The anaesthetic management of patients undergoing caesarean section surgery and its impact on post-operative analgesia

A Thesis submitted to the Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, in fulfilment of the requirements for the degree of Doctor of Philosophy. 14th October 2016 in JohannesburgPoorly controlled pain following caesarean section surgery can have a debilitating effect on the physical and emotional well being of a woman during the post-operative period. Good intra-operative anaesthetic management during caesarean section surgery is requisite to improve post-operative analgesia, and thereby contribute to the well being of the patient. In South Africa (SA) there are currently no national obstetric anaesthesia practice guidelines. Anaesthetic service providers therefore rely on knowledge acquired during their anaesthetic training and recommendations from international guidelines (which may not be applicable in SA). In order to establish a reference standard of anaesthetic care for obstetric patients in SA, a semi-structured interview was conducted with the heads of department and/or their representatives from the eight anaesthesiology academic departments in SA in 2012. The experts provided recommendations on the intra-operative anaesthetic management of patients for elective and emergency caesarean sections, as well as the post-operative monitoring and analgesic management of these patients. The recommendations were based on the experts’ understanding of the uniquely local healthcare environment in SA. Following the establishment of the SA reference standard, a national survey of anaesthetic service providers was conducted in 2014 to establish what the practises are in South Africa for caesarean section anaesthetics. Ninehundred- and-thirty-three survey responses were analysed, which equated to a 58% response rate. The majority of anaesthesia providers (97.8%) perform single shot spinal anaesthesia for caesarean sections. Thirty percent of respondents chose to use Quincke spinal needles, despite the increased risk of this needle causing post-dural puncture headaches (PDPH). The preferred local anaesthetic drug was 0.5% bupivacaine with dextrose, and fentanyl was the most commonly used additive agent, as opposed to common international practice, which advocates morphine. The survey also revealed that 58% of doctors work in hospitals that do not have a post-operative monitoring protocol for patients following caesarean section surgery. This contrasts to recommendations suggested by the national experts regarding patient monitoring requirements. A clinical trial was then conducted to compare the analgesic efficacy of two different doses of intrathecal morphine (50μg and 100μg) with 25μg fentanyl. Patients in both morphine treatment groups had significantly lower postoperative opioid requirements than patients in the fentanyl group. The pain numerical rating scale (NRS) scores were however not statistically different and there was also no difference in the side effects profile or emotional parameters measured, between the groups. This study highlights the differences in the recommended practise of obstetric anaesthesia in SA compared to other countries and demonstrates how obstetric anaesthesia is practised in SA. The final component of this study has demonstrated how international best practices can be easily implemented in SA to improve the anaesthetic care of the obstetric patient.MT201

Salmonella Typhi – a Quiet Bacteria with a Loud Message: an ICU Case Report

Typhoid fever, caused by Salmonella enterica, serovar Typhi, is restricted to humans as its host and evades the human immune system with ease. This quality has been one of the many reasons why it is commonly found as an endemic bacterium in emerging economies. Also, due to a remarkably low yield from blood cultures (median of 1 CFU/mL of blood), Salmonella septicemia is uncommon. New evidence gathered together with clinical investigations have provided insight into the mechanisms that underlie the pathogenesis of typhoid, host restriction as well as antibiotic and vaccine susceptibility. However, very little has been done to curb the persistence of disease and emergence of resistant strains. We discuss a case of Salmonella Septic Shock in the Intensive Care Unit (ICU) that takes us through various aspects in diagnosis, the treatment potential and the problems surrounding prevention

On the Measurement of “Grayness” of Cities

We consider a situation where individuals belonging to multiple groups inhabit a space that can be divided into smaller distinguishable units, a feature characterizing many cities in the world. When data on an economic attribute (in our case, income) is available, we conceptualize a phenomenon that we refer to as “Grayness” - a combination of spatial integration based upon group-identity and income. Grayness is high when cities display a high degree of spatial co-existence in terms of both identity and income. We lay down some desirable properties of a measure of Grayness and develop a simple and intuitive index that satisfies them. We provide an illustration by using data from the Indian city of Hyderabad, and selected American cities

The Influence of Dosimetric Parameters on Quality of Life for Early Stage Non-small Cell Lung Cancer Patients Treated with Stereotactic Body Radiation Therapy

Background: Lung stereotactic body radiotherapy (SBRT) has become a standard treatment option for early stage non-small cell lung cancer (NSCLC) patients who are medically inoperable. The influence of radiation dose/volume parameters on quality of life is not known. Our hypothesis is that clinically meaningful declines in quality of life over time will be associated with increased radiation lung dose/volume parameters. Objectives: To investigate clinical toxicity and quality of life (QOL) outcomes of stage I NSCLC patients after SBRT as a function of radiation dose/volume parameters. Methods: In this IRB-approved study, 55 stage I NSCLC patients who received SBRT (12 Gy x 4) and completed QOL forms were analyzed. Clinical symptoms and QOL were measured at baseline and at 3, 6, 12, 18, 24, and 36 months post-SBRT. Clinical toxicity was graded using the common terminology criteria for adverse effects (CTCAE v4.0). Quality of life was followed using the validated Functional Assessment of Cancer Therapy-Trial Outcome Index (FACT-TOI) instrument. Dosimetric parameters, including the mean lung radiation dose (MLD), and the volume of normal lung receiving \u3e 5, 10, 13 or 20 Gy (V5, V10, V13, and V20) were measured from the radiation treatment plan. Student\u27s t-test and Pearson correlation analyses were used to examine the relationships between radiation lung metrics and clinically meaningful changes in QOL and/or clinical toxicities. Kaplan-Meier method was used to estimate rates of local control (LC), disease free survival (DFS), and overall survival (OS). Results: With a median follow-up of 24 months, the 3 year LC, DFS, and OS were 93%, 65% and 84%, respectively, with 5.5% grade 3 toxicity and no grade 4 or 5 toxicities. Clinically meaningful declines in patient reported QOL (FACT-TOI, lung cancer subscale, physical well-being, and/or functional well-being) post-treatment significantly correlated with increased dosimetric parameters, such as V10, V13, and V20. Conclusions: While lung SBRT is associated with excellent LC and minimal clinical toxicity for early stage NSCLC, clinically meaningful declines in QOL significantly correlated with increasing lung dose/volume parameters. This suggests that further improvements in the techniques of lung SBRT have the potential to further enhance patients\u27 QOL following this treatment

The Influence of Dosimetric Parameters on Quality of Life for Early Stage Non-small Cell Lung Cancer Patients Treated with Stereotactic Body Radiation Therapy

Background: Lung stereotactic body radiotherapy (SBRT) has become a standard treatment option for early stage non-small cell lung cancer (NSCLC) patients who are medically inoperable. The influence of radiation dose/volume parameters on quality of life is not known. Our hypothesis is that clinically meaningful declines in quality of life over time will be associated with increased radiation lung dose/volume parameters. Objectives: To investigate clinical toxicity and quality of life (QOL) outcomes of stage I NSCLC patients after SBRT as a function of radiation dose/volume parameters. Methods: In this IRB-approved study, 55 stage I NSCLC patients who received SBRT (12 Gy x 4) and completed QOL forms were analyzed. Clinical symptoms and QOL were measured at baseline and at 3, 6, 12, 18, 24, and 36 months post-SBRT. Clinical toxicity was graded using the common terminology criteria for adverse effects (CTCAE v4.0). Quality of life was followed using the validated Functional Assessment of Cancer Therapy-Trial Outcome Index (FACT-TOI) instrument. Dosimetric parameters, including the mean lung radiation dose (MLD), and the volume of normal lung receiving \u3e 5, 10, 13 or 20 Gy (V5, V10, V13, and V20) were measured from the radiation treatment plan. Student\u27s t-test and Pearson correlation analyses were used to examine the relationships between radiation lung metrics and clinically meaningful changes in QOL and/or clinical toxicities. Kaplan-Meier method was used to estimate rates of local control (LC), disease free survival (DFS), and overall survival (OS). Results: With a median follow-up of 24 months, the 3 year LC, DFS, and OS were 93%, 65% and 84%, respectively, with 5.5% grade 3 toxicity and no grade 4 or 5 toxicities. Clinically meaningful declines in patient reported QOL (FACT-TOI, lung cancer subscale, physical well-being, and/or functional well-being) post-treatment significantly correlated with increased dosimetric parameters, such as V10, V13, and V20. Conclusions: While lung SBRT is associated with excellent LC and minimal clinical toxicity for early stage NSCLC, clinically meaningful declines in QOL significantly correlated with increasing lung dose/volume parameters. This suggests that further improvements in the techniques of lung SBRT have the potential to further enhance patients\u27 QOL following this treatment

Thermo-responsive non-woven scaffolds for "smart" 3D cell culture

The thermo-responsive polymer poly(N-isopropylacrylamide) has received widespread attention for its in vitro application in the non-invasive, non-destructive release of adherent cells on two dimensional surfaces. In this study, 3D non-woven scaffolds fabricated from poly(propylene) (PP), poly(ethylene terephthalate) (PET) and nylon that had been grafted with PNIPAAm were tested for their ability to support the proliferation and subsequent thermal release of HC04 and HepG2 hepatocytes. Hepatocyte viability and proliferation was estimated using the Alamar Blue assay and Hoechst 33258 total DNA quantification. The assays revealed that the pure and grafted non-woven scaffolds maintained the hepatocytes within the matrix and promoted 3D proliferation comparable to that of the commercially available AlgimatrixTM alginate scaffold. Albumin production and selected cytochrome P450 genes expression was found to be superior in cells growing on pure and grafted non-woven PP scaffolds as compared to cells grown as a 2D monolayer. Two scaffolds, namely, PP-g- PNIPAAm-A and PP-g-PNIPAAm-B were identified as having far superior thermal release capabilities; releasing the majority of the cells from the matrices within 2 h. This is the first report for the development of 3D non-woven, thermo-responsive scaffolds able to release cells from the matrix without the use of any enzymatic assistance or scaffold degradation.The Council for Scientific and Industrial Researchhttp://onlinelibrary.wiley.com/journal/10.1002/(ISSN)1097-0290hb2016Biochemistr

Development of thermoresponsive poly(propylene-g-N-isopropylacrylamide) non-woven 3D scaffold for smart cell culture using oxyfluorination-assisted graft polymerisation

Growing cells on 3D scaffolds is far superior to the conventional 2D monolayer culture method. In this study, a novel 3D thermoresponsive poly(propylene-g-N-isopropylacrylamide) (PP-g-PNIPAAm) nonwoven fabric (gNWF) was developed for cell culture using oxyfluorination-assisted graft polymerisation (OAGP). New polar functional groups were detected on the oxyfluorinated NWF (oNWF), and PNIPAAm was confirmed in the gNWF by attentuated total-reflectance Fourier transform infrared (ATR-FTIR) and scanning X-ray photoelectron spectroscopy (S-XPS). Scanning electron microscopy (SEM) revealed a rough surface morphology and confinement of the PNIPAAm graft layer to the surface of the fibres in the gNWF. The OAGP method did not affect the crystalline phase of bulk PP, however, twin-melting thermal peaks were detected for the oNWF and gNWF indicating crystal defects. Contact angle studies showed that the surface of the gNWF exhibited a thermoresponsive behaviour. Hepatocyte cells attached onto gNWF disks in a bioreactor at 37 ◦C and remained viable for 10 days in culture. Upon cooling the cell culture media to 20 ◦C, cells were spontaneously released as 3D multi-cellular constructs without requiring destructive enzymes. The development of 3D thermoresponsive scaffolds capable of non-invasive 3D cell culture could provide a more reliable in vitro model for cells.http://www.elsevier.com/locate/colsurfahb201

System-level policies on appropriate opioid use, a multi-stakeholder consensus

Background:  This consensus statement was developed because there are concerns about the appropriate use of opioids for acute pain management, with opposing views in the literature. Consensus statement on policies for system-level interventions may help inform organisations such as management structures, government agencies and funding bodies. Methods:  We conducted a multi-stakeholder survey using a modified Delphi methodology focusing on policies, at the system level, rather than at the prescriber or patient level. We aimed to provide consensus statements for current developments and priorities for future developments. Results:  Twenty-five experts from a variety of fields with experience in acute pain management were invited to join a review panel, of whom 23 completed a modified Delphi survey of policies designed to improve the safety and quality of opioids prescribing for acute pain in the secondary care setting. Strong agreement, defined as consistent among> 75% of panellists, was observed for ten statements. Conclusions:  Using a modified Delphi study, we found agreement among a multidisciplinary panel, including patient representation, on prioritisation of policies for system-level interventions, to improve governance, pain management, patient/consumers care, safety and engagement.Publisher PDFPeer reviewe