Systematic review and meta-analysis of pre-hospital diagnostic accuracy studies

Introduction: Paramedics are involved in examining, treating and diagnosing patients. The accuracy of these diagnoses is evaluated using diagnostic accuracy studies. We undertook a systematic review of published literature to provide an overview of how accurately paramedics diagnose patients compared with hospital doctors. A bivariate meta-analysis was incorporated to examine the range of diagnostic sensitivity and specificity. Methods :We searched MEDLINE, CINAHL, Embase, AMED and the Cochrane Database from 1946 to 7 May 2016 for studies where patients had been given a diagnosis by paramedics and hospital doctors. Keywords focused on study type (‘diagnostic accuracy’), outcomes (sensitivity, specificity, likelihood ratio?, predictive value?) and setting (paramedic*, pre-hospital, ambulance, ‘emergency service?’, ‘emergency medical service?’, ‘emergency technician?’ Results: 2941 references were screened by title and/or abstract. Eleven studies encompassing 384 985 patients were included after full-text review. The types of diagnoses in one of the studies encompassed all possible diagnoses and in the other studies focused on sepsis, stroke and myocardial infarction. Sensitivity estimates ranged from 32% to 100% and specificity estimates from 14% to 100%. Eight of the studies were deemed to have a low risk of bias and were incorporated into a meta-analysis which showed a pooled sensitivity of 0.74 (0.62 to 0.82) and a pooled specificity of 0.94 (0.87 to 0.97. Discussion: Current published research suggests that diagnoses made by paramedics have high sensitivity and even higher specificity. However, the paucity and varying quality of studies indicates that further prehospital diagnostic accuracy studies are warranted especially in the field of non-life-threatening conditions

Patients report improvements in continuity of care when quality of life assessments are used routinely in oncology practice: Secondary outcomes of a randomised controlled trial.

INTRODUCTION AND AIM: In a randomised trial investigating the effects of regular use of health-related quality of life (HRQOL) in oncology practice, we previously reported an improvement in communication (objective analysis of recorded encounters) and patient well-being. The secondary aims of the trial were to measure any impact on patient satisfaction and patients' perspectives on continuity and coordination of their care. METHODS: In a prospective trial involving 28 oncologists, 286 cancer patients were randomised to: (1) intervention arm: regular touch-screen completion of HRQOL with feedback to physicians; (2) attention-control arm: completion of HRQOL without feedback; and (3) control arm: no HRQOL assessment. Secondary outcomes were patients' experience of continuity of care (Medical Care Questionnaire, MCQ) including 'Communication', 'Coordination' and 'Preferences to see usual doctor' subscales, patients' satisfaction, and patients' and physicians' evaluation of the intervention. Analysis employed mixed-effects modelling, multiple regression and descriptive statistics. RESULTS: Patients in the intervention arm rated their continuity of care as better than the control group for 'Communication' subscale (p=0.03). No significant effects were found for 'Coordination' or 'Preferences to see usual doctor'. Patients' evaluation of the intervention was positive. More patients in the intervention group rated the HRQOL assessment as useful compared to the attention-control group (86% versus 29%), and reported their doctors considered daily activities, emotions and quality of life. CONCLUSION: Regular use of HRQOL measures in oncology practice brought changes to doctor-patient communication of sufficient magnitude and importance to be reported by patients. HRQOL data may improve care through facilitating rapport and building inter-personal relationships

Patient Experiences of Continuity of Cancer Care: Development of a new Medical Care Questionnaire (MCQ) for Oncology Outpatients

Objectives: To adapt the Components of Primary Care Index (CPCI) to be applicable to oncology outpatients and to assess the reliability and validity of the adapted instrument (renamed the Medical Care Questionnaire (MCQ)). Methods: The development and validation of the MCQ took place in four phases. Phase 1 reviewed the literature and examined existing measures. In Phase 2 the selected instrument (CPCI) was reviewed by a panel of experts using a stepwise consensus procedure. In Phase 3 the adapted 21-item MCQ was administered to 200 outpatients attending oncology appointments. The instrument was refined to 15-items and in Phase 4 it was completed by 477 oncology outpatients. The psychometric properties of the new instrument were assessed using exploratory factor analysis, multi-trait scaling analysis and by comparing MCQ scores between known groups. Results: Exploratory factor analysis of the 15-item MCQ suggested 3 subscales with acceptable to good reliability: “Communication” α=0.69; “Coordination” α=0.84; and “Preferences” α=0.75. Comparing known groups showed that patients who saw fewer doctors during their clinic visits reported stronger “Preferences” to see their usual doctor and rated “Communication” with their doctors as better than patients who saw more doctors during their clinic visits. Conclusion: The MCQ demonstrates good psychometric properties in the target population. It is a brief and simple to use instrument, which provides a valid perspective on patients’ experiences of communicating with doctors and their perceptions of the continuity and coordination of their cancer care. Patient Experiences of Continuity of Cancer Care: Development of a new Medical Care Questionnaire (MCQ) for Oncology Outpatient

Levels of State and Trait Anxiety in Patients Referred to Ophthalmology by Primary Care Clinicians: A Cross Sectional Study

Purpose There is a high level of over-referral from primary eye care leading to significant numbers of people without ocular pathology (false positives) being referred to secondary eye care. The present study used a psychometric instrument to determine whether there is a psychological burden on patients due to referral to secondary eye care, and used Rasch analysis to convert the data from an ordinal to an interval scale. Design Cross sectional study. Participants and Controls 322 participants and 80 control participants. Methods State (i.e. current) and trait (i.e. propensity to) anxiety were measured in a group of patients referred to a hospital eye department in the UK and in a control group who have had a sight test but were not referred. Response category analysis plus infit and outfit Rasch statistics and person separation indices were used to determine the usefulness of individual items and the response categories. Principal components analysis was used to determine dimensionality. Main Outcome Measure Levels of state and trait anxiety measured using the State-Trait Anxiety Inventory. Results State anxiety scores were significantly higher in the patients referred to secondary eye care than the controls (p0.1). Rasch analysis highlighted that the questionnaire results needed to be split into “anxiety-absent” and “anxiety-present” items for both state and trait anxiety, but both subscales showed the same profile of results between patients and controls. Conclusions State anxiety was shown to be higher in patients referred to secondary eye care than the controls, and at similar levels to people with moderate to high perceived susceptibility to breast cancer. This suggests that referral from primary to secondary eye care can result in a significant psychological burden on some patients

Recommending video content for use in group-based reminiscence therapy

REMPAD is a semi-automated cloud-based system used to facilitate digital reminiscence therapy for patients with mild-to-moderate dementia, enacted in a group setting. REMPAD uses profiles for participants and groups to proactively recommend interactive video content from the Internet to match these profiles. In this chapter, we focus on the design of the system and then the system architecture, the system build, data curation, and usage scenarios. We also report a series of steps carried out as part of our user-centered design approach to system development, and a series of analyses on interaction logs which indicate various levels of effectiveness for different configurations of the recommendation algorithm we use. The results indicate high user satisfaction when using the system, and strong tendency towards repeated use in future

ATRX dysfunction Induces replication defects in primary mouse cells

The chromatin remodeling protein ATRX, which targets tandem repetitive DNA, has been shown to be required for expression of the alpha globin genes, for proliferation of a variety of cellular progenitors, for chromosome congression and for the maintenance of telomeres. Mutations in ATRX have recently been identified in tumours which maintain their telomeres by a telomerase independent pathway involving homologous recombination thought to be triggered by DNA damage. It is as yet unknown whether there is a central underlying mechanism associated with ATRX dysfunction which can explain the numerous cellular phenomena observed. There is, however, growing evidence for its role in the replication of various repetitive DNA templates which are thought to have a propensity to form secondary structures. Using a mouse knockout model we demonstrate that ATRX plays a direct role in facilitating DNA replication. Ablation of ATRX alone, although leading to a DNA damage response at telomeres, is not sufficient to trigger the alternative lengthening of telomere pathway in mouse embryonic stem cells

A case study in serendipity: Environmental researchers use of traditional and social media for dissemination

In the face of demands for researchers to engage more actively with a wider range of publics and to capture different kinds of research impacts and engagements, we explored the ways a small number of environmental researchers use traditional and social media to disseminate research. A questionnaire was developed to investigate the impact of different media as a tool to broker contact between researchers and a variety of different stakeholders (for example, publics, other researchers, policymakers, journalists) as well as how researchers perceive that their use of these media has changed over the past five years. The questionnaire was sent to 504 researchers whose work had featured in a policy-oriented e-news service. 149 valid responses were received (29%). Coverage in traditional media (newspapers, broadcast) not only brokers contact with other journalists, but is a good source of contact from other researchers (n=47, 62%) and members of the public (n=36, 26%). Although the use of social media was limited amongst our sample, it did broker contact with other researchers (n=17, 47%) and the public (n=10, 28%). Nevertheless, few environmental researchers were actively using social media to disseminate their research findings, with many continuing to rely on academic journals and face-to-face communication to reach both academic and public audiences. © 2013 Wilkinson, Weitkamp

Dolutegravir twice-daily dosing in children with HIV-associated tuberculosis: a pharmacokinetic and safety study within the open-label, multicentre, randomised, non-inferiority ODYSSEY trial

Background: Children with HIV-associated tuberculosis (TB) have few antiretroviral therapy (ART) options. We aimed to evaluate the safety and pharmacokinetics of dolutegravir twice-daily dosing in children receiving rifampicin for HIV-associated TB. Methods: We nested a two-period, fixed-order pharmacokinetic substudy within the open-label, multicentre, randomised, controlled, non-inferiority ODYSSEY trial at research centres in South Africa, Uganda, and Zimbabwe. Children (aged 4 weeks to <18 years) with HIV-associated TB who were receiving rifampicin and twice-daily dolutegravir were eligible for inclusion. We did a 12-h pharmacokinetic profile on rifampicin and twice-daily dolutegravir and a 24-h profile on once-daily dolutegravir. Geometric mean ratios for trough plasma concentration (Ctrough), area under the plasma concentration time curve from 0 h to 24 h after dosing (AUC0–24 h), and maximum plasma concentration (Cmax) were used to compare dolutegravir concentrations between substudy days. We assessed rifampicin Cmax on the first substudy day. All children within ODYSSEY with HIV-associated TB who received rifampicin and twice-daily dolutegravir were included in the safety analysis. We described adverse events reported from starting twice-daily dolutegravir to 30 days after returning to once-daily dolutegravir. This trial is registered with ClinicalTrials.gov (NCT02259127), EudraCT (2014–002632-14), and the ISRCTN registry (ISRCTN91737921). Findings: Between Sept 20, 2016, and June 28, 2021, 37 children with HIV-associated TB (median age 11·9 years [range 0·4–17·6], 19 [51%] were female and 18 [49%] were male, 36 [97%] in Africa and one [3%] in Thailand) received rifampicin with twice-daily dolutegravir and were included in the safety analysis. 20 (54%) of 37 children enrolled in the pharmacokinetic substudy, 14 of whom contributed at least one evaluable pharmacokinetic curve for dolutegravir, including 12 who had within-participant comparisons. Geometric mean ratios for rifampicin and twice-daily dolutegravir versus once-daily dolutegravir were 1·51 (90% CI 1·08–2·11) for Ctrough, 1·23 (0·99–1·53) for AUC0–24 h, and 0·94 (0·76–1·16) for Cmax. Individual dolutegravir Ctrough concentrations were higher than the 90% effective concentration (ie, 0·32 mg/L) in all children receiving rifampicin and twice-daily dolutegravir. Of 18 children with evaluable rifampicin concentrations, 15 (83%) had a Cmax of less than the optimal target concentration of 8 mg/L. Rifampicin geometric mean Cmax was 5·1 mg/L (coefficient of variation 71%). During a median follow-up of 31 weeks (IQR 30–40), 15 grade 3 or higher adverse events occurred among 11 (30%) of 37 children, ten serious adverse events occurred among eight (22%) children, including two deaths (one tuberculosis-related death, one death due to traumatic injury); no adverse events, including deaths, were considered related to dolutegravir. Interpretation: Twice-daily dolutegravir was shown to be safe and sufficient to overcome the rifampicin enzyme-inducing effect in children, and could provide a practical ART option for children with HIV-associated TB

Neuropsychiatric manifestations and sleep disturbances with dolutegravir-based antiretroviral therapy versus standard of care in children and adolescents: a secondary analysis of the ODYSSEY trial

BACKGROUND: Cohort studies in adults with HIV showed that dolutegravir was associated with neuropsychiatric adverse events and sleep problems, yet data are scarce in children and adolescents. We aimed to evaluate neuropsychiatric manifestations in children and adolescents treated with dolutegravir-based treatment versus alternative antiretroviral therapy. METHODS: This is a secondary analysis of ODYSSEY, an open-label, multicentre, randomised, non-inferiority trial, in which adolescents and children initiating first-line or second-line antiretroviral therapy were randomly assigned 1:1 to dolutegravir-based treatment or standard-of-care treatment. We assessed neuropsychiatric adverse events (reported by clinicians) and responses to the mood and sleep questionnaires (reported by the participant or their carer) in both groups. We compared the proportions of patients with neuropsychiatric adverse events (neurological, psychiatric, and total), time to first neuropsychiatric adverse event, and participant-reported responses to questionnaires capturing issues with mood, suicidal thoughts, and sleep problems. FINDINGS: Between Sept 20, 2016, and June 22, 2018, 707 participants were enrolled, of whom 345 (49%) were female and 362 (51%) were male, and 623 (88%) were Black-African. Of 707 participants, 350 (50%) were randomly assigned to dolutegravir-based antiretroviral therapy and 357 (50%) to non-dolutegravir-based standard-of-care. 311 (44%) of 707 participants started first-line antiretroviral therapy (ODYSSEY-A; 145 [92%] of 157 participants had efavirenz-based therapy in the standard-of-care group), and 396 (56%) of 707 started second-line therapy (ODYSSEY-B; 195 [98%] of 200 had protease inhibitor-based therapy in the standard-of-care group). During follow-up (median 142 weeks, IQR 124–159), 23 participants had 31 neuropsychiatric adverse events (15 in the dolutegravir group and eight in the standard-of-care group; difference in proportion of participants with ≥1 event p=0·13). 11 participants had one or more neurological events (six and five; p=0·74) and 14 participants had one or more psychiatric events (ten and four; p=0·097). Among 14 participants with psychiatric events, eight participants in the dolutegravir group and four in standard-of-care group had suicidal ideation or behaviour. More participants in the dolutegravir group than the standard-of-care group reported symptoms of self-harm (eight vs one; p=0·025), life not worth living (17 vs five; p=0·0091), or suicidal thoughts (13 vs none; p=0·0006) at one or more follow-up visits. Most reports were transient. There were no differences by treatment group in low mood or feeling sad, problems concentrating, feeling worried or feeling angry or aggressive, sleep problems, or sleep quality. INTERPRETATION: The numbers of neuropsychiatric adverse events and reported neuropsychiatric symptoms were low. However, numerically more participants had psychiatric events and reported suicidality ideation in the dolutegravir group than the standard-of-care group. These differences should be interpreted with caution in an open-label trial. Clinicians and policy makers should consider including suicidality screening of children or adolescents receiving dolutegravir