The Inhalation Characteristics of Patients When They Use Different Dry Powder Inhalers

Background: The characteristics of each inhalation maneuver when patients use dry powder inhalers (DPIs) are important, because they control the quality of the emitted dose. Methods: We have measured the inhalation profiles of asthmatic children [CHILD; n=16, mean forced expiratory volume in 1 sec (FEV1) 79% predicted], asthmatic adults (ADULT; n=53, mean predicted FEV1 72%), and chronic obstructive pulmonary disease (COPD; n=29, mean predicted FEV1 42%) patients when they inhaled through an Aerolizer, Diskus, Turbuhaler, and Easyhaler using their “real-life” DPI inhalation technique. These are low-, medium-, medium/high-, and high-resistance DPIs, respectively. The inhalation flow against time was recorded to provide the peak inhalation flow (PIF; in L/min), the maximum pressure change (ΔP; in kPa), acceleration rates (ACCEL; in kPa/sec), time to maximum inhalation, the length of each inhalation (in sec), and the inhalation volume (IV; in liters) of each inhalation maneuver. Results: PIF, ΔP, and ACCEL values were consistent with the order of the inhaler's resistance. For each device, the inhalation characteristics were in the order ADULT>COPD>CHILD for PIF, ΔP, and ACCEL (p4 L and ΔP >4 kPa. Conclusion: The large variability of these inhalation characteristics and their range highlights that if inhalation profiles were used with compendial in vitro dose emission measurements, then the results would provide useful information about the dose patients inhale during routine use. The inhalation characteristics highlight that adults with asthma have greater inspiratory capacity than patients with COPD, whereas children with asthma have the lowest. The significance of the inhaled volume to empty doses from each device requires investigation

Can Archival Tissue Reveal Answers to Modern Research Questions?: Computer-Aided Histological Assessment of Neuroblastoma Tumours Collected over 60 Years.

Despite neuroblastoma being the most common extracranial solid cancer in childhood, it is still a rare disease. Consequently, the unavailability of tissue for research limits the statistical power of studies. Pathology archives are possible sources of rare tissue, which, if proven to remain consistent over time, could prove useful to research of rare disease types. We applied immunohistochemistry to investigate whether long term storage caused any changes to antigens used diagnostically for neuroblastoma. We constructed and quantitatively assessed a tissue microarray containing neuroblastoma archival material dating between 1950 and 2007. A total of 119 neuroblastoma tissue cores were included spanning 6 decades. Fourteen antibodies were screened across the tissue microarray (TMA). These included seven positive neuroblastoma diagnosis markers (NB84, Chromogranin A, NSE, Ki-67, INI1, Neurofilament Protein, Synaptophysin), two anticipated to be negative (S100A, CD99), and five research antibodies (IL-7, IL-7R, JAK1, JAK3, STAT5). The staining of these antibodies was evaluated using Aperio ImageScope software along with novel pattern recognition and quantification algorithms. This analysis demonstrated that marker signal intensity did not decrease over time and that storage for 60 years had little effect on antigenicity. The construction and assessment of this neuroblastoma TMA has demonstrated the feasibility of using archival samples for research

Evaluation of a chest radiograph reading and recording system for tuberculosis in a HIV-positive cohort.

Aim To assess the impact of introducing a chest radiograph reading and recording system (CRRS) with a short training session, on the accuracy and inter-reader variability of tuberculosis (TB) interpretation of chest radiographs (CXRs) by a group of non-expert readers in a human immunodeficiency virus (HIV)-positive cohort. Materials and methods A set of 139 CXRs was reviewed by a group of eight physicians pre- and post-intervention at two clinics in Shan State, Myanmar, providing HIV/TB diagnosis and treatment services. The results were compared against the consensus of expert radiologists for accuracy. Results Overall accuracy was similar pre- and post-intervention for most physicians with an average area under the receiver operating characteristic curve difference of 0.02 (95% confidence interval: –0.03, 0.07). The overall agreement among physicians was poor pre- and post-intervention (Fleiss κ=0.35 and κ=0.29 respectively). The assessment of agreement for specific disease patterns associated with active TB in HIV-infected patients showed that for intrinsically subtle findings, the agreement was generally poor but better for the more intrinsically obvious disease patterns: pleural effusion (Cohen’s kappa range = 0.37–0.67) and milliary nodular pattern (Cohen’s kappa range = 0.25–0.52). Conclusion This study demonstrated limited impact of the introduction of a CRRS on CXR accuracy and agreement amongst non-expert readers. The role in which CXRs are used for TB diagnosis in a HIV-positive cohort in similar clinical contexts should be reviewed

Towards the probabilistic analysis of small bowel capsule endoscopy features to predict severity of duodenal histology in patients with villous atrophy

Small bowel capsule endoscopy (SBCE) can be complementary to histological assessment of celiac disease (CD) and serology negative villous atrophy (SNVA). Determining the severity of disease on SBCE using statistical machine learning methods can be useful in the follow up of patients. SBCE can play an additional role in differentiating between CD and SNVA. De-identified SBCEs of patients with CD and SNVA were included. Probabilistic analysis of features on SBCE were used to predict severity of duodenal histology and to distinguish between CD and SNVA. Patients with higher Marsh scores were more likely to have a positive SBCE and a continuous distribution of macroscopic features of disease than those with lower Marsh scores. The same pattern was also true for patients with CD when compared to patients with SNVA. The validation accuracy when predicting the severity of Marsh scores and when distinguishing between CD and SNVA was 69.1% in both cases. When the proportions of each SBCE class group within the dataset were included in the classification model, to distinguish between the two pathologies, the validation accuracy increased to 75.3%. The findings of this work suggest that by using features of CD and SNVA on SBCE, predictions can be made of the type of pathology and the severity of disease

Improving Diagnostic Yield of Capsule Endoscopy in Coeliac Disease: Can Flexible Spectral Imaging Colour Enhancement Play a Role?

Introduction: Flexible spectral imaging colour enhancement (FICE) is a form of virtual chromoendoscopy that is incorporated in the capsule reading software and that can be used by reviewers to enhance the delineation of lesions in the small bowel. This has been shown to be useful in the detection of pigmented (ulcers, angioectasias) lesions. However, its application to coeliac disease (CD) images from small bowel capsule endoscopies (SBCEs) has rarely been studied. Methods: This was a European, multicentre study that included 5 expert capsule reviewers who were asked to evaluate a number of normal and abnormal de-identified images from SBCEs of patients with CD to determine whether the use of FICE and blue light can improve the detection of CD-related changes. Results: Sensitivity and specificity of conventional white light in the delineation of CD-related changes were 100%. The next best image modification was FICE 1 with a sensitivity of 80% and a specificity of 100%. There was no difference between conventional white light, FICE and blue light for the identification of CD-related changes. There was a low agreement (Fleiss kappa 0.107; p = 0.147) between expert reviewers in selecting the best image modification that detected CD-related changes. Conclusions: FICE and blue light were not found to be superior to conventional white light in the delineation of macroscopic changes related to CD on SBCEs

What is the role of small bowel capsule endoscopy in established coeliac disease?

Introduction Patients with established coeliac disease (CD) can present with signs and symptoms requiring small bowel capsule endoscopy (SBCE) to assess for persistent disease beyond the duodenum and to rule out complications. There is paucity of data on extent of disease on SBCE in relation to histology, clinical and serological parameters. The aim of this study was to assess the relationship between symptoms, CD serology and Marsh classification of disease and extent of disease on SBCE in patients with established CD. Methods Hundred patients with established CD and 200 controls underwent a SBCE. SBCEs were reviewed by expert reviewers. Extent of disease on SBCE, CD findings and small bowel transit were recorded. Results Considering duodenal histology (D2; Marsh 3a or above) as the gold standard for diagnosing CD activity, the sensitivity of SBCE to delineate active disease was 87.2%. The specificity was 89.0%. Age at SBCE (P = 0.006), albumin (P = 0.004) and haemoglobin (P = 0.0001), Marsh score of histology from the duodenal bulb (D1) (P = 0.0001) and the second part of the duodenum (P = 0.0001), refractory CD (P = 0.007) on histology correlated with extent of affected small bowel (SB) mucosa on univariate analysis. On multiple regression analysis, albumin (P = 0.036) and Marsh score of histology (D1) (P = 0.019), vitamin B12 (P = 0.001) and folate levels (P = 0.008) were statistically significant. Extent of affected SB mucosa (11.0% vs 1.35%) was greater in patients with complications including those with refractory CD (P = 0.008). Conclusions This is the first study showing correlation between extent of disease and severity of duodenal histology, markers of malabsorption such as folate levels and vitamin B12 and complications of CD

Clinical impact of baseline chronic kidney disease in patients undergoing transcatheter or surgical aortic valve replacement

ObjectivesTo assess the treatment effect of TAVR versus SAVR on clinical outcomes to 3 years in patients stratified by chronic kidney disease (CKD) by retrospectively studying patients randomized to TAVR or SAVR.BackgroundThe impact of CKD on mid‐term outcomes of patients undergoing TAVR versus SAVR is unclear.MethodsPatients randomized to TAVR or SAVR in the CoreValve US Pivotal High Risk Trial were retrospectively stratified by eGFR: none/mild or moderate/severe CKD. To evaluate the impact of baseline CKD in TAVR patients only, all patients undergoing an attempted TAVR implant in the US Pivotal Trial and CAS were stratified by baseline eGFR into none/mild, moderate, and severe CKD. The primary endpoint was major adverse cardiovascular and renal events (MACRE), a composite of all‐cause mortality, myocardial infarction, stroke/TIA, and new requirement of dialysis.ResultsModerate/severe CKD was present in 62.7% and 60.7% of high‐risk patients randomized to TAVR or SAVR, respectively. Baseline characteristics were similar between TAVR and SAVR patients in both CKD subgroups, except for higher rates of diabetes and higher serum creatinine in SAVR patients. Among high‐risk patients with moderate/severe CKD, TAVR provided a lower 3‐year MACRE rate compared with SAVR: 42.1% vs. 51.0, P = .04. Of 3,733 extreme‐ and high‐risk TAVR patients, 39.9% had none/mild, 53.8% moderate, and 6.4% severe CKD. Worsening baseline CKD was associated with increased 3‐year MACRE rates [none/mild 51.5%, moderate 54.5%, severe 63.1%, P = .001].ConclusionsTAVR results in lower 3‐year MACRE versus SAVR in high‐risk patients with moderate/severe CKD. In patients undergoing TAVR, worsening CKD increases mid‐term mortality and MACRE. Randomized trials of TAVR vs. SAVR in patients with moderate‐severe CKD would help elucidate the best treatment for these complex patients.Trial RegistrationCoreValve US Pivotal Trial: NCT01240902.CoreValve Continued Access Study: NCT01531374.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/148361/1/ccd27928_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/148361/2/ccd27928.pd

Lil Rużar Briffa

Ġabra ta’ poeżiji u proża li tinkludi: Fil-mewt tat-tabib Rużar Briffa ta’ Ġużè Chetcuti – Fil-mewt ta’ Rużar Briffa ta’ P. Valentin Barbara – Lil Rużar ta’ qalbi ta’ Ġorġ Pisani – Poeżiji ta’ Rużar Briffa mhux ippubblikati – Vjolin Marid – Il-każin Malti – Frammenti – Il-ħmar – Lil Rużar Briffa, il-ġenna ta’ Albert M. Cassola – Kellimni fuq Rużar ta’ Ġużè Cardona – Lil F.S. Caruana ta’ R. Briffa – Lil Rużar Briffa ta’ F.S. Caruana.peer-reviewe

Identifying a gender-inclusive pedagogy from Maltese science teachers' personal practical knowledge

Teachers bring with them into the science classrooms their own gendered identitities and their views and perceptions about how boys and girls learn and achieve in science. This paper tries to explore the way in which fourteen Maltese science teachers use their own 'personal practical knowledge' to identify their views about gender and science and create their own individual gender-inclusive pedagogy. The study suggests that the science teachers focus more on the individuality of students and on the social and cultural background of the students in their classrooms rather than on gender. The teachers try to develop pedagogies and assessment practices which take into consideration the personal constructs of individual learners. The ideas for such a gender-inclusive pedagogy emerge from their common-sense experience in the classroom, their training as teachers and are closely interrelated to current ideas of social constructivism