My Personal Teaching Philosophy: A Commentary

Beyond striving to ensure that students learn the fundamental content of the courses, the objectives as any professor should be: (a) to foster critical thinking skills; (b) to facilitate the acquisition of lifelong learning skills; and (c) to prepare students to function as highly skilled and competent communicators across the scope of their career. Furthermore, my overall teaching philosophy is based on two principles, which are supported extensively in the literature, constructivist, and social cognitive theory

Population Pharmacokinetic Modeling of Total and Free Ceftriaxone in Critically Ill Children and Young Adults and Monte Carlo Simulations Support Twice Daily Dosing for Target Attainment

Critical illness, including sepsis, causes significant pathophysiologic changes that alter the pharmacokinetics (PK) of antibiotics. Ceftriaxone is one of the most prescribed antibiotics in patients admitted to the pediatric intensive care unit (PICU). We sought to develop population PK models of both total ceftriaxone and free ceftriaxone in children admitted to a single-center PICU using a scavenged opportunistic sampling approach. We tested if the presence of sepsis and phase of illness (before or after 48 h of antibiotic treatment) altered ceftriaxone PK parameters. We performed Monte Carlo simulations to evaluate whether dosing regimens commonly used in PICUs in the United States (50 mg/kg of body weight every 12 h versus 24 h) resulted in adequate antimicrobial coverage. We found that a two-compartment model best described both total and free ceftriaxone concentrations. For free concentrations, the population clearance value is 6.54 L/h/70 kg, central volume is 25.4 L/70 kg, and peripheral volume is 19.6 L/70 kg. For both models, we found that allometric weight scaling, postmenstrual age, creatinine clearance, and daily highest temperature had significant effects on clearance. The presence of sepsis or phase of illness did not have a significant effect on clearance or volume of distribution. Monte Carlo simulations demonstrated that to achieve free concentrations above 1 mu g/ml for 100% of the dosing intervals, a dosing regimen of 50 mg/kg every 12 h is recommended for most patients. A continuous infusion could be considered if the target is to maintain free concentrations four times above the MICs (4 mu g/ml)

Mind the gap between policy imperatives and service provision: a qualitative study of the process of respiratory service development in England and Wales

The research was funded by the National Institute for Health Research Service Delivery and Organisation Programme. SDO/99/2005.Background: Healthcare systems globally are reconfiguring to address the needs of people with long-term conditions such as respiratory disease. Primary Care Organisations (PCOs) in England and Wales are charged with the task of developing cost-effective patient-centred local models of care. We aimed to investigate how PCOs in England and Wales are reconfiguring their workforce to develop respiratory services, and the background factors influencing service redesign. Methods: Semi-structured qualitative telephone interviews with the person(s) responsible for driving respiratory service reconfiguration in a purposive sample of 30 PCOs. Interviews were recorded, transcribed, coded and thematically analysed. Results: We interviewed representatives of 30 PCOs with diverse demographic profiles planning a range of models of care. Although the primary driver was consistently identified as the need to respond to a central policy to shift the delivery of care for people with long-term conditions into the community whilst achieving financial balance, the design and implementation of services were subject to a broad range of local, and at times serendipitous, influences. The focus was almost exclusively on the complex needs of patients at the top of the long-term conditions (LTC) pyramid, with the aim of reducing admissions. Whilst some PCOs seemed able to develop innovative care despite uncertainty and financial restrictions, most highlighted many barriers to progress, describing initiatives suddenly shelved for lack of money, progress impeded by reluctant clinicians, plans thwarted by conflicting policies and a PCO workforce demoralised by job insecurity. Conclusion: For many of our interviewees there was a large gap between central policy rhetoric driving workforce change, and the practical reality of implementing change within PCOs when faced with the challenges of limited resources, diverse professional attitudes and an uncertain organisational context. Research should concentrate on understanding these complex dynamics in order to inform the policymakers, commissioners, health service managers and professionals.Publisher PDFPeer reviewe

COVID-19 trajectories among 57 million adults in England: a cohort study using electronic health records

BACKGROUND: Updatable estimates of COVID-19 onset, progression, and trajectories underpin pandemic mitigation efforts. To identify and characterise disease trajectories, we aimed to define and validate ten COVID-19 phenotypes from nationwide linked electronic health records (EHR) using an extensible framework. METHODS: In this cohort study, we used eight linked National Health Service (NHS) datasets for people in England alive on Jan 23, 2020. Data on COVID-19 testing, vaccination, primary and secondary care records, and death registrations were collected until Nov 30, 2021. We defined ten COVID-19 phenotypes reflecting clinically relevant stages of disease severity and encompassing five categories: positive SARS-CoV-2 test, primary care diagnosis, hospital admission, ventilation modality (four phenotypes), and death (three phenotypes). We constructed patient trajectories illustrating transition frequency and duration between phenotypes. Analyses were stratified by pandemic waves and vaccination status. FINDINGS: Among 57 032 174 individuals included in the cohort, 13 990 423 COVID-19 events were identified in 7 244 925 individuals, equating to an infection rate of 12·7% during the study period. Of 7 244 925 individuals, 460 737 (6·4%) were admitted to hospital and 158 020 (2·2%) died. Of 460 737 individuals who were admitted to hospital, 48 847 (10·6%) were admitted to the intensive care unit (ICU), 69 090 (15·0%) received non-invasive ventilation, and 25 928 (5·6%) received invasive ventilation. Among 384 135 patients who were admitted to hospital but did not require ventilation, mortality was higher in wave 1 (23 485 [30·4%] of 77 202 patients) than wave 2 (44 220 [23·1%] of 191 528 patients), but remained unchanged for patients admitted to the ICU. Mortality was highest among patients who received ventilatory support outside of the ICU in wave 1 (2569 [50·7%] of 5063 patients). 15 486 (9·8%) of 158 020 COVID-19-related deaths occurred within 28 days of the first COVID-19 event without a COVID-19 diagnoses on the death certificate. 10 884 (6·9%) of 158 020 deaths were identified exclusively from mortality data with no previous COVID-19 phenotype recorded. We observed longer patient trajectories in wave 2 than wave 1. INTERPRETATION: Our analyses illustrate the wide spectrum of disease trajectories as shown by differences in incidence, survival, and clinical pathways. We have provided a modular analytical framework that can be used to monitor the impact of the pandemic and generate evidence of clinical and policy relevance using multiple EHR sources. FUNDING: British Heart Foundation Data Science Centre, led by Health Data Research UK

Linked electronic health records for research on a nationwide cohort of more than 54 million people in England: data resource

Abstract: Objective: To describe a novel England-wide electronic health record (EHR) resource enabling whole population research on covid-19 and cardiovascular disease while ensuring data security and privacy and maintaining public trust. Design: Data resource comprising linked person level records from national healthcare settings for the English population, accessible within NHS Digital’s new trusted research environment. Setting: EHRs from primary care, hospital episodes, death registry, covid-19 laboratory test results, and community dispensing data, with further enrichment planned from specialist intensive care, cardiovascular, and covid-19 vaccination data. Participants: 54.4 million people alive on 1 January 2020 and registered with an NHS general practitioner in England. Main measures of interest: Confirmed and suspected covid-19 diagnoses, exemplar cardiovascular conditions (incident stroke or transient ischaemic attack and incident myocardial infarction) and all cause mortality between 1 January and 31 October 2020. Results: The linked cohort includes more than 96% of the English population. By combining person level data across national healthcare settings, data on age, sex, and ethnicity are complete for around 95% of the population. Among 53.3 million people with no previous diagnosis of stroke or transient ischaemic attack, 98 721 had a first ever incident stroke or transient ischaemic attack between 1 January and 31 October 2020, of which 30% were recorded only in primary care and 4% only in death registry records. Among 53.2 million people with no previous diagnosis of myocardial infarction, 62 966 had an incident myocardial infarction during follow-up, of which 8% were recorded only in primary care and 12% only in death registry records. A total of 959 470 people had a confirmed or suspected covid-19 diagnosis (714 162 in primary care data, 126 349 in hospital admission records, 776 503 in covid-19 laboratory test data, and 50 504 in death registry records). Although 58% of these were recorded in both primary care and covid-19 laboratory test data, 15% and 18%, respectively, were recorded in only one. Conclusions: This population-wide resource shows the importance of linking person level data across health settings to maximise completeness of key characteristics and to ascertain cardiovascular events and covid-19 diagnoses. Although this resource was initially established to support research on covid-19 and cardiovascular disease to benefit clinical care and public health and to inform healthcare policy, it can broaden further to enable a wide range of research

Linked electronic health records for research on a nationwide cohort of more than 54 million people in England: data resource

Abstract: Objective: To describe a novel England-wide electronic health record (EHR) resource enabling whole population research on covid-19 and cardiovascular disease while ensuring data security and privacy and maintaining public trust. Design: Data resource comprising linked person level records from national healthcare settings for the English population, accessible within NHS Digital’s new trusted research environment. Setting: EHRs from primary care, hospital episodes, death registry, covid-19 laboratory test results, and community dispensing data, with further enrichment planned from specialist intensive care, cardiovascular, and covid-19 vaccination data. Participants: 54.4 million people alive on 1 January 2020 and registered with an NHS general practitioner in England. Main measures of interest: Confirmed and suspected covid-19 diagnoses, exemplar cardiovascular conditions (incident stroke or transient ischaemic attack and incident myocardial infarction) and all cause mortality between 1 January and 31 October 2020. Results: The linked cohort includes more than 96% of the English population. By combining person level data across national healthcare settings, data on age, sex, and ethnicity are complete for around 95% of the population. Among 53.3 million people with no previous diagnosis of stroke or transient ischaemic attack, 98 721 had a first ever incident stroke or transient ischaemic attack between 1 January and 31 October 2020, of which 30% were recorded only in primary care and 4% only in death registry records. Among 53.2 million people with no previous diagnosis of myocardial infarction, 62 966 had an incident myocardial infarction during follow-up, of which 8% were recorded only in primary care and 12% only in death registry records. A total of 959 470 people had a confirmed or suspected covid-19 diagnosis (714 162 in primary care data, 126 349 in hospital admission records, 776 503 in covid-19 laboratory test data, and 50 504 in death registry records). Although 58% of these were recorded in both primary care and covid-19 laboratory test data, 15% and 18%, respectively, were recorded in only one. Conclusions: This population-wide resource shows the importance of linking person level data across health settings to maximise completeness of key characteristics and to ascertain cardiovascular events and covid-19 diagnoses. Although this resource was initially established to support research on covid-19 and cardiovascular disease to benefit clinical care and public health and to inform healthcare policy, it can broaden further to enable a wide range of research

The Relationship between Negative Trauma-Related Cognitions and Psychosocial Functioning in Veterans with Posttraumatic Stress Disorder and Alcohol Use Disorder

Background: The comorbidity of posttraumatic stress disorder (PTSD) and alcohol use disorder (AUD) is highly prevalent and associated with especially poor psychosocial functioning. Negative trauma-related cognitions are theoretically proposed to be associated with poor psychosocial functioning in PTSD, but few studies have examined the association between negative trauma-related cognitions and psychosocial functioning in PTSD/AUD. Evaluating this association may provide evidence of a potential treatment target for improving psychosocial functioning in PTSD/AUD. We hypothesized that negative trauma-related cognitions, including cognitions about the self, world, and self-blame, would be independently associated with poor psychosocial functioning in the following domains: vitality, psychosocial well-being, role limitations due to emotional distress, and social functioning. Methods: We examined the relationship between negative trauma-related cognitions and psychosocial functioning in 145 treatment-seeking veterans with PTSD/AUD using multiple linear regression analyses while controlling for PTSD and alcohol abuse and dependence severity. Results: Our hypotheses were partially supported. We found that negative trauma-related cognitions were uniquely associated with greater psychosocial functional impairment, independent of PTSD and alcohol abuse and dependence severity. Specifically, negative trauma-related cognitions about the self were associated with greater psychosocial functional impairment across all domains, cognitions about the world were associated with worse social functioning and psychological well-being, and self-blame was associated with impaired psychological well-being. Conclusions: Given that improvements in negative trauma-related cognitions are a mechanism of trauma-focused treatment, future studies should examine whether changes in negative trauma-related cognitions through trauma-focused treatment are associated with improved psychosocial functioning

The Association Between Negative Trauma‐Related Cognitions and Pain‐Related Functional Status Among Veterans With Posttraumatic Stress Disorder and Alcohol Use Disorder

Among veterans with posttraumatic stress disorder (PTSD), alcohol use disorders (AUDs) are highly prevalent. Furthermore, PTSD frequently co-occurs with chronic pain (CP), and CP is associated with an increased risk of AUD. Pain-related beliefs and appraisals are significantly associated with poorer pain-related functional status, yet few studies have examined negative trauma-related cognitions and their impact on pain-related functional disability in veterans with co-occurring PTSD and AUD. Accordingly, we examined the association between negative trauma-related cognitions and pain severity and pain disability in 137 veterans seeking treatment for PTSD and AUD. Using hierarchical multiple linear regression, we found that higher levels of negative trauma-related cognitions (e.g., "I am completely incompetent") were associated with a higher level of pain severity, after controlling for PTSD symptom severity and frequency of alcohol use, total R2 = .07, ΔR2 = .06. Additionally, as hypothesized, we found that higher levels of negative trauma-related cognitions were associated with higher levels of pain disability, after controlling for PTSD symptom severity, frequency of alcohol use, and pain severity, total R2 = .46, ΔR2 = .03. Given that negative trauma-related cognitions contributed to pain severity and pain disability, even when controlling for PTSD severity and frequency of alcohol use, future studies should explore the potential impact of interventions that address negative trauma-related cognitions (e.g., prolonged exposure or cognitive processing therapy) on pain severity and disability

Pharmacokinetic parameters over time during sepsis and the association of target attainment and outcomes in critically ill children and young adults receiving ceftriaxone

Introduction: Early sepsis results in pharmacokinetic (PK) changes due to physiologic alterations. PK changes can lead to suboptimal drug target attainment, risking inadequate coverage from antibiotics like ceftriaxone. Little is known about how ceftriaxone PK and target attainment quantitatively change over time in patients with sepsis or the association between target attainment and outcomes in critically ill children and young adults. Methods: A retrospective analysis of a prospective study was conducted in a single-center pediatric intensive care unit. Septic patients given at least one ceftriaxone dose (commonly as 50 mg/kg every 12 h) and who had blood obtained in both the first 48 h of therapy (early) and afterwards (late) were included. Normalized clearance and central volume were estimated and compared in both sepsis phases. We evaluated target attainment, defined as concentrations above 1× or 4× the minimum inhibitory concentration (MIC) for 100% of dosing intervals, and investigated the association between target attainment and clinical outcomes. Results: Fifty-five septic patients (median age: 7.5 years) were included. Normalized clearance and central volume were similar in both phases (6.18 ± 1.48 L/h/70 kg early vs. 6.10 ± 1.61 L/h/70 kg late, p = 0.60; 26.6 [IQR 22.3, 31.3] L/70 kg early vs. 24.5 [IQR 22.0, 29.4] L/70 kg late, p = 0.18). Individual percent differences in normalized clearance and central volume between sepsis phases ranged from −39% to 276% and −51% to 212% (reference, late sepsis), respectively. Fewer patients attained the 1× MIC target in late sepsis (82% late vs. 96% early, p = 0.013), which was associated with transition to once daily dosing, typically done due to transfer from the pediatric intensive care unit (PICU) to a lower acuity unit. Failure to attain either target in late sepsis was associated with antibiotic broadening. Conclusion: Ceftriaxone PK parameters were similar between early and late sepsis, but there were large individual differences. Fewer patients attained MIC targets in late sepsis and all who did not attain the less stringent target received once daily dosing during this period. The failure to attain targets in late sepsis was associated with antibiotic broadening and could be an area for antibiotic stewardship intervention.</p