A research report submitted to the Faculty of Health Sciences, University of the Witwatersrand, Johannesburg in partial fulfilment of the requirements for the degree of Master of Science in Nursing Johannesburg, 2015 / Background: Despite the empirical evidence of the significance of weaning protocols in Intensive Care Units, variations still exist in the adoption of weaning protocols. Multidisciplinary teams hold the responsibility for the introduction and development of weaning protocols in PICU. Purpose: To explore and describe the opinions of multidisciplinary teams practicing in the paediatric and cardiothoracic ICU at an academic hospital in Johannesburg concerning weaning protocols from mechanical ventilation. Design: Qualitative descriptive. Method: Data was collected from multidisciplinary team comprising of registered nurses (n=8) and doctors (n=2) practicing in PICU and CTICU who were purposively selected using semi-structured interviews to obtain qualitative information on their opinions regarding weaning protocols. Data collected was analysed using a Braun and Clarke method of qualitative thematic analysis. Seven categories were identified in which three themes, which provided the fundamental structure of the findings for the discussion, emerged and included the following:  Unstructured weaning – the current practice.  Recognition of the need for weaning protocols.  Being not in favour of weaning. Results: The majority of the multidisciplinary team members recognise the need to develop weaning protocols in PICU for standardisation of practice. Currently there are no weaning protocols and a multidisciplinary approach was identified as an important strategy to develop the protocols. However, nurses practicing in PICU are not trained in Critical Care nursing which poses a challenge to the practice. Conclusion This study indicates that there is need for the development of weaning protocols in PICU. Although nurses are weaning patients in PICU, there are no standardised weaning protocols to guide the practice. The study therefore suggests the need to develop weaning protocols through multidisciplinary approach and training of nurses in critical care nursing to improve knowledge base and skills. Keywords: Mechanical ventilation, weaning, protocols, paediatric patients, opinions/perception and multidisciplinary team.

Evidenced based practice (EBP) guidelines have been developed to reduce variation in weaning, provide quality of care and patient satisfaction. Nurse led weaning has been shown to reduce weaning time, and therefore it was important to identify whether nurses have sufficient knowledge to implement EBP regarding weaning (Hansen, Fjaelberg, Nilsen et al, 2008);(Crocker, 2002:272). Weaning protocols are associated with 25.0% reduction in the duration of mechanical ventilation time, a 78.0% reduction in weaning duration, and 10.0% reduction for length of stay in ICU (Blackwood, Alderdice, Burns et al, 2011:9). The purpose of the study was to evaluate and describe intensive care nurses’ knowledge of EBP guidelines with regard to weaning the mechanically ventilated patient. Five adult intensive care units at two tertiary public sector academic hospitals were used to conduct the study in order to determine barriers to EBP. A non-experimental, descriptive, prospective two-staged design was utilized in this two part study. In Stage I of the study, the sample size comprised six (n=6) specialist expert members selected from the ICU’s at the study site using a non-probability purposive sampling method. In Stage II of the study, the sample size comprised eighty (n=80) intensive care nurse respondents selected from the ICU’s using simple random sampling. The data collection instrument developed by the researcher comprised 40 items relevant to nursing practice derived from EBP weaning guidelines. Respondents were asked to rate all the items independently using a 4-point Likert scale. Findings indicated that intensive care nurses lack adequate knowledge on weaning the critically ill patient from the mechanical ventilator. The Dreyfuss model of skill acquisition shows that improved skill performance in nursing is based on experience as well as education, yet this study showed the opposite (Dracup & Bryan-Brown, 2004). Years of experience did not influence nurses’ knowledge level, as there was no statistical difference in these items. Differences in knowledge scores between the primary nurse and shift leaders were minimal, although significant (p<0.05), indicating that shift leaders were more knowledgeable than primary nurses.

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Bacteria, while traditionally studied in liquid suspensions, are often found in nature as biofilms, aggregates of cells enclosed in self-produced matrices. Cells in biofilms have a fitness advantage over those that are free-living, as the biofilm lifestyle is correlated with increased resistance to various assaults, including antimicrobials, UV exposure, and dehydration. These biofilm-associated characteristics have important clinical implications, as biofilm-based bacterial infections are a major cause of morbidity in immunocompromised individuals. With this increased resiliency, however, comes a major challenge that arises during biofilm growth: the formation of resource gradients. My thesis work focused on one particular gradient, that of oxygen, which is established in biofilms formed by Pseudomonas aeruginosa. This bacterium has multiple mechanisms for coping with limited access to oxygen, including a highly-branched respiratory system for optimal oxygen scavenging and production and utilization of redox-active molecules called phenazines. The purpose of this thesis has been to investigate the different strategies used by P. aeruginosa to deal with the oxygen limitation precipitated by the biofilm lifestyle. In Chapter 1, I will provide the necessary background for understanding the principles of redox balancing, metabolism, respiration, biofilm physiology, and phenazine utilization in P. aeruginosa. The work described in Chapter 2 provides evidence for the formation of a novel terminal oxidase complex that plays a biofilm-specific role in P. aeruginosa growth. The results in this chapter also suggest that specific terminal oxidase complexes differ in the timing of their contributions to biofilm growth and implicate the novel complex in mediating reduction of phenazines in biofilms. Chapter 3 expands upon the principle of metabolic versatility exemplified by the results discussed in Chapter 2. The research presented in this chapter looks at how varying the source of electrons that feed into the respiratory chain influences downstream electron transfer steps, including terminal oxidase activities and phenazine production and utilization. The data presented in Chapters 2 and 3 add to the growing body of evidence that bacterial growth in liquid culture is distinct from that in biofilms and underscores the need for more biofilm-based research that can inform treatment strategies for P. aeruginosa infections. The results described in Chapter 4 take an even broader look at the strategies used by P. aeruginosa to sustain efficient metabolism under conditions of potential stress. An important node of central metabolism is pyruvate, which can be transformed in a number of ways. In this chapter, I will consider two pathways of pyruvate metabolism: fermentation to lactate and carboxylation to oxaloacetate. I will present data indicating that a previously-uncharacterized lactate dehydrogenase contributes to P. aeruginosa growth under specific growth conditions and that pyruvate carboxylation contributes to optimal progress through central metabolic pathways. I will also describe experiments that characterize the contributions of another carboxylase, previously thought to function as the pyruvate carboxylase, to P. aeruginosa’s ability to grow on selected nutrient sources. Finally, I will discuss how redox state informs biofilm formation in a phylogenetically distinct bacterium, Bacillus subtilis, highlighting the universality of redox reactions in driving metabolic processes. In sum, the research presented in this thesis broadens our understanding of the immense respiratory and metabolic flexibility of P. aeruginosa and serves as an important reminder of the discrete factors that govern liquid culture and biofilm growth.

Objetivo: Determinar os valores normativos da área de secção transversa mínima nasofaríngea de indivíduos sem anomalias craniofaciais e em diferentes faixas etárias. Método: Participaram do estudo 96 indivíduos sem anomalias craniofaciais, de ambos os sexos, subdivididos em 4 grupos etários: crianças com idade entre 6 e 10 anos (G1), adolescentes de 11 a 17 anos (G2), adultos jovens entre 18 e 39 anos (G3) e adultos de meia-idade entre 40 e 59 anos (G4). Verificou-se o índice de massa corpórea (IMC), a partir das medidas de peso e altura, e a circunferência cervical (CC), por meio de fita métrica pediátrica. A área de secção transversa mínima nasofaríngea (área nasofaríngea ANF) foi determinada por meio de rinomanometria anterior modificada (técnica fluxo-pressão), utilizando o sistema PERCI-SARS (versão 3.50 Microtronics Corp.). A significância da diferença entre as médias dos quatro grupos etários foi verificada por meio do teste Kruskal-Wallis, para amostras não pareadas. A correlação entre ANF e IMC, e ANF e CC, em cada grupo estudado, foi verificada por meio do coeficiente de correlação de Spearman. Foram aceitos como significantes os valores de p<0,05. Resultados: Todos os indivíduos apresentaram IMC indicativo de peso normal, exceto um único adulto jovem que apresentou índice de sobrepeso. A CC média de mulheres e homens adultos (G3 e G4) apresentou-se dentro da normalidade, sugerindo ausência de risco para obesidade. Os valores médios±DP da ANF foram de 1,025±0,054cm2, 1,055±0,081cm2, 1,050±0,083cm2 e 1,054±0,081cm2, respectivamente, para G1, G2, G3 e G4, não havendo diferença entre as 4 faixas etárias. Não houve correlação entre a ANF e o IMC e a ANF e a CC, em nenhum dos grupos estudados. Conclusão: Os valores normativos de ANF foram determinados para indivíduos sem anomalias craniofaciais de diferentes faixas etarias e servirão como referência em estudos envolvendo obstrução nasofaríngea. / Objective: To establish normative values of minimum cross-sectional nasopharyngeal area in individuals without craniofacial anomalies at different age ranges. Method: Ninety-six individuals of both genders, without craniofacial anomalies were evaluated. Participants were divided into 4 age groups: children, aged 6 to 10 years (G1); adolescents, aged 11 to 17 years (G2); young adults, 18 to 39 years (G3) and middle-aged adults, 40 to 59 years (G4). The body mass index (BMI) was calculated based on weight and height, and neck circumference (NC) was measured with a pediatric measuring tape. Minimum cross-sectional nasopharyngeal area (nasopharyngeal area NPA) was assessed by means of modified anterior rhinomanometry (pressure-flow technique) using a PERCI-SARS system (version 3.50 Microtronics Corp.). The difference between the mean values of the 4 age groups were verified by the Kruskal-Wallis test, for unpaired samples. Correlations between NPA and BMI, and NPA and NC were verified for each group by the Spearmans correlation coefficient. Differences were analyzed at a significance level of 5%. Results: All individuals presented normal BMI, except one young adult, which presented BMI suggestive of overweight. Mean NC values from adult women and men (G3 and G4) were within the normal range, suggesting no risk for obesity. Mean±SD values of NPA were 1.025±0.054cm2, 1.055±0.081cm2, 1.050±0.083cm2 and 1.054±0.081cm2 respectively, for groups G1, G2, G3 and G4, showing that there were no differences between the four age ranges. There was no correlation between NPA and BMI, and NPA and NC, in none of the studied groups. Conclusion: Normative data of NPA were established for individuals without craniofacial anomalies from different age ranges and may be used as reference values for future studies concerning nasopharyngeal obstruction.

Mechanical ventilation (MV) is the defining event of intensive care unit (ICU) management. Although it is a lifesaving intervention in patients with acute respiratory failure and other diseases, a major goal of critical care clinicians should be to liberate patients from MV as early as possible to avoid the multitude of complications and risks associated with prolonged MV. Such complications include an increase in mortality, morbidity and ICU length of stay (LOS), as well as reduced functional status and quality of life (Moodie et al 2011; Gosselink et al 2008). Rapid weaning however has its own potential problems such as fatigue or cardiovascular instability, either of which may ultimately delay the weaning process. Premature extubation, leading to reintubation, is associated with increased risk of pneumonia and mortality (Brown et al 2011; Meade et al 2001 (a)). In view of this, there has been increasing interest in delivering more consistent practice in ICUs by developing weaning protocols that provide structured guidelines to achieve prompt and successful weaning. Many studies have shown the benefit of allied health care worker (nurses and physiotherapists) driven weaning protocols in decreasing MV days and costs (MacIntyre 2005; Dries et al 2004; Ely et al 2001). Objectives: The objectives of this study were to determine a) if the number of patients in the ICU has an influence on physiotherapists’ involvement in the weaning of patients from MV, b) if the type of ICU has an influence on physiotherapists’ involvement in the weaning of patients from MV, c) if physiotherapists are involved in the development and implementation of weaning protocols for mechanically ventilated patients in their ICUs, d) if physiotherapists are involved in titration of ventilator settings for patients during the weaning process, e) what modalities physiotherapists in South Africa use to facilitate respiratory muscle strengthening to assist weaning of patients on MV, f) if physiotherapists in South Africa are involved in the extubation of ventilated patients, g) if there is a difference in involvement in weaning of mechanically ventilated patients between newly qualified physiotherapists and experienced physiotherapists. The last objective of this study was to determine if current physiotherapy involvement in the weaning of patients from MV in South Africa is in line with international physiotherapy practice according to the literature. Method: A questionnaire was developed by the researcher using available literature on the nature of involvement of physiotherapists in the weaning of mechanically ventilated patients. Content validation of the questionnaire was achieved after a panel of senior cardiopulmonary physiotherapists analysed each question and their recommendations and adjustments were implemented. Physiotherapists who practice cardiopulmonary physiotherapy in adult ICUs of hospitals in the public and private sectors in South Africa were sought and targeted for the study. The self-administered questionnaire was then posted or emailed to the physiotherapists identified for inclusion into the study. Results: A total of 425 questionnaires were distributed to physiotherapists who practice cardiopulmonary physiotherapy in adult ICUs of hospitals in South Africa. Of the 425 questionnaires distributed, 200 questionnaires were sent via the postal system and 225 were sent via email with a link to an online survey. The response rate for the postal questionnaires was 54.5% (n=109) and 33.3% (n=75) for the emailed questionnaire, giving a combined response rate of 43.3%. The results showed that 76% of South African physiotherapists are not or are seldom involved in the weaning of mechanically ventilated patients in adult ICUs. They are not involved in the development of weaning protocols (74%, n=51), titration and adjustment of MV settings (>80%, n=154), spontaneous breathing trails (67%, n=119) and non-invasive ventilation (58%, n=101). Physiotherapists working in South Africa are somewhat involved in extubation (16%, n=28). The most common physiotherapy modalities used in ICU to facilitate respiratory muscle strengthening are exercises (81%, n= 138), early mobilisation out of bed and deep breathing exercises. (77%, n=134). Physiotherapists’ involvement in the weaning of mechanically ventilated patients are not influenced by the type of ICU they work in (p>0.05), type of physiotherapy degree they have (p=0.24) or whether they are newly qualified physiotherapists or experienced physiotherapists (p=0.43). Conclusion: This survey shows that most physiotherapists who work in adult ICUs in South Africa are not involved in the weaning of mechanically ventilated patients. The survey does show that there is a need for physiotherapists to reconsider their role in ICU with regards to weaning patients from MV as current practice is not in keeping with the international practice of respiratory therapists in the United States of America (USA) and physiotherapists in the United Kingdom (UK), Australia and Europe.

Biological functions take place within tightly controlled parameters, including pH, which is managed in part through the ventilatory chemoreflex. This reflex is mediated by central respiratory chemoreceptors (CRCs) specialized to detect blood pH/CO2. Two neuronal populations are thought to mediate this response: the serotonergic (5-HT) neurons of the medullary raphé, and the Phox2b expressing neurons of the retrotrapezoid nucleus (RTN). These groups are both responsive to CO2 stimuli in vivo and in vitro. There are also apparent one-way connections from the raphé to the RTN, which is sensitive to 5-HT. Due to its complex innervation, study of RTN neurons while isolated from other cells, especially 5-HT neurons, has been limited. Here, we developed a culture model that simplifies this circuit, limiting cell types to those found in the rostral ventral medulla. This protocol yielded healthy RTN and 5-HT neurons in vitro, as well as other cell types from that area. Upon study with patch-clamp electrophysiology, cultured RTN neurons responded to CO2 and 5-HT in similar ways to what is reported for different RTN neuron preparations. Using this model, RTN neuron chemosensitivity was significantly decreased during application of 5-HT7 antagonists (SB258719, SB269970) and a 5-HT2A antagonist (MDL 11,939). The effect of 5-HT7 antagonists was recapitulated in slice recordings. Therefore, signaling at 5-HT7 and 5-HT2A receptors is necessary for RTN neuron chemosensitivity. Exogenous 5-HT application also increased RTN neuron firing rate without potentiating the response to CO2, most likely indicating that the necessary 5-HT stimulation must come from neurons that can alter their activity during acidosis. We conclude that RTN neuron chemosensitivity is largely driven by chemosensitive 5-HT neurons, and should be considered an integrative or relay center, rather than an independently chemosensitive one.

No description available.

Introduction: The enzyme, inducible nitric oxide synthase (iNOS), is upregulated in the airway epithelium in patients with allergic asthma resulting increased nitric oxide production. The concentration of nitric oxide in exhaled air (FENO) correlates with the degree of eosinophilic airway inflammation and has been proposed as a new breath test to assist in the management of asthma. Key Aims: To determine the predictive accuracy of FENO compared with conventional testing in the diagnosis of asthma. To assess the performance characteristics of FENO to predict steroid responsiveness compared with the conventional approach in patients presenting with non-specific respiratory symptoms. To assess the role of FENO compared with conventional guidelines-based approach as a guide to adjusting inhaled corticosteroid therapy in patients with chronic persistent asthma. Methods: Consecutive patients referred with chronic undiagnosed respiratory symptoms were enrolled. Comparisons were made between FENO, induced sputum analysis and other conventional tests (including peak flow variation, spirometry, response to oral steroid challenge) for predicting the presence of asthma in the first study, and for predicting response to four weeks inhaled fluticasone treatment in the second study. In the third study, 110 subjects with chronic persistent asthma were enrolled into a single-blind placebo-controlled study during which subjects were randomly allocated to have their corticosteroid (fluticasone) dose adjusted on the basis of either FENO measurements or an algorithm based on conventional guidelines. The main outcomes were the frequency of asthma exacerbations and the mean daily dose of inhaled corticosteroid. Results: In the first study, 17 of 47 consecutive patients were diagnosed with asthma. Sensitivities for the conventional tests (0-47%) were lower than for FENO (88%) and sputum eosinophils (86%), with overall significantly greater diagnostic accuracy for FENO and sputum eosinophils. Fifty-two consecutive subjects completed the second study. When compared to the conventional tests, the predictive powers for FENO were consistently greater than for almost all other baseline measurements used to predict steroid responsiveness, with an optimum cut point of 47 ppb. In the third study, the exacerbation rates were 0.49 (95% C.I. 0.20, 0.78) per patient per year in the FENO group and 0.90 (95% C.I. 0.31, 1.49) in the control group, representing a nonsignificant reduction of 45.6 percent (95% C.I. -78.5, 54.5%) in the FENO group. The final mean daily doses of fluticasone were significantly lower in for the FENO group compared with the conventional group (370 [mu]g/day (95% C.I. 263, 477) vs 641 [mu]g/day (95% C.I. 526, 756) respectively; p=0.003). There were no significant differences in other markers of asthma control, use of oral prednisone, pulmonary function, or levels of airway inflammation (sputum eosinophils). Conclusions: FENO is comparable to induced sputum analysis and superior to the conventional methods currently used including peak flows and spirometry as a dignositic for asthma and as a predictor of steroid responsiveness in patients with chronic respiratory symptoms. FENO measurements as a guide to adjusting inhaled corticosteroid therapy compared to the conventional guidelines based approach results in significantly lower maintenance doses being achieved without compromising asthma control. The results of this thesis provide evidence to support the use of FENO measurements in routine clinical practice as a tool to improve the overall management and diagnosis of asthma.

<p><strong>Abstract</strong></p><p>Målet för den naturvetenskapliga undervisningen är att ge eleverna kännedom om och förståelse för grundläggande begrepp och sammanhang. Fotosyntesen är en avgörande förutsättning för liv. För att förstå hur ekosystem hänger ihop krävs en förståelse för att atomer varken nybildas eller försvinner utan att alla processer innebär att atomerna är de byggstenar som används om och om igen. Denna insikt hos enskilda individer kan vara avgörande för hur mänskligheten lyckas hantera globala miljöproblem i ett större samhällsperspektiv.</p><p> </p><p>Undersökningsgruppen består av 24 elever i årskurs 8. De fick inledningsvis formulera sig skriftligt om hur de tänker kring materiaomvandling i samband med fotosyntes och förbränning. Under 5 veckor fick de följa ett slutet kretslopp, samtidigt som de undervisades om materiaomvandling i samband med fotosyntesen. Eleverna deltog i en strukturerad halvklassdiskussion runt ett slutet kretslopp. Frågeställningarna behandlade vanliga vardagstankar och de baserades på några av de svårigheter som finns för fördjupad förståelse för fotosyntesen enligt NO-didaktikforskaren Björn Andersson. Undersökningen avslutades med att eleverna återigen fick formulera sina tankar skriftligt.</p><p> </p><p>Undersökningens resultat verifierar övrig didaktisk forskning som pekat på svårigheter att förstå materiaomvandling. De undersökta eleverna visade inte upp det molekylbegrepp som innebär att samma atomer som ingår i en process återfinns som produkter efteråt.</p><p> </p><p>Studien pekar också på att elevernas kvalitativa förståelse hänger samman med hur undervisningsstoffet presenteras. Varje individ lever i sin unika verklighet. Dessa elevers förståelse verkar fördjupas när de upplever en verkligt kvalitativ skillnad mellan förförståelsen och den undervisning som presenteras. I annat fall läggs nya fakta till gamla strukturer och eleven har lärt sig något annat än det som pedagogen avsåg att förmedla</p>