for children improving efficiency, lowering costs and ultimately improving the future health care of children.

<p>Bakgrunden till detta arbete var att vår hälsouppfattning påverkas av en mängd faktorer. Inom familjer var detta något som starkt relaterades till övriga familjemedlemmars välmående och välbefinnande. Inom den pediatriska vården beskrevs samarbete mellan patienter, föräldrar och vårdpersonal som en viktig faktor. Denna familjecentrerade vård kunde, beroende på hur den fungerade, påverka samtliga parters uppfattningar och upplevelser på positiva och negativa sätt. Denna litteraturstudies uppgift var att undersöka hur den pediatriska vården på sjukhus fungerade i praktiken med syftet <strong>att belysa patienters, föräldrars och vårdares uppfattningar och upplevelser av pediatrisk omvårdnad. Studien bedrevs genom artikelsökning i sökmotorer</strong>. Funna artiklar valdes ut i tre steg. Först genom en snabb genomblick för relevans, sedan genom en noggrannare genomläsning där inklusions- och exklusionskriterier användes för artikelurval. I det sista steget genomgick artiklarna en djupare granskning för kvalitetsbedömning. Resultatet pekade främst på brister i kommunikation och samarbete mellan föräldrar och vårdare samt på barnens upplevelser kring sitt sjukdomstillstånd och deras sjukhusvistelse. Andra uppdagade faktorer var bland annat hur föräldrar uppfattade sitt vakande över barnet och personalens syn på föräldrar i den pediatriska omvårdnaden. I diskussionen framhävdes att arbeta med en helhetssyn på familjen där det är viktigt att lyssna på varje enskild familjs behov.</p>

<p>Barns sätt att uttrycka sig varierar mycket från vuxnas beteende och dessa faktorer tillsammans gör det svårt att vårda barn med smärta. I prehospital vård möts man av barn med smärta och situationen kan göra det svårt att smärtbedöma barnet. Vid behandling av smärta är smärtskattningsinstrument ett redskap för att få ett konkret värde på smärtans intensitet. Det finns olika instrument anpassade för olika åldrar. Syftet var att beskriva olika metoder för smärtbedömning av barn vilket gjordes genom en systematisk litteraturstudie. Sökningar efter artiklar genomfördes i databaser. Artiklarna kvalitetsgranskades utifrån granskningsmallar och 19 artiklar inkluderades. Artiklarnas resultat sammanfattades och smärtskattnings-</p><p>instrumenten delades in i tre grupper: fysiologiska-, beteendeskalor/fysiologiska-beteendeskalor samt observationsskalor och självskattningsskalor. Det visade sig att det finns många olika skalor och bedömningsformulär för självskattning och bedömning av vårdare för barns smärta i olika åldrar. En del metoder lämpar sig bättre i en ålderskategori och typ av smärta medan andra passar sig för en annan smärttyp och åldersgrupp. Vår slutsats blev att FLACC, CHEOPS och MBPS skulle vara lämpliga för smärtskattning av barn i ambulans. Vidare anser vi att forskning kring smärtskalor på barn i prehospitala vård är angeläget att göra då många av de skalor som analyserats är provade mest på inneliggande barn med smärta. Det är få skalor som är testade på akut sjuka eller skadade barn just i den prehospitala vården.</p>

Bakgrunden till detta arbete var att vår hälsouppfattning påverkas av en mängd faktorer. Inom familjer var detta något som starkt relaterades till övriga familjemedlemmars välmående och välbefinnande. Inom den pediatriska vården beskrevs samarbete mellan patienter, föräldrar och vårdpersonal som en viktig faktor. Denna familjecentrerade vård kunde, beroende på hur den fungerade, påverka samtliga parters uppfattningar och upplevelser på positiva och negativa sätt. Denna litteraturstudies uppgift var att undersöka hur den pediatriska vården på sjukhus fungerade i praktiken med syftet att belysa patienters, föräldrars och vårdares uppfattningar och upplevelser av pediatrisk omvårdnad. Studien bedrevs genom artikelsökning i sökmotorer. Funna artiklar valdes ut i tre steg. Först genom en snabb genomblick för relevans, sedan genom en noggrannare genomläsning där inklusions- och exklusionskriterier användes för artikelurval. I det sista steget genomgick artiklarna en djupare granskning för kvalitetsbedömning. Resultatet pekade främst på brister i kommunikation och samarbete mellan föräldrar och vårdare samt på barnens upplevelser kring sitt sjukdomstillstånd och deras sjukhusvistelse. Andra uppdagade faktorer var bland annat hur föräldrar uppfattade sitt vakande över barnet och personalens syn på föräldrar i den pediatriska omvårdnaden. I diskussionen framhävdes att arbeta med en helhetssyn på familjen där det är viktigt att lyssna på varje enskild familjs behov.

Barns sätt att uttrycka sig varierar mycket från vuxnas beteende och dessa faktorer tillsammans gör det svårt att vårda barn med smärta. I prehospital vård möts man av barn med smärta och situationen kan göra det svårt att smärtbedöma barnet. Vid behandling av smärta är smärtskattningsinstrument ett redskap för att få ett konkret värde på smärtans intensitet. Det finns olika instrument anpassade för olika åldrar. Syftet var att beskriva olika metoder för smärtbedömning av barn vilket gjordes genom en systematisk litteraturstudie. Sökningar efter artiklar genomfördes i databaser. Artiklarna kvalitetsgranskades utifrån granskningsmallar och 19 artiklar inkluderades. Artiklarnas resultat sammanfattades och smärtskattnings- instrumenten delades in i tre grupper: fysiologiska-, beteendeskalor/fysiologiska-beteendeskalor samt observationsskalor och självskattningsskalor. Det visade sig att det finns många olika skalor och bedömningsformulär för självskattning och bedömning av vårdare för barns smärta i olika åldrar. En del metoder lämpar sig bättre i en ålderskategori och typ av smärta medan andra passar sig för en annan smärttyp och åldersgrupp. Vår slutsats blev att FLACC, CHEOPS och MBPS skulle vara lämpliga för smärtskattning av barn i ambulans. Vidare anser vi att forskning kring smärtskalor på barn i prehospitala vård är angeläget att göra då många av de skalor som analyserats är provade mest på inneliggande barn med smärta. Det är få skalor som är testade på akut sjuka eller skadade barn just i den prehospitala vården.

This study investigated the experiences of paediatric care nurses in a public, resource-poor hospital in Durban, KwaZulu-Natal to. A mixed methods design was used . The quantitative aspect focused on how contextual factors influenced nurses’ perceptions of the hospital ward where they worked. The Moos Ward Atmosphere Scale was used to assess ward environment. The Maslach Burnout Inventory Scale was used to explore the role of various aspects of vicarious job burnout. The study took place in four phases, baseline, pre-intervention, intervention and post-intervention. Quantitative analysis was done to explore possible relationships in burnout and ward atmosphere. A repeated (paired) measures t-test design was used to compare the pre- and post-intervention data, to test if the intervention process had any effect on the ward atmosphere and nurse burnout. As this was a small data set, quantitative analysis was done as an exploration for future research. The qualitative aspect explored how the intervention was utilized; how nurses talked about their issues in the support group and what issues they reported. Thematic analysis was used as the focus of this research was describe the experiences of nursing in a resource-poor setting, with the expectation that this could raise complex and new challenges faced in the context of HIV and AIDS. Although nurses in this study reported many challenges resulting from health sector problems, such as the shortage of staff and resources, they did not achieve high scores on the Maslach Burnout Inventory. The possible reasons for this are explored. The study also revealed that newly employed nurses expressed having more miscommunication problems with caregivers and other staff members. Other themes identified included, lack of HIV and AIDS disclosure, stressors related to the current South African context and trauma as a result of the death of patients and colleagues. / Thesis (M.Soc.Sci.)-University of KwaZulu-Natal, Pietermaritzburg, 2009.

No abstract available. / Thesis (Ph.D.)-University of Natal, Durban, 1989.

Functional magnetic resonance imaging (fMRI) enables non-invasive investigation of the neural functions with excellent spatial resolution. Although fMRI has primarily been developed in young adult populations, its use is becoming widespread in paediatrics. However, there are many differences, both behavioural and physical, between adults and children requiring adjustments to imaging and analysis methodology to optimise the results in children. This thesis examines fMRI analysis methodology to improve the detection of developmental changes in the brain. The work uses an emotional and familiar face paradigm that elicits strong BOLD fMRI responses in the fusiform, a region that is still developing across childhood. This face paradigm also enables the comparison of the fusiform responses to the primary visual cortex to link to extensive results in the literature. Thirty five 4-8 year old children and fourteen adults (18-30 years old) were scanned. To address the concern of anatomical size differences between the brains of adults and children, the anatomical variability of the fusiform was measured and the validity of stereotaxic transformation into an adult template was confirmed for the children. To investigate the effect of threshold settings between the adults and children, individual subject analyses of the peak activation location, estimated signal percent change and noise values were calculated using the general linear model (GLM). Similar functional peak locations between individuals were quantitatively selected using a novel application of the activation likelihood estimation (ALE). Also, several different preprocessing steps were evaluated for their ability to correct for the increased motion frequently seen in children, in a quantitative framework (NPAIRS) using canonical variates analysis (CVA), a data driven multivariate model as well as the standard univariate GLM. Functional differences between the adults and the children were identified in the fusiform by applying these optimised procedures. The results of this thesis demonstrate that thresholding and preprocessing pipelines must be made in a group-specific fashion. These methods can also be extended to elderly populations, enabling the investigation of the complete ageing spectrum with fMRI.

Functional magnetic resonance imaging (fMRI) enables non-invasive investigation of the neural functions with excellent spatial resolution. Although fMRI has primarily been developed in young adult populations, its use is becoming widespread in paediatrics. However, there are many differences, both behavioural and physical, between adults and children requiring adjustments to imaging and analysis methodology to optimise the results in children. This thesis examines fMRI analysis methodology to improve the detection of developmental changes in the brain. The work uses an emotional and familiar face paradigm that elicits strong BOLD fMRI responses in the fusiform, a region that is still developing across childhood. This face paradigm also enables the comparison of the fusiform responses to the primary visual cortex to link to extensive results in the literature. Thirty five 4-8 year old children and fourteen adults (18-30 years old) were scanned. To address the concern of anatomical size differences between the brains of adults and children, the anatomical variability of the fusiform was measured and the validity of stereotaxic transformation into an adult template was confirmed for the children. To investigate the effect of threshold settings between the adults and children, individual subject analyses of the peak activation location, estimated signal percent change and noise values were calculated using the general linear model (GLM). Similar functional peak locations between individuals were quantitatively selected using a novel application of the activation likelihood estimation (ALE). Also, several different preprocessing steps were evaluated for their ability to correct for the increased motion frequently seen in children, in a quantitative framework (NPAIRS) using canonical variates analysis (CVA), a data driven multivariate model as well as the standard univariate GLM. Functional differences between the adults and the children were identified in the fusiform by applying these optimised procedures. The results of this thesis demonstrate that thresholding and preprocessing pipelines must be made in a group-specific fashion. These methods can also be extended to elderly populations, enabling the investigation of the complete ageing spectrum with fMRI.

Background Human T cell Lymphotropic Virus Type I (HTLV-I) associated infective dermatitis, first described by Sweet in Jamaican children, is a pattern of eczema characterized by exudation, crusting around the nostrils, ears and scalp with eventual appearance of a generalized fine papular rash. More recently LeGranade and co-workers have proposed major and minor criteria in establishing the diagnosis of HTLV-I associated infective dermatitis (HAID). HTLV-I has been aetiologically linked to Adult T cell leukaemia/lymphoma (ATLL) and tropical spastic paraparesis (TSP). HAID is not only a marker of childhood infection with HTLV-I but may be a harbinger of more serious HTLV-I associated diseases later on in life such as ATLL or TSP. The pathogenesis of HAID is poorly understood so are the histopathological features of this entity. The effects of co-infection with human immunodeficiency virus- 1 (HIV-1) are inconclusive. HAID is described in Sub Saharan Africa, Senegal but no data is published on this entity in Southern Africa, characterizing the clinical, laboratory features and the histopathology of this entity. Aims and Objectives 1) To describe the clinical and histological features of HTLV-I associated infective dermatitis in KZN, South Africa 2) To determine the virological characteristics of HTLV-I in KZN, South Africa 3) To assess for HTLV-I / HIV co-infection Methods This was a prospective study of all patients with HAID who presented to King Edward VIII hospital (KEH), outpatient department over a period of 42 months. These were patients who fulfilled the clinical criteria of HAID. Enrolled patients were subjected to a confirmatory HTLV-I serology testing. Demographic data was obtained from all HTLV-I seropositive patients. Their clinical examination included dermatological, neurological and pathological examination. A blood count, immunoglobulin levels, serum protein electrophoresis measuring albumin levels and globulin fractions were measured. For bacteriological assessment skin swabs were taken from the affected sites with stool samples examined for parasites, ova and cysts. The HIV-1 status together with HIV-1 viral load were determined on those enrolled. The CD4 count, CD8 counts and CD4/CD8 ratio were also calculated. Skin biopsies were taken for histological examination. PCR for HTLV subtyping was performed on a subset of the cohort. Results Demography Of the 60 patients recruited, 33 fulfilled criteria for HAID. The majority of patients fell between age categories of 6 to lOyears. The male to female ratio was 1:1. There were more females in the adult group than there were within the childhood group. All of the patients in our cohort were African. Clinical features The lesions were erythematous, scaly, exudative, and crusted in all cases. The distribution of lesions was as follows: scalp (77.4%), retroauricular areas (71%), the axilla (65%) and paranasal areas (58%) were the sites more commonly affected. Nasal crusting was not a significant feature in this series. Bacteriology Culture was positive for Staphylococcus aureus (S. aureus) in 90%, with streptococcal group of organisms found in 68% of the skin swabs taken from the lesional skin. Haematological Our patients were mildly anaemic as has been shown in previous studies. They had a mean Hb of 11.5g/dl. In 12 of the 14 patients tested, the erythrocyte sedimentation rate (ESR) was elevated. Serum protein electrophoresis and levels of Immunoglobulin A, G and M were raised. The mean CD4 count in the entire group was elevated at 1730 cells/fil, CD8 was 1299 cells/ul Histopathology The major histological findings were as follows: 38% demonstrated a superficial and deep perivascular inflammatory infiltrate, 28% had a superficial and deep perivascular inflammatory infiltrate together with a lichenoid dermatitis, 12.9% had features of superficial and deep inflammatory infiltrate with an interface dermatitis, 6.4% revealed features of seborrhoeic dermatitis. Genotyping Our patients were infected with the strains belonging to the Cosmopolitan, A Subtype (HTLV-Ia). Complications Complications were low in this series with the commonest being scabies in 6(18.1%), corneal opacities in 3(8.6%), 2(6 %) with HAM/TSP. No parasitic worm infestations were isolated. HIV/HTLV-I co-infection Of the 33 patients, 9 (30 %) were co-infected with HIV. The mean viral load in this group was 52 000 copies/ml. Their mean CD4 count was also elevated at 1505cells/^il with a CD8 of 1704 cells/Mi and a CD4/CD8 ratio of 1.15. Discussion Thirty three of the 60 patients enrolled met the diagnosis for HAID according to the established criteria. The mean age in this series was 17 years (range: 8 months-46 years)however; almost a third (30.3%) were children under 12 years, reinforcing the entity as a childhood infective condition. There was an equal male female distribution in the childhood group and a female predominance in the adult group. Clinically patients presented with infected erythematous, scaly lesions mainly on the scalp, neck and post- auricular area. The clinical features were in keeping with other series worldwide. The complication rate was low in our cohort. S. aureus was the predominant organism in both anterior nares and lesional skin. The most common histological pattern was superficial and deep perivascular inflammatory infiltrate. The subtype in our series was the Cosmopolitan Subtype A (HTLV-Ia) as opposed to subtype B in Japan. We share with Brazil a common subtype. A subset of our patients (30%) was co-infected with HIV. The CD4 cell count in this subgroup was lower than the entire group but this was not statistically significant. The histological patterns found in this subgroup infected with HIV were similar to the rest of the group except for a more intense eosinophilic infiltrate in these skin biopsy specimens. Conclusion HTLV-I associated infective dermatitis is distinct entity which affects the African population of KwaZulu Natal, South Africa. It is predominantly a disease of childhood with an equal female to male ratio in children. The clinical features are an exudative, erythematous scaly rash most commonly found involving the scalp, axillae, paranasal and retroauricular areas. HTLV-I positivity is essential for the diagnosis; the Cosmopolitan Subtype A is commonest in South Africa. The commonest histological pattern is a superficial and deep perivascular infiltrate in 38%. A subset, 30%, was co-infected with HIV. / Thesis (M.Med.)-University of KwaZulu-Natal, Durban, 2008.