Persistent physical symptoms: definition, genesis, and management.

Persistent physical symptoms (synonymous with persistent somatic symptoms) is an umbrella term for distressing somatic complaints that last several months or more, regardless of their cause. These symptoms are associated with substantial disability and represent a major burden for patients, health-care professionals, and society. Persistent physical symptoms can follow infections, injuries, medical diseases, stressful life events, or arise de novo. As symptoms persist, their link to clearly identifiable pathophysiology often weakens, making diagnosis and treatment challenging. Multiple biological and psychosocial risk factors and mechanisms contribute to the persistence of somatic symptoms, including persistent inflammation; epigenetic profiles; immune, metabolic and microbiome dysregulation; early adverse life experiences; depression; illness-related anxiety; dysfunctional symptom expectations; symptom focusing; symptom learning; and avoidance behaviours, with many factors being common across symptoms and diagnoses. Basic care consists of addressing underlying pathophysiology and using person-centred communication techniques with validation, appropriate reassurance, and biopsychosocial explanation. If basic care is insufficient, targeted psychological and pharmacological interventions can be beneficial. A better understanding of the multifactorial persistence of somatic symptoms should lead to more specific, personalised, and mechanism-based treatment, and a reduction in the stigma patients commonly face.

Effectiveness of a symptom-clinic intervention delivered by general practitioners with an extended role for people with multiple and persistent physical symptoms in England: the Multiple Symptoms Study 3 pragmatic, multicentre, parallel-group, individually randomised controlled trial.

BACKGROUND: People with multiple and persistent physical symptoms have impaired quality of life and poor experiences of health care. We aimed to evaluate the effectiveness of a community-based symptom-clinic intervention in people with multiple and persistent physical symptoms, hypothesising that this symptoms clinic plus usual care would be superior to usual care only. METHODS: The Multiple Symptoms Study 3 was a pragmatic, multicentre, parallel-group, individually randomised controlled trial conducted in 108 general practices in the UK National Health Service in four regions of England between Dec 6, 2018, and June 30, 2023. Participants were individually randomised (1:1) to the symptom-clinic intervention plus usual care or to usual care only via a computer-generated, pseudo-random list stratified by trial centre. Allocation was done by the trial statistician and concealed with a centralised, web-based randomisation system; masking participants was not possible due to the nature of the intervention. The symptom-clinic intervention was a sequence of up to four medical consultations that aimed to elicit a detailed clinical history, fully hear and validate the participant, offer rational explanations for symptoms, and assist the participant to develop ways of managing their symptoms; it was delivered by general practitioners with an extended role. The primary outcome was Patient Health Questionnaire-15 (PHQ-15) score 52 weeks after randomisation, analysed by intention to treat. The trial is registered on the ISRCTN registry (ISRCTN57050216). FINDINGS: 354 participants were randomly assigned; 178 (50%) were assigned to receive the community-based symptoms clinic plus usual care and 176 (50%) were assigned to receive usual care only. At the primary-outcome point of 52 weeks, PHQ-15 scores were 14·1 (SD 3·7) in the group receiving usual care and 12·2 (4·5) in the group receiving the intervention. The adjusted between-group difference of -1·82 (95% CI -2·67 to -0·97) was statistically significantly in favour of the intervention group (p<0·0001). There were 39 adverse events in the group receiving usual care and 36 adverse events in the group receiving the intervention. There were no statistically significant between-group differences in the proportion of participants who had non-serious adverse events (-0·03, 95% CI -0·11 to 0·05) or serious adverse events (0·02, -0·02 to 0·07). No serious adverse event was deemed to be related to the trial intervention. INTERPRETATION: Our symptom-clinic intervention, which focused on explaining persistent symptoms to participants in order to support self-management, led to sustained improvement in multiple and persistent physical symptoms. FUNDING: UK National Institute for Health and Care Research.

Syrian hamster convalescence from prototype SARS-CoV-2 confers measurable protection against the attenuated disease caused by the Omicron variant.

The mutation profile of the SARS-CoV-2 Omicron (lineage BA.1) variant posed a concern for naturally acquired and vaccine-induced immunity. We investigated the ability of prior infection with an early SARS-CoV-2 ancestral isolate (Australia/VIC01/2020, VIC01) to protect against disease caused by BA.1. We established that BA.1 infection in naïve Syrian hamsters resulted in a less severe disease than a comparable dose of the ancestral virus, with fewer clinical signs including less weight loss. We present data to show that these clinical observations were almost absent in convalescent hamsters challenged with the same dose of BA.1 50 days after an initial infection with ancestral virus. These data provide evidence that convalescent immunity against ancestral SARS-CoV-2 is protective against BA.1 in the Syrian hamster model of infection. Comparison with published pre-clinical and clinical data supports consistency of the model and its predictive value for the outcome in humans. Further, the ability to detect protection against the less severe disease caused by BA.1 demonstrates continued value of the Syrian hamster model for evaluation of BA.1-specific countermeasures.

Cost-effectiveness of an extended-role general practitioner clinic for persistent physical symptoms: results from the Multiple Symptoms Study 3 (MSS3) pragmatic randomised controlled trial.

OBJECTIVES: To evaluate the cost-effectiveness of an extended-role general practitioner (GP) symptoms clinic (SC), added to usual care (UC) for patients with multiple persistent physical symptoms (sometimes known as "medically unexplained symptoms"). METHODS: A 52-week within-trial cost-utility analysis of a pragmatic multicentre randomised controlled trial comparing SC+UC (n=178) against UC alone (n=176), conducted from the primary perspective of the UK National Health Service (NHS) and personal and social services (PSS). Base-case quality-adjusted life-years (QALYs) were measured using EQ-5D-5L. Missing data were imputed using multiple imputation (MI). Cost-effectiveness results were presented as incremental cost-effectiveness ratios (ICERs) and incremental net monetary benefits (INMBs). Uncertainty was explored using cost-effectiveness acceptability curves (using 1000 non-parametric bootstrapped samples) and sensitivity analysis (including societal costs, using SF-6D and capability ICECAP-A outcomes to estimate QALYs and years of full capability (YFC) respectively, varying intervention costs, missing data mechanism assumptions). RESULTS: Multiple imputation analysis showed that, compared to UC alone, SC+UC was more expensive [(adjusted mean cost difference: 704; 95% CI:£605, £807)] and more effective [(adjusted mean QALY difference: 0.0447 (95% CI:0.0067, 0.0826)] yielding an ICER of £15,765/QALY, INMB of £189.22 (95% CI:-£573.62, £948.28) and a 69% probability of the SC+UC intervention arm being cost-effective at a threshold of £20000 per QALY. Results were robust to most sensitivity analyses, but sensitive to missing data assumptions (2 of the 8 scenarios investigated), SF-6D and ICECAP-A quality of life outcomes. CONCLUSIONS: A Symptoms Clinic is likely to be a potentially cost-effective treatment for patients with persistent physical symptoms.

Use of emergency departments by children and young people following telephone triage: a large database study.

BACKGROUND: Although one objective of NHS 111 is to ease the strain on urgent and emergency care services, studies suggest the telephone triage service may be contributing to increased demand. Moreover, while parents and caregivers generally find NHS 111 satisfactory, concerns exist about its integration with the healthcare system and the appropriateness of advice. This study aimed to analyse the advice provided in NHS 111 calls, the duration between the call and ED attendance, and the outcomes of such attendances made by children and young people (C&YP). METHODS: A retrospective cohort study was carried out of C&YP (≤17) attending an ED in the Yorkshire and Humber region of the UK following contact with NHS 111 between 1 April 2016 and 31 March 2017. This linked-data study examined NHS 111 calls and ED outcomes. Lognormal mixture distributions were fit to compare the time taken to attend ED following calls. Logistic mixed effects regression models were used to identify predictors of low-acuity NHS 111-related ED attendances. RESULTS: Our study of 348 401 NHS 111 calls found they were primarily concerning children aged 0-4 years. Overall, 13.1% of calls were followed by an ED attendance, with a median arrival time of 51 minutes. Of the 34 664 calls advising ED attendance 41% complied, arriving with a median of 38 minutes-27% of which defined as low-acuity. Although most calls advising primary care were not followed by an ED attendance (93%), those seen in an ED generally attended later (median 102 minutes) with 23% defined as low-acuity. Younger age (<1) was a statistically significant predictor of low-acuity ED attendance following all call dispositions apart from home care. CONCLUSION: More tailored options for unscheduled healthcare may be needed for younger children. Both early low-acuity attendance and late high-acuity attendance following contact with NHS 111 could act as useful entry points for clinical audits of the telephone triage service.

Examining the effect of interventions in emergency care for older people using a system dynamics decision support tool.

BACKGROUND: Rising demand for Emergency and Urgent Care is a major international issue and outcomes for older people remain sub-optimal. Embarking upon large-scale service development is costly in terms of time, energy and resources with no guarantee of improved outcomes; computer simulation modelling offers an alternative, low risk and lower cost approach to explore possible interventions. METHOD: A system dynamics computer simulation model was developed as a decision support tool for service planners. The model represents patient flow through the emergency care process from the point of calling for help through ED attendance, possible admission, and discharge or death. The model was validated against five different evidence-based interventions (geriatric emergency medicine, front door frailty, hospital at home, proactive care and acute frailty units) on patient outcomes such as hospital-related mortality, readmission and length of stay. RESULTS: The model output estimations are consistent with empirical evidence. Each intervention has different levels of effect on patient outcomes. Most of the interventions show potential reductions in hospital admissions, readmissions and hospital-related deaths. CONCLUSIONS: System dynamics modelling can be used to support decisions on which emergency care interventions to implement to improve outcomes for older people.

Factors associated with longer wait times, admission and reattendances in older patients attending emergency departments: an analysis of linked healthcare data.

BACKGROUND AND OBJECTIVE: Care for older patients in the ED is an increasingly important issue with the ageing society. To better assess the quality of care in this patient group, we assessed predictors for three outcomes related to ED care: being seen and discharged within 4 hours of ED arrival; being admitted from ED to hospital and reattending the ED within 30 days. We also used these outcomes to identify better-performing EDs. METHODS: The CUREd Research Database was used for a retrospective observational study of all 1 039 251 attendances by 368 754 patients aged 75+ years in 18 type 1 EDs in the Yorkshire and the Humber region of England between April 2012 and March 2017. We estimated multilevel logit models, accounting for patients' characteristics and contact with emergency services prior to ED arrival, time variables and the ED itself. RESULTS: Patients in the oldest category (95+ years vs 75-80 years) were more likely to have a long ED wait (OR=1.13 (95% CI=1.10 to 1.15)), hospital admission (OR=1.26 (95% CI=1.23 to 1.29)) and ED reattendance (OR=1.09 (95% CI=1.06 to 1.12)). Those who had previously attended (3+ vs 0 previous attendances) were more likely to have long wait (OR=1.07 (95% CI=1.06 to 1.08)), hospital admission (OR=1.10 (95% CI=1.09 to 1.12)) and ED attendance (OR=3.13 (95% CI=3.09 to 3.17)). Those who attended out of hours (vs not out of hours) were more likely to have a long ED wait (OR=1.33 (95% CI=1.32 to 1.34)), be admitted to hospital (OR=1.19 (95% CI=1.18 to 1.21)) and have ED reattendance (OR=1.07 (95% CI=1.05 to 1.08)). Those living in less deprived decile (vs most deprived decile) were less likely to have any of these three outcomes: OR=0.93 (95% CI=0.92 to 0.95), 0.92 (95% CI=0.90 to 0.94), 0.86 (95% CI=0.84 to 0.88). These characteristics were not strongly associated with long waits for those who arrived by ambulance. Emergency call handler designation was the strongest predictor of long ED waits and hospital admission: compared with those who did not arrive by ambulance; ORs for these outcomes were 1.18 (95% CI=1.16 to 1.20) and 1.85 (95% CI=1.81 to 1.89) for those designated less urgent; 1.37 (95% CI=1.33 to 1.40) and 2.13 (95% CI=2.07 to 2.18) for urgent attendees; 1.26 (95% CI=1.23 to 1.28) and 2.40 (95% CI=2.36 to 2.45) for emergency attendees; and 1.37 (95% CI=1.28 to 1.45) and 2.42 (95% CI=2.26 to 2.59) for those with life-threatening conditions. We identified two EDs whose patients were less likely to have a long ED, hospital admission or ED reattendance than other EDs in the region. CONCLUSIONS: Age, previous attendance and attending out of hours were all associated with an increased likelihood of exceeding 4 hours in the ED, hospital admission and reattendance among patients over 75 years. These differences were less pronounced among those arriving by ambulance. Emergency call handler designation could be used to identify those at the highest risk of long ED waits, hospital admission and ED reattendance.

Infection-competent monkeypox virus contamination identified in domestic settings following an imported case of monkeypox into the UK.

An imported case of monkeypox was diagnosed in December 2019 in a traveller returning from Nigeria to the UK. Subsequently, environmental sampling was performed at two adjoining single-room residences occupied by the patient and their sibling. Monkeypox virus DNA was identified in multiple locations throughout both properties, and monkeypox virus was isolated from several samples 3 days after the patient was last in these locations. Positive samples were identified following the use of both vacuum and surface sampling techniques; these methodologies allowed for environmental analysis of potentially contaminated porous and non-porous surfaces via real-time quantitative reverse transcriptase PCR analysis in addition to viral isolation to confirm the presence of infection-competent virus. This report confirms the potential for infection-competent monkeypox virus to be recovered in environmental settings associated with known positive cases and the necessity for rapid environmental assessment to reduce potential exposure to close contacts and the general public. The methods adopted in this investigation may be used for future confirmed cases of monkeypox in order to establish levels of contamination, confirm the presence of infection-competent material and to identify locations requiring additional cleaning.

Dose-Dependent Response to Infection with Ebola Virus in the Ferret Model and Evidence of Viral Evolution in the Eye.

Filoviruses cause high-consequence infections with limited approved medical countermeasures (MCMs). MCM development is dependent upon well-characterized animal models for the assessment of antiviral agents and vaccines. Following large-scale Ebola virus (EBOV) disease outbreaks in Africa, some survivors are left with long-term sequelae and persistent virus in immune-privileged sites for many years. We report the characterization of the ferret as a model for Ebola virus infection, reproducing disease and lethality observed in humans. The onset of clinical signs is rapid, and EBOV is detected in the blood, oral, and rectal swabs and all tissues studied. We identify viral RNA in the eye (a site of immune privilege) and report on specific genomic changes in EBOV present in this structure. Thus, the ferret model has utility in testing MCMs that prevent or treat long-term EBOV persistence in immune-privileged sites. IMPORTANCE Recent reemergence of Ebola in Guinea that caused over 28,000 cases between 2013 and 2016 has been linked to the original virus from that region. It appears the virus has remained in the region for at least 5 years and is likely to have been maintained in humans. Persistence of Ebola in areas of the body for extended periods of time has been observed, such as in the eye and semen. Despite the importance of reintroduction of Ebola from this route, such events are rare in the population, which makes studying medical interventions to clear persistent virus difficult. We studied various doses of Ebola in ferrets and detected virus in the eyes of most ferrets. We believe this model will enable the study of medical interventions that promote clearance of Ebola virus from sites that promote persistence.

Learning from COVID-19 related trial adaptations to inform efficient trial design-a sequential mixed methods study.

BACKGROUND: Many clinical trial procedures were often undertaken in-person prior to the COVID-19 pandemic, which has resulted in adaptations to these procedures to enable trials to continue. The aim of this study was to understand whether the adaptations made to clinical trials by UK Clinical Trials Units (CTUs) during the pandemic have the potential to improve the efficiency of trials post-pandemic. METHODS: This was a mixed methods study, initially involving an online survey administered to all registered UK CTUs to identify studies that had made adaptations due to the pandemic. Representatives from selected studies were qualitatively interviewed to explore the adaptations made and their potential to improve the efficiency of future trials. A literature review was undertaken to locate published evidence concerning the investigated adaptations. The findings from the interviews were reviewed by a group of CTU and patient representatives within a workshop, where discussions focused on the potential of the adaptations to improve the efficiency of future trials. RESULTS: Forty studies were identified by the survey. Fourteen studies were selected and fifteen CTU staff were interviewed about the adaptations. The workshop included 15 CTU and 3 patient representatives. Adaptations were not seen as leading to direct efficiency savings for CTUs. However, three adaptations may have the potential to directly improve efficiencies for trial sites and participants beyond the pandemic: a split remote-first eligibility assessment, recruitment outside the NHS via a charity, and remote consent. There was a lack of published evidence to support the former two adaptations, however, remote consent is widely supported in the literature. Other identified adaptations may benefit by improving flexibility for the participant. Barriers to using these adaptations include the impact on scientific validity, limitations in the role of the CTU, and participant's access to technology. CONCLUSIONS: Three adaptations (a split remote-first eligibility assessment, recruitment outside the NHS via a charity, and remote consent) have the potential to improve clinical trials but only one (remote consent) is supported by evidence. These adaptations could be tested in future co-ordinated 'studies within a trial' (SWAT).

Heterogeneity of reasons for attendance in frequent attenders of emergency departments and its relationship to future attendance.

BACKGROUND: EDs globally are under increasing pressure through rising demand. Frequent attenders are known to have complex health needs and use a disproportionate amount of resources. We hypothesised that heterogeneity of patients' reason for attendance would be associated with multimorbidity and increasing age, and predict future attendance. METHOD: We analysed an anonymised dataset of all ED visits over the course of 2014 in Yorkshire, UK. We identified 15 986 patients who had five or more ED encounters at any ED in the calendar year. Presenting complaint was categorised into one of 14 categories based on the Emergency Care Data Set (ECDS). We calculated measures of heterogeneity (count of ECDs categories and entropy of categories) and examined their relationship to total number of ED visits and to patient characteristics. We examined the predictive value of these and other features on future attendance. RESULTS: Most frequent attenders had more than one presenting complaint type. Heterogeneity increased with number of attendances, but heterogeneity adjusted for number of attendances did not vary substantially with age or sex. Heterogeneity was associated with the presence of one or more contacts for a mental health problem. For a given number of attendances, prior mental health contact but not heterogeneity was associated with further attendance. CONCLUSIONS: Heterogeneity of presenting complaint can be quantified and analysed for ED use: it is increased where there is a history of mental disorder but not with age. This suggests it reflects more than the number of medical conditions.

Frequent attendance at the emergency department shows typical features of complex systems: analysis of multicentre linked data.

OBJECTIVE: Frequent attendance at the ED is a worldwide problem. We hypothesised that frequent attendance could be understood as a feature of a complex system comprising patients, healthcare and society. Complex systems have characteristic statistical properties, with stable patterns at the level of the system emerging from unstable patterns at the level of individuals who make up the system. METHODS: Analysis of a linked dataset of routinely collected health records from all 13 hospital trusts providing ED care in the Yorkshire and Humber region of the UK (population 5.5 million). We analysed the distribution of attendances per person in each of 3 years and measured the transition of individual patients between frequent, infrequent and non-attendance. We fitted data to power law distributions typically seen in complex systems using maximum likelihood estimation. RESULTS: The data included 3.6 million attendances at EDs in 13 hospital trusts. 29/39 (74.3%) analyses showed a statistical fit to a power law; 2 (5.1%) fitted an alternative distribution. All trusts' data fitted a power law in at least 1 year. Differences over time and between hospital trusts were small and partly explained by demographics. In contrast, individual patients' frequent attendance was unstable between years. CONCLUSIONS: ED attendance patterns are stable at the level of the system, but unstable at the level of individual frequent attenders. Attendances follow a power law distribution typical of complex systems. Interventions to address ED frequent attendance need to consider the whole system and not just the individual frequent attenders.

Multi-site evaluation of advanced practice hand therapy clinics for the management of patients with trigger digit.

STUDY DESIGN: Prospective cohort design. BACKGROUND: Patient time on Australian public hospital surgical outpatient department (SOPD) waitlists often exceeds clinical recommendations for chronic hand conditions. Diversion to allied health is an alternative option, however evidence regarding patient and organizational outcomes in hand therapy is lacking. PURPOSE OF THE STUDY: To evaluate clinical and organizational efficacy, patient outcomes and satisfaction of diversion of referrals for patients with trigger digit (TD) from SOPD waitlists to Advanced Practice Hand Therapy (APHT) at 3 Australian hospitals. METHODS: Data was collected from eligible patients with TD through chart reviews and telephone satisfaction surveys. Data included number of patients requiring SOPD review, repeat referral to SOPD in the 12 months following APHT discharge, patient-rated outcomes, satisfaction scores, wait times to SOPD review and conversion to surgery-rates. Mann Whitney-U, t-test, Pearson's chi-squared test and a Binary Logistic Regression analysis were performed. RESULTS: 104 patients completed APHT treatment. Seventy patients (67%) did not require return to the SOPD waitlist. Repeat referral to SOPD within 12 months of APHT discharge occurred for only 1 patient. Patients requiring SOPD review after APHT treatment were seen within target time frames and demonstrated 88% conversion to surgery-rates. Michigan Hand Outcome Questionnaire scores showed greater improvement in those not requiring SOPD review (P< .001~25.9 vs 4.2). Regression analysis identified a negative association between initial total Michigan Hand Outcome Questionnaire scores and unfavorable discharge outcomes (OR 0.96, P= .007). Most (81%-93%) patients indicated satisfaction with the APHT service. CONCLUSION: Diversion of referrals for TD from SOPD to APHT is an effective waitlist management strategy, with the propensity to reduce waiting times, improve patient flow, whilst resulting in favorable clinical and patient-rated outcomes and satisfaction.

Performance and impact of disposable and reusable respirators for healthcare workers during pandemic respiratory disease: a rapid evidence review.

OBJECTIVES: To synthesise evidence concerning the range of filtering respirators suitable for patient care and guide the selection and use of different respirator types. DESIGN: Comparative analysis of international standards for respirators and rapid review of their performance and impact in healthcare. DATA SOURCES: Websites of international standards organisations, Medline and Embase, hand-searching of references and citations. STUDY SELECTION: Studies of healthcare workers (including students) using disposable or reusable respirators with a range of designs. We examined respirator performance, clinician adherence and performance, comfort and impact, and perceptions of use. RESULTS: We included standards from eight authorities across Europe, North and South America, Asia and Australasia and 39 research studies. There were four main findings. First, international standards for respirators apply across workplace settings and are broadly comparable across jurisdictions. Second, effective and safe respirator use depends on proper fitting and fit testing. Third, all respirator types carry a burden to the user of discomfort and interference with communication which may limit their safe use over long periods; studies suggest that they have little impact on specific clinical skills in the short term but there is limited evidence on the impact of prolonged wearing. Finally, some clinical activities, particularly chest compressions, reduce the performance of filtering facepiece respirators. CONCLUSION: A wide range of respirator types and models is available for use in patient care during respiratory pandemics. Careful consideration of performance and impact of respirators is needed to maximise protection of healthcare workers and minimise disruption to care.

Can-Pain-a digital intervention to optimise cancer pain control in the community: development and feasibility testing.

PURPOSE: To develop a novel digital intervention to optimise cancer pain control in the community. This paper describes intervention development, content/rationale and initial feasibility testing. METHODS: Determinants of suboptimal cancer pain management were characterised through two systematic reviews; patient, caregiver and healthcare professional (HCP) interviews (n = 39); and two HCP focus groups (n = 12). Intervention mapping was used to translate results into theory-based content, creating the app "Can-Pain". Patients with/without a linked caregiver, their general practitioners and community palliative care nurses were recruited to feasibility test Can-Pain over 4 weeks. RESULTS: Patients on strong opioids described challenges balancing pain levels with opioid intake, side effects and activities and communicating about pain management problems with HCPs. Can-Pain addresses these challenges through educational resources, contemporaneous short-acting opioid tracking and weekly patient-reported outcome monitoring. Novel aspects of Can-Pain include the use of contemporaneous breakthrough analgesic reports as a surrogate measure of pain control and measuring the level at which pain becomes bothersome to the individual. Patients were unwell due to advanced cancer, making recruitment to feasibility testing difficult. Two patients and one caregiver used Can-Pain for 4 weeks, sharing weekly reports with four HCPs. Can-Pain highlighted unrecognised problems, promoted shared understanding about symptoms between patients and HCPs and supported shared decision-making. CONCLUSIONS: Preliminary testing suggests that Can-Pain is feasible and could promote patient-centred pain management. We will conduct further small-scale evaluations to inform a future randomised, stepped-wedge trial. TRIAL REGISTRATION: Qualitative research: ClinicalTrials.gov , reference NCT02341846 Feasibility study: NIHR CPMS database ID 34172.

Antibiotic prescribing for respiratory tract infection: exploring drivers of cognitive effort and factors associated with inappropriate prescribing.

BACKGROUND: Antibiotics are over-prescribed for upper respiratory tract infection (URTI). It is unclear how factors known to influence prescribing decisions operate 'in the moment': dual process theories, which propose two systems of thought ('automatic' and 'analytical'), may inform this. OBJECTIVE(S): Investigate cognitive processes underlying antibiotic prescribing for URTI and the factors associated with inappropriate prescribing. METHODS: We conducted a mixed methods study. Primary care physicians in Scotland (n = 158) made prescribing decisions for patient scenarios describing sore throat or otitis media delivered online. Decision difficulty and decision time were recorded. Decisions were categorized as appropriate or inappropriate based on clinical guidelines. Regression analyses explored relationships between scenario and physician characteristics and decision difficulty, time and appropriateness. A subgroup (n = 5) verbalized their thoughts (think aloud) whilst making decisions for a subset of scenarios. Interviews were analysed inductively. RESULTS: Illness duration of 4+ days was associated with greater difficulty. Inappropriate prescribing was associated with clinical factors suggesting viral cause and with patient preference against antibiotics. In interviews, physicians made appropriate decisions quickly for easier cases, with little deliberation, reflecting automatic-type processes. For more difficult cases, physicians deliberated over information in some instances, but not in others, with inappropriate prescribing occurring in both instances. Some interpretations of illness duration and unilateral ear examination findings (for otitis media) were associated with inappropriate prescribing. CONCLUSION: Both automatic and analytical processes may lead to inappropriate prescribing. Interventions to support appropriate prescribing may benefit from targeting interpretation of illness duration and otitis media ear exam findings and facilitating appropriate use of both modes of thinking.

Antibiotics are often used to treat the common cold and ear/nose/throat infections but typically do not work for these issues. We explored the reasons why this prescribing may happen and some of the difficulties doctors might experience when making these treatment decisions. Doctors reviewed written descriptions of patients and decided whether or not to prescribe antibiotics. Some of these doctors also took part in an interview where they 'thought aloud' (said what they were thinking as they were thinking it) while considering the patient descriptions. When the patient had been ill for four or more days, this made decisions more difficult. Sometimes decisions to prescribe due to this illness duration and due to findings from an ear exam were not in line with guidelines for prescribing. Some decisions to prescribe seemed to be more related to automatic habits, while others occurred after careful deliberation over the information. Doctors need more support to make decisions involving these factors and may benefit from strategies to help them use their automatic/habitual thinking and their deliberative thinking in the best ways.

Functional somatic disorders: discussion paper for a new common classification for research and clinical use.

BACKGROUND: Functional somatic symptoms and disorders are common and complex phenomena involving both bodily and brain processes. They pose major challenges across medical specialties. These disorders are common and have significant impacts on patients' quality of life and healthcare costs. MAIN BODY: We outline five problems pointing to the need for a new classification: (1) developments in understanding aetiological mechanisms; (2) the current division of disorders according to the treating specialist; (3) failure of current classifications to cover the variety of disorders and their severity (for example, patients with symptoms from multiple organs systems); (4) the need to find acceptable categories and labels for patients that promote therapeutic partnership; and (5) the need to develop clinical services and research for people with severe disorders. We propose 'functional somatic disorders' (FSD) as an umbrella term for various conditions characterised by persistent and troublesome physical symptoms. FSDs are diagnosed clinically, on the basis of characteristic symptom patterns. As with all diagnoses, a diagnosis of FSD should be made after considering other possible somatic and mental differential diagnoses. We propose that FSD should occupy a neutral space within disease classifications, favouring neither somatic disease aetiology, nor mental disorder. FSD should be subclassified as (a) multisystem, (b) single system, or (c) single symptom. While additional specifiers may be added to take account of psychological features or co-occurring diseases, neither of these is sufficient or necessary to make the diagnosis. We recommend that FSD criteria are written so as to harmonise with existing syndrome diagnoses. Where currently defined syndromes fall within the FSD spectrum - and also within organ system-specific chapters of a classification - they should be afforded dual parentage (for example, irritable bowel syndrome can belong to both gastrointestinal disorders and FSD). CONCLUSION: We propose a new classification, 'functional somatic disorder', which is neither purely somatic nor purely mental, but occupies a neutral space between these two historical poles. This classification reflects both emerging aetiological evidence of the complex interactions between brain and body and the need to resolve the historical split between somatic and mental disorders.

Analysis of Inactivation of SARS-CoV-2 by Specimen Transport Media, Nucleic Acid Extraction Reagents, Detergents, and Fixatives.

The COVID-19 pandemic has necessitated a multifaceted rapid response by the scientific community, bringing researchers, health officials, and industry together to address the ongoing public health emergency. To meet this challenge, participants need an informed approach for working safely with the etiological agent, the novel human coronavirus SARS-CoV-2. Work with infectious SARS-CoV-2 is currently restricted to high-containment laboratories, but material can be handled at a lower containment level after inactivation. Given the wide array of inactivation reagents that are being used in laboratories during this pandemic, it is vital that their effectiveness is thoroughly investigated. Here, we evaluated a total of 23 commercial reagents designed for clinical sample transportation, nucleic acid extraction, and virus inactivation for their ability to inactivate SARS-CoV-2, as well as seven other common chemicals, including detergents and fixatives. As part of this study, we have also tested five filtration matrices for their effectiveness at removing the cytotoxic elements of each reagent, permitting accurate determination of levels of infectious virus remaining following treatment. In addition to providing critical data informing inactivation methods and risk assessments for diagnostic and research laboratories working with SARS-CoV-2, these data provide a framework for other laboratories to validate their inactivation processes and to guide similar studies for other pathogens.

Clinical features in primary care electronic records before diagnosis of ankylosing spondylitis: a nested case-control study.

BACKGROUND: Ankylosing spondylitis (AS) often has a long period from first symptom presentation to diagnosis. We examined the occurrence of symptoms, prescriptions and diagnostic tests in primary care electronic records over time prior to a diagnosis of AS. METHODS: Nested case-control study using anonymised primary care electronic health records from Scotland. Cases were 74 adults with a first diagnosis of AS between 2000 and 2010. Controls were matched for age, sex and GP practice: (a) 296 randomly selected adults (b) 169 adults whose records contained codes indicating spinal conditions or symptoms. We extracted clinical features (symptoms, AS-related disorders, prescriptions and diagnostic tests). Conditional logistic regression was used to examine the association between clinical features (both individually and in combinations) and diagnosis of AS. We examined the associations between clinical features and diagnosis over time prior to diagnosis. RESULTS: Several new composite pointers were predictive of AS: including distinct episodes of axial pain separated by more than 6 months (OR 12.7, 95% CI 4.7 to 34.6); the occurrence of axial pain with and tendon symptoms within the same year (OR 21.7, 95% CI 2.6 to 181.5); and the co-occurrence (within 30 days) of axial pain and a prescription for nonsteroidal anti-inflammatory drug (OR 10.4, 95%CI 4.9 to 22.1). Coded episodes of axial pain increased steadily over the 3 years before diagnosis. In contrast, large joint symptoms and enthesopathy showed little or no time trend prior to diagnosis. CONCLUSIONS: We identified novel composite pointers to a diagnosis of AS in GP records. These may represent valuable targets for diagnostic support systems.

Brief smoking cessation in acute Welsh hospitals: a realist approach.

This implementation study sought to determine what works to support brief smoking cessation (BSC) in acute hospital settings, through exploration of organizational delivery and the role of healthcare professionals (HCPs). We used a realist approach, with embedded stakeholder engagement, within a large health organization. We conducted interviews (n = 27), a survey (n = 279) and organization documentation review (n = 44). The final programme theory suggests HCPs implement BSC when they value it as part of their role in contributing to improved patient outcomes; this is due to personal and professional influences, such as knowledge or experience. Organizational support, training and working in an environment where BSC is visible as standard care, positively influences implementation. However, the context exerts a strong influence on whether BSC is implemented, or not. HCPs make nuanced judgements on whether to implement BSC based on their assessment of the patient's responses, the patient's condition and other acute care demands. HCPs are less likely to implement BSC in dynamic and uncertain environments, as they are concerned about adversely impacting on the clinician-patient relationship and prioritize other acute care requirements. Organizations should actively promote BSC as a core function of the acute hospital setting and improve professional practice through leadership, training, feedback and visible indicators of organizational commitment. HCPs can be persuaded that implementing BSC is an acute care priority and an expectation of standard practice for improving patient outcomes.