The drivers of antimicrobial use across institutions, stakeholders and economic settings: a paradigm shift is required for effective optimization.

OBJECTIVES: Significant antimicrobial overuse persists worldwide, despite overwhelming evidence of antimicrobial resistance and knowledge that optimization of antimicrobial use will slow the development of resistance. It is critical to understand why this occurs. This study aims to consider the social influences on antimicrobial use within hospitals in Australia, via an in-depth, multisite analysis. METHODS: We used a qualitative multisite design, involving 222 individual semi-structured interviews and thematic analysis. Participants (85 doctors, 79 nurses, 31 pharmacists and 27 hospital managers) were recruited from five hospitals in Australia, including four public hospitals (two metropolitan, one regional and one remote) and one private hospital. RESULTS: Analysis of the interviews identified social relationships and institutional structures that may have a strong influence on antimicrobial use, which must be addressed concurrently. (i) Social relationships that exist across settings: these include the influence of personal risk, hierarchies, inter- and intraprofessional dynamics and sense of futility in making a difference long term in relation to antimicrobial resistance. (ii) Institutional structures that offer context-specific influences: these include patient population factors (including socioeconomic factors, geographical isolation and local infection patterns), proximity and resource issues. CONCLUSIONS: The success of antimicrobial optimization rests on adequate awareness and incorporation of multilevel influences. Analysis of the problem has tended to emphasize individual 'behaviour improvement' in prescribing rather than incorporating the problem of overuse as inherently multidimensional and necessarily incorporating personal, interpersonal and institutional variables. A paradigm shift is urgently needed to incorporate these critical factors in antimicrobial optimization strategies.

Ebola outbreak preparedness planning: a qualitative study of clinicians' experiences.

OBJECTIVES: The 2014-15 Ebola outbreak in West Africa highlighted the challenges many hospitals face when preparing for the potential emergence of highly contagious diseases. This study examined the experiences of frontline health care professionals in an Australian hospital during the outbreak, with a focus on participant views on information, training and preparedness, to inform future outbreak preparedness planning. STUDY DESIGN: Semi-structured interviews were conducted with 21 healthcare professionals involved in Ebola preparedness planning, at a hospital in Australia. METHODS: The data were systematically coded to discover key themes in participants' accounts of Ebola preparedness. RESULTS: Three key themes identified were: 1) the impact of high volumes of-often inconsistent-information, which shaped participants' trust in authority; 2) barriers to engagement in training, including the perceived relative risk Ebola presented; and finally, 3) practical and environmental impediments to preparedness. CONCLUSIONS: These clinicians' accounts of Ebola preparedness reveal a range of important factors which may influence the relative success of outbreak preparedness and provide guidance for future responses. In particular, they illustrate the critical importance of clear communication and guidelines for staff engagement with, and implementation of training. An important outcome of this study was how individual assessments of risk and trust are produced via, and overlap with, the dynamics of communication, training and environmental logistics. Consideration of the dynamic ways in which these issues intersect is crucial for fostering an environment that is suitable for managing an infectious threat such as Ebola.

Women's attitudes towards the use of complementary and alternative medicine products during pregnancy.

The aim of this study was to analyse women's attitudes towards the use of complementary and alternative medicine (CAM) products during pregnancy. The study sample was obtained via the Australian Longitudinal Study on Women's Health or ALSWH. A response rate of 79.2% (n = 1,835) was attained. Women who use herbal medicines (34.5%, n = 588) view CAM as a preventative measure, are looking for something holistic and are concerned about evidence of clinical efficacy when considering the use of these products during pregnancy. Women who use aromatherapy (17.4%, n = 319) and homoeopathy (13.3%, n = 244) want more personal control over their body and are concerned more about their own personal experience of the efficacy of CAM than clinical evidence of efficacy. As CAM use in pregnancy appears to be increasingly commonplace, insights into women's attitudes towards CAM are valuable for maternity healthcare providers.

Negotiating palliative care in the context of culturally and linguistically diverse patients.

There is an increasing emphasis on meeting the healthcare needs of culturally and linguistically diverse (CALD) communities in Australia. Negotiating the point of futility and the transition to specialist palliative care requires not only effective communication but also sensitivity to cultural and linguistic specificities. This can be a challenging process for clinicians, patients and families. Here, we outline some of the key challenges currently facing many clinicians in the context of CALD patients, with particular reference to the transitioning of patients to specialist palliative care. We suggest a focus on further research that can systematically document and model existing CALD-specific clinical processes and pathways, which can then support the development of targeted educational interventions. This includes developing a multi-stakeholder understanding of the CALD experience that moves beyond cultural stereotyping and predicting need.

Referral to specialist palliative care.

Recent literature has suggested that earlier referral to palliative care can improve quality of life and prognosis. The decision to refer to palliative care is a complex process that can involve an interplay of interpersonal, subjective and institutional factors. Negotiating this referral process can be challenging to a medical specialist from a professional and personal viewpoint. What remains unknown is what actually influences the individual clinician to refer a patient to palliative care.

Experiences of the SARS-CoV-2 pandemic amongst Australian healthcare workers: from stressors to protective factors.

BACKGROUND: The SARS-CoV-2 pandemic has critically challenged healthcare systems globally. Examining the experiences of healthcare workers (HCWs) is important for optimizing ongoing and future pandemic responses. OBJECTIVES: In-depth exploration of Australian HCWs' experiences of the SARS-CoV-2 pandemic, with a focus on reported stressors vis-à-vis protective factors. METHODS: Individual interviews were performed with 63 HCWs in Australia. A range of professional streams and operational staff were included. Thematic analysis was performed. RESULTS: Thematic analysis identified stressors centred on paucity of, or changing, evidence, leading to absence of, or mistrust in, guidelines; unprecedented alterations to the autonomy and sense of control of clinicians; and deficiencies in communication and support. Key protective factors included: the development of clear guidance from respected clinical leaders or recognized clinical bodies, interpersonal support, and strong teamwork, leadership, and a sense of organizational preparedness. CONCLUSIONS: This study provides insights into the key organizational sources of emotional stress for HCWs within pandemic responses and describes experiences of protective factors. HCWs experiencing unprecedented uncertainty, fear, and rapid change, rely on clear communication, strong leadership, guidelines endorsed by recognized expert groups or individuals, and have increased reliance on interpersonal support. Structured strategies for leadership and communication at team, service group and organizational levels, provision of psychological support, and consideration of the potential negative effects of centralizing control, would assist in ameliorating the extreme pressures of working within a pandemic environment.

The use of traditional, complementary and alternative medicine in Sri Lankan cancer care: results from a survey of 500 cancer patients.

OBJECTIVES: While the introduction of biomedicine within the Sri Lankan healthcare system has resulted in reduced reliance on traditional, complementary and alternative medicine (TCAM) over the last century in Sri Lanka, treatment modalities such as Ayurveda, Sinhala and traditional religious practices still receive considerable public support. Cancer is an increasing burden in Sri Lanka, and whilst Sri Lankans are known to use TCAM for everyday ailments, there has been no research examining the role of TCAM in the context of cancer. The aim of this study was to evaluate the prevalence and patterns of TCAM use by cancer patients. STUDY DESIGN: Cross-sectional survey. METHODS: Data were obtained from two Sri Lankan hospitals using a consecutive convenience sample of 500 cancer patients currently receiving biomedical treatment, over a 10-week period in 2008. RESULTS: Analyses showed that 67.4% of those surveyed used one or more TCAM in conjunction with biomedicine for cancer treatment. The most common were Sinhala, Ayurveda and traditional religious practices. Of those patients who used TCAM, 95.0% gave the main reason for usage as 'they thought it would cure their cancer'. The strongest reason for not using TCAM was on advice from their doctor (80.5%). CONCLUSIONS: The high use of TCAM amongst cancer patients in Sri Lanka raises numerous important issues, including those related to patient safety, potential benefit, interactions with biomedical cancer treatments, and delays in seeking biomedical cancer care. Further research is needed to explore the decision-making processes of cancer patients, including the perceived benefits/limitations of key processes in biomedical and TCAM care.

Aerosol-generating procedures and infective risk to healthcare workers from SARS-CoV-2: the limits of the evidence.

The transmission behaviour of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is still being defined. It is likely that it is transmitted predominantly by droplets and direct contact and it is possible that there is at least opportunistic airborne transmission. In order to protect healthcare staff adequately it is necessary that we establish whether aerosol-generating procedures (AGPs) increase the risk of transmission of SARS-CoV-2. Where we do not have evidence relating to SARS-CoV-2, guidelines for safely conducting these procedures should consider the risk of transmitting related pathogens. Currently there is very little evidence detailing the transmission of SARS-CoV-2 associated with any specific procedures. Regarding AGPs and respiratory pathogens in general, there is still a large knowledge gap that will leave clinicians unsure of the risk to themselves when offering these procedures. This review aimed to summarize the evidence (and gaps in evidence) around AGPs and SARS-CoV-2.

Determination of mosquito (Diptera: Culicidae) bloodmeal sources in Western Australia: implications for arbovirus transmission.

A double-antibody enzyme-linked immunosorbent assay was used to determine the bloodmeal sources of adult mosquitoes (Diptera: Culicidae) collected in encephalitis vector surveillance mosquito traps in Western Australia between May 1993 and August 2004. In total, 2,606 blood-fed mosquitoes, representing 29 mosquito species, were tested, and 81.7% reacted with one or more of the primary antibodies. Aedes camptorhynchus (Thomson) and Culex annulirostris Skuse were the most common species tested, making up 47.2% (1,234) and 35.6% (930), respectively. These species obtained bloodmeals from a variety of vertebrate hosts but particularly marsupials and cows. In contrast, Culex pullus Theobald (72.7%; 24/33), Culiseta atra (Lee) (70.0%; 7/10), Culex globocoxitus Dobrotworsky (54.5%; 12/22), and Culex quinquefasciatus Say (39.3%; 22/56) often obtained bloodmeals from birds. Although Ae. camptorhynchus and Cx. annulirostris are well established vectors of arboviruses, other mosquitoes also may have a role in enzootic and/ or epizootic transmission.

Synovial fluid cell counts and its role in the diagnosis of paediatric septic arthritis.

PURPOSE: Clinical presentation of paediatric septic arthritis (SA) can be similar to other joint pathologies. Despite potential for infection in all major joints, most diagnostic criteria are based on values from the hip. This study identifies the best joint aspirate values in diagnosing SA in all joints. METHODS: In all, 166 patients who underwent 172 joint aspirations at the authors' institution between 01 September 2004 and 01 September 2014 were retrospectively identified. Recorded measures included age, sex, duration of symptoms, fever history, weight-bearing status, aspiration results, serum results and antibiotic administration. Patients were placed in the following four categories: 'culture confirmed SA' (C-SA), 'suspected SA' (S-SA), 'Other' and 'Other-rheumatologic' (Other-R), a subcategory of 'Other'. RESULTS: Most common sites of aspiration were the knee (55%) and hip (29%). Diagnostic grouping was as follows: C-SA = 44, S-SA = 45, Other = 83 (Other-R = 21). Fever and non-weight-bearing prior to admission were useful predictors of SA, though in C-SA patients, 21% did not have a fever and 23% could weight bear at the time of admission. Aspirate white blood cell (WBC) count was significantly greater in both C-SA (92 000 cells/hpf) and S-SA (54 000) than in Other (10 000) and Other-R (18 000) patients. The percentage of polymorphonuclear (%PMN) was also significantly greater in C-SA (81.1%) and S-SA (80.9%) than in Other (57.9%) and Other-R (63.3%). CONCLUSION: Joint aspirate values, especially %PMN, are valuable in diagnosing SA. Additionally, antibiotics pre-aspiration did not affect %PMN, facilitating subsequent diagnosis of infection. Lastly, while aspirate WBC count was a valuable indicator of SA, this finding is not as definitive as previous research suggests. LEVEL OF EVIDENCE: IV Case Series.

Context-sensitive antibiotic optimization: a qualitative interviews study of a remote Australian hospital setting.

BACKGROUND: Antibiotic optimization is an urgent international issue. Regulatory frameworks, including the requirement to have a functioning antimicrobial stewardship (AMS) programme, are now ubiquitous across the hospital sector nationally and internationally. However, healthcare is ultimately delivered in a diverse range of institutional settings and social contexts. There is emerging evidence that implementation of antibiotic optimization strategies may be inappropriate or even counterproductive to attempts to optimize in atypical healthcare settings. AIM: To document the experiences and perspectives of clinical staff in a remote healthcare setting in Australia with respect to antimicrobial use, and strategies for optimization in that environment. METHODS: Semi-structured qualitative interviews were conducted with 30 healthcare professionals, including doctors, nurses and pharmacists, from a remote hospital in Queensland, Australia. FINDINGS: Four themes were identified from the analysis as key challenges to antibiotic optimization: (i) AMS as externally driven, and local knowledge sidelined; (ii) perceptions of heightened local population risks, treatment failure and the subsequent pressure to over-use of antimicrobials; (iii) interprofessional relationship dynamics including medical hierarchical structures perceived as a barrier to AMS; (iv) a clinical workforce dominated by transient locum staff and other process issues were perceived as significant barriers. CONCLUSION: The perceptions of healthcare professionals in this site lead to the conclusion that antimicrobial regulations and practice improvement strategies more generally are unlikely to succeed if they fail to accommodate and respect the context of care, the resource and structural constraints of the setting, and the specificities of particular populations (and subsequent clinical 'know-how').

How do hospital respiratory clinicians perceive antimicrobial stewardship (AMS)? A qualitative study highlighting barriers to AMS in respiratory medicine.

BACKGROUND: Suboptimal antibiotic use in respiratory infections is widespread in hospital medicine and primary care. Antimicrobial stewardship (AMS) teams within hospitals, commonly led by infectious diseases physicians, are frequently charged with optimizing the use of respiratory antibiotics, but there is limited information on what drives antibiotic use in this area of clinical medicine, or on how AMS is perceived. AIM: To explore the perceptions of hospital respiratory clinicians on AMS in respiratory medicine. METHODS: In-depth interviews were conducted with 28 clinicians (13 doctors and 15 nurses) from two hospitals in Australia. Data were analysed thematically using the framework approach. FINDINGS: Four key barriers to the integration of AMS processes within respiratory medicine, from the participants' perspectives, were identified: CONCLUSIONS: AMS processes are introduced in hospitals with established social structures and knowledge bases. This study found that AMS in respiratory medicine challenges and conflicts with many of these dynamics. If the influence of these dynamics is not considered, AMS processes may not be effective in containing antibiotic use in hospital respiratory medicine.

Individual care versus broader public health: A qualitative study of hospital doctors' antibiotic decisions.

OBJECTIVES: This study aimed to examine how hospital doctors balance competing concerns around antibiotic use and resistance, with a focus on individual care versus broader public health considerations. METHODS: Sixty-four doctors across two hospitals in Australia participated in semi-structured interviews about their perspectives on antibiotic resistance and prescribing decisions. Results were analysed using the framework approach. RESULTS: The first theme focused on the significance of antimicrobial resistance (AMR) and the role of hospital doctors. Participants did not perceive resistance to be central to clinical decision-making, and externalised the resistance threat. They perceived themselves as separated from the issue of escalating resistance, viewing the key drivers to be overseas use, use in agriculture, and community prescribing. The second theme was around balancing risks. Immediate clinical risks were described as prioritised over long term population risk. Participants described concern around reputational and legal risks, which were perceived to be associated with under-prescribing of antibiotics. Over-prescribing was described by participants to be easier and without perceived immediate risk to them or to patients. CONCLUSION: Hospital doctors perceived antimicrobial resistance as externally produced and described clinical concerns taking precedence in individual antibiotic decisions. These dual processes mean that a population health model has limited traction in the hospital context. The externalisation of resistance leads to a sense of futility in changing practice, which combines with the pressures of acute medicine to prioritise immediate patient outcomes. Such dynamics are leading to antibiotic optimisation as a low or absent priority in hospital clinician antibiotic decision-making.

Cytotoxicity, uptake, polyglutamate formation, and antileukemic effects of 8-deaza analogues of methotrexate and aminopterin in mice.

In contrast to methotrexate (MTX) and aminopterin (AMT), the 8-deaza analogues of these antifolates are not substrates for rabbit liver aldehyde oxidase. Since they are not converted to 7-hydroxy derivatives, they have been investigated with regard to their cytotoxicity for CCRF-CEM cells, transport into these cells, and conversion to polyglutamate forms. For this purpose 3H-labeled analogues were synthesized. The drug concentrations of the analogues required to inhibit cell growth by 50% are significantly lower than for the parent compounds particularly for a short exposure of cells to the drug. Vmax and Km for unidirectional influx do not differ greatly among the four drugs, but amounts of uptake over 1 h are markedly different and increase in the order MTX less than 8-deazaMTX less than AMT less than 8-deazaAMT. During 1 h of uptake a much greater proportion of the 8-deaza analogues is converted to polyglutamate forms than in the case of parent drugs. Only 52% of MTX is converted to polyglutamates, whereas in the case of the other three compounds the conversion is greater than or equal to 90%. However, MTX is relatively efficient in adding two glutamate residues, whereas the other drugs predominantly accumulate as forms with only one additional glutamate (+Glu1). During 1 h of efflux the drugs without additional glutamates decrease to low concentrations and there is also a major loss of +Glu1 form, but there is also an increase in longer chain forms, especially in the case of MTX. The net result is a still greater disparity in total intracellular levels of the four drugs after the period of efflux. MTX has much lower toxicity in mice in vivo than the other three compounds, 8-deazaAMT being the most toxic. At the maximum tolerated dose MTX produced a considerably greater increase in life span for mice bearing P388 than any of the other drugs, and a somewhat greater increase for mice bearing L1210. Thus the 8-deaza analogues do not offer a therapeutic advantage over MTX against leukemias in the mouse, primarily due to their much greater toxicity.

The characteristics of women who use hypnotherapy for intrapartum pain management: Preliminary insights from a nationally-representative sample of Australian women.

OBJECTIVES: This manuscript presents a preliminary examination of the characteristics of women who choose intrapartum hypnosis for pain management. DESIGN: Cross-sectional analysis of 2445 women (31-36 years) from a sub-study of the Australian Longitudinal Study on Women's Health (ALSWH), employing Fisher exact tests. SETTING: Australia. MAIN OUTCOME MEASURES: Use of intrapartum hypnosis, or hypnobirthing, for pain management during labour and birth. RESULTS: Women using hypnobirthing were more likely to have consulted with an acupuncturist or naturopath, or attended yoga/meditation classes during pregnancy (p<0.0001). Use of CM products such as herbal medicines, aromatherapy oils, homoeopathy, herbal teas or flower essences (p<0.001) was also more common amongst these women. Women choosing hypnotherapy for intrapartum pain management less commonly identified as feeling safer knowing that an obstetrician is providing their care (p<0.001), and were more likely to labour in a birth centre or in a community centre (i.e. at home). CONCLUSIONS: This analysis provides preliminary analysis into an as yet unexamined topic in contemporary maternity health service utilisation. The findings from this analysis may be useful for maternity health professionals and policy makers when responding to the needs of women choosing to use hypnotherapy for intrapartum pain management.

Barriers to uptake of antimicrobial advice in a UK hospital: a qualitative study.

BACKGROUND: The role of infectious diseases (ID) and clinical microbiology (CM) in hospital settings has expanded in response to increasing antimicrobial resistance, leading to widespread development of hospital antimicrobial stewardship (AMS) programmes, the majority of which include antibiotic approval systems. However, inappropriate antibiotic use in hospitals continues, suggesting potential disjunctions between technical advice and the logics of antibiotic use within hospitals. AIM: To examine the experiences of doctors in a UK hospital with respect to AMS guidance of antibiotic prescribing, and experiences of a verbal postprescription antibiotic approval process. METHODS: Twenty doctors in a teaching hospital in the UK participated in semi-structured interviews about their experiences of antibiotic use and governance. NVivo10 software was used to conduct a thematic content analysis systematically. FINDINGS: This study identified three key themes regarding doctors' relationships with ID/CM clinicians that shaped their antibiotic practices: (1) competing hierarchical influences limiting active consultation with ID/CM; (2) non-ID/CM consultants' sense of ownership over clinical decision-making and concerns about challenges to clinical autonomy; and (3) tensions between evidence-based practice and experiential-style learning. CONCLUSIONS: This study illustrates the importance of examining relations between ID/CM and non-ID/CM clinicians in the hospital context, indicating that AMS models that focus exclusively on delivering advice rather than managing interprofessional relationships may be limited in their capacity to optimize antibiotic use. AMS and, specifically, antibiotic approval systems would likely be more effective if they incorporated time and resources for fostering and maintaining professional relationships.

Optimizing antibiotic usage in hospitals: a qualitative study of the perspectives of hospital managers.

BACKGROUND: Antibiotic optimization in hospitals is an increasingly critical priority in the context of proliferating resistance. Despite the emphasis on doctors, optimizing antibiotic use within hospitals requires an understanding of how different stakeholders, including non-prescribers, influence practice and practice change. AIM: This study was designed to understand Australian hospital managers' perspectives on antimicrobial resistance, managing antibiotic governance, and negotiating clinical vis-à-vis managerial priorities. METHODS: Twenty-three managers in three hospitals participated in qualitative semi-structured interviews in Australia in 2014 and 2015. Data were systematically coded and thematically analysed. FINDINGS: The findings demonstrate, from a managerial perspective: (1) competing demands that can hinder the prioritization of antibiotic governance; (2) ineffectiveness of audit and monitoring methods that limit rationalization for change; (3) limited clinical education and feedback to doctors; and (4) management-directed change processes are constrained by the perceived absence of a 'culture of accountability' for antimicrobial use amongst doctors. CONCLUSION: Hospital managers report considerable structural and interprofessional challenges to actualizing antibiotic optimization and governance. These challenges place optimization as a lower priority vis-à-vis other issues that management are confronted with in hospital settings, and emphasize the importance of antimicrobial stewardship (AMS) programmes that engage management in understanding and addressing the barriers to change.

Polyribonucleotides containing thiopurines. Synthesis and properties of poly(1-methyl-6-thioguanylic acid).

The synthesis of 1-methyl-6-thioguanosine 5'-diphosphate and its conversion to poly(1-methyl-6-thioguanylic acid) by means of polynucleotide phosphorylase are described. The polymer exhibited cooperative behavior (Tm = 294 K in the absence of added NaCl) characteristic of a highly stacked single-stranded helical array. In a high salt environment (0.5 M NaCl) the melting was much less cooperative and gave a higher Tm (313 K); this is suggestive of interstrand aggregation involving hydrogen bonding. The polynucleotide exhibited a remarkably high pKa (6.2) compared to that of the mononucleotide (2.6), and formed a very stable acid structure (Tm = 356 K in 50% ethylene glycol). Comparisons with poly(1-methyl-6-thioinosinic acid) and poly(6-thioguanylic acid) establish that both the 2-amino group and the 1-methyl group are required for the formation of the stable acid structure.

Poly(8-bromo-2'-deoxyadenylic acid): the syn/anti relationship.

The synthesis of a high-molecular-weight, putatively all-syn DNA analogue, poly(8-bromo-2'-deoxyadenylic acid), is described. The syn----anti transition was shown to be both salt and temperature dependent. Conditions were found which favored 'normal' Watson-Crick pairing and duplex formation with poly(dT).