Doctors', Patients' and Physician Associates' Perceptions of the Physician Associate Role in the Emergency Department.

INTRODUCTION: The Emergency Department (ED) has seen increased patient attendance and difficulty meeting demands. New healthcare professions such as Physician Associates (PAs) are being utilised to complement the existing medical workforce. Despite the growth of their professions in the United Kingdom, little evidence is available about the perceptions of their roles. OBJECTIVE: This study aims to provide evidence of doctors', PAs' and patients' perceptions of the PA role in the UK ED. METHODS: A mixed methods approach consisted of the following: 1. An online exploratory survey of ED doctors at one English ED over 1 month (February-March 2022). 2. Post consultation semi-structured patient questionnaires over 2 weeks (April 2022). 3. Semi-structured virtual interviews with ED consultants across the four regions of the United Kingdom (3 months in 2022). 4. Semi-structured virtual interviews with ED PAs across the four regions of the United Kingdom (3 months in 2022). The analysis methods that were used included frequency counts and percentages from closed questions, and hybrid thematic analysis of free text and interview transcripts. RESULTS: Four ED consultants and four ED PAs across the United Kingdom were interviewed. Twenty-eight ED doctors participated in the online survey. Fifty-seven patients completed the post consultation questionnaire. Four main themes (PAs being fit for purpose; patient recognition of PAs, PAs providing continuity of care, and future PAs and regulation) were deduced as per the General Medical Council, Good Medical Practice domains (knowledge, skills and development; patients, partnership and communication; colleagues, culture and safety; and trust and professionalism). Other subthemes were induced via hybrid thematic analysis. In this study, doctors and patients had mixed comments about the role of PAs. Most of them were positive as doctor participants perceived PAs to be knowledgeable, highly skilled, with mostly good communication skills, team players, providing continuity of care and overall being fit for purpose. However, some doctor participants commented negatively about PAs for providing little quality healthcare and being inexperienced. There was a desire for career progression among the PA participants and a need to work to their full potential. Although the clinicians of this study displayed a clear understanding of the PA role in the ED, a high frequency of surveyed patients mistook PAs for doctors. It was suggested that future PAs could complete a postqualification programme in emergency medicine, combine roles, be paid on an alternative scale and be formally regulated. CONCLUSION: In this study, mixed views were expressed by ED consultants, ED junior doctors and patients regarding the role of the PA in the ED. Stakeholders can use the information presented to develop a better understanding of the perceptions of the PA role within the UK ED. PATIENT OR PUBLIC CONTRIBUTION: The Patient and Public Involvement and Engagement (PPIE) group, led by Healthwatch, made significant contributions to the study's design by providing valuable feedback on the information sheets and consent forms utilised. The patients' responses helped guide the study's direction and shape its future work. As part of the dissemination activities, the study findings was shared with both the PPIE team and Healthwatch media production team.

Preregistration nursing students' motivation for speaking up for patient safety: An integrated literature review.

AIM: The aim of this review was to uncover what motivates preregistration nursing students to speak up for patient safety during work integrated learning (WIL) and to develop an evidence-based safety motivation framework for use by educators, clinicians, and preregistration nursing students. DESIGN: This study used an integrative literature review design guided by Whittemore and Knafl's methodological framework. DATA SOURCES: Five research databases, CINAHL, MEDLINE, PubMed, Scopus, and Web of Science, were searched for relevant peer reviewed research literature published in English between January 2011 and January 2024. The use of MeSH terms "undergraduate nursing student," or "preregistration nursing student" and "speaking up," "patient safety," and "motivation," resulted in 489 search returns. Following application of filters and inclusion criteria fifty-four (n = 54) studies were identified as being relevant to the research aim. REVIEW METHODS: The fifty-four (n = 54) research studies were reviewed using the JBI Critical Appraisal tool relevant to the study methodology. The JBI critical appraisal tools are checklists used to determine research quality, validity, results, and meaning. Following appraisal, 27 studies were included in the integrative literature review. RESULTS: Authentic learning, view of self as a nurse, and positive work integrated learning experiences were found to be the primary motivators for preregistration nursing students to speak up for patient safety during work integrated learning. These three motivators provided the foundation for an evidence-based framework, underpinned by self-determination theory, that can be used to enhance preregistration nursing students' motivation to speak up for patient safety. CONCLUSIONS: The integrative review design enabled the development of the evidence-based Safety Motivation Framework to support preregistration nursing students' during work integrated learning however missing from the literature was information about the lived experience of this group of students when speaking up for patient safety.

An integrative literature review of factors contributing to hypothermia in adults during the emergent (ebb) phase of a severe burn injury.

BACKGROUND: During the emergent (ebb) phase (first 72 h), the adult person with a severe burn experiences loss of body heat, decreased metabolism, and poor tissue perfusion putting them at risk of hypothermia, increased morbidity, and mortality. Therefore, timely and targeted care is imperative. AIM: The aim of this integrative literature review was to develop a framework of the factors contributing to hypothermia in adults with a severe burn injury during the emergent (ebb) phase. METHODS: An integrative review of research literature was undertaken as it provides an orderly process in the sourcing and evaluation of the literature. Only peer reviewed research articles, published in scholarly journals were selected for inclusion (n = 26). Research rigor and quality for each research article was determined using JBI Global appraisal tools relevant to the methodology of the selected study. FINDINGS: Contributing factors were classified under three key themes: Individual, Pre-hospital, and In-hospital factors. CONCLUSION: The structured approach enabled the development of an evidence-based framework identifying factors contributing to hypothermia in adults with a severe burn injury during the emergent (ebb) phase and adds knowledge to improve standardized care of the adult person with a severe burn injury.

'Waiting for the verdict': the experience of being assessed under the Mental Health Act.

BACKGROUND: Following the Independent Mental Health Act review, there is increasing focus on this coercive part of mental health services and a call for service user views to be central to proposed changes. Although there are numerous studies into being detained in hospital, there is a lack of data exploring the service user experiences of the assessment process. AIM: To explore the subjective experience of being assessed under the Mental Health Act (MHA). METHOD: 10 participants were interviewed about their recent assessment experience and the transcribed interviews were analysed using framework approach. RESULTS: The overarching theme of person centred care emerged from these interviews with interconnecting sub themes: 1) information and options; 2) "the barrage of three"; 3) "sit down and listen"; and 4) service user voice. CONCLUSION: As one of the first studies into service user experiences of MHA assessments, this exploratory study indicates that there is lack of person centeredness. The Independent Mental Health Act review has set a challenge for treating person as individual and increasing rights and involvement of service users. This study suggests service user's experiences do not yet meet this aspiration and they want to discuss these experiences and have their voices heard.

Factors contributing to the restoration of normothermia after hypothermia in people with a major burn injury in the first 24 h of hospital admission.

BACKGROUND: People with burn injury experiencing hypothermia are at risk of serious complications such as shock, multisystem organ failure, and death. There is limited information available for health professionals with regard to factors that contribute to restoration of normothermia after hypothermia in people with a major burn injury. OBJECTIVE: The aim of the study was to identify factors that contribute to normothermia restoration after hypothermia in people with 10% or more total body surface area (TBSA) burn in the first 24 h of admission to a burn care hospital. METHODS: The study was guided by the Gearing Framework for retrospective chart audit. The sample comprised medical charts of all adult people (n = 113) with a burn injury more than 10% of their TBSA admitted to a single-site burn care hospital intensive care unit in Victoria, Australia, between May 31, 2013, and June 1, 2015. Descriptive statistics were used to describe the sample, and logistic regression was conducted to predict variables contributing to return to normothermia in people with burn injury. Charts with incomplete data were excluded. FINDINGS: The sample (n = 50) recorded a median initial temperature on admission to the emergency department (ED) of 35.4°C (range = 31.9-37.2°C) and took on an average of 6.2 (standard deviation [SD] = 4.96) hours to return to normothermia (36.5°C). Women took around 6 h longer than men to return to normothermia (mean = 11.14 h, SD = 5.58; mean = 5.38 h, SD = 4.41). Positive correlations were noted between TBSA%, the length of time between admission to the ED and the intensive care unit, and the hours taken to reach normothermia. Regression analysis suggests the initial recorded temperature on admission to the ED was the main predictor of the time body temperature takes to return to normothermia (ß = .513, p < .001). CONCLUSION: This study provides information for practice changes by highlighting the need for guidelines and education programs for health professionals to ensure the delivery of optimum care to people with burn injury.

Personal qualities needed by undergraduate nursing students for a successful work integrated learning (WIL) experience.

BACKGROUND: International research has shown that during work integrated learning (WIL) undergraduate nursing students may experience stress, self-doubt, and coping issues, however personal qualities these students bring to their WIL journey or those needed to succeed during WIL remain unknown. OBJECTIVE: To describe the views of students midway through their Bachelor of Nursing program regarding personal qualities they bring to and need for WIL success. DESIGN: This article reports on a descriptive study that used an electronic questionnaire to collect the data. SETTINGS AND PARTICIPANTS: Bachelor of nursing students (n = 421), who were studying fulltime or part time equivalent, at a regional university in Queensland Australia, were invited to complete the anonymous electronic questionnaire that was developed by the research team following an extensive review of literature. Inclusion criteria required participants to have completed at least one WIL experience and be midway through their three-year Bachelor of Nursing program. METHODS: Data were collected during January and February 2017. The electronic questionnaire consisted of demographic, forced choice questions, and open-ended questions. This paper presents the qualitative analysis of responses to two of the open-ended questions that focused on personal strengths and work integrated learning experiences. Data were analysed using the inductive content analysis approach. RESULTS: Six personal qualities were identified including: enthusiasm to succeed, commitment to learning, self-motivation, confidence, effective communication skills, and compassion. CONCLUSIONS: Pre-entry screening of applicants to bachelor level nursing programs and the delivery of learning opportunities that encourages both reflection and debriefing may assist in describing personal qualities needed to succeed in WIL.

Development and validation of a screening tool for early identification of bloodstream infection in acute burn injury patients.

BACKGROUND: Standard diagnostic criteria are not useful for identifying bloodstream infection in patients with an acute burn injury patients. The study objective was to develop and validate a tool using common laboratory, clinical, and patient parameters for early identification of bloodstream infection after acute burn injury (within 10 days after a burn). METHODS: We retrospectively and prospectively reviewed for tool development the hospital course of patients with an acute burn injury (n = 156) and validated the tool in different cohorts (retrospective [n = 26] and prospective [n = 90]). The Pearson correlation identified independent variables associated with bloodstream infection (P < .1) in the development cohort that were then analyzed using binary logistic regression to identify the simplest model (P < .05; adjusted odds ratio >1). Classification and regression tree analysis was used to identify tool parameter breakpoints. Performance metrics were completed to evaluate and validate the tool. RESULTS: The best model (P < .05) was: Ln [odds of bloodstream infection] = -96.749 + 3.230 (platelet volatility) + 2.235 (max temperature [°C]) + 0.339 (% full burn) + 0.242 (% partial burn) + 0.045 (max heart rate [bpm]), with a threshold probability categorizing bloodstream infection of >48%. The sensitivity, specificity, accuracy, false positive rate, false negative rate, and positive (+) and negative (-) likelihood ratios of the tool in the developmental cohort (n = 156) were 89%, 98%, 96%, 2%, 11%, 53, and 0·11, respectively; and in the prospective validation cohort (n = 90 were 91%, 90%, 90%, 10%, 9%, 9, and 0·1, respectively (n = 90). CONCLUSION: The validated bloodstream infection screening tool in patients with acute burn injury has excellent predictive ability to assist in the identification of patients for whom blood cultures should be requested.

Using Prior Culture Results to Improve Initial Empiric Antibiotic Prescribing: An Evaluation of a Simple Clinical Heuristic.

BACKGROUND: A patient's prior cultures can inform the subsequent risk of infection from resistant organisms, yet prescribers often fail to incorporate these results into their empiric antibiotic selection. Given that timely initiation of adequate antibiotics has been associated with improved outcomes, there is an urgent need to address this gap. METHODS: In order to better incorporate prior culture results in the selection of empiric antibiotics, we performed a pragmatic, prospective, hospital-wide intervention: (1) empiric antibiotic prescriptions were assessed for clinically significant discordance with the most recent methicillin-resistant Staphylococcus aureus (MRSA) surveillance swab, previous cultures for extended-spectrum beta-lactamases (ESBLs), and the most recent culture for a Gram-negative (GN) organism; and (2) if discordant, an antimicrobial stewardship pharmacist provided recommendations for alternative therapy. The impact was analyzed using a quasi-experimental design comparing two 9-month periods (pre- and postintervention) at a large academic, tertiary care institution. RESULTS: Clinically significant discordance was identified 99 times in the preintervention period and 86 times in the intervention period. The proportion of patients that received concordant therapy increased from 73% (72/99) in the control group to 88% (76/86) in the intervention group (P = .01). The median time to concordant therapy was shorter in the intervention group than the control group (25 vs 55 hrs, respectively; P < .001; adjusted hazard ratio = 1.95 [95% confidence interval {CI}, 1.37-2.77; P < .001]). The median duration of unnecessary vancomycin therapy was reduced by 1.1 days (95% CI, .5-1.6 days; P < .001). CONCLUSIONS: This intervention improved prescribing, with a shorter time to concordant therapy and an increased proportion of patients receiving empiric therapy concordant with prior culture results. The use of unnecessary vancomycin was also reduced.

Monte Carlo simulation evaluation of tigecycline dosing for bacteria with raised minimum inhibitory concentrations in non-critically ill adults.

PURPOSE: Tigecycline is one of few antibiotics active against multidrug-resistant bacteria; however, the assessment of dosing strategies to optimize its activity is needed. The purpose was to use Monte Carlo Simulation (MCS) to determine if safe tigecycline dosing options attaining breakpoints for pharmacokinetic/pharmacodynamic (PK-PD) targets in non-critically ill adults could be identified. METHODS: Publications that evaluated tigecycline dosing regimens and provided mean PK variables of interest (minimum 2 of: elimination rate constant or half-life and volume of distribution or clearance), with SDs, were included. Weighted mean (±SDs) for each PK parameter were determined. Food and Drug Administration minimum inhibitory concentration (MIC) tigecycline breakpoints for susceptible (MIC ≤ 2 µg/mL), intermediate (MIC 4 µg/mL), and resistant (MIC ≥ 8 µg/mL) Enterobacteriaceae were used. MCS probability distributions for PK-PD target attainment of AUC for total tigecycline plasma concentration from 0 to 24 h following an intravenous dose (AUCtotal, 0-24h) to MIC ratios of ≥ 18, 7, and 4.5 were generated, with success defined as ≥ 80% probability of target attainment at a given MIC. RESULTS: Ten studies (n = 442) were eligible. Tigecycline 150 mg IV q12h for ward patients with resistant bacteria up to a MIC of 0.48, 1, and 2 µg/mL for an AUCtotal, 0-24h/MIC target attainment of 18, 7, and 4.5, respectively, may be appropriate. CONCLUSION: Bacterial infections with tigecycline MICs ≥ 0.48-2 µg/mL, depending on AUCtotal, 0-24h/MIC target, may require treatment with alternate antibiotics due to target attainment failure.

Improving Decision Making in Empiric Antibiotic Selection (IDEAS) for Gram-negative Bacteremia: A Prospective Clinical Implementation Study.

BACKGROUND: Timely selection of adequate empiric antibiotics has become increasingly difficult due to rising resistance rates and the competing desire to apply antimicrobial stewardship (AMS) principles. Individualized clinical prediction models offer the promise of reducing broad-spectrum antibiotic use and preserving/improving adequacy of treatment, but few have been validated in the clinical setting. METHODS: Multivariable models were used to predict the probability of susceptibility for gram-negative (GN) bacteria in bloodstream infections (bacteremia) to ceftriaxone, ciprofloxacin, ceftazidime, piperacillin-tazobactam, and meropenem. The models were combined with existing resistance-prediction methods to generate optimized and individualized suggestions for empiric therapy that were provided to prescribers by an AMS pharmacist. De-escalation of empiric antibiotics and adequacy of therapy were analyzed using a quasi-experimental design comparing two 9-month periods (pre- and postintervention) at a large academic tertiary care institution. RESULTS: Episodes of bacteremia (n = 182) were identified in the preintervention and postintervention (n = 201) periods. Patients who received the intervention were more likely to have their therapy de-escalated (29 vs 21%; aOR = 1.77; 95% CI, 1.09-2.87; P = .02). The intervention also increased the proportion of patients who were on the narrowest adequate therapy at the time of culture finalization (44% in the control and 55% in the intervention group; aOR = 2.04; 95% CI, 1.27-3.27; P = .003). Time to adequate therapy was similar in the intervention and control groups (5 vs 4 hours; P = .95). CONCLUSIONS: An AMS intervention, based on individualized predictive models for resistance, can influence empiric antibiotic selections for GN bacteremia to facilitate early de-escalation of therapy without compromising adequacy of antibiotic coverage.

The influence of personal communities in understanding avoidable emergency department attendance: qualitative study.

BACKGROUND: Use of emergency department (ED) care globally seems to be increasing at a faster rate than population growth (Baker, House of Commons Library. Accident and Emergency Statistics, Demand, Performance, 2017). In the UK there has been a reported 16% rise in emergency admissions over the past 5 years. Estimates that between 11 and 40% of ED attendances are non-urgent, with 11% of patients being discharged from the ED without treatment (NHS Digital 2017), and a further 44% require no follow-up treatment (NHS Digital, Hospital Accident and Emergency Activity 2016-17, 2019) is cited as evidence that these patients did not require this level of care. The solution to not using the most appropriate point in the system has traditionally been seen as a knowledge problem, requiring, improved sign-posting and information to enable people to self-manage or use health care management for minor ailments. However research about help-seeking behaviour suggests that the problem may not be an informational one. A considerable literature points to help seeking as a social process influenced by a range of contingencies and contextual factors including the way in which lay people influence health care utilisation (Giebel et al. BMJ Open 9:1, 2019). Personal communities comprise a variety of active and significant social ties which have potential to influence individual capacity to seek help. Here we extend and unpack further influencing decisions about seeking formal health care with reference to how they are shaped and informed by and within personal social networks. METHODS: We undertook a personal network mapping and qualitative interview-based study to look at, problematize and understand attendance for non-urgent problems. We used network analysis and methods to map and characterise the personal communities of people seeking help from ED for minor ailments and semi-structured interviews with 40 people attending a single ED and associated GP hub providing equivalent care. Interviews were built around an ego network mapping activity and a topic guide structured to explore attender's narratives about why they had visited the ED. This ego network activity uses a diagram consisting of three concentric circles (Fiori et al. J Gerontol B-Psychol 62: 322-30, 2007), representing closest social network members (in the centre) and those at further distance. Participants were initially presented with one of these diagrams and asked to write names of people or resources that had played a role in their attendance and the interviewer probed the interviewee to discuss the actions, input and value of the people and services that supported the visit to the ED. RESULTS: We analysed number and type of network connections and undertook a thematic analysis to identify how imagined and actual network members and influences were implicated in ED attendance. The network maps created during the interviews were examined and a typology of networks was developed and used to distinguish different types of networks informed by our reading of the data, and a Network Typology Scoring Tool, a measure of frequency of contact and relationship type in networks. CONCLUSIONS: Our study suggests that faced with acute minor illness or injury people's networks narrow: they do not (and perhaps cannot) mobilise their imagined care network because the resources or connections may not be there or are difficult to engage. In addition we identified important system drivers of behaviour, notably that these patients are often directed to the ED by 'professional influencers' including health services staff.

Retrospective multicentre matched cohort study comparing safety and efficacy outcomes of intermittent-infusion versus continuous-infusion vancomycin.

BACKGROUND: Patients with good renal function receiving intermittent-infusion vancomycin (IIV) may require total daily doses ≥4 g to achieve trough concentrations of 15-20 mg/L, increasing the risk of vancomycin-associated nephrotoxicity. Continuous-infusion vancomycin (CIV) may be associated with a lower risk of vancomycin-associated nephrotoxicity compared with IIV, but studies comparing safety of both dosing strategies are lacking. OBJECTIVES: To compare the risk of nephrotoxicity with CIV versus IIV when target concentration ranges were the same with both dosing modalities. METHODS: A retrospective multicentre matched cohort study of admitted patients between 1 January 2010 and 31 December 2016 was completed. Adult patients who received ≥48 h of vancomycin with at least one steady-state vancomycin concentration were eligible. The primary outcome was to compare the rates of nephrotoxic risk and renal injury, defined by the RIFLE criteria, between CIV and IIV. RESULTS: Of 2136 patients who received vancomycin during the study period, 146 CIV patients were eligible and matched to 146 IIV patients. After adjustment of potential confounders, CIV was found to have a lower odds of developing nephrotoxic risk (OR 0.42, 95% CI 0.21-0.98, P = 0.025) and renal injury (OR 0.19, 95% CI 0.05-0.59, P = 0.004). CONCLUSIONS: CIV is associated with a lower odds of nephrotoxicity compared with IIV when targeting the same concentration range and should be an alternative dosing strategy for patients who will receive prolonged therapy or require >4 g/day to achieve therapeutic levels.

Development and validation of a screening tool for early identification of bloodstream infection in older patients - a retrospective case-control study.

BACKGROUND: Delayed diagnosis of bloodstream infection (BSI) occurs in > 20% of older patients, with misdiagnosis in 35%. Our objective was to develop and validate a clinically useful screening tool to identify older patients with a high probability of having a BSI. METHODS: Hospitalized patients > 80 years old with BSI (n = 105/group) were evaluated for the tool development in this retrospective matched case-controlled study (learn cohort). The tool was validated in different retrospectively matched case and control patients > 80 years old (n = 120/group) and 65 to 79 years old (n = 250/group) (test cohort). Binary logistic regression was used to develop a screening tool using laboratory and clinical parameters that were significantly associated with BSI (P < 0.05; adjusted odds ratio (OR) > 1); and Classification and Regression Tree (CART) analysis was used to identify parameter breakpoints. Performance metrics were used to evaluate and validate the tool. RESULTS: The significant parameters associated with BSI were maximum temperature (Tmax)(> 37.55C)(OR = 42.575), neutrophils (> 7.95)(OR = 1.923), a change in level of consciousness (LOC) (Yes = 1, No = 0)(OR = 1.571), blood urea nitrogen (BUN)(> 10.05)(OR = 1.359), glucose (> 7.35)(OR = 1.167), albumin (< 33.5)(OR = 1.038) and alanine aminotransferase (ALT) (> 19.5)(OR = 1.005). The optimal screening tool [Ln (odds of BSI) = - 150.299 + 3.751(Tmax) + 0.654(neutrophils) + 0.452(change in LOC) + 0.307(BUN) + 0.154(glucose) + 0.038(albumin) + 0.005(ALT)] had favorable performance metrics in the learn and test cohorts (sensitivity, specificity and accuracy of 95% in the learn cohort and 77, 89, and 81% in the total test cohort); and performed better than using only temperature and neutrophil count. CONCLUSIONS: The validated tool had high predictive value which may improve early identification and management of BSI in older patients.

Impact of a Comprehensive Antimicrobial Stewardship Program on Institutional Burden of Antimicrobial Resistance: A 14-Year Controlled Interrupted Time-series Study.

BACKGROUND: Antimicrobial resistance (AMR) constitutes an international public health threat widely believed to result from excessive antimicrobial use (AMU). Numerous authorities have recommended antimicrobial stewardship programs (ASPs) to curb the selection of AMR, but there is a lack of data confirming this benefit. METHODS: A controlled interrupted time-series study spanning 14 years was performed to assess impact of a comprehensive hospital-based ASP that included pharmacist-led audit and feedback on institutional AMR. Patient-level microbiologic and AMU data were obtained from October 2002 to September 2016. Poisson regression models were used to identify changes in the incidence and trend of hospital-acquired (HA) antibiotic-resistant organisms (AROs) and multidrug-resistant organisms (MDROs). Changes in community-acquired (CA)-ARO, CA-MDRO, and inpatient AMU were assessed as controls and process outcomes. RESULTS: Statistically significant shifts in AMU, HA-ARO, and HA-MDRO trends coinciding with ASP implementation were observed, corresponding with a 9% reduction in HA-ARO burden (incidence rate ratio [IRR], 0.91 [95% confidence interval {CI}, .83-.99]; P = .03) and a 13% reduction in HA-MDRO burden (IRR, 0.87 [95% CI, .73-1.04]; P = .13) in the intervention period. In contrast, CA-ARO and CA-MDRO incidence continued to rise, with 40% (IRR, 1.40 [95% CI, 1.28-1.54]; P < .0001) and 68% (IRR, 1.68 [95% CI, 1.57-1.82]; P < .0001) increases in burden found, respectively. CONCLUSIONS: Implementation of a comprehensive ASP resulting in reduced AMU was associated with a significant reduction in institutional AMR, even though community AMR increased during the same period. These results confirm that ASPs play an important role in the fight against AMR.

Voriconazole prophylaxis in leukemic patients: A retrospective single-center study.

BACKGROUND: Invasive fungal infections commonly occur in acute myeloid and lymphoblastic leukemia patients receiving chemotherapy. In these patients with acute leukemia, posaconazole prophylaxis is recommended; however, voriconazole may be a less costly alternative. OBJECTIVES: The objective of this study was to evaluate the efficacy and safety of voriconazole prophylaxis in acute leukemia patients. METHODS: A retrospective chart review of inpatients at Sunnybrook Health Sciences Centre between 2005 and 2017 was completed. Hospitalized adult acute leukemia patients who received voriconazole prophylaxis (cases) were compared to patients who received fluconazole or no prophylaxis during chemotherapy (controls). Statistical analyses comparing baseline characteristics, safety, and efficacy outcomes between the study cohorts were completed. A posaconazole literature-based weighted mean risk was compared to the voriconazole risk of invasive fungal infection identified in this study. RESULTS: Of 490 acute myeloid leukemia or acute lymphoblastic leukemia patients, 83 controls and 92 cases were eligible. Case patients received an average of 24.4 ± 10.8 days of voriconazole prophylaxis. The incidence of proven or probable invasive fungal infections with voriconazole was 3.3% (3/92) versus 7.2% (6/83) in the control cohort (p > 0.05) and was comparable to the literature reported weighted incidence of invasive fungal infection with posaconazole (2.4 ± 2.1%; 95% CI 1.3%-3.4%; p > 0.05). Voriconazole was well tolerated by patients (91%; 84/91; seven discontinued due to asymptomatic elevated liver function tests). CONCLUSIONS: Voriconazole prophylaxis was found to be safe, effective, and comparable to literature-based efficacy data for risk of invasive fungal infection with posaconazole antifungal prophylaxis in patients with acute leukemia undergoing chemotherapy and could represent a significant cost advantage.

Women's successful transition to motherhood during the early postnatal period: A qualitative systematic review of postnatal and midwifery home care literature.

OBJECTIVE: To undertake a systematic review of available qualitative research literature to determine what women need to successfully transition to motherhood during the early postnatal period and whether postnatal home care delivered by midwives supports this process. DESIGN: The transition from woman to mother is a significant occurrence, one that requires adjustments on physical, psychological and social levels. A qualitative systematic review design was chosen to ensure both humanistic and interactive concepts related to what women need to successfully transition to motherhood during the early postnatal period were identified. The systematic and structured search uncovered 33 research articles for detailed review. Two team members, using the qualitative research checklist from the Critical Appraisal Skills Programme, appraised the quality of the research articles. A total of 19 articles met the quality criteria and were included in the data evaluation process. SETTING AND PARTICIPANTS: Research teams from Asia-Pacific, Europe, Middle East and North America generated the 19 qualitative journal articles. MEASUREMENTS AND FINDINGS: Data evaluation included identification of research aim, presence of a research question, type of methodology, data collection processes, sample information, data analysis techniques and study outcomes. Data was analysed using an inductive content analysis approach. Four themes were identified from the qualitative systematic review process including: women and midwives connecting, identification and meeting of women's individual needs, family and cultural influences and, education and support. KEY CONCLUSIONS: The ability of women to connect with midwives during the early postnatal period assisted them overcome barriers and to successfully transitioning to motherhood. Although all four themes were determined to be key to effective postnatal transition, overwhelmingly the findings showed postnatal midwifery home care to be important in women's successful transition to motherhood in the early postnatal period. IMPLICATIONS FOR PRACTICE: Strategies are needed ensure women have access to midwives in the early postnatal period.

Optimizing gentamicin conventional and extended interval dosing in neonates using Monte Carlo simulation - a retrospective study.

BACKGROUND: Although aminoglycosides are routinely used in neonates, controversy exists regarding empiric dosing regimens. The objectives were to determine gentamicin pharmacokinetics in neonates, and develop initial mg/kg dosing recommendations that optimized target peak and trough concentration attainment for conventional and extended-interval dosing (EID) regimens. METHODS: Patient demographics and steady-state gentamicin concentration data were retrospectively collected for 60 neonates with no renal impairment admitted to a level III neonatal intensive care unit. Mean pharmacokinetics were calculated and multiple linear regression was performed to determine significant covariates of clearance (L/h) and volume of distribution (L). Classification and regression tree (CART) analysis identified breakpoints for significant covariates. Monte Carlo Simulation (MCS) was used to determine optimal dosing recommendations for each CART-identified sub-group. RESULTS: Gentamicin clearance and volume of distribution were significantly associated with weight at gentamicin initiation. CART-identified breakpoints for weight at gentamicin initiation were: ≤ 850 g, 851-1200 g, and > 1200 g. MCS identified that a conventional dose of gentamicin 3.5 mg/kg given every 48 h or an EID of 8-9 mg/kg administered every 72 h in neonates weighing ≤ 850 g, and every 24 and 48 h, respectively, in neonates weighing 851-1200 g, provided the best probability of attaining conventional (peak: 5-10 mg/L and trough: ≤ 2 mg/L) and EID targets (peak:12-20 mg/L, trough:≤ 0.5 mg/L). Insufficient sample size in the > 1200 g neonatal group precluded further investigation of this weight category. CONCLUSIONS: This study provides initial gentamicin dosing recommendations that optimize target attainment for conventional and EID regimens in neonates weighing ≤ 1200 g. Prospective validation and empiric dose optimization for neonates > 1200 g is needed.

Development, evaluation and validation of a screening tool for late onset bacteremia in neonates - a pilot study.

BACKGROUND: Clinical and laboratory parameters can aid in the early identification of neonates at risk for bacteremia before clinical deterioration occurs. However, current prediction models have poor diagnostic capabilities. The objective of this study was to develop, evaluate and validate a screening tool for late onset (> 72 h post admission) neonatal bacteremia using common laboratory and clinical parameters; and determine its predictive value in the identification of bacteremia. METHODS: A retrospective chart review of neonates admitted to a neonatal intensive care unit (NICU) between March 1, 2012 and January 14, 2015 and a prospective evaluation of all neonates admitted between January 15, 2015 and March 30, 2015 were completed. Neonates with late-onset bacteremia (> 72 h after NICU admission) were eligible for inclusion in the bacteremic cohort. Bacteremic patients were matched to non-infected controls on several demographic parameters. A Pearson's Correlation matrix was completed to identify independent variables significantly associated with infection (p < 0.05, univariate analysis). Significant parameters were analyzed using iterative binary logistic regression to identify the simplest significant model (p < 0.05). The predictive value of the model was assessed and the optimal probability cut-off for bacteremia was determined using a Receiver Operating Characteristic curve. RESULTS: Maximum blood glucose, heart rate, neutrophils and bands were identified as the best predictors of bacteremia in a significant binary logistic regression model. The model's sensitivity, specificity and accuracy were 90, 80 and 85%, respectively, with a false positive rate of 20% and a false negative rate of 9.7%. At the study bacteremia prevalence rate of 51%, the positive predictive value, negative predictive value and negative post-test probability were 82, 89 and 11%, respectively. CONCLUSION: The model developed in the current study is superior to currently published neonatal bacteremia screening tools. Validation of the tool in a historic data set of neonates from our institution will be completed.

Fluoroquinolone Antibiotic Prophylaxis to Prevent Post-Traumatic Bacterial Infectious Endophthalmitis: Using Monte Carlo Simulation to Evaluate the Probability of Success.

Purpose: Patients with open globe injuries routinely receive fluoroquinolone (FQ) prophylaxis to prevent bacterial infectious endophthalmitis. Owing to the rarity of this infection, there is an absence of clinical trials evaluating optimal prophylactic FQ dosing. To address this knowledge gap, we conducted a Monte Carlo simulation (MCS)-based study to identify the FQ dosing option(s) that optimize pharmacokinetic-pharmacodynamic FQ target attainment against common bacterial pathogens implicated in post-traumatic bacterial infectious endophthalmitis (PTBIE). Methods: Weighted mean pharmacokinetic parameters and standard deviations for ciprofloxacin, levofloxacin, and moxifloxacin were calculated from published studies in healthy volunteers. The incidence and FQ susceptibility profiles for the most common bacteria causing PTBIE were extracted from the literature. MCS was used to determine the cumulative fraction of response (CFR) for 5 FQ dosing options to determine the probability of attaining pathogen-specific target 24-hour area under the curve to minimum inhibitory concentration ratios in the vitreous humor of the eye against the 4 most common causative bacteria seen in PTBIE. Results: Moxifloxacin 400 mg po daily (M400) achieved the highest CFR (72%). Levofloxacin dosing options achieved CFRs between 54% and 63%. Ciprofloxacin dosing options achieved CFRs between 28% and 35%. Conclusion: M400 optimized the likelihood of prophylactic success in the prevention of PTBIE, and based on the study findings, M400 is predicted to optimize the probability of success compared with ciprofloxacin and levofloxacin dosing options currently endorsed by expert opinion.