Tedizolid: a service evaluation in a large UK teaching hospital.

Tedizolid is a new oxazolidinone antibiotic with little real-life data on use outside of skin and soft tissue infections. There is a paucity of safety evidence in courses greater than 6 days. Our centre uses tedizolid predominantly when linezolid-associated adverse events have occurred. This service evaluation describes our experience to date. We performed a retrospective service evaluation by reviewing case notes, prescription charts, and laboratory system results for each patient prescribed tedizolid at our hospital and recording patient demographics, clinical details, and outcomes. Sixty patients received tedizolid between May 2016 and November 2018. Most were treated for bone or joint infections and had stopped linezolid prior to tedizolid prescription. Mean length of tedizolid therapy was 27 days. Haematological adverse effects were infrequent. Most patients (72%) finished the course and their clinical condition improved during treatment (72%). Adverse events were common, but often not thought to be tedizolid related. Tedizolid appears to be safe in prolonged courses within this context. It may be suitable for longer-term antibiotic therapy within a complex oral and parenteral outpatient antibiotic therapy (COPAT) service. Patients who do not tolerate linezolid can be safely switched to tedizolid if appropriate.

Reducing the Risk and Impact of Brachial Plexus Injury Sustained From Prone Positioning-A Clinical Commentary.

INTRODUCTION: Prone positioning is deployed as a critical treatment for improving oxygenation in patients with Acute Respiratory Distress Syndrome. This regimen is currently highly prevalent in the COVID-19 pandemic. The pandemic has brought about increased concern about how best to safely avoid brachial plexus injuries when caring for unconscious proned patients. METHODS: A review of the published literature on brachial plexus injuries secondary to proning ventilated patients was performed. This was combined with a review of available international critical care guidelines in order to produce a succinct set of guidelines to aid critical care departments in reducing brachial plexus injuries during these challenging times. DISCUSSION: There is no one manner in which prone positioning an unconscious patient can be made universally safe. This paper provides 6 key steps to reducing the incidence of brachial plexus injuries while proning and suggests a safe and sensible management and referral pathway for the conscious patient in which a brachial plexus injury is identified. CONCLUSION: There is in truth no completely safe position for every patient and certainly there will be anomalies in anatomy that will predispose certain individuals to nerve injury. Thus the injury rate cannot be reduced to zero but an understanding of the principles of protection will inform those undertaking positioning.

What prevents the intravenous to oral antibiotic switch? A qualitative study of hospital doctors' accounts of what influences their clinical practice.

OBJECTIVES: Escalating antimicrobial resistance worldwide necessitates urgent optimization of antimicrobial prescribing to preserve antibiotics for future generations. Early intravenous (iv) to oral switch campaigns are one strategy that hospital-based antimicrobial stewardship programmes can incorporate to minimize inappropriate antibiotic use. Yet, iv antibiotics continue to be offered for longer than is clinically indicated, increasing hospital length of stay, increasing costs and placing patients at risk (e.g. cannula-related infections). This study aims to identify why this inappropriate prescribing trend continues. METHODS: Twenty doctors (9 females and 11 males) working at a teaching hospital in north-east England participated in semi-structured interviews about their experiences of antibiotic use. NVivo10 software was used to conduct a thematic content analysis of the full interview transcripts driven by the framework approach. Results are reported according to COREQ guidelines. RESULTS: Decisions around the choice of iv over oral antibiotics were influenced by three key issues: (i) consumerism, i.e. participants were concerned about the risk of litigation or complaints if patient expectations were not met; (ii) hierarchy of the medical team structure limited opportunities for de-escalation of antibiotics; and (iii) iv antibiotics were perceived as more potent and having significant mythical qualities, which participants acknowledged were not necessarily evidence based. CONCLUSIONS: The iv to oral switch interventions should tailor strategies to demystify iv versus oral antibiotic efficacy, engage consumers around the negative effects of iv antibiotic overuse and examine strategies to streamline team decision-making. Addressing these issues has the potential to reduce inappropriate antibiotic use and resistance.

A qualitative process evaluation of a randomised controlled trial of a parenting intervention in community (school) settings for children at risk of attention deficit hyperactivity disorder (ADHD).

BACKGROUND: Interventions for parents of children experiencing emotional and/or behavioural difficulties can help to improve their children's health, educational and social outcomes. However, the desirability and acceptability of screening and offering such interventions for attention-deficit hyperactivity disorder (ADHD)-type problems are currently unclear. This article is a qualitative process evaluation of a pragmatic cluster randomised controlled trial (Trial registration: ISRCTN87634685; reported elsewhere) to assess the feasibility and acceptability of a school-based parenting intervention programme for parents and teachers of children with high levels of ADHD symptoms. METHODS: Parents (n = 22) and teaching staff (n = 29) took part in semi-structured group or individual interviews, either by telephone or face-to-face, following the main trial. Interviews were digitally-recorded, transcribed verbatim and subjected to thematic analysis. RESULTS: The parenting intervention was acceptable to parents and teachers, and they were enthusiastic about the need for parenting groups in the school environment and stressed the importance of parent-school collaboration. Parents generally stated a preference for universal recruitment approaches to such programmes whilst teachers described the need to target specific parents. Most parents who took part in the parenting intervention described it favourably and many saw benefits, at least in the short-term. Parents differed in their preferred group size, with some desiring one-to-one sessions and others favouring a larger group. Non-attending parents reported barriers to attendance such as fear of attending in a group, previous use of the programme, work and other commitments. Suggestions to improve the programme included: clearer communication; offering booster sessions; and greater collaboration with teachers. CONCLUSIONS: It is feasible to deliver parenting intervention programmes within or near schools. The intervention was acceptable to the majority of parents, thus retention was high, but recruitment was difficult and reaching the parents with the most need was challenging. The findings of the process evaluation identified greater benefits to families than were apparent in the main trial. Recommendations identified by parents and teaching staff may be used to inform service delivery and future research to enhance recruitment to parenting interventions in the school environment.

Particulate matter components, sources, and health: Systematic approaches to testing effects.

UNLABELLED: Exposure to particulate matter (PM) is associated with adverse health outcomes. There has long been a question as to whether some components of the PM mixture are of greater public health concern than others so that the sources that emit the more toxic components could be controlled. In this paper, we describe the National Particle Component Toxicity (NPACT) initiative, a comprehensive research program that combined epidemiologic and toxicologic approaches to evaluate this critical question, partly relying on information from a national network of air quality monitors that provided data on speciated PM2.5 (PM with an aerodynamic diameter<2.5 µm) starting in 2000. We also consider the results of the NPACT program in the context of selected research on PM components and health in order to assess the current state of the field. Overall, the ambitious NPACT research program found associations of secondary sulfate and, to a somewhat lesser extent, traffic sources with health effects. Although this and other research has linked a variety of health effects to multiple groups of PM components and sources of PM, the collective evidence has not yet isolated factors or sources that would be closely and unequivocally more strongly related to specific health outcomes. If greater success is to be achieved in isolating the effects of pollutants from mobile and other major sources, either as individual components or as a mixture, more advanced approaches and additional measurements will be needed so that exposure at the individual or population level can be assessed more accurately. Enhanced understanding of exposure and health effects is needed before it can be concluded that regulations targeting specific sources or components of PM2.5 will protect public health more effectively than continuing to follow the current practices of targeting PM2.5 mass as a whole. IMPLICATIONS: This paper describes a comprehensive epidemiologic and toxicologic research program to evaluate whether some components and sources of PM may be more toxic than others. This question is important for regulatory agencies in setting air quality standards to protect people's health. The results show that PM from coal and oil combustion and from traffic sources was associated with adverse health outcomes, but other components and sources could not definitively be ruled out. Thus, given current knowledge, the current practice of setting air quality standards for PM mass as a whole likely remains an effective approach to protecting public health.

Prevalence and Implementation Characteristics of Weekend Food Assistance Programs in U.S. Schools.

INTRODUCTION: Amid national efforts to align priorities for nutrition and food assistance programs, little is known about the implementation of community-led efforts for children. This study aimed to estimate U.S. public school participation in weekend backpack programs (WBPs), to document program structure, and to consider characteristics of programs with more nutritious food offerings. METHODS: The prevalence of WBP participation in 2022 was estimated using a state-stratified, random sample of n=413 public schools. Administrators from WBPs at 49 schools completed measures of implementation characteristics and nutritional quality of foods offered. In 2022-2023, using a multivariable-adjusted linear regression model, the authors explored the association between hypothesized implementation characteristics and Healthy Eating Index-2015 scores of foods provided. RESULTS: Half of public schools (53.7%, 95% CI: 46.8%, 60.7%) in the national sample reported participating in WBPs. Many WBPs in the subsample were affiliated with anti-hunger organizations (41%), led by school counselors and volunteers (55%), and funded by grants (51%). WBPs spent an average of $0.56 (sd=$0.36) per item. Foods provided averaged a Healthy Eating Index-2015 score of 58.4 (sd=12.3), similar to children's average diets. About half of WBPs (41%) reported accessing nutrition resources. CONCLUSIONS: Despite the decentralized structure and absence of dedicated funding mechanisms, WBPs were common in our national sample of schools, suggesting widespread perceptions of unmet food needs and extensive efforts from community members to mitigate weekend hunger. Further research on food procurement methods and program impacts on child nutrition outcomes is needed to advance national priorities for nutrition and food security.

Clinical Consultation During a Trauma-Focused Cognitive Behavioral Therapy Community-Based Learning Collaborative: Examination of Consultation Content, Consultative Strategies, and Provider Engagement.

Consultation following evidence-based practice (EBP) training enhances the uptake of EBPs. Yet, little is known about what occurs during consultation, and it is often difficult for providers to engage in consultation. This study examined provider engagement in consultation and the content and strategies used during consultation following training in Trauma-focused Cognitive Behavioral Therapy (TF-CBT) as part of a community-based learning collaborative (CBLC). Minute-to-minute live coding of consultation calls revealed most content was clinically-oriented and the most common strategies used by consultants were didactic in nature. Providers with more years of professional experience and those with greater TF-CBT knowledge attended significantly more consultation calls. Providers with a greater average weekly caseload and providers who were supervisors presented significantly more cases on calls. Providers with greater TF-CBT knowledge spoke significantly more minutes on calls. Consistent with previous work, findings highlight difficulties with provider engagement in consultation and that providers with more baseline expertise are most likely to be engaged. Findings suggest tailoring EBP training efforts to better engage providers at greatest risk for low engagement.

Repurposing tetracyclines for acute respiratory distress syndrome (ARDS) and severe COVID-19: a critical discussion of recent publications.

INTRODUCTION: Drug repurposing can be a successful approach to deal with the scarcity of cost-effective therapies in situations such as the COVID-19 pandemic. Tetracyclines have previously shown efficacy in preclinical acute respiratory distress syndrome (ARDS) models and initial predictions and experimental reports suggest a direct antiviral activity against SARS-CoV2. Furthermore, a few clinical reports indicate their potential in COVID-19 patients. In addition to the scarcity and limitations of the scientific evidence, the effectiveness of tetracyclines in experimental ARDS has been proven extensively, counteracting the overt inflammatory reaction and fibrosis sequelae due to a synergic combination of pharmacological activities. AREAS COVERED: This paper discusses the scientific evidence behind the application of tetracyclines for ARDS/COVID-19. EXPERT OPINION: The benefits of their multi-target pharmacology and their safety profile overcome the limitations, such as antibiotic activity and low commercial interest. Immunomodulatory tetracyclines and novel chemically modified non-antibiotic tetracyclines have therapeutic potential. Further drug repurposing studies in ARDS and severe COVID-19 are necessary.

Demographics and Outcomes of Initial Phase of COVID-19 Medicines Delivery Units Across 4 UK Centers During Peak B1.1.529 Omicron Epidemic: A Service Evaluation.

Background: COVID-19 medicines delivery units (CMDU) were established in late December 2021 to deliver early antiviral therapy to patients classified as at risk with the aim of preventing hospitalization. Methods: We performed a service evaluation at 4 CMDUs in England. We assessed demographics and triage outcomes of CMDU referral, uptake of antiviral therapy, and the rate of subsequent hospitalizations within 2 weeks of CMDU referral. Results: Over a 3-week period, 4788 patients were referred and 3989 were ultimately assessed by a CMDU. Overall, 832 of the patients referred (17%) were judged eligible for treatment and 628 (13%) were ultimately prescribed an antiviral agent. The overall rate of admission within 14 days was 1%. Patients who were admitted were significantly older than those who did not require hospitalization. Of patients prescribed molnupiravir and sotrovimab, 1.8% and 3.2%, respectively, were admitted. Conclusions: There was a high volume of referrals to CMDU service during the initial surge of the Omicron wave in the United Kingdom. A minority of patients were judged to be eligible for therapy. In a highly vaccinated population, the overall hospitalization rate was low.

Diagnostic and prognostic biomarkers of sepsis in critical care.

Sepsis is a leading cause of mortality in critically ill patients. Delay in diagnosis and initiation of antibiotics have been shown to increase mortality in this cohort. However, differentiating sepsis from non-infectious triggers of the systemic inflammatory response syndrome (SIRS) is difficult, especially in critically ill patients who may have SIRS for other reasons. It is this conundrum that predominantly drives broad-spectrum antimicrobial use and the associated evolution of antibiotic resistance in critical care environments. It is perhaps unsurprising, therefore, that the search for a highly accurate biomarker of sepsis has become one of the holy grails of medicine. Procalcitonin (PCT) has emerged as the most studied and promising sepsis biomarker. For diagnostic and prognostic purposes in critical care, PCT is an advance on C-reactive protein and other traditional markers of sepsis, but is not accurate enough for clinicians to dispense with clinical judgement. There is stronger evidence, however, that measurement of PCT has a role in reducing the antibiotic exposure of critical care patients. For units intending to incorporate PCT assays into routine clinical practice, the cost-effectiveness of this is likely to depend on the pre-implementation length of an average antibiotic course and the subsequent impact of implementation on emerging antibiotic resistance. In most of the trials to date, the average baseline duration of the antibiotic course was longer than is currently standard practice in many UK critical care units. Many other biomarkers are currently being investigated. To be highly useful in clinical practice, it may be necessary to combine these with other novel biomarkers and/or traditional markers of sepsis.

Sixty-eight consecutive patients assessed for COVID-19 infection: Experience from a UK Regional infectious diseases Unit.

BACKGROUND: Assessment of possible infection with SARS-CoV-2, the novel coronavirus responsible for COVID-19 illness, has been a major activity of infection services since the first reports of cases in December 2019. OBJECTIVES: We report a series of 68 patients assessed at a Regional Infection Unit in the UK. METHODS: Between 29 January 2020 and 24 February 2020, demographic, clinical, epidemiological and laboratory data were collected. We compared clinical features between patients not requiring admission for clinical reasons or antimicrobials with those assessed as needing either admission or antimicrobial treatment. RESULTS: Patients assessed were aged from 0 to 76 years; 36/68 were female. Peaks of clinical assessments coincided with updates to the case definition for suspected COVID-19. Microbiological diagnoses included SARS-CoV-2, mycoplasma pneumonia, influenza A, non-SARS/MERS coronaviruses and rhinovirus/enterovirus. Nine of sixty-eight received antimicrobials, 15/68 were admitted, 5 due to inability to self-isolate. Patients requiring admission on clinical grounds or antimicrobials (14/68) were more likely to have fever or raised respiratory rate compared to those not requiring admission or antimicrobials. CONCLUSIONS: The majority of patients had mild illness, which did not require clinical intervention. This finding supports a community testing approach, supported by clinicians able to review more unwell patients. Extensions of the epidemiological criteria for the case definition of suspected COVID-19 lead to increased screening intensity; strategies must be in place to accommodate this in time for forthcoming changes as the epidemic develops.

Cognitive behaviour therapy for non-cardiac pain in the chest (COPIC): a multicentre randomized controlled trial with economic evaluation.

BACKGROUND: Most patients with chest pain have nothing wrong with their cardiac function. Psychological forms of treatment for this condition are more likely to be successful than others. METHODS/DESIGN: A two-arm parallel controlled randomized trial of standard care versus a modified form of cognitive behaviour therapy for chest pain (CBT-CP) in patients who have attended emergency hospital services. Inclusion criteria include (i) emergency attendance more than once in the previous year with chest pain when no physical pathology has been found, (ii) aged between 16 and 75, (iii) signed consent to take part in the study. Exclusion criteria are (i) under current psychiatric care, (ii) those who have had new psychotropic drugs prescribed within the last two months, (iii) are receiving or about to receive a formal psychological treatment. Those satisfying these criteria will be randomized to 4-10 sessions of CBT-CP or to continue with standard care. Participants are randomized using a remote web-based system using permuted stacked blocks stratified by study centre. Assessment is carried out at baseline by researchers subsequently masked to allocation and at 6 months and 1 year after randomization. The primary outcome is the Health Anxiety Inventory score at 6 months, and secondary outcomes are generalised anxiety and depressive symptoms, the Lucock Health Anxiety Questionnaire adapted for chest pain, visual analogue scales for chest pain and discomfort (Inskip Scale), the Schedule for Evaluating Persistent Symptoms (SEPS), health related quality of life, social functioning and medical resource usage. Intention to treat analyses will be carried out with clinical and functioning data, and a cost-utility analysis will compare differences in total costs and differences in quality of life using QALYs derived from the EQ-5D. The data will also be linked to another parallel study in New Zealand where 126 patients with the same inclusion criteria have been treated in a similar trial; the form of analysis of the combined data has yet to be determined. DISCUSSION: The morbidity and costs of non-cardiac chest pain are substantial and if a simple psychological treatment given by health professionals working in medical departments is beneficial it should prove to be of great value. Combining data with a similar study in New Zealand is an additional asset. TRIAL REGISTRATION: ISRCTN14711101 (registered 05/03/2015).

A study of indoor carbon dioxide levels and sick leave among office workers.

BACKGROUND: A previous observational study detected a strong positive relationship between sick leave absences and carbon dioxide (CO2) concentrations in office buildings in the Boston area. The authors speculated that the observed association was due to a causal effect associated with low dilution ventilation, perhaps increased airborne transmission of respiratory infections. This study was undertaken to explore this association. METHODS: We conducted an intervention study of indoor CO2 levels and sick leave among hourly office workers employed by a large corporation. Outdoor air supply rates were adjusted periodically to increase the range of CO2 concentrations. We recorded indoor CO2 concentrations every 10 minutes and calculated a CO2 concentration differential as a measure of outdoor air supply per person by subtracting the 1-3 a.m. average CO2 concentration from the same-day 9 a.m. - 5 a.m. average concentration. The metric of CO2 differential was used as a surrogate for the concentration of exhaled breath and for potential exposure to human source airborne respiratory pathogens. RESULTS: The weekly mean, workday, CO2 concentration differential ranged from 37 to 250 ppm with a peak CO2 concentration above background of 312 ppm as compared with the American Society of Heating, Refrigeration and Air-conditioning Engineers (ASHRAE) recommended maximum differential of 700 ppm. We determined the frequency of sick leave among 294 hourly workers scheduled to work approximately 49,804.2 days in the study areas using company records. We found no association between sick leave and CO2 differential CONCLUSIONS: The CO2 differential was in the range of very low values, as compared with the ASHRAE recommended maximum differential of 700 ppm. Although no effect was found, this study was unable to test whether higher CO2 differentials may be associated with increased sick leave.

Hantavirus: an infectious cause of acute kidney injury in the UK.

We present a case of an undifferentiated febrile illness in a 59-year-old man from East Yorkshire. He was initially treated for leptospirosis due to the fact that he had farm exposure and the findings of acute kidney injury (AKI), thrombocytopenia and a raised alanine transferase (ALT) on his initial blood results. Serology tests later proved him to have had another rodent-borne illness: hantavirus. An investigation by Public Health England (formerly known as Health Protection Agency) (PHE) went on to prove the presence of the same serotype of hantavirus in rats caught on the patient's property. After an initial deterioration, the patient made a relatively uneventful recovery and all his blood tests returned to normal levels.

Penicillium marneffei presenting as an immune reconstitution inflammatory syndrome (IRIS) in a patient with advanced HIV.

A 62-year-old British man with advanced HIV was established on antiretroviral therapy and treatment for disseminated Mycobacterium avium complex and Cytomegalovirus infections. One month later he re-presented with epigastric pain, an epigastric mass and skin lesions. Abdominal imaging revealed large volume lymphadenopathy, which was not present on previous imaging. Blood cultures yielded Penicillium marneffei, a dimorphic fungus endemic to South-east Asia. The patient had spent several years travelling in Thailand prior to the diagnosis of HIV. Penicilliosis is a common AIDS-defining illness in endemic areas, but remains rare in Europe. In this case, it presented in the context of a rapidly decreasing viral load as an immune reconstitution inflammatory syndrome. The challenges of management in the context of multiple comorbidities and polypharmacy are discussed.