In Malawi, 236 participants from the Advancing Cryptococcal Meningitis Treatment for Africa trial were followed for 12 months. The trial outcomes reported at 10 weeks were sustained to 1 year. One-week amphotericin B plus flucytosine was associated with the lowest 1 year mortality (27.5% [95% confidence interval, 16.3 to 44.1]).
BACKGROUND Assessment of students’ clinical competence in healthcare education typically involves the evaluation of their performance during a patient consultation. Direct observation of students with actual patients is important for the assessment of clinical skills prior to professional registration. The mini-clinical evaluation exercise (mini-CEX) has been widely established as part of a broad clinical assessment profile. The paper form has previously been validated in a number of healthcare scenarios including pre-registration osteopathic practice. Differences in satisfaction, when deploying the instrument through different media, are not widely explored. OBJECTIVE This study explored osteopathy students’ and tutors’ rating of satisfaction using the mini-CEX when administered via online and paper-based media. This was with a view to answer the following research question: Does the method of capture influence assessment satisfaction scores in the use of the mini-CEX? METHODS An online mini-CEX was developed using Google Forms and was initially trialled as a data entry process, with administration staff keying-in the completed paper assessment details post-hoc. Subsequently, Android-based tablets were used for direct capture of the observed clinical practice evaluation of students by tutors. This facilitated a comparison to the paper counterpart over the course of three academic years. The influence of gender and methods of assessment capture (paper and online) was explored with binary regression, Spearman's correlation and Kruskal Wallis test, with dependent variables of student and tutor satisfaction. RESULTS A total of 736 mini-CEX assessments of patient encounters were analysed, and 550 (75%) were completed online. The influence of the paper capture of assessment on satisfaction scores, compared to the online process, was not significant (odds ratio 1, CI 0.86 – 1.15). Student satisfaction ratings for female students assessed by male tutors indicated lower summary scores compared to same-sex pairings (P<.007). Correlation between all student and tutor satisfaction ratings was moderate (r2=0.62, 95% CI 0.57 – 0.66, P<.00001). CONCLUSIONS The findings suggest that there is no statistically significant difference between the two methods of delivery in terms of satisfaction of use for either examiner or student, potentially indicative of the suitability of the online version. While this has relevance to the teaching environment within osteopathy, there is applicability to other clinical healthcare. The role of gender as an influence in the satisfactory conduct of assessment warrants further investigation CLINICALTRIAL N/A
Treatment of chronic obstructive pulmonary disease (COPD) with inhaled and oral corticosteroids is common, although their exact role is unclear. Previous studies suggest these drugs may reduce decline in lung function in this group of patients. We report a study investigating the effect of inhaled beclomethasone diproprionate (BDP) on lung function and symptoms in a group of patients with COPD. Treatment was given for 2 years, and the decline in FEV 1 in individual patients calculated over this period. Ninety‐eight patients were randomized for the study, 59 completing 2 years of treatment. Patients withdrawn had more severe airflow obstruction. Decline in FEV 1 , measured both prior to and after bronchodilator, was less in patients receiving inhaled BDP, although the differences failed to reach statistical significance except in a subgroup of patients with more severe airflow obstruction. Exacerbation rates were also reduced by inhaled BDP, but again the differences failed to reach conventional levels of statistical significance. The results of this study are consistent with previous published work, but further insight into the long‐term role of corticosteroids in COPD await the publication of large studies which have recently been completed. Although the changes seen in this study and others are numerically small, the rate of decline in FEV 1 returned to normal levels expected from age‐related decline, and hence such treatment combined with other strategies may well have a significant role in the long‐term treatment of this condition.
Abstract Enteroviruses are a diverse selection of viruses which include polioviruses, coxsackieviruses, echoviruses and others. Severe or persistent enteroviral infection is well-documented in patients with antibody deficiency, mostly in those with X-linked agammaglobulinemia (XLA) or following anti-CD20 monoclonal antibody therapy[1]. Here we report the first case of enteroviral meningoencephalitis in a patient with Good’s syndrome and discuss the possible aetiopathogenic mechanisms involved.
We present a serendipitous case of clinically significant pan-hypogammaglobulinaemia, diagnosed after routine serological testing for possible coeliac disease led first to identification of IgA deficiency (discovered as a low background in IgA-based routine serological screening), and subsequently to confirmed pan-hypogammaglobulinaemia (antibody immunodeficiency). Hypogammaglobulinaemia is a relatively rare diagnosis (estimated at 1 in 36,000), in which delayed diagnosis and treatment are associated with chronic organ damage including bronchiectasis. Routine serological testing for coeliac disease using the IgA anti-tissue transglutaminase (IgA TTG) test is in widespread use and provides an opportunity for early diagnosis of hypogammaglobulinaemia. Routine serological screening for coeliac disease may uncover IgA deficiency, and we suggest that all IgA-deficient cases identified should also be checked for antibody deficiency by quantifying the other immunoglobulins (IgG, IgM).
The frequency content of the first second of the maximum forced expiratory manoeuvre (MFEM) was measured to determine if the currently accepted frequency limit of 20 Hz for MFEM is adequate for recording peak expiratory flow (PEF). The frequency response of a Fleisch pneumotachograph (PT) was measured and used to record MFEM from 24 patients attending a lung-function laboratory and 26 normal volunteers. The first 1.024 s of the signal recorded at 1,000 Hz for that blow with maximum PEF, underwent fast Fourier transformation using a triangular window function, applied after 0.75 s to reduce flow linearly to zero. All the frequencies above a set limit were removed, followed by inverse transformation to reconstitute the blow. The limits for this frequency cut-off were progressively varied from 100 Hz down to 15 Hz, with the resulting PEF being compared with the PEF from the reconstituted blow with no frequency reduction. The average±sd age for the group was 47±18 yrs and the average PEF was 450±187 L·min −1 , which, when expressed as a standardized residual, was 0.1±2.1, with a range from −4.5–3.9 indicating a good spread around normal values. Average rise time to PEF was 83±38 ms and dwell time >90% PEF was 45±25 ms. Cut-off >20 Hz reduced the mean PEF of the group by 8.5 L·min −1 (95% confidence limit 5.5–11.4 L·min −1 ), whereas cut-off >30 Hz reduced mean PEF by 4.4 L·min −1 (2.6–6.2). In the present study subjects, 30 Hz was on the 95th percentile of frequencies for defining the upper limit for 98% of the power spectrum for the first second of the blow. It has been shown that there are frequencies >20 Hz that contribute to peak expiratory flow enough to influence readings made using conventional hand-held peak expiratory flow meters, such as the mini-Wright. Devices used for recording flow from a maximum forced expiratory manoeuvre should therefore have an adequate frequency response of up to 30 Hz.
Journal Article Pyoderma gangrenosum‐like ulcer caused by Helicobacter cinaedi in a patient with x‐linked agammaglobulinaemia Get access J. Dua, J. Dua Departments of Immunology,*Dermatology, †Microbiology, and ‡Histopathology, Barts and the London NHS Trust, London, UK Dr Janet Dua, c/o Dr Hilary Longhurst, 2nd Floor, Pathology and Pharmacy Building, The Royal London Hospital, 80 Newark Street, London E1 2ES, UK E‐mail: janetdua3000@yahoo.co.uk Search for other works by this author on: Oxford Academic Google Scholar E. Elliot, E. Elliot Departments of Immunology,*Dermatology, †Microbiology, and ‡Histopathology, Barts and the London NHS Trust, London, UK Search for other works by this author on: Oxford Academic Google Scholar P. Bright, P. Bright Departments of Immunology,*Dermatology, †Microbiology, and ‡Histopathology, Barts and the London NHS Trust, London, UK Search for other works by this author on: Oxford Academic Google Scholar S. Grigoriadou, S. Grigoriadou Departments of Immunology,*Dermatology, †Microbiology, and ‡Histopathology, Barts and the London NHS Trust, London, UK Search for other works by this author on: Oxford Academic Google Scholar R. Bull, R. Bull Departments of Immunology,*Dermatology, †Microbiology, and ‡Histopathology, Barts and the London NHS Trust, London, UK Search for other works by this author on: Oxford Academic Google Scholar M. Millar, M. Millar Departments of Immunology,*Dermatology, †Microbiology, and ‡Histopathology, Barts and the London NHS Trust, London, UK Search for other works by this author on: Oxford Academic Google Scholar N. Wijesuriya, N. Wijesuriya Departments of Immunology,*Dermatology, †Microbiology, and ‡Histopathology, Barts and the London NHS Trust, London, UK Search for other works by this author on: Oxford Academic Google Scholar H. J. Longhurst H. J. Longhurst Departments of Immunology,*Dermatology, †Microbiology, and ‡Histopathology, Barts and the London NHS Trust, London, UK Search for other works by this author on: Oxford Academic Google Scholar Clinical and Experimental Dermatology, Volume 37, Issue 6, 1 August 2012, Pages 642–645, https://doi.org/10.1111/j.1365-2230.2011.04293.x Published: 01 August 2012
Therapeutic immunoglobulin G (IgG) products are produced from numerous plasma donations, and are infused in many medical conditions. The serological testing of patients who have received IgG infusions may well produce falsely positive and misleading results from this infused IgG, rather than endogenously produced IgG. We present two example cases of clinical situations where this could cause concern. We tested multiple IgG products with a range of serological tests performed in infective or autoimmune conditions, including hepatitis B, syphilis, human immunodeficiency virus, human T-lymphotropic virus, anti-neutrophil cytoplasmic antibody (ANCA), anti-nuclear antibody (ANA), anti-cardiolipin antibodies and anti-double stranded DNA (dsDNA) antibody. We found positivity within these products for hepatitis B surface and core antibody, syphilis, ANCA, ANA, anti-cardiolipin IgG and dsDNA antibody, which may result from specific or non-specific reactivity. The serological testing of patients who have received IgG treatment detects the administered IgG in addition to IgG produced by the patient.
Abstract Secondary immunodeficiency (SID) refers to an acquired immunodeficiency secondary to an extrinsic cause (e.g. disease, treatment) and can occur when any condition or treatment causes a reduction in number or function of immune components. Opportunistic or particularly severe infections should raise the suspicion of SID. SID is relatively common, and worldwide the most prevalent causes include malnutrition and advancing age. The aetiologies of SID can be loosely grouped into those caused by the related abnormalities of general health, underlying disease, barrier integrity or iatrogenic influences. Issues with general health that result in SID include malnutrition, advancing age, smoking and alcohol. Underlying diseases that cause SID include haematological malignancies, splenectomy/hyposplenism and some infections (e.g. human immunodeficiency virus (HIV)). Many diverse injuries, treatments or diseases can reduce barrier integrity resulting in SID, as well as a wide range of iatrogenic interventions. The treatment of SID depends on both the presentation and aetiology. Key Concepts Secondary immunodeficiency refers to an acquired immunodeficiency secondary to an extrinsic cause. The aetiology of secondary immunodeficiency is often multifactorial and may present with diverse opportunistic infections. Secondary immunodeficiency is common, and the most common aetiology worldwide is malnutrition. Causes of secondary immunodeficiency can be loosely defined by aetiology into disorders of general health, barrier integrity, relating to underlying diseases or as iatrogenic. Severe presentations of common infections and certain characteristic opportunistic infections should raise the suspicion of secondary immunodeficiency. Many secondary immunodeficiencies relate to the use of medications, particularly the new generation of biological agents. Infections, as well as being a result of immunodeficiency, may also cause secondary immunodeficiency. The treatment of secondary immunodeficiency is complicated and dependent on both the presentation and the aetiology of the immunodeficiency.
Abstract Purpose To define the burden of morbidity and mortality arising from COVID-19 in individuals with primary (PID) and secondary immunodeficiency (SID) in the United Kingdom. Methods In March 2020, the United Kingdom Primary Immunodeficiency Network (UKPIN) established a registry of cases to collate the outcomes of individuals with PID and SID following SARS-CoV-2 infection and treatment. Anonymised demographic data, pre-SARS-CoV-2 infection lymphocyte counts, co-morbidities, targeted treatments and outcomes were collected. Three groups were analysed in further detail: individuals with common variable immunodeficiency (CVID), individuals with any PID, including CVID, receiving immunoglobulin replacement therapy (IgRT) and individuals with secondary immunodeficiency. Results A total of 310 cases of SARS-CoV-2 infection in individuals with PID or SID have now been reported in the UK. The overall mortality within the cohort was 17.7% (n = 55/310). Individuals with CVID demonstrated an infection fatality rate (IFR) of 18.3% (n = 17/93), individuals with PID receiving IgRT had an IFR of 16.3% (n = 26/159) and individuals with SID, an IFR of 27.2% (n = 25/92). Individuals with PID and SID, had higher inpatient mortality and died at a younger age than the general population. Increasing age, low pre-SARS-CoV-2 infection lymphocyte count and the presence of common co-morbidities increased the risk of mortality in PID. Access to specific COVID-19 treatments in this cohort was limited: only 22.9% (n = 33/144) of patients admitted to hospital received dexamethasone, remdesivir, an anti-SARS-CoV-2 antibody-based therapeutic (e.g. REGN-COV2 or convalescent plasma) or tocilizumab as a monotherapy or in combination. Dexamethasone, remdesivir and anti-SARS-CoV-2 antibody-based therapeutics appeared efficacious in PID and SID. Conclusion Compared to the general population, individuals with PID or SID are at high risk of mortality following SARS-CoV-2 infection. Increasing age, low baseline lymphocyte count and the presence of co-morbidities are additional risk factors for poor outcome in this cohort.
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