Exploring NICU nurses' views of a novel genetic point-of-care test identifying neonates at risk of antibiotic-induced ototoxicity: A qualitative study.

AIM: To explore the views of neonatal intensive care nursing staff on the deliverability of a novel genetic point-of-care test detecting a genetic variant associated with antibiotic-induced ototoxicity. DESIGN: An interpretive, descriptive, qualitative interview study. METHODS: Data were collected using semi-structured interviews undertaken between January and November 2020. Participants were neonatal intensive care nursing staff taking part in the Pharmacogenetics to Avoid Loss of Hearing trial. RESULTS: Thematic analysis resulted in four themes: perceived clinical utility; the golden hour; point-of-care device; training and support. Recommendations were made to streamline the protocol and ongoing training and support were considered key to incorporating the test into routine care. CONCLUSION: Exploring the views of nurses involved in the delivery of the point-of-care test was essential in its implementation. By the study endpoint, all participants could see the value of routine clinical introduction of the point-of care test. IMPLICATIONS FOR THE PROFESSION AND/OR PATIENT CARE: Nurses are in a key position to support the delivery of point-of-care genetic testing into mainstream settings. This study has implications for the successful integration of other genetic point-of-care tests in acute healthcare settings. IMPACT: The study will help to tailor the training and support required for routine deployment of the genetic point-of-care test. The study has relevance for nurses involved in the development and delivery of genetic point-of-care tests in other acute hospital settings. REPORTING METHOD: This qualitative study adheres to the Standards for Reporting Qualitative Research EQUATOR guidelines and utilizes COREQ and SRQR checklists. PATIENT OR PUBLIC CONTRIBUTION: All staff working on the participating neonatal intensive care units were trained to use the genetic point-of-care test. All inpatients on the participating units were eligible to have testing via the point-of-care test. The Pharmacogenetics to Avoid Loss of Hearing Patient and Public Involvement and Engagement group provided valuable feedback. TRIAL AND PROTOCOL REGISTRATION: Registered within the University of Manchester. Ethics approval reference numbers: IRAS: 253102 REC reference: 19/NW/0400. Also registered with the ISRCTN ref: ISRCTN13704894.

Parents on the Concept of Physical Literacy: What Do They Know, What Do They Do, and What Do They Want?

Physical literacy development in early childhood, viewed by many as the foundation for lifelong physical activity engagement, is significantly influenced by parents. Our aim was to explore parents' understanding of physical literacy and gain insight into their perspectives on physical literacy promotion. We recruited 18 parents of children between 5 and 8 years old in Australia. Using semistructured interviews and thematic analysis, we identified several key issues regarding parents' understanding and implementation of physical literacy. Parents expressed interest in improving their implementation of physical literacy practices and had (often unintentionally) provided support for physical literacy subcomponents in the past. However, they described difficulties prioritizing physical literacy above other parental demands and expressed conflicting perceptions regarding where the responsibility should lie for developing their child's physical literacy (e.g., at home or at school). To ensure that the physical literacy "message" reaches parents, we encourage physical literacy promoters to consider the target (e.g., responsibility, priorities, and awareness) of their promotional strategies. Further investigation into the influence of sociocultural and economic factors on parents' understanding and application of physical literacy is warranted.

Nanofiltration as a robust method contributing to viral safety of plasma-derived therapeutics: 20 years' experience of the plasma protein manufacturers.

BACKGROUND: Nanofiltration entails the filtering of protein solutions through membranes with pores of nanometric sizes that have the capability to effectively retain a wide range of viruses. STUDY DESIGN AND METHODS: Data were collected from 754 virus validation studies (individual data points) by Plasma Protein Therapeutics Association member companies and analyzed for the capacity of a range of nanofilters to remove viruses with different physicochemical properties and sizes. Different plasma product intermediates were spiked with viruses and filtered through nanofilters with different pore sizes using either tangential or dead-end mode under constant pressure or constant flow. Filtration was performed according to validated scaled-down laboratory conditions reflecting manufacturing processes. Effectiveness of viral removal was assessed using cell culture infectivity assays or polymerase chain reaction (PCR). RESULTS: The nanofiltration process demonstrated a high efficacy and robustness for virus removal. The main factors affecting nanofiltration efficacy are nanofilter pore size and virus size. The capacity of nanofilters to remove smaller, nonenveloped viruses was dependent on filter pore size and whether the nanofiltration process was integrated and designed with the intention to provide effective parvovirus retention. Volume filtered, operating pressure, and total protein concentration did not have a significant impact on the effectiveness of virus removal capacity within the investigated ranges. CONCLUSIONS: The largest and most diverse nanofiltration data collection to date substantiates the effectiveness and robustness of nanofiltration in virus removal under manufacturing conditions of different plasma-derived proteins. Nanofiltration can enhance product safety by providing very high removal capacity of viruses including small non-enveloped viruses.

Compassionate Use of Cefiderocol as Adjunctive Treatment of Native Aortic Valve Endocarditis Due to Extremely Drug-resistant Pseudomonas aeruginosa.

Serious infections such as endocarditis due to extremely drug-resistance gram-negative bacteria are an increasing challenge. Here, we present successful adjunctive use of cefiderocol for a patient with persistently bacteremic healthcare-associated native aortic valve endocarditis due to an extended-spectrum beta-lactamase-positive Pseudomonas aeruginosa susceptible in vitro only to colistin, following failure of conventional therapeutic options.

High throughput profiling of whole plasma N-glycans in type II diabetes mellitus patients and healthy individuals: A perspective from a Ghanaian population.

Aberrant protein glycosylation may reflect changes in cell metabolism of type II diabetes mellitus (T2DM) and offers fresh vistas for discovering potential biomarkers. However, the functional significance of T2DM N-glycan alterations is underexplored, since to date, N-glycan profiling studies have been performed in selected populations. Geographically and genetically isolated populations are needed for validation of specific biomarkers. This age-sex matched cross sectional study comprising 232 T2DM patients and 219 controls was conducted in Ghana, Western Africa. Blood plasma samples were collected for clinical assessment after which plasma N-glycans were freed and analysed by ultra-performance liquid chromatography (UPLC). High branching (HB) [W = 46328; q = 0.00072], tri-galactosylated (G3) [W = 44076; q = 0.00096], antennary fucosylated (FUC_A) [W = 43055; q = 0.0000763], and triantennary (TRIA) [W = 44624; q = 0.0025], N-glycan structures were increased in T2DM whereas low branching (LB) [W = 46328; q = 0.00072], non-sialylated (S0) [W = 46929; q = 0.00292], monogalactosylation (G1) [W = 44091; q = 0.0000763], core fucosylation (FUC_C), [W = 46497; q = 0.00096], biantennary galactosylation (A2G) [W = 45663; q = 0.000763], and biantennary (BA) [W = 46376; q = 0.00072], structures were decreased compared to controls. Nine N-glycan peaks (GPs (GP1, GP4, GP7, GP11, GP17, GP19, GP22, GP26, GP29)) were found to predict case status based on Akaike's information criterion (AIC) and Bayesian information criterion (BIC) model selection. Adjusting for age, sex and other co-variates in this model yielded an area under the curve (AUC) of 80.5% with sensitivity of 79% and specificity of 73%, indicating the predicting power of N-glycans as robust biomarkers. Our results show that hyperglycemia influences N-glycan complexities among Ghanaians. N-glycan profiling in distinct populations has affirmed the potentiality of N-glycan profiles as generic biomarkers which may facilitate better prognosis for T2DM.

Development of an intravenous immunoglobulin with improved safety and functional activity.

The development and properties of a liquid intravenous immunoglobulin (Gammaplex(®)), of high purity, stability and functional activity, is described. Virus and TSE reduction by specific steps in the process were evaluated by spiking studies using small-scale models. The removal of procoagulant activity was determined using immunochemical and functional activity assays. Neutralisation and opsonic activity were used to demonstrate the functional activity of the IgG. The final low pH formulated product was stable at room temperature and was of high purity and functional activity. Three dedicated virus inactivation steps, i.e. solvent detergent, low pH and virus filtration, were shown to be effective. When combined with the B + I ethanol precipitation step, this gave a total reduction of >21 to >24 log for the enveloped and >10 to >13 log for the non-enveloped viruses tested. Several steps in the process were shown to contribute to TSE removal using scrapie. Potential procoagulant activity including Factor XI/XIa, was reduced to very low/undetectable levels in the final product. A new high purity liquid IVIG product has been developed, of high purity and good functional activity and stability. The process includes various steps for the removal of pathogens and procoagulant activity.

Virus elimination during the recycling of chromatographic columns used during the manufacture of coagulation factors.

Various chromatographic procedures are used during the purification and manufacture of plasma products such as coagulation factors. These steps contribute to the overall safety of such products by removing potential virus contamination. Virus removal by two affinity chromatography procedures, i.e. monoclonal antibody chromatography and metal chelate chromatography (immobilised metal ion affinity chromatography), used during the manufacture of the high purity factor VIII (Replenate®) and factor IX (Replenine®-VF), respectively, has been investigated. In addition, as these columns are recycled after use, the effectiveness of the sanitisation procedures for preventing possible cross-contamination, has also been investigated. Both chromatographic steps proved effective for eliminating a range of model enveloped and non-enveloped viruses by 4 to >6 and 5 to >8 log for the monoclonal and metal chelate columns, respectively. The effectiveness of the relatively mild column sanitisation conditions used, i.e. ethanol for factor IX and acetic acid for factor VIII, was confirmed using non-spiked column runs. The chemicals used contributed to virus elimination by inactivation and/or by physical removal of the virus. In summary, these studies demonstrate that potential virus contamination between chromatographic runs can be prevented when an effective column recycling and sanitisation procedure is included.

Becoming a podiatrist: an exploration of the practices and processes which underpin the acquisition of a professional identity.

BACKGROUND: Undergraduate podiatry degrees are designed to enable students to become professional podiatrists. To be successful students must manage academic and practical activity to ultimately acquire a professional identity. Little is known about the practices and processes which underpin the acquisition of a professional podiatry identity. It is the aim of this paper to begin to address this absence of knowledge. Community of Practice theory, arguably the dominant contemporary learning theory, represents identity shift as an interaction of imagination, engagement and alignment which enables students to successfully participate in higher education, and ultimately, the professional context. This success is underpinned through assisting students to develop an enabling identity in their learning and doing. METHODS: Here we present findings that emerged from a yearlong ethnography in a successful higher education podiatry department. The project followed students and staff in the classroom and the clinic and explored their experiences through interviews. RESULTS: The findings suggest that the journey to professional identity is facilitated through meaningful learning relationships between staff and students and clarity around professional practices. Here we discuss how those relationships form and enable undergraduates to become podiatrists. CONCLUSIONS: Our findings offer a model for the transition from student to professional and highlight the importance of relationship and experience in becoming a podiatrist. There is a paucity of research around not only podiatry but also other allied health professions around this topic and given the increasing emphasis around employability skills in HE, more research in a range of contexts is needed.

Gecko adhesion based sea star crawler robot.

Over the years, efforts in bioinspired soft robotics have led to mobile systems that emulate features of natural animal locomotion. This includes combining mechanisms from multiple organisms to further improve movement. In this work, we seek to improve locomotion in soft, amphibious robots by combining two independent mechanisms: sea star locomotion gait and gecko adhesion. Specifically, we present a sea star-inspired robot with a gecko-inspired adhesive surface that is able to crawl on a variety of surfaces. It is composed of soft and stretchable elastomer and has five limbs that are powered with pneumatic actuation. The gecko-inspired adhesion provides additional grip on wet and dry surfaces, thus enabling the robot to climb on 25° slopes and hold on statically to 51° slopes.

Welfare and Management of Civets in Civet Coffee Tourism Plantations.

Civet coffee is produced with coffee beans that have passed through the digestive tract of civets which are then processed for drinking. Outlets, known as civet coffee tourism plantations are popular tourist attractions in Bali, Indonesia. These outlets keep caged civets for public viewing and sell civet coffee. We assessed civet welfare in 29 civet coffee tourism plantations to assess husbandry factors, the five freedoms and body condition scores. We also assessed civet welfare in eight wildlife markets where civets are sourced for civet coffee tourism and calculated turnover of civets. We found 99 civets in civet coffee tourism plantations and 136 in markets, where. Annually between 400 and 800 civets are sold. Welfare standards do not meet the Indonesian laws and regulations. Diet, hygiene, presence of water and mobility affected body condition scores and no civet met all of the five freedoms. Enforcement of welfare and trade laws is needed to improve civet welfare, and to curb the illegal civet trade. Tourists frequenting civet coffee tourism plantations should be made aware of the low welfare standards to inform their choice about supporting this industry.

The impacts of a global pandemic on the efficacy and stability of contemporary wildlife conservation: South Africa as a case study.

Conservationists speculated on potential benefits to wildlife of lockdown restrictions because of the COVID-19 pandemic but voiced concern that restrictions impeded nature conservation. We assessed the effects of lockdown restrictions on biodiversity conservation in South Africa, a biodiverse country with economic inequality and reliance on wildlife resources. We solicited expert opinion using the IUCN's Threats Classification Scheme to structure a questionnaire and illustrated responses with individual case studies from government parastatal and non-governmental conservation organisations. The most highly reported threats were biological resource use, residential/commercial developments, invasive species, and human intrusions. The trends reported by 90 survey respondents were supported by case studies using environmental compliance data from parastatal conservation organisations. Lack of tourism revenue and funding were cited as hindrances to conservation. Mechanisms to prevent environmental degradation in the face of global emergencies must be implemented and 'ring-fenced' to ensure conservation is not a casualty during future global crises.

Kinase Mutations and Imatinib Response in Patients With Metastatic Gastrointestinal Stromal Tumor.

PURPOSE: Most gastrointestinal stromal tumors (GISTs) express constitutively activated mutant isoforms of KIT or kinase platelet-derived growth factor receptor alpha (PDGFRA) that are potential therapeutic targets for imatinib mesylate. The relationship between mutations in these kinases and clinical response to imatinib was examined in a group of patients with advanced GIST. PATIENTS AND METHODS: GISTs from 127 patients enrolled onto a phase II clinical study of imatinib were examined for mutations of KIT or PDGFRA. Mutation types were correlated with clinical outcome. RESULTS: Activating mutations of KIT or PDGFRA were found in 112 (88.2%) and six (4.7%) GISTs, respectively. Most KIT mutations involved exon 9 (n = 23) or exon 11 (n = 85). All KIT mutant isoforms, but only a subset of PDGFRA mutant isoforms, were sensitive to imatinib, in vitro. In patients with GISTs harboring exon 11 KIT mutations, the partial response rate (PR) was 83.5%, whereas patients with tumors containing an exon 9 KIT mutation or no detectable mutation of KIT or PDGFRA had PR rates of 47.8% (P = .0006) and 0.0% (P < .0001), respectively. Patients whose tumors contained exon 11 KIT mutations had a longer event-free and overall survival than those whose tumors expressed either exon 9 KIT mutations or had no detectable kinase mutation. CONCLUSION: Activating mutations of KIT or PDGFRA are found in the vast majority of GISTs, and the mutational status of these oncoproteins is predictive of clinical response to imatinib. PDGFRA mutations can explain response and sensitivity to imatinib in some GISTs lacking KIT mutations.

Contrived Materials and a Data Set for the Evaluation of Liquid Biopsy Tests: A Blood Profiling Atlas in Cancer (BLOODPAC) Community Study.

The Blood Profiling Atlas in Cancer (BLOODPAC) Consortium is a collaborative effort involving stakeholders from the public, industry, academia, and regulatory agencies focused on developing shared best practices on liquid biopsy. This report describes the results from the JFDI (Just Freaking Do It) study, a BLOODPAC initiative to develop standards on the use of contrived materials mimicking cell-free circulating tumor DNA, to comparatively evaluate clinical laboratory testing procedures. Nine independent laboratories tested the concordance, sensitivity, and specificity of commercially available contrived materials with known variant-allele frequencies (VAFs) ranging from 0.1% to 5.0%. Each participating laboratory utilized its own proprietary evaluation procedures. The results demonstrated high levels of concordance and sensitivity at VAFs of >0.1%, but reduced concordance and sensitivity at a VAF of 0.1%; these findings were similar to those from previous studies, suggesting that commercially available contrived materials can support the evaluation of testing procedures across multiple technologies. Such materials may enable more objective comparisons of results on materials formulated in-house at each center in multicenter trials. A unique goal of the collaborative effort was to develop a data resource, the BLOODPAC Data Commons, now available to the liquid-biopsy community for further study. This resource can be used to support independent evaluations of results, data extension through data integration and new studies, and retrospective evaluation of data collection.

Immunolocalisation of 11ß-HSD-1 and -2, glucocorticoid receptor, mineralocorticoid receptor and Na+ K+-ATPase during the postnatal development of the rat epididymis.

Glucocorticoids have been implicated in male reproductive function and 11ß-HSD-1 and -2, the glucocorticoid receptor (GR) and mineralocorticoid receptor (MR), all of which are known to modulate glucocorticoid action, have been localised in the adult rat epididymis, but their developmental expression has not been investigated. Na(+)K(+)-ATPase activity, responsible for sodium transport, is induced by both mineralocorticoids and glucocorticoids in the kidney and colon, and has been localised in epididymal epithelium. This study examined the immunolocalisation of 11ß-HSD-1 and -2, GR, MR and Na(+)K(+)-ATPase in rat epididymal epithelium (n = 5) at postnatal days (pnd) 1, 7, 15, 28, 40, 60, 75 and 104, and relative mRNA expression of 11ß-HSD-1 and -2, and GR at pre-puberty (pnd 28) and post-puberty (pnd 75). 11ß-HSD-1, GR and MR were localised in the epididymal epithelium from pnd 1, and 11ß-HSD-2 and Na(+)K(+)-ATPase reactivity from pnd 15. At pnd 28 there was maximal immunoreactivity for both the GR and MR and 11ß-HSD-1 and -2. 11ß-HSD-1 mRNA expression in the caput increased from pre- to post-puberty, whereas 11ß-HSD-2 mRNA expression fell over the same period (P < 0.01). GR mRNA expression was similar at pre- and post-puberty in both caput and cauda. Developmental changes in expression of 11ß-HSD-1 and -2 suggest that overall exposure of the epididymis to glucocorticoids increases post-puberty, but cell-specific expression of the 11ß-HSD enzymes still provides a capacity for intricate local control of glucocorticoid exposure.

Virus reduction in an intravenous immunoglobulin by solvent/detergent treatment, ion-exchange chromatography and terminal low pH incubation.

Virus reduction by several steps in the manufacturing process for the intravenous immunoglobulin Vigam(®), has been investigated. The solvent/detergent step based on treatment with 0.3% tri-n-butyl phosphate and 1% polysorbate 80 at 37 °C, was confirmed to be effective for a range of enveloped viruses. Virus infectivity was undetectable i.e. >6 log inactivation within 30 min of the standard 6 h process. This was consistent over the range of conditions tested i.e. solvent/detergent and protein concentration, temperature and pH. The ion-exchange chromatography step in the process was also able to remove some viruses. Virus spiked followed by blank column runs confirmed the effectiveness of the sanitisation step for ensuring there was no virus cross contamination between column runs. The terminal low pH incubation step was also able to inactivate enveloped viruses, as well as some non-enveloped viruses. The combination of these three steps ensures a high margin of virus safety for this product.

The role of the vascular surgeon in anterior lumbar spine surgery.

OBJECTIVES: Advances in spinal fusion techniques have led to an increase in the need for safe access to the lumbar spine anteriorly. The aim of this study is to examine the procedure-related complications of anterior lumbar inter-body fusion (ALIF) or anterior lumbar disc replacement (ALDR) when performed jointly by a vascular-surgeon and a neurosurgeon in a single centre. METHODS: A retrospective cohort analysis was conducted for all patients who underwent ALIF or ALDR between 2004 and 2010. Operative notes were examined to identify any procedure-specific complications. In-hospital postoperative complications were recorded. Outpatients' records were reviewed to record any late-onset postoperative complications. RESULTS: A total of 121 patients (68 female and 53 males) were included. Mean age was 44 years (range of 25-76). Eighty patients (66%) had ALIF while 24 patients (20%) underwent ALDR. The remaining 17 patients (14%) had combined procedure for multilevel disease. In all patients, a transperitoneal approach was performed by vascular surgeon. The main indication (88%) for performing surgery was degenerative lumbar disc disease. No visceral or 'major vascular' complications were reported in any patients. Only three patients had 'minor vascular' injuries. The only significant postoperative complication was self-limiting paralytic ileus affecting 18 patients (14.8%). Hospital stay ranged from 4 to 9 days (median of 5 days). CONCLUSIONS: The anterior lumbar approach is not generally favoured by many neurosurgeons, despite its many advantages, due to the significant risk of vascular injuries as reported in the literature. This risk is especially acknowledged by the emerging generation of neurosurgeons with very little general surgical exposure during the training years. Adopting a combined vascular and neurosurgical approach has been reported to reduce the risk of vascular injury in anterior lumbar surgery acceptably low. This team approach provides an excellent opportunity to preserve some key 'general' surgical skills for neurosurgeons and ensure safe outcome for the patients.

Can interprofessional research enhance health care students' understanding and knowledge towards evidence based practice: A cross sectional study.

AIM: To explore how inter-professional collaboration in the teaching and learning of research skills prepares undergraduate students for their professional roles in healthcare via an evaluation of inter-professional research modules from the student perspective. PARTICIPANTS AND SETTINGS: Participants were selected from a university in the North of England where all undergraduate Healthcare students were taught Research and Evidence Based Practice (EBP) through interprofessional education (n = 400). METHODS: Quantitative data was collected using an adapted Attitudes Towards Interprofessional Education Scale and internally-designed pilot instruments. Qualitative data was also collected via open comment to evaluate the taught research module. RESULTS: 50 students completed the survey pre-module and 49 students completed the survey post-module. The participants' views towards inter-professional education (IPE) are generally positive: the median responses of 4 single-item measures assessing inter-professional learning on 7-point Likert scales were 5 or above (where higher scores represented more positive perceptions). Scores on the Attitudes towards Interprofessional Education scale also generally represented positive opinions, with a mean post-test score of 58.8 on a scale from 5 to 75, with higher scores indicating greater levels of positivity. No evidence for a statistically significant improvement from the pre- to post- 3rd year experience of the IPE/research theme was revealed. Qualitative data identified six themes: promoting team working, developing awareness of other health care professional's roles, polarising research and practice, multidisciplinary team (MDT) working or not working, logistical issues and developing research skills. CONCLUSIONS: This study raised questions about the appropriateness of "unnatural" pairings for undertaking research projects. Whilst the students valued working together in the research process, they do not appear to have perceived a universal benefit to their inter-professional clinical practice.

The role of podiatry in the early identification and prevention of lower limb venous disease: an ethnographic study.

BACKGROUND: Lower limb venous disease can cause significant pain, loss of mobility, and can be detrimental to an individual's quality of life. Manifestations of venous disease often pose a substantially negative impact on patients and place a high demand on finite healthcare resources. Whilst this problem is internationally recognised, most research and discourse has predominantly focussed on treatment of leg ulceration and prevention of recurrence. Prevention of lower limb venous disease progression to the first ulceration has received far less attention. Overall, the care of this condition appears to rest in the domain of medicine and nursing yet podiatry, a profession with responsibility for the lower limb and foot, is conspicuous by its absence from the literature.  METHODS: An ethnographic approach was used to gather data from 26 participants through observation, semi-structured interviews, and a focus group interview. Qualitative analysis was conducted using the framework approach. RESULTS: The findings revealed an identity crisis within the podiatry profession. Evidence emerged of ritual and routine practices that did not include lower limb venous disease. External control over practice limited the professional autonomy of podiatrists determining their own activities. Inter-professional relationships with nursing, and perceptions of boundaries that venous disease was a nursing role were also found to be limiting factors. CONCLUSIONS: This research revealed that podiatry does not occupy a substantive role in contributing to the early identification and prevention of lower limb venous disease. Policy, education, research and practice changes are all required to enhance the contribution of podiatry to reduce the burden of this disease.

Rapid Point-of-Care Genotyping to Avoid Aminoglycoside-Induced Ototoxicity in Neonatal Intensive Care.

Importance: Aminoglycosides are commonly prescribed antibiotics used for the treatment of neonatal sepsis. The MT-RNR1 m.1555A>G variant predisposes to profound aminoglycoside-induced ototoxicity (AIO). Current genotyping approaches take several days, which is unfeasible in acute settings. Objective: To develop a rapid point-of-care test (POCT) for the m.1555A>G variant before implementation of this technology in the acute neonatal setting to guide antibiotic prescribing and avoid AIO. Design, Setting, and Participants: This pragmatic prospective implementation trial recruited neonates admitted to 2 large neonatal intensive care units between January 6, 2020, and November 30, 2020, in the UK. Interventions: Neonates were tested for the m.1555A>G variant via the rapid POCT on admission to the neonatal intensive care unit. Main Outcomes and Measures: The primary outcome assessed the proportion of neonates successfully tested for the variant of all infants prescribed antibiotics. Secondary outcomes measured whether implementation was negatively associated with routine clinical practice and the performance of the system. The study was statistically powered to detect a significant difference between time to antibiotic administration before and after implementation of the MT-RNR1 POCT. Results: A total of 751 neonates were recruited and had a median (range) age of 2.5 (0-198) days. The MT-RNR1 POCT was able to genotype the m.1555A>G variant in 26 minutes. Preclinical validation demonstrated a 100% sensitivity (95% CI, 93.9%-100.0%) and specificity (95% CI, 98.5%-100.0%). Three participants with the m.1555A>G variant were identified, all of whom avoided aminoglycoside antibiotics. Overall, 424 infants (80.6%) receiving antibiotics were successfully tested for the variant, and the mean time to antibiotics was equivalent to previous practice. Conclusions and Relevance: The MT-RNR1 POCT was integrated without disrupting normal clinical practice, and genotype was used to guide antibiotic prescription and avoid AIO. This approach identified the m.1555A>G variant in a practice-changing time frame, and wide adoption could significantly reduce the burden of AIO.