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QJM - current issue

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Proton pump inhibitors in IPF: beyond mere suppression of gastric acidity


Proton pump inhibitors (PPIs) are structurally composed of benzimidazole core; a pharmacologically common scaffold that makes up nearly one quarter of the hundred most selling drugs including anticancer, opioid, antihistaminic and antihelmintic drugs. In medicinal chemistry, benzimidazoles are coined as privileged scaffolds due to their ability to recognize and bind diverse biological targets. In this regard, PPIs have been linked to other extra-intestinal functions including direct modulation of airway epithelial, vascular endothelial and immune cells. PPIs have been reported to improve outcomes in idiopathic pulmonary fibrosis (IPF) including slowing the decline in measures of lung function, reducing episodes of acute exacerbations and prolonging transplant-free survival. Recently, the evidence-based guidelines for IPF treatment conditionally recommended the use of PPIs in IPF. However, no prospective clinical trial has been conducted to empirically evaluate the safety and efficacy of PPIs in IPF. Here, we discuss emerging anti-inflammatory and antifibrotic activity of PPIs in the context of IPF. We also discuss possible molecular mechanisms by which PPIs may unleash their beneficial effect in IPF.

How we will diagnose IPF in the future


The recent approval of two safe and effective treatments for patients with idiopathic pulmonary fibrosis (IPF) had as a direct consequence the absolute need for an accurate and early diagnosis. The standard approach to IPF diagnosis has proven to be effective and emphasized the importance of clinical and laboratory evaluations to exclude known causes of pulmonary fibrosis. At the same time, chest high-resolution computed tomography (HRCT) has proven to be the crucial initial diagnostic test, by identifying those patients who should undergo surgical lung biopsy to secure a confident diagnosis and an adequate treatment. However, this diagnostic approach showed over the years some limitations. First, many suspected IPF patients present with atypical HRCT appearances and at the same time are unfit (or unwilling) for surgical lung biopsy, therefore making a confident diagnosis of IPF impossible. Although the current recommendations indicate the need for an iterative multidisciplinary process incorporating available clinical, laboratory, imaging and histological features, recent work has identified new tools which might improve the overall accuracy of this process. Genomic techniques have been already applied to molecularly phenotype patients with interstitial lung disease and it is likely that in the near future clinicians will utilize blood or lung-specific molecular markers in combination with other clinical, physiological, or imaging features. The availability of new sampling procedures (e.g. transbronchial cryobiopsies), together with innovative imaging technologies (e.g. microCT) will most likely support and enhance diagnostic efforts, refine prognostic recommendations and ultimately influence therapeutic options.

Antipsychotic prescription amongst hospitalized patients with dementia


Background: Antipsychotic drugs are used to treat behavioural and psychological symptoms of dementia, despite significant safety concerns regarding increased risk of stroke and mortality. The numbers of patients with dementia and related behavioural symptoms being treated in acute hospitals is increasing.

Aim: (i) to determine pre-admission and in-hospital prevalence of antipsychotic use in a national sample of patients with dementia and acute illness; (ii) identify reasons for antipsychotic use; (iii) assess features of the ward environment which impact on patients with dementia; (iv) determine availability of dementia-specific policies, training, appraisal and mentorship programs which influence service delivery.

Design and Methods: Four-part standardized audit in 35 public acute hospitals comprising (i) retrospective healthcare record review (n = 660); (ii) prospective assessment of ward environment (n = 77); (iii) ward organization interview with clinical managers (n = 77); (iv) hospital organisation interview with senior managers (n = 35).

Results: Antipsychotic drugs were prescribed to 29% of patients with dementia before hospitalization and to 41% during hospitalization; one quarter received new or additional prescriptions. Assessments for delirium (45%), dementia symptoms (39%), mood (26%), mental state (64%) and distress-provoking factors (3%) were suboptimal. Drug indications were documented in 78%. Non-pharmacological interventions were not documented. Most wards lacked environmental cues to promote orientation. Dementia-specific care pathways existed in 2 of 35 hospitals. Staff support and training programmes were suboptimal. 12% of patients were discharged with new antipsychotic prescriptions.

Conclusion: Antipsychotic medications are commonly prescribed for hospitalized patients with dementia in Ireland. Ward environments and dementia-related governance structures are suboptimal.

Cytomegalovirus infection is associated with an increase in systolic blood pressure in older individuals


Background: Cytomegalovirus (CMV) is a chronic infection that is widely distributed in the population. CMV infects a range of tissues, including endothelium, and viral replication is suppressed by the host immune system. Infection is associated with increased risk of mortality from vascular disease in older people, but the mechanisms behind this have not been determined.

Aim: We investigated the association between CMV infection and cardiovascular phenotype in a cohort of healthy elderly donors.

Design: CMV serostatus and cardiovascular parameters were determined in the Lothian Birth cohort, which comprises 1091 individuals aged 70 years in whom many environmental, biochemical and radiological correlates of vascular function have been determined.

Methods: CMV serostatus was determined by enzyme-linked immunosorbant assay and correlated with a range of biochemical and phenotypic measures.

Results: Sixty-five percent of participants were CMV seropositive, which indicates chronic infection. The mean sitting systolic blood pressure (SBP) was 149.2 mmHg in CMV seropositive individuals compared with 146.2 mmHg in CMV seronegative subjects (SD 18.7 vs. 19.7; P < 0.017). This association between CMV infection and SBP was not attenuated after adjustment for a wide range of biological and socio-economic factors.

Conclusions: These data show that CMV infection is associated with an increase in SBP in individuals at age 70 years. The magnitude is comparable to environmental variables such as obesity, diabetes or high salt intake. This is the first evidence to show that a chronic infection may be an important determinant of blood pressure and could have significant implications for the future management of hypertension.

Qualitative effects of omalizumab on concomitant IgE-mediated disease in a severe asthmatic population: a real life observational study


Introduction: Omalizumab is a recombinant humanized monoclonal antibody (anti-IgE) licensed for use in GINA 5 asthma or for chronic idiopathic urticaria. Many patients with asthma have concomitant allergic diseases such as dermatitis and sinusitis. IgE is also implicated in allergic-bronchopulmonary disease (ABPA). In addition, extreme sensitivity to allergen can prevent the initiation of allergen immunotherapy.

Aim: The aim of this study was to assess the efficacy of omalizumab on symptoms of concomitant non asthmatic IgE-mediated allergic disease in a population of severe GINA 5 in a real life observational setting.

Design: This study is a retrospective, observational study assessing patients reported allergic, non-asthmatic symptom response to omalizumab treatment.

Methods: Fifty-six severe asthmatics treated with omalizumab were studied. Thirty-seven patients had concomitant rhino-sinusitis, 13 had dermatitis and 4 ABPA. Subjects were asked to grade the improvement in their symptom scores on an analogue scale from 0 (no response) to 10 (excellent response).

Results: Mean improvement from baseline was 5 and 1.8 in patients with allergic rhino-sinusitis and dermatitis, respectively. Mean improvement from baseline in respiratory symptoms in patients with ABPA was 4.0.

Conclusions: The results from our study suggest that omalizumab may have a role in allergic disease outside of its current license.

Medical undergraduates contributions to publication output of worlds top universities in 2013


Background: Medical undergraduates’ (UGs) involvement in research activities is thought to be mutually beneficial to students, their mentors and the scholarly productivity of their universities. However, most evidence in favor of such assumption relies on subjective measures such as the self-reported gains in skills or knowledge rather than robust objective estimates for assessing impact.

Aim: We aimed to objectively track and describe publications with UG co-authors—their proportion to the total publication output of world’s top universities, their characteristics and their potential impact on biomedical literature.

Methods: We contacted the corresponding authors of the 2013’s Medline-indexed publications affiliated to world’s top 10 universities to investigate if any of their co-authors was an UG. Articles with UG co-authors were further assessed to determine, along with other variables: the type of study design, field of the article, publishing journal and its impact factor (IF), and number of received citations.

Results: Out of 25 152 publications, 2537 articles (10.1%) contained at least one UG co-author who was the first author in 635 papers (25%). Articles with UG co-authors were published in 1114 journals with a median IF of 3.661. Most UGs’ co-authored publications (82.7%, n = 2098) were cited at least once within 1 year, for a median of three citations per article.

Conclusion: UGs contributed to one in every 10 publications affiliated to top universities. Their papers were published in journals with good IFs and received a fair number of citations, which would reflect the relatively good quality and impact of these articles.

Thyrotoxic hypokalemic periodic paralysis


Osler-Weber-Rendu syndrome


Hepatoid adenocarcinoma of the lung


Pneumothorax and deep sulcus sign


Left atrial myxoma


Chilaiditi syndrome


Pericardial mesothelioma


'Epidemic of hand deformities in the French Renaissance paintings of Jean and Francois Clouet


This article analyses the nature of the multiple finger anomalies found in portraits by the French Renaissance artistic dynasty, the Clouets. The multiplicity of finger anomalies could be either innocent congenital variants, or pathological and traumatic deformities. In view of the presence of such `beautifying variations' in the works of other Renaissance artists, the authors decided that these features were not the result of an epidemic of deformities, but instead represented a stylistic approach in paintings of this period at the French Court.