Regular treatment with formoterol and inhaled steroids for chronic asthma: serious adverse events (Review)

Background Epidemiological evidence has suggested a link between beta2-agonists and increases in asthma mortality. There has been much debate about possible causal links for this association, and whether regular (daily) long-acting beta2-agonists are safe when used alone or in conjunction with inhaled corticosteroids. Objectives The aim of this review is to assess the risk of fatal and non-fatal serious adverse events in trials that randomised patients with chronic asthma to regular formoterol with inhaled corticosteroids versus the same dose of inhaled corticosteroids alone. Search strategy Trials were identified using the Cochrane Airways Group Specialised Register of trials. Web sites of clinical trial registers were checked for unpublished trial data and Food and Drug Administration (FDA) submissions in relation to formoterol were also checked. The date of the most recent search was October 2008. Selection criteria Controlled parallel design clinical trials on patients of any age and severity of asthma were included if they randomised patients to treatment with regular formoterol and inhaled corticosteroids, and were of at least 12 weeks duration. Data collection and analysis Two authors independently selected trials for inclusion in the review. Outcome data were independently extracted by two authors. Unpublished data on mortality and serious adverse events were obtained from the sponsors. Main results The review included 14 studies on adults and adolescents (8,028 participants) and seven studies on children and adolescents (2,788 participants). Data on all cause fatal and non-fatal serious adverse events were found for all studies, and the overall risk of bias was low.Four deaths occurred on regular formoterol with inhaled corticosteroids, and none on regular inhaled corticosteroids alone. All the deaths were in adults, and one was reported to be asthma-related. The difference was not statistically significant. Non-fatal serious adverse events of any cause were very similar in adults [Peto Odds Ratio 0.99 (95% CI 0.74 to 1.33)], and an increase in events in children on regular formoterol was not statistically significant [Peto Odds Ratio 1.62 (95% CI 0.80 to 3.28)]. Asthma related serious adverse events on formoterol were lower in adults [Peto Odds Ratio 0.53 (95% CI 0.28 to 1.00)] and although they were higher in children [Peto Odds Ratio 1.49 ( 95% CI 0.48 to 4.61)], this was not statistically significant. Authors' conclusions It is not possible, from the data in this review, to reassure people with asthma that inhaled corticosteroids with regular formoterol carries no risk of increasing mortality in comparison to inhaled corticosteroids alone as all four deaths occurred among 6,594 people using inhaled corticosteroids with formoterol. On the other hand, we have found no conclusive evidence of harm and there was only one asthma related death registered during over 3,000 patient year observation on formoterol. In adults, the decrease in asthma-related serious adverse events on regular formoterol with inhaled corticosteroids was not accompanied by a decrease in all cause serious adverse events. In children the number of events was too small, and consequently the results too imprecise, to determine whether the increase in all cause non-fatal serious adverse events found in the previous meta-analysis on regular formoterol alone is abolished by the additional use of inhaled corticosteroids. Clinical decisions and information for patients regarding regular use of formoterol have to take into account the balance between known symptomatic benefits of formoterol and the degree of uncertainty and concern associated with its potential harmful effects

Transient neurological symptoms in the older population:report of a prospective cohort study--the Medical Research Council Cognitive Function and Ageing Study (CFAS)

Transient ischaemic attack (TIA) is a recognised risk factor for stroke in the older population requiring timely assessment and treatment by a specialist. The need for such TIA services is driven by the epidemiology of transient neurological symptoms, which may not be caused by TIA. We report prevalence and incidence of transient neurological symptoms in a large UK cohort study of older people

From Less to More: The clinician’s experience of the transition from non-intensive to intensive psychoanalytic psychotherapy with looked-after and adopted children.

The aim of this study is to explore the clinician’s experience of the transition from non- intensive (once-weekly) to intensive (three-times-weekly) psychoanalytic psychotherapy with looked-after and adopted children (referred to as LAAC) in the NHS Child and Adolescent Mental Health Services (referred to as CAMHS). The study aims to understand more about the processes involved in this transition when it takes place with children who have experienced early and often traumatic discontinuity, as well as the possible impact upon the therapy of this transition. The literature review reveals that the subject of transitions across session frequencies with LAAC has not yet been studied, despite its prevalence and significance as a clinical practice, confirming this to be a new and valid piece of research. The data for this study was collected through semi-structured interviews and analysed using Reflexive Thematic Analysis. The results offer insight into the complexity and challenges involved in this transition, raising questions about the process and arguing for greater understanding of the meaning for each patient of this change in session frequency. The findings conclude that moving LAAC patients out of once-weekly psychotherapy and into intensive treatment is a vastly more complex undertaking than is often acknowledged; attention is drawn to the difference between a successfully managed transition and an unsettling disruption, cautioning that change to the care plan requires significant preparation and understanding of the patient’s object relationship so that the risk of enacting early, traumatic discontinuities may be minimised. This study suggests that increasing session frequency may not always enable hoped-for developments and that, for some children, once-weekly frequency may be preferable. The findings indicate areas for further research while highlighting the need for greater understanding of this practice to enhance clinical judgement when considering this move and its possible implications for the therapy

Patients’ anticipated actions following transient ischaemic attack symptoms: a qualitative vignette-based study

Background: Transient Ischaemic Attack (TIA) requires urgent investigation and management. Urgent management reduces the risk of subsequent stroke markedly, but non-presentation or delays in patient presentation to health services have been found to compromise timely management. We aimed to explore general practice patients' anticipated responses to TIA symptoms. Methods: This was a qualitative study employing semi-structured telephone interviews. Participants were recruited from respondents in an earlier quantitative study based in Australian general practices. Maximum variation purposive sampling of patients from that study (on the basis of age, rurality, gender and previous experience of stroke/TIA) continued until thematic saturation was achieved. After initial interviews explored knowledge of TIA and potential responses, subsequent interviews further explored anticipated responses via clinical vignettes containing TIA and non-TIA symptoms. Transcribed interviews were coded independently by two researchers. Data collection and analysis were concurrent and cumulative, using a process of iterative thematic analysis and constant comparison. A schema explaining participants' anticipated actions emerged during this process and was iteratively tested in later interviews. Results: Thirty-seven interviews were conducted and a 'spectrum of action', from watchful waiting (only responding if symptoms recurred) to summoning an ambulance immediately, was established. Intermediate actions upon the spectrum were: intending to mention the episode to a general practitioner (GP) at a routine appointment; consulting a GP non-urgently; consulting a general practitioner (GP) urgently; and attending an Emergency Department urgently. The substrate for decision-making relating to this spectrum operated via three constructs: the 'individual set' of the participant (their inherent disposition towards action in response to health matters in general), their 'discriminatory power' (the ability to discriminate TIA symptoms from non-TIA symptoms) and their 'effective access' to health-care services. Conclusions: Policies to improve patients' accessing care (and accessing care urgently) post-TIA should address these three determinants of anticipated action

From Less to More: The clinician’s experience of the transition from non-intensive to intensive psychoanalytic psychotherapy with looked-after and adopted children

The aim of this study is to explore the clinician’s experience of the transition from non- intensive (once-weekly) to intensive (three-times-weekly) psychoanalytic psychotherapy with looked-after and adopted children (referred to as LAAC) in the NHS Child and Adolescent Mental Health Services (referred to as CAMHS). The study aims to understand more about the processes involved in this transition when it takes place with children who have experienced early and often traumatic discontinuity, as well as the possible impact upon the therapy of this transition. The literature review reveals that the subject of transitions across session frequencies with LAAC has not yet been studied, despite its prevalence and significance as a clinical practice, confirming this to be a new and valid piece of research. The data for this study was collected through semi-structured interviews and analysed using Reflexive Thematic Analysis. The results offer insight into the complexity and challenges involved in this transition, raising questions about the process and arguing for greater understanding of the meaning for each patient of this change in session frequency. The findings conclude that moving LAAC patients out of once-weekly psychotherapy and into intensive treatment is a vastly more complex undertaking than is often acknowledged; attention is drawn to the difference between a successfully managed transition and an unsettling disruption, cautioning that change to the care plan requires significant preparation and understanding of the patient’s object relationship so that the risk of enacting early, traumatic discontinuities may be minimised. This study suggests that increasing session frequency may not always enable hoped-for developments and that, for some children, once-weekly frequency may be preferable. The findings indicate areas for further research while highlighting the need for greater understanding of this practice to enhance clinical judgement when considering this move and its possible implications for the therapy

Understanding tensions and identifying clinician agreement on improvements to early-stage chronic kidney disease monitoring in primary care : a qualitative study

Funding This article presents independent research funded by the National Institute for Health Research School for Primary Care Research (NIHR SPCR) (reference:120). JE was also supported by the NIHR Programme Grants for Applied Research programme (Reference: RP-PG-1210-12012). DSL and LL are supported by the NIHR Oxford Biomedical Research CentrePeer reviewedPublisher PD

Are referrals to hospital from out-of-hours primary care associated with National Early Warning Scores?

Background: The National Early Warning Scores (NEWS) is used in various healthcare settings to augment clinical decision making, and there is growing interest in its application in primary care. This research aimed to determine the distribution of NEWS among patients in UK out-of-hours (OOH) general practice and explore the relationship between NEWS and referral of patients to hospital. Methods: A historical cohort study using routinely collected data from the Birmingham Out-of-hours general practice Research Database. This includes patients who attended a large out-of-hours general practice provider in the West Midlands, UK, between July 2013 and July 2018. All adults who were seen face to face who had a full set of physiological observations recorded were included. NEWS was calculated post hoc, and subsequent hospital referral was the outcome of interest. Results: A NEWS was calculated for 74 914 consultations. 46.9% of patients had a NEWS of 0, while 30.6% had a NEWS of 1. Patients were referred to hospital in 8.5% of all encounters. Only 6.9% (95% CI 6.3% to 7.5%) of the 6878 patients referred to hospital had a NEWS of ≥5. Of the 1509 patients with a NEWS ≥5, 68.6% (95%CI 66.2% to 70.9%) were not referred to hospital. When considering how NEWS was related to hospital referral, the area under the receiver operating characteristic (AUROC) for patients seen in their own home was 0.731 (95%CI 0.681 to 0.787). For patient seen in treatment centres, the AUROC was 0.589 (95% CI 0.582 to 0.596). Conclusions: Patients seen in out-of-hours general practice have low physiological acuity. Those referred to hospital have a slightly higher NEWS overall. NEWS is poorly associated with hospital referral, although the association is stronger for patients seen in at home compared with patients seen in treatment centres. Implementing NEWS-based referral from OOH general practice is likely to increase hospital admissions.</p

Chronic kidney disease: a large-scale population-based study of the effects of introducing the CKD-EPI formula for eGFR reporting

Objective To evaluate the effects of introducing the Chronic Kidney Disease-Epidemiology Collaboration (CKD-EPI) formula for estimated glomerular filtration rate (eGFR) reporting in the adult population in routine clinical practice with clinician-directed testing. Design Retrospective study of all creatinine measurements and calculation of eGFRs using Modification of Diet in Renal Disease (MDRD) and CKD-EPI formulae. Setting General population, Oxfordshire, UK. Participants An unselected population of around 660 000. Interventions Reporting of eGFRs using MDRD or CKD-EPI formulae. Primary and secondary outcome measures Evaluation of the effects of the CKD-EPI formula on the prevalence of different stages of chronic kidney disease (CKD). Results The CKD-EPI formula reduced the prevalence of CKD (stages 2-5) by 16.4% in patients tested in primary care. At the important stage 2-stage 3 cut-off, there was a relative reduction of 7.5% in the prevalence of CKD stages 3-5 from 15.7% to 14.5%. The CKD-EPI formula reduced the prevalence of CKD stages 3-5 in those aged &lt;70 but increased it at ages &gt;70. Above 70 years, the prevalence of stages 3-5 was similar with both equations for women (around 41.2%) but rose in men from 33.3% to 35.5%. CKD stages 4-5 rose by 15% due exclusively to increases in the over 70s, which could increase specialist referral rates. The CKD classification of 18.3% of all individuals who had a creatinine measurement was altered by a change from the MDRD to the CKD-EPI formula. In the UK population, the classification of up to 3 million patients could be altered, the prevalence of CKD could be reduced by up to 1.9 million and the prevalence of CKD stages 3-5 could fall by around 200 000. Conclusions Introduction of the CKD-EPI formula for eGFR reporting will reduce the prevalence of CKD in a primary care setting with current testing practice but will raise the prevalence in the over 70s age group. This has implications for clinical practice, healthcare policy and current prevalence-based funding arrangements