An evaluation of the implementation of interventions to reduce post-operative infections and optimise antibiotic use across the surgical pathway in India: A mixed methods exploratory study protocol

Introduction: Postoperative infections represent a significant burden of disease, demanding antibiotic prescriptions, and are contributing to antimicrobial resistance. The burden of infection as a surgical complication is greater in low- and middle-income countries (LMICs). We report the protocol of a pilot study for the co-design, implementation and evaluation of two infection prevention and control (IPC) and antimicrobial stewardship (AMS) interventions across the surgical pathway in a teaching hospital in India. Methods and analysis: The two interventions developed following in-depth qualitative enquiry are (i) surveillance and feedback of postoperative infections to optimise the use of antibiotics in two surgical departments (gastrointestinal and cardiovascular and thoracic surgery) and (ii) raising awareness amongst patients, carers and members of public about IPC and AMS. We will conduct a prospective study, formatively evaluating the implementation process of delivering the two co-designed interventions using implementation science frameworks. The study will systematically assess the context of intervention delivery, so that implementation support for the interventions may be adapted to the needs of stakeholders throughout the study. Analysis of implementation logs and interviews with stakeholders upon completion of the implementation period, will offer insights into the perceived acceptability, appropriateness, feasibility and sustainability of the interventions and their implementation support. Implementation costs will be captured descriptively. Feasibility of clinical data collection to investigate effectiveness of interventions will also be assessed for a future larger study. Thematic framework analysis and descriptive statistics will be used to report the qualitative and quantitative data, respectively. Strengths and limitations of this study: • The paired interventions have been co-designed from their inception with involvement of stakeholders at different stages in the surgical pathway. • Simultaneous evaluation of implementation and clinical outcomes will inform the development of a future larger study to enable/assess the scalability of interventions • The study offers a novel combination of implementation theory-informed, stakeholder-driven and clinically relevant evaluation, carried out in the context of a middle-income country hospital. • The project may not be applicable to every low-resource setting and surgical context due to differences in healthcare systems and cultures. However, the application of implementation science concepts may facilitate transferability and adaptation to other settings

Are current infection prevention and control expectations fit for purpose? Interim results from an ethnographic study in South India

Copyright © 2020 The Authors). Background: Carer involvement around the world has varied impact on infection prevention and control (IPC) practices in hospitals. We investigated the experiences of patients and carers in the surgical pathway of a tertiary hospital in south India, exploring their involvement in IPC and therapeutic decision-making along the patient pathway. Methods and materials: Ethnographic study through observations from ward rounds, semi-structured interviews, in-depth case studies and documentary analysis. Field notes from observations and interview transcripts were subsequently coded using NVivo and analysed using grounded theory. Data collection and analysis were iterative, recursive and continued until thematic saturation was achieved. Results: We conducted 48 interviews (44 healthcare professionals, 4 patients), over 100 hours of observations, and 2 in-depth case studies aided by documentary analysis of patient records. Institutional expectations of families are formalised in policies which demand that patients are accompanied by a relative at all times. Such intense presence embeds families in the care environment of the patients, as demonstrated by their high engagement not only in direct personal care (i.e. bathing patients) but also clinical tasks (i.e. wound care), hence playing an important yet implicit IPC role. The informal carers actively discussed the patient's progress with healthcare workers, received post-discharge advice and, more often than not, decided on therapeutic options on behalf of patients. Such care leadership was assumed and accepted by patients (aware of such involvement in decision-making), healthcare workers and the institution (where policies about additional relatives staying in the ward were routinely ignored), reflecting a culture of communal and collective care. For patients and relatives, infections were ‘brought in’ by other visitors, resulting in recently discharged patients being kept within the home, where the environment could be controlled and visitors restricted. This approach further highlights the importance of relatives as community carers and gatekeepers of care-related infection. Conclusion: Applying the current worldwide IPC perspectives focused on patients as sole decision-makers in India may overlook the wider social-cultural context and the constellation of persons who play a role in care and by extension decisions about IPC. Culture-sensitive IPC policy which embrace the roles that informal carers play is urgently needed

Indispensable yet invisible: A qualitative study of the roles of carers in infection prevention in a South Indian hospital

Copyright © 2022 The Authors. Objectives: We investigated the roles of patient carers in infection-related care on surgical wards in a South Indian hospital from the perspective of healthcare workers (HCWs), patients, and their carers. Methods: Ethnographic study included ward-round observations (138 hours) and face-to-face interviews (44 HCWs, 6 patients/carers). Data (field notes, interview transcripts) were coded in NVivo 12 and thematically analyzed. Data collection and analysis were iterative, recursive, and continued until thematic saturation. Results: Carers have important, unrecognized roles. At the study site, institutional expectations are formalized in policies, demanding a carer to always accompany in-patients. Such intense presence embeds families in the patient care environment, as demonstrated by their high engagement in direct personal (bathing patients) and clinical care (wound care). Carers actively participate in discussions on patient progress with HCWs, including therapeutic options. There is a misalignment between how carers are positioned by the organization (through policy mandates, institutional practices, and HCWs expectations), and the role that they play in practice, resulting in their role, though indispensable, remaining unrecognized. Conclusion: Current models of patient and carer involvement in infection prevention and control are poorly aligned with sociocultural and contextual aspects of care. Culture-sensitive infection prevention and control policies which embrace the roles that carers play are urgently needed.Economic and Social Research Council Grant number: ES/P008313/1

Interventional research to tackle antimicrobial resistance in Low Middle Income Countries in the era of the COVID-19 pandemic: lessons in resilience from an international consortium

This article summarizes the consequences of the COVID-19 pandemic, on an international project to tackle antimicrobial resistance (AMR). The research leadership and process, the access to data, and stakeholders were deeply disrupted by the national and international response to the pandemic, including the interruption of healthcare delivery, lockdowns, and quarantines. The key principles to deliver the research through the pandemic were mainly the high degree of interdisciplinary engagement with integrated teams, and equitable partnership across sites with capacity building and leadership training. The level of preexisting collaboration and partnership were also keys to sustaining connections and involvements throughout the pandemic. The pandemic offered opportunities for realigning research priorities. Flexibility in funding timelines and projects inputs are required to accommodate variance introduced by external factors. The current models for research collaboration and funding need to be critically evaluated and redesigned to retain the innovation that was shown to be successful through this pandemic

Long-COVID cognitive impairments and reproductive hormone deficits in men may stem from GnRH neuronal death

BACKGROUND: We have recently demonstrated a causal link between loss of gonadotropin-releasing hormone (GnRH), the master molecule regulating reproduction, and cognitive deficits during pathological aging, including Down syndrome and Alzheimer's disease. Olfactory and cognitive alterations, which persist in some COVID-19 patients, and long-term hypotestosteronaemia in SARS-CoV-2-infected men are also reminiscent of the consequences of deficient GnRH, suggesting that GnRH system neuroinvasion could underlie certain post-COVID symptoms and thus lead to accelerated or exacerbated cognitive decline. METHODS: We explored the hormonal profile of COVID-19 patients and targets of SARS-CoV-2 infection in post-mortem patient brains and human fetal tissue. FINDINGS: We found that persistent hypotestosteronaemia in some men could indeed be of hypothalamic origin, favouring post-COVID cognitive or neurological symptoms, and that changes in testosterone levels and body weight over time were inversely correlated. Infection of olfactory sensory neurons and multifunctional hypothalamic glia called tanycytes highlighted at least two viable neuroinvasion routes. Furthermore, GnRH neurons themselves were dying in all patient brains studied, dramatically reducing GnRH expression. Human fetal olfactory and vomeronasal epithelia, from which GnRH neurons arise, and fetal GnRH neurons also appeared susceptible to infection. INTERPRETATION: Putative GnRH neuron and tanycyte dysfunction following SARS-CoV-2 neuroinvasion could be responsible for serious reproductive, metabolic, and mental health consequences in long-COVID and lead to an increased risk of neurodevelopmental and neurodegenerative pathologies over time in all age groups. FUNDING: European Research Council (ERC) grant agreements No 810331, No 725149, No 804236, the European Union Horizon 2020 research and innovation program No 847941, the Fondation pour la Recherche Médicale (FRM) and the Agence Nationale de la Recherche en Santé (ANRS) No ECTZ200878 Long Covid 2021 ANRS0167 SIGNAL, Agence Nationale de la recherche (ANR) grant agreements No ANR-19-CE16-0021-02, No ANR-11-LABEX-0009, No. ANR-10-LABEX-0046, No. ANR-16-IDEX-0004, Inserm Cross-Cutting Scientific Program HuDeCA, the CHU Lille Bonus H, the UK Medical Research Council (MRC) and National Institute of Health and care Research (NIHR)

Survey of healthcare worker perceptions of changes in infection control and antimicrobial stewardship practices in India and South Africa during the COVID-19 pandemic

OBJECTIVE: To identify perceptions and awareness of changes in infection prevention and control (IPC) and antimicrobial stewardship (AMS) practices among healthcare workers (HCWs) during the COVID-19 pandemic in India and South Africa (SA). METHOD: A self-administered online survey which included participant demographics, knowledge and sources of COVID-19 infection, perceived risks and barriers, and self-efficacy. Data were analysed using descriptive statistics. RESULTS: The study received 321 responses (response rate: 89.2%); 131/321 (40.8%) from India and 190/321 (59.2%) from SA; male to female response rate was 3:2, with majority of respondents aged 40-49 (89/321, 27.7%) and 30-39 (87/321, 27.1%) years. Doctors comprised 47.9% (57/119) of respondents in India and 74.6% (135/181) in SA. Majority of respondents in India (93/119, 78.2%) and SA (132/181, 72.9%) were from the private and public sectors, respectively, with more respondents in SA (123/174, 70.7%) than in India (38/104, 36.5%) involved in antimicrobial prescribing.Respondents reported increased IPC practices since the pandemic and noted a need for more training on case management, antibiotic and personal protective equipment (PPE) use. While they noted increased antibiotic prescribing since the pandemic, they did not generally associate their practice with such an increase. A willingness to be vaccinated, when vaccination becomes available, was expressed by 203/258 (78.7%) respondents. CONCLUSIONS: HCWs reported improved IPC practices and changes in antibiotic prescribing during the COVID-19 pandemic. Targeted education on correct use of PPE was an identified gap. Although HCWs expressed concerns about antimicrobial resistance, their self-perceived antibiotic prescribing practices seemed unchanged. Additional studies in other settings could explore how our findings fit other contexts

Hollow-core Optical Fiber Gas Lasers (HOFGLAS): a review [Invited]

International audienceThe development of hollow core photonic crystal fibers with low losses over a broad spectral region in the near IR enabled the demonstration of a novel laser type - Hollow-core Optical Fiber Gas Laser (HOFGLAS). The laser combines attractive features of fiber lasers such as compactness and long interaction length of pump and laser radiation with those of gas lasers such as the potential for high output power and narrow line width. This paper summarizes recent developments and describes the demonstration of C2H2 and HCN prototype lasers. Avenues to extend laser emission further into the IR are discussed

Degradability of cross-linked polyurethanes based on synthetic polyhydroxybutyrate and modified with polylactide

In many areas of application of conventional non-degradable cross-linked polyurethanes (PUR), there is a need for their degradation under the influence of specific environmental factors. It is practiced by incorporation of sensitive to degradation compounds (usually of natural origin) into the polyurethane structure, or by mixing them with polyurethanes. Cross-linked polyurethanes (with 10 and 30%wt amount of synthetic poly([R,S]-3-hydroxybutyrate) (R,S-PHB) in soft segments) and their physical blends with poly([d,l]-lactide) (PDLLA) were investigated and then degraded under hydrolytic (phosphate buffer solution) and oxidative (CoCl2/H2O2) conditions. The rate of degradation was monitored by changes of samples mass, morphology of surface and their thermal properties. Despite the small weight losses of samples, the changes of thermal properties of polymers and topography of their surface indicated that they were susceptible to gradual degradation under oxidative and hydrolytic conditions. Blends of PDLLA and polyurethane with 30 wt% of R,S-PHB in soft segments and PUR/PDLLA blends absorbed more water and degraded faster than polyurethane with low amount of R,S-PHB

The involvement of tau in nucleolar transcription and the stress response

Tau is known for its pathological role in neurodegenerative diseases, including Alzheimer’s disease (AD) and other tauopathies. Tau is found in many subcellular compartments such as the cytosol and the nucleus. Although its normal role in microtubule binding is well established, its nuclear role is still unclear. Here, we reveal that tau localises to the nucleolus in undifferentiated and differentiated neuroblastoma cells (SHSY5Y), where it associates with TIP5, a key player in heterochromatin stability and ribosomal DNA (rDNA) transcriptional repression. Immunogold labelling on human brain sample confirms the physiological relevance of this finding by showing tau within the nucleolus colocalises with TIP5. Depletion of tau results in an increase in rDNA transcription with an associated decrease in heterochromatin and DNA methylation, suggesting that under normal conditions tau is involved in silencing of the rDNA. Cellular stress induced by glutamate causes nucleolar stress associated with the redistribution of nucleolar non-phosphorylated tau, in a similar manner to fibrillarin, and nuclear upsurge of phosphorylated tau (Thr231) which doesn’t colocalise with fibrillarin or nucleolar tau. This suggests that stress may impact on different nuclear tau species. In addition to involvement in rDNA transcription, nucleolar non-phosphorylated tau also undergoes stress-induced redistribution similar to many nucleolar protein

What does antimicrobial stewardship look like where you are? Global narratives from participants in a Massive Open Online Course

Introduction Whilst Antimicrobial Stewardship (AMS) is being implemented in different countries, different contexts continue to present unique challenges. We investigated the challenges to implementing AMS in different countries by examining comments from clinical, academic, and lay learners participating in a Massive Open Online Course (MOOC) on tackling antimicrobial resistance (AMR). Methods A 3-week MOOC titled “Tackling AMR: A social science approach” was developed with a global faculty in collaboration with the British Society of Antimicrobial Chemotherapy and Imperial College London and launched in November 2019. Learners were asked specific questions about their experiences of AMS throughout the MOOC which included 38 optional free text prompts. Learners' free text responses from first three-course runs (November 2019 – July 2020) were collated and coded in NVivo 12 using a conventional content analysis approach to identify challenges to implementing AMS across countries. Results Representing 114 countries, 1464 learners enrolled, with largest representation from the United Kingdom, India, Nigeria, Australia, and Pakistan. The learners described a range of AMS activities and team compositions. While recognising the importance of pharmacist and nurse roles in AMS, the learners reported that such roles remain ill-defined across countries, restricting the reach and potential of AMS strategies. A range of challenges to implementing AMS were described, including: limited awareness and engagement by the general public and healthcare workers (HCW) on the impact of AMR on human health, lack of adequate of governance and policy; inconsistencies in surveillance for antibiotic consumption and AMR, impeding feedback loops and improvement processes; human resource and technological constraints; variable access to key antibiotics; lack of ownership of antibiotic decision-making and buy-in from different clinical specialties. Patients’ knowledge, experiences and perspectives were recognised as a valuable source of information that needed to be incorporated in AMS initiatives to overcome cultural barriers to the judicious use of antibiotics. Conclusion Analysis of learner comments and reflections identified a range of enablers and barriers to AMS implementation across different healthcare economies. Common challenges to AMS implementation included the role of non-physician health care professionals, resources, knowledge of AMR and patient engagement and involvement in AMS