Endothelial progenitor cell-derived small extracellular vesicles for myocardial angiogenesis and revascularization.

Background: Endothelial progenitor cells (EPCs) have been well-studied for their differentiation potential and paracrine activity in vitro and in experimental animal studies. EPCs are the precursors of endothelial cells (ECs) and a rich source of pro-angiogenic factors, and hence, possess enormous potential to treat ischemic heart through myocardial angiogenesis. Their proven safety and efficacy observed during the pre-clinical and clinical studies have portrayed them as a near ideal cell type for cell-based therapy of ischemic heart disease.In response to the chemical cues from the ischemic heart, EPCs from the bone marrow and peripheral circulation home-in to the ischemic myocardium and participate in the intrinsic repair process at the molecular and cellular levels through paracrine activity and EC differentiation. EPCs also release small extracellular vesicles (sEVs) loaded with bioactive molecules as part of their paracrine activity for intercellular communication to participate in the reparative process in the heart. Aim: This literature review is based on the published data regarding the characteristic features of EPC-derived sEVs and their proteomic and genomic payload, besides facilitating safe and effective repair of the ischemic myocardium. In light of the encouraging published data, translational and clinical assessment of EPC-derived sEVs is warranted. We report the recent experimental animal studies and their findings using EPC-derived sEVs on cardiac angiogenesis and preservation of cardiac function. Relevance for Patients: With the promising results from pre-clinical studies, clinical trials should be conducted to assess the clinical utility of EPC-derived sEVs in the treatment of the ischemic myocardium.

Can biomarkers of extracellular matrix remodelling and wound healing be used to identify high risk patients infected with SARS-CoV-2?: lessons learned from pulmonary fibrosis.

Pulmonary fibrosis has been identified as a main factor leading to pulmonary dysfunction and poor quality of life in post-recovery Severe Acute Respiratory Syndrome (SARS) survivor's consequent to SARS-Cov-2 infection. Thus there is an urgent medical need for identification of readily available biomarkers that in patients with SARS-Cov-2 infection are able to; (1) identify patients in most need of medical care prior to admittance to an intensive care unit (ICU), and; (2) identify patients post-infection at risk of developing persistent fibrosis of lungs with subsequent impaired quality of life and increased morbidity and mortality. An intense amount of research have focused on wound healing and Extracellular Matrix (ECM) remodelling of the lungs related to lung function decline in pulmonary fibrosis (PF). A range of non-invasive serological biomarkers, reflecting tissue remodelling, and fibrosis have been shown to predict risk of acute exacerbations, lung function decline and mortality in PF and other interstitial lung diseases (Sand et al. in Respir Res 19:82, 2018). We suggest that lessons learned from such PF studies of the pathological processes leading to lung function decline could be used to better identify patients infected with SARS-Co-V2 at most risk of acute deterioration or persistent fibrotic damage of the lung and could consequently be used to guide treatment decisions.

Variation in the vertebral levels of the origins of the abdominal aorta branches: a retrospective imaging study.

Our aim was to investigate the variation in the vertebral levels of the origins of the celiac artery, superior and inferior mesenteric arteries, paired renal arteries, and common iliac arteries. We conducted a retrospective imaging study in a large public secondary hospital on a nonrandom sample of 227 participants. We consecutively included adult patients who had undergone computed tomography angiography of the abdomen and excluded patients with a history of any vertebral abnormality or whose images revealed evidence of a vertebral abnormality or a congenital anomaly of any of the branches of the abdominal aorta. The primary outcome was the frequency distribution of the vertebral levels of the landmarks. The secondary outcomes were the intercorrelations of the vertebral levels of the landmarks and their relationships with age, sex, weight, height, and body mass index. The celiac artery originated at T11/T12-L1/L2, followed by the superior mesenteric artery at T12-L2, the paired renal arteries at T12/L1-L2/L3, the inferior mesenteric artery at L2-L4, and the common iliac arteries at L3-L5. The vertebral levels of the landmarks were positively intercorrelated and stronger between proximate pairs. In addition, the vertebral levels of the landmarks were related to age, but not sex, weight, height, or body mass index. The intercorrelations suggest that a considerable proportion of the variation is accounted for by 'trickle-down' variation; variation in the vertebral level of a proximal landmark results in variation in the vertebral level of the immediate distal landmark. The overarching parameter remains unidentified.

Inhibition of Fatty Acid Amide Hydrolase (FAAH) by Macamides.

The pentane extract of the Peruvian plant, Lepidium meyenii (Maca), has been demonstrated to possess neuroprotective activity in previous in vitro and in vivo studies (Pino-Figueroa et al. in Ann N Y Acad Sci 1199:77-85, 2010; Pino-Figueroa et al. in Am J Neuroprot Neuroregener 3:87-92, 2011). This extract contains a number of macamides that may act on the endocannabinoid system (Pino-Figueroa et al. in Ann N Y Acad Sci 1199:77-85, 2010; Pino-Figueroa et al., 2011; Dini et al. in Food Chem 49:347-349, 1994). The aim of this study was to characterize the inhibitory activity of four of these maccamides (N-benzylstearamide, N-benzyloleamide, N-benzyloctadeca-9Z,12Z-dienamide, and N-benzyloctadeca-9Z,12Z,15Z-trienamide) on fatty acid amide hydrolase (FAAH), an enzyme that is responsible for endocannabinoid degradation in the nervous system (Kumar et al. in Anaesthesia 56:1059-1068, 2001). The four compounds were tested at concentrations between 1 and 100 µM, utilizing an FAAH inhibitor screening assay. The results demonstrated concentration-dependent FAAH inhibitory activities for the four macamides tested. N-Benzyloctadeca-9Z,12Z-dienamide demonstrated the highest FAAH inhibitory activity whereas N-benzylstearamide had the lowest inhibitory activity. In addition, N-benzylstearamide, N-benzyloleamide, and N-benzyloctadeca-9Z,12Z-dienamide demonstrated time-dependent inhibition when tested after a pre-incubation period, indicating that the mechanism of inhibition for these compounds most likely is irreversible. Of interest, unsaturation in the fatty acid moiety resulted in greater FAAH inhibitory activity. LC/MS/MS analysis demonstrated that FAAH was able to hydrolyze N-benzyloctadeca-9Z,12Z-dienamide, suggesting that N-benzyloctadeca-9Z,12Z-dienamide is also a slow substrate for FAAH. These results provide useful information about the mechanism of action of Lepidium meyenii and may help with the development of new compounds with FAAH inhibitory or modulatory activity.

Dorsal metacarpal veins: anatomic variation and potential clinical implications.

The dorsal metacarpal veins are frequently cannulated. Cannulation success is determined by several variable anatomic features. The objective of this study is to classify, for the first time, the anatomic variants of the dorsal metacarpal veins. In this cross-sectional study, 520 university students and staff were conveniently recruited. The dorsal metacarpal veins in 1040 hands were studied. Venous visibility was enhanced by either tourniquet application or near-infrared illumination. Variant patterns of the dorsal metacarpal veins were classified. The final analysis included 726 hands, for an exclusion rate of 30 %. Eight pattern types were identified. Three anatomic features informed the variation. Bilateral symmetry of the dorsal metacarpal veins was present in 352 participants (83 % of the total). The overall frequency distribution of variants in both hands was similar (P = 0.8). The frequency distribution of variants was subject to sexual dimorphism (P = 0.001), ethnic variation (P < 0.001), and technical variation (P < 0.001). The anatomic variants of the dorsal metacarpal veins were sorted into decreasingly frequent primary, secondary, and tertiary groups. The groups may signify a progressive increase in difficulty of peripheral cannulation, in the mentioned order. As such, primary patterns are the most common and likely the easiest to cannulate, while tertiary patterns are the least common and likely the most difficult to cannulate. The preceding premise, in tandem with the bilateral asymmetry of the veins, is clinically significant. With cannulation difficulty likely signifying an underlying tertiary pattern, the contralateral dorsal metacarpal veins are probabilistically characterized by a primary pattern and are, as such, the easier option for peripheral venous cannulation.

Morphometric analysis of the foramen magnum / Análisis morfométrico del foramen magno

SUMMARY: The foramen magnum is morphometrically typified by two perpendicular diameters and a distinct margin. This important anatomical landmark is subject to high interindividual variation. The objective of this study was to evaluate the dimensions and morphology of the foramen magnum in a Jordanian population. In this retrospective study, 247 individuals were consecutively sampled using the institutional picture archiving and communication system. The anteroposterior and transverse diameters of the foramen magnum were measured; the foramen magnum index was calculated; and, the shape of the foramen magnum was visually assessed. The sex-pooled anteroposterior and transverse diameters were 35.1 ± 3.2 mm and 29.3 ± 2.5 mm, respectively. The sex-pooled foramen magnum index was 1.20 ± 0.10. The diameters were significantly different (P<0.001) and positively correlated (r=0.52, P<0.001). Participant age was negatively correlated with the anteroposterior (rs=-0.15, P=0.02) and transverse (rs=-0.14, P=0.03) diameters. After controlling for participant age, there was a statistically significant difference in the anteroposterior diameter (P<0.001), the transverse diameter (P<0.001), and the foramen magnum index (P=0.02) between sexes. The foramen magnum was most commonly irregular in shape (36 % of all cases). In contrast to previous studies, we report, for the first time, a negative correlation between age and the diameters of the foramen magnum. In addition, a predominance of irregularly shaped foramen magnum was found. The finding makes an already heterogenous group of published data even more variable, prompting reconsideration of the role of visual assessment in morphometric studies.

RESUMEN: El foramen magno está morfométricamente tipificado por dos diámetros perpendiculares y un margen. Este punto importante de referencia anatómica está sujeto a una alta variación interindividual. El objetivo del estudio fue evaluar las dimensiones y la morfología del foramen magno en una población jordana. En este estudio retrospectivo, 247 individuos fueron muestreados consecutivamente utilizando el sistema institucional y de comunicación de imágenes. Se midieron los diámetros anteroposterior y transversal del foramen magno; Se calculó el índice del foramen magno y se evaluó visualmente la forma dede éste. Los diámetros anteroposterior y transversal agrupados por sexo fueron 35,1±3,2 mm y 29,3±2,5 mm, respectivamente. El índice del foramen magno, agrupado por sexo, fue 1,20±0,10. Los diámetros fueron significativamente diferentes (P <0,001) y positivamente correlacionados (r = 0,52, P <0,001). La edad de los participantes se correlacionó negativamente con los diámetros anteroposterior (rs = -0,15, P = 0,02) y transversal (rs = -0,14, P = 0,03). Después de verificar la edad de los participantes, hubo una diferencia estadísticamente significativa entre el diámetro anteroposterior (P <0,001), el diámetro transversal (P <0,001) y el foramen magno (P = 0,02) entre ambos sexos. El foramen magno era más comúnmente de forma irregular (36 % de todos los casos). A diferencia de estudios anteriores, se informa por primera vez de una correlación negativa entre la edad y los diámetros del foramen magno. Además, se encontró un predominio de forámenes de forma irregular. El hallazgo indica que un grupo heterogéneo de datos ya publicados, sea aún más variable, lo que lleva a reconsiderar el papel de la evaluación visual en los estudios morfométricos.

Coconut oil has less satiating properties than medium chain triglyceride oil.

It is well established that the consumption of medium-chain triglycerides (MCT) can increase satiety and reduce food intake. Many media articles promote the use of coconut oil for weight loss advocating similar health benefits to that of MCT. The aim of this study was to examine the effect of MCT oil compared to coconut oil and control oil on food intake and satiety. Following an overnight fast, participants consumed a test breakfast smoothie containing 205kcal of either (i) MCT oil (ii) coconut oil or (iii) vegetable oil (control) on three separate test days. Participants recorded appetite ratings on visual analogue scales and were presented with an ad libitum lunch meal of preselected sandwiches 180min after consumption of the breakfast. The results showed a significant difference in energy and macronutrient intakes at the ad libitum meal between the three oils with the MCT oil reducing food intake compared to the coconut and control oil. Differences in food intake throughout the day were found for energy and fat, with the control having increased food intake compared to the MCT and coconut. The MCT also increased fullness over the three hours after breakfast compared to the control and coconut oils. The coconut oil was also reported as being less palatable than the MCT oil. The results of this study confirm the differences that exist between MCT and coconut oil such that coconut oil cannot be promoted as having similar effects to MCT oil on food intake and satiety.

A Cost-Effectiveness Analysis of Nintedanib in Idiopathic Pulmonary Fibrosis in the UK.

BACKGROUND: International guidelines recommend nintedanib (OFEV®) as an option for the treatment of idiopathic pulmonary fibrosis (IPF). OBJECTIVE: The objective of this study was to assess the cost effectiveness of nintedanib versus pirfenidone, N-acetylcysteine and best supportive care (BSC) for the treatment of IPF from a UK payer's perspective. METHODS: A Markov model was designed to capture the changes in the condition of adults with IPF. Efficacy outcomes included mortality, lung function decline and acute exacerbations. Treatment safety (serious adverse events) and tolerability (overall discontinuation) were also considered. The baseline risk of these events was derived from patient-level data from the placebo arms of nintedanib clinical trials (TOMORROW, INPULSIS-1, INPULSIS-2). A network meta-analysis (NMA) was conducted to estimate the relative effectiveness of the comparator treatments. Quality of life and healthcare resource use data from the clinical trials were also incorporated in the economic model. RESULTS: Nintedanib showed statistically significant differences against placebo on acute exacerbation events avoided and lung function decline. In the cost-effectiveness analysis, the results were split between two treatments with relative low costs and modest effectiveness (BSC and N-acetylcysteine) and two that showed improved effectiveness (lung function) and higher costs (nintedanib and pirfenidone). All comparators were assumed to have similar projected survival and the difference in quality-adjusted life-years (QALYs) was driven by the acute exacerbations and lung function estimates. In the base-case deterministic pairwise comparison with pirfenidone, nintedanib was found to have fewer acute exacerbations and resulted in less costs and more QALYs gained. CONCLUSIONS: Compared with BSC (placebo), nintedanib and pirfenidone were the only treatments to show statistical significance in the efficacy parameters. We found substantial uncertainty in the overall cost-effectiveness results between nintedanib and pirfenidone. N-Acetylcysteine was largely similar to BSC but with a worse survival profile. INPULSIS-1 and INPULSIS-2 ClinicalTrials.gov numbers, NCT01335464 and NCT01335477.

Clinical predictors of involuntary detention among voluntary inpatients in St Patrick's University Hospital (SPUH).

BACKGROUND: Few studies have described clinical characteristics of patients subject to an involuntary detention in an Irish context. The Irish Mental Health Act 2001 makes provision under Section 23(1), whereby a person who has voluntary admission status can be detained. Aims This study aimed to describe all involuntary admissions to St Patrick's University Hospital (SPUH) (2011-2013) and to evaluate clinical characteristics of voluntary patients who underwent Mental Health Act assessment during 2011 to determine differences in those who had involuntary admission orders completed and those who did not. METHODS: All uses of Mental Health Act 2001 within SPUH 2011-2013 were identified. All uses of Section 23(1) during 2011 were reviewed and relevant documents/case-notes examined using a pro forma covering clinical data, factors recognized to influence involuntary admissions and validated scales were used to determine diagnoses, insight, suicide and violence risk. RESULTS: Over 2011-2013, 2.5-3.8% of all admissions were involuntary with more detained after use of Section 23(1) than Section 14(2). The majority of initiations of Section 23(1) did not result in an involuntary admission (72%), occurred out of hours (52%) and many occurred early after admission (<1 week, 43%). Initiation of Section 23(1) by a consultant psychiatrist (p=0.001), suicide risk (p=0.03) and lack of patient insight into treatment (p=0.007) predicted conversion to involuntary admission. CONCLUSION: This study predicts a role for patient insight, suicide risk and consultant psychiatrist decision making in the initiation of Mental Health Act assessment of voluntary patients. Further data describing the involuntary admissions process in an Irish setting are needed.

Double inferior vena cava detected by CT venography and confirmed by magnetic resonance venography: embryogenesis and literature review / Doble vena cava inferior detectada a través de venografía por tomografía computada y confirmada con venografía por resonancia magnética: embriogénesis y revisión de la literatura

A hospital based prospective study was conducted from July 2001 to July 2015 at the Department of Radiology, Jordan University Hospital, Amman, Jordan. During that period, five cases of double inferior vena cava (DIVC) were discovered among a cohort of 7722 patients (3861 men and 3861 women, 49.5±16.9 years, range 16­78 years). Cases were diagnosed by contrast-enhanced Spiral CT venography (CTV) and confirmed by turbo three-dimensional (3D) time-of-flight contrast-enhanced MR venography. The majority of patients 3166 (41 %) were referred for staging and follow-up of malignancy, postoperative complications 1777 (23 %), non-specific abdominal pain 1467 (19 %), preoperative assessment 849 (11 %) and trauma 463 (6 %). Magnetic resonance venography showed higher sensitivity, diagnostic accuracy and noninvasive modality for assessment of IVC map. MRV is a more useful, noninvasive modality for assessment of IVC map. DIVC is a common anomaly, its incidence in our study found to be 0.064 %. The incidence, literature review, embryogenesis, and importance of this anomaly are discussed. In addition, sample figures of relevant cases are provided.

En el Departamento de Radiología del Hospital de la Universidad de Jordania, Amman, Jordania, se llevó a cabo un estudio prospectivo entre el mes de julio de 2001 al mes de julio del 2015. Durante ese período se descubrieron cinco casos de vena cava inferior doble (VCID) en una cohorte de 7722 pacientes (3861 hombres y mujeres 3861, de 49,5 ± 16,9 años, con un rango de edad de 16-78 años). Los casos fueron diagnosticados por medio de venografía por tomografía computada espiral con contraste (TCV) y confirmados por medio de venografía por estudio tridimensional turbo. La mayoría de los pacientes (3166, 41 %) fueron remitidos para estadificación y seguimiento de tumores malignos. Se presentaron complicaciones postoperatorias en 1777 pacientes (23 %), dolor abdominal no especificado en 1467 (19 %), evaluación preoperatoria en 849 (11 %) y traumatismo en 463 pacientes (6 %). La venografía por resonancia magnética (RMV) mostró una mayor sensibilidad, precisión diagnóstica, y resultando no invasiva para la evaluación de la vena cava inferior (VCI). RMV es una modalidad más útil, no invasiva para la evaluación de la VCI. VCID es una anomalía frecuente, encontrándose en nuestro estudio una incidencia de 0,064 %. Además se realizó una revisión de la literatura, la embriogénesis, y la importancia de esta anomalía. También, se proporcionaron cifras de muestras de los casos relevantes.

Sex-specific parameters of ascending aorta, descending aorta and pulmonary trunk by computed tomographic angiography with impact of age, hypertension, smoking and diabetes / Parámetros específicos de la parte ascendente de la aorta, parte descendente de la aorta y tronco pulmonar analizados mediante angiografía por tomografía computadorizada relacionados con el sexo, impacto de la edad, hipertensión, tabaquismo y diabetes

This study aims at establishing whether transverse diameter (TD) and cross sectional-area (CSA) of the ascending aorta (AA), descending aorta (DA) and pulmonary trunk (PT) measured by computerized tomographic angiography (CTA) altered by sex, age, hypertension, smoking and diabetes. CTA examinations of the TD and CSA of the AA, DA and PT of 100 patients aged 49.5±16.9 years (range 16­78 years) selected between January 2009 to May 2011 from those referred to Radiology Department, Jordan University Hospital, Faculty of Medicine, University of Jordan, Amman, Jordan for advanced evaluation. Measurements were made in the axial plane at the upper border of the six thoracic vertebrae. Patients were divided into three age groups. Significance of differences in parameters between age groups was calculated. Assessment ratios were considered. It was found that parameters of the three arteries were significantly larger in men than in women (P= < 0.05) and increased with age. Hypertension increased diameters of AA and DA in both genders (P= 0.001) and of PT in men (P= 0.01). Smoking significantly decreased parameters of PT in men (P= 0.01). Diabetes increased parameters of the three arteries in both genders, significantly increased parameters of PT in men (P= <0.05) and parameters of DA in women (P= <0.05). It is concluded that studied parameters were larger in men and increased with age of our patients. Distinctive differences in measurements appeared in hypertensive, smokers, and diabetic patients.

El objetivo fue determinar si el sexo, edad, hipertensión, tabaquismo y la diabetes alteran el diámetro transversal (DT) y área transversal (AT) de la parte ascendente de la aorta (AA), parte descendente de la aorta (AD) y tronco pulmonar (TP), medidos por angiografía por tomografía computadorizada (ATC). Exámenes de ATC de 100 pacientes de 49,5±16,9 años (rango 16­78 años) fueron seleccionados entre enero del año 2009 a mayo del año 2011 por el Departamento de Radiología, Hospital de la Universidad de Jordania, Facultad de Medicina de la Universidad de Jordania, Amman, Jordania para una evaluación avanzada del DT y AT de la AA, AD y TP. Las mediciones se realizaron en el plano axial en el margen superior de las seis vértebras torácicas. Los pacientes fueron divididos en tres grupos según edad. Se determinó la existencia de significancia estadística de los diferentes parámetros entre los grupos etarios. La evaluación de las razones también fueron consideradas. Se encontró que los parámetros de las tres arterias fueron significativamente mayores en los hombres que en las mujeres (p= <0,05) y que aumentaron con la edad. La hipertensión aumentó los diámetros de la AA y AD en ambos sexos (p= 0,001) y del TP en los hombres (p= 0,01). En fumadores disminuyeron significativamente los parámetros del TP en los hombres (p= 0,01). La diabetes aumentó los parámetros de las tres arterias en ambos sexos. Ademas, aumentaron significativamente los parámetros del TP en los hombres (p= <0,05) y los parámetros de la AD en las mujeres (p = <0,05). Se concluye que los parámetros estudiados eran mayores en los hombres y aumentaron con la edad de nuestros pacientes. Diferencias distintivas en las mediciones aparecieron en hipertensos, fumadores y pacientes diabéticos.

Nintedanib in idiopathic pulmonary fibrosis.

Idiopathic pulmonary fibrosis (IPF) conveys a median survival of 3 years and until recently has lacked effective therapies. Nintedanib, an orally available, small-molecule tyrosine kinase inhibitor with selectivity for vascular endothelial growth factor (VEGF), platelet-derived growth factor (PDGF) and fibroblast growth factor (FGF) receptors has recently been shown, in two pivotal phase III studies, to effectively slow IPF disease progression. Consequently, nintedanib was given accelerated approval by the FDA in October 2014 for the treatment of IPF. This monograph explores the preclinical rationale for the antifibrotic role of nintedanib and provides an overview of the available data on pharmacokinetics, efficacy and safety.

Ultrasonographic assessment of splenic volume and its correlation with body parameters in a Jordanian population.

OBJECTIVES: To estimate normal linear dimensions and volume of spleen in Jordanians using ultrasonography, and to correlate splenic volume with age and body parameters: height, weight, body surface area (BSA), and body mass index (BMI). METHODS: A prospective pilot study was conducted on 205 volunteers (115 males and 90 females) not known to have any conditions likely to be associated with splenomegaly. The study was performed at the Radiology Department, Jordanian University Hospital, Amman, Jordan, between December 2013 and August 2014. All linear dimensions of spleen were measured, and splenic volume (index) was calculated using the standard prolate ellipsoid formula (length × width × depth × 0.523). The splenic volume was then analyzed with age and body parameters using the Pearson's correlation coefficient. RESULTS: The mean (± SD) splenic dimensions were 10.72±1.37 cm in length, 7.40±1.52 cm in width, 4.40±1.47 cm in depth, and 184.15±79.56 cm3 in volume. Men had larger spleens than women (p less than 0.0001). Age had no significant effect on spleen volume (r=0.11, p=0.12). There was a significant moderate positive correlation (p less than 0.0001), using Pearson's correlation coefficient, between the spleen volume, and other parameters (height, weight, BSA, and BMI), with correlation coefficients exceeding 0.3. CONCLUSION: A local reference of spleen dimensions was established with a different range of values reported previously.

Idiopathic pulmonary fibrosis: Recent advances on pharmacological therapy.

Idiopathic pulmonary fibrosis (IPF) is the most common and lethal of the idiopathic interstitial pneumonias with an estimated 5-year survival of approximately 20%. In the last two decades our understanding of disease pathogenesis has substantially evolved and novel compounds have been developed consequent to the increasing knowledge of the mechanisms underlying disease pathobiology. The disease appears to be driven - following chronic injury - by abnormal/dysfunctional alveolar epithelial cells that promote fibroblast recruitment and proliferation, resulting in scarring of the lung and irreversible loss of function. With very few exceptions, clinical trials evaluating novel potential therapies have provided disappointing results. More recently, pirfenidone and nintedanib, two compounds with pleiotropic mechanisms of action, have proven effective in slowing functional decline and disease progression in IPF patients with mild to moderate functional impairment, highlighting the importance of timely diagnosis and administration of treatment in early stages of disease. However, due to the complexity and uncertainties intrinsic to IPF, it is essential that each therapeutic strategy be tailored to the individual patient, after evaluation of potential benefits and risks. This article provides an overview of the most recent clinical trials in IPF and discusses how their results are going to change the clinical and clinical research landscape in IPF. A number of agents with high potential are currently being tested and many more are ready for clinical trials. Their completion is critical for achieving the ultimate goal of curing patients with IPF.

Provision of home mechanical ventilation and sleep services for England survey.

The Department of Health is promoting the generation of specialist networks to manage long term ventilatory weaning and domiciliary non-invasive ventilation patients. Currently the availability of these services in England is not known. We performed a short survey to establish the prevalence of sleep and ventilation diagnostic and treatment services. The survey focussed on diagnostic services and Home Mechanical Ventilation (HMV) provision, and was divided into (a) availability of diagnostics, (b) funding, and (c) patient groups. This survey has confirmed that the majority of Home Mechanical Ventilation set-ups are currently for Obesity Related Respiratory Failure and Chronic Obstructive Pulmonary Disease. We have found that there is variable provision of diagnostic services, with the majority of units offering overnight oximetry (95%) but only 55% of responders providing a home mechanical ventilation service. Even more interestingly, less than two thirds of units charged their primary care trust for this service. These data may assist in the development of regional networks and specialist home mechanical ventilation centres.

A structured process for reviewing the operation of the Mental Health Act 2001 in an Irish mental health service.

This paper provides a description of a structured template which allows review of the operation of the Mental Health Act 2001 at St Patrick's Mental Health Services (incorporating St Patrick's University Hospital, St Edmundsbury Hospital and Willow Grove Adolescent Unit). These structured processes were implemented to ensure rigorous monitoring of all clinical governance activities associated with adherence to the Mental Health Act (MHA) 2001. The paper describes in detail the information contained in the St Patrick's Mental Health Services dashboard for 2012. The dashboard displays the key performance indicators that are monitored and the paper describes how these were reviewed by the Hospital's Clinical Governance Committee on a weekly basis for the three approved centres. The dashboard has also been used by the Clinical Governance Committee to provide ongoing education and engagement with staff in order to improve the operation of the MHA 2001. The use of this structured monitoring process has allowed the hospital to measure adherence to the MHA 2001 and also to measure activities that impact directly on the care and treatment of patients detained under the Act. The use of structured monitoring tools (i.e. the dashboard) to review the operation of the MHA 2001 allows for coherent observation of key events and issues which can cause concern in terms of the operation of the Act.

Elevated nocturnal desaturation index predicts mortality in interstitial lung disease.

BACKGROUND: Nocturnal desaturation may contribute to long-term pulmonary vascular stress in interstitial lung disease (ILD). We study the prevalence, severity and prognostic utility of nocturnal desaturation across ILD. METHODS: ILD patients with overnight oximetry (June 2006-August 2008) were reviewed (n = 134). Significant nocturnal desaturation was considered as > 10% of sleep with SpO2 < 90%. Desaturation index (DI) was defined as the number of desaturation events > 4%/hr. Covariates, including indices of nocturnal desaturation, were evaluated against mortality. RESULTS: Nocturnal desaturation was present in 49 (37%) patients. 31% of patients had pulmonary hypertension (PH) on echocardiography. Increased DI was associated with higher mortality independent of age, gender and BMI (HR 1.04; 95% CI 1.00, 1.06; p = 0.009). In separate models, DI and a) elevated brain natriuretic peptide (BNP; HR 1.04; 95% CI 1.00, 1.08; p = 0.04); b) moderate-severe PH on echocardiography (HR 3.15; 95% CI 1.24, 8.00; p = 0.02); and c) daytime resting SpO2 (HR 0.92; 95% CI 0.85, 0.99; p = 0.04) independently predicted mortality following adjustment for age, gender and BMI. CONCLUSION: Nocturnal desaturation is common and may be severe in ILD. Elevated nocturnal DI predicts higher mortality across ILD, independent of other vascular parameters. This finding may have important implications for the pathogenesis of PH in IPF.

Significance of connective tissue disease features in idiopathic interstitial pneumonia.

In idiopathic interstitial pneumonia (IIP), the significance of connective tissue disease (CTD) features in the absence of a specific CTD diagnosis remains unclear. We studied the clinical and prognostic utility of a diagnosis of undifferentiated CTD (UCTD) in patients with biopsy-proven IIP. IIP patients undergoing surgical lung biopsy (1979-2005) were studied (nonspecific interstitial pneumonia (NSIP), n = 45; idiopathic pulmonary fibrosis, n = 56). UCTD was considered present when serum autoantibodies were present and symptoms or signs suggested CTD. The relationship between UCTD and NSIP histology was evaluated. A clinical algorithm that best predicted NSIP histology was constructed using a priori variables. The prognostic utility of UCTD, and of this algorithm, was evaluated. UCTD was present in 14 (31%) NSIP and seven (13%) IPF patients. UCTD was not associated with a survival benefit. The algorithm predictive of NSIP (OR 10.4, 95% CI 3.21-33.67; p<0.0001) consisted of the absence of typical high-resolution computed tomography (HRCT) features for IPF and 1) a compatible demographic profile (females aged <50 yrs) or 2) Raynaud's phenomenon. In patients with an HRCT scan not typical for IPF, this algorithm predicted improved survival (hazard ratio 0.35, 95% CI 0.14-0.85; p = 0.02) independent of IIP severity. UCTD is associated with NSIP histology. However, the diagnostic and prognostic significance of UCTD in IIP patients remains unclear.