The reaction of defense stocks to war news : an event study

Investigates the reaction of over 60 defense industry stocks to war news. With results from six recent wars, 1967-1991

Implementing PCOC: A guide for services

The purpose of this guide is to assist services in the implementation of the Palliative Care Outcomes Collaboration (PCOC) program. Implementing the PCOC program is a three stage process requiring action in the following areas: leadership and governance, routine assessment, orientation and ongoing education, data management and quality improvement

Renal Evaluation in Women with Preeclampsia

Background/Aims: Preeclampsia (PE) is a cause of glomerulopathy worldwide. Urinary retinol-binding protein (RBP) is a marker of proximal tubular dysfunction, albuminuria is an endothelial injury marker, urine protein:creatinine ratio (PCR) may have a predictive value for renal disease later in life, and, recently, podocyturia has been proposed as a sensitive tool in pregnancy, but it needs to be tested. The aim of this study was to evaluate renal involvement in PE and healthy pregnancy. Methods: Case-control study with 39 pregnant women assessed after 20 weeks of gestation (25 in the control group, CG, and 14 in the PE group) by performing urinary tests. Results: Mean (±SD) age and gestational age of the CG were 26.9 ± 6.4 years and 37.1 ± 5.0 weeks, and of the PE group 26.4 ± 6.9 years and 30.6 ± 5.6 weeks, respectively (p = 0.001). Mean (±SD) urinary RBP (p = 0.017), albuminuria (p = 0.002), and urinary albumin concentration (UAC) ratio (p = 0.006) of the CG were 0.4 ± 0.7 mg/l, 7.3 ± 6.9 mg/l, and 8.2 ± 6.7 mg/g and of the PE group 2.0 ± 4.4 mg/l, 2,267.4 ± 2,130.8 mg/l (p = 0.002), and 3,778.9 ± 4,296.6 mg/g (p = 0.006), respectively. Mean (±SD) urine PCR in the PE group was 6.7 ± 6.1 g/g (p Conclusions: Urinary RBP, PCR, albuminuria, and UAC ratio were elevated in the PE group in comparison to the CG. Podocyturia did not predict PE

Risk factors for recurrence in patients with Clostridium difficile infection due to 027 and non-027 ribotypes

Objectives: Our objective was to evaluate factors associated with recurrence in patients with 027+ and 027– Clostridium difficile infection (CDI). Methods: Patients with CDI observed between January and December 2014 in six hospitals were consecutively included in the study. The 027 ribotype was deduced by the presence of tcdB, tcdB, cdt genes and the deletion Δ117 in tcdC (Xpert® C. difficile/Epi). Recurrence was defined as a positive laboratory test result for C. difficile more than 14 days but within 8 weeks after the initial diagnosis date with reappearance of symptoms. To identify factors associated with recurrence in 027+ and 027– CDI, a multivariate analysis was performed in each patient group. Subdistributional hazard ratios (sHRs) and 95% confidence intervals (95%CIs) were calculated. Results: Overall, 238 patients with 027+ CDI and 267 with 027– CDI were analysed. On multivariate analysis metronidazole monotherapy (sHR 2.380, 95%CI 1.549–3.60, p <0.001) and immunosuppressive treatment (sHR 3.116, 95%CI 1.906–5.090, p <0.001) were factors associated with recurrence in patients with 027+ CDI. In this patient group, metronidazole monotherapy was independently associated with recurrence in both mild/moderate (sHR 1.894, 95%CI 1.051–3.410, p 0.033) and severe CDI (sHR 2.476, 95%CI 1.281–4.790, p 0.007). Conversely, non-severe disease (sHR 3.704, 95%CI 1.437–9.524, p 0.007) and absence of chronic renal failure (sHR 16.129, 95%CI 2.155–125.000, p 0.007) were associated with recurrence in 027– CDI. Conclusions: Compared to vancomycin, metronidazole monotherapy appears less effective in curing CDI without relapse in the 027+ patient group, independently of disease severity

Beneficial effect of prolonged heme oxygenase 1 activation in a rat model of chronic heart failure.

SUMMARY We and others have previously demonstrated that heme oxygenase 1 (HO-1) induction by acute hemin administration exerts cardioprotective effects. Here, we developed a rat model of heart failure to investigate whether a long-term induction of HO-1 by chronic hemin administration exerted protective effects. Sprague Dawley rats that underwent permanent ligation of the left coronary artery were closely monitored for survival rate analysis and sacrificed on day 28 post-operation. Administration of hemin (4 mg/kg body weight) every other day for 4 weeks induced a massive increase in HO-1 expression and activity, as shown by the increased levels of the two main metabolic products of heme degradation, bilirubin and carbon monoxide (CO). These effects were associated with significant improvement in survival and reduced the extension of myocardial damage. The ischemic hearts of the hemin-treated animals displayed reduced oxidative stress and apoptosis in comparison with the non-treated rats, as shown by the decreased levels of lipid peroxidation, free-radical-induced DNA damage, caspase-3 activity and Bax expression. Besides, chronic HO-1 activation suppressed the elevated levels of myeloperoxidase (MPO) activity, interleukin 1β (IL-1β) production and tumor necrosis factor-α (TNFα) production that were evoked by the ischemic injury, and increased the plasma level of the anti-inflammatory cytokine IL-10. Interestingly, HO-1 inhibitor zinc protoporphyrin IX (ZnPP-IX; 1 mg/kg) lowered bilirubin and CO concentrations to control values, thus abolishing all the cardioprotective effects of hemin. In conclusion, the results demonstrate that chronic HO-1 activation by prolonged administration of hemin improves survival and exerts protective effects in a rat model of myocardial ischemia by exerting a potent antioxidant activity and disrupting multiple levels of the apoptotic and inflammatory cascade

Long-Term safety and efficacy of adalimumab in psoriasis. A multicentric study focused on infections (connecting study)

Introduction: This Italian multicenter retrospective study evaluated safety and efficacy of the anti-TNF drug, adalimumab, in a cohort of patients affected by tuberculosis (TB), hepatitis B virus (HBV), hepatitis C virus (HCV) or human immunodeficiency virus (HIV). Psoriasis is an autoimmune disease affecting around 3% of the Italian population and associated with several comorbidities, including arthritis, cardio-metabolic diseases and depression. In its moderate-To-severe form, psoriasis profoundly impairs quality of life of patients. Aim: Therefore, these patients deserve systemic treatments including conventional DMARDS (disease modifying anti-rheumatic drugs) and biologics. Management of moderate and severe psoriasis patients affected by relevant infections such as TB, HBV, HCV and HIV may be difficult because of the toxicity of the conventional systemic treatment. Material and methods: The CONNECTING study analysed 28 moderate to severe psoriasis patients infected by TB, HBV, HCV and HIV who were treated with adalimumab for up to 96 weeks together with respective prophylactic treatment. Results: We observed a rapid decrease in PASI (psoriasis area severity index) reaching a 75% improvement in 91% of patients. Some of these patients (n = 9) were also affected by arthritic comorbidity. The patients experienced a rapid decrease in pain, measured by pain VAS (visual analogic scale) that reached 0 in all of them. Monitoring of the respective infection did not show any worsening or reactivation of infection or any severe adverse events during the entire observation period. Conclusions: Adalimumab is effective and safe in patients affected by these important infections

Protocol for the development and validation procedure of the managing the link and strengthening transition from child to adult mental health care (MILESTONE) suite of measures

Background: Mental health disorders in the child and adolescent population are a pressing public health concern. Despite the high prevalence of psychopathology in this vulnerable population, the transition from Child and Adolescent Mental Health Services (CAMHS) to Adult Mental Health Services (AMHS) has many obstacles such as deficiencies in planning, organisational readiness and policy gaps. All these factors contribute to an inadequate and suboptimal transition process. A suite of measures is required that would allow young people to be assessed in a structured and standardised way to determine the on-going need for care and to improve communication across clinicians at CAMHS and AMHS. This will have the potential to reduce the overall health economic burden and could also improve the quality of life for patients travelling across the transition boundary. The MILESTONE (Managing the Link and Strengthening Transition from Child to Adult Mental Health Care) project aims to address the significant socioeconomic and societal challenge related to the transition process. This protocol paper describes the development of two MILESTONE transition-related measures: The Transition Readiness and Appropriateness Measure (TRAM), designed to be a decision-making aide for clinicians, and the Transition Related Outcome Measure (TROM), for examining the outcome of transition. Methods: The TRAM and TROM have been developed and were validated following the US FDA Guidance for Patient-reported Outcome Measures which follows an incremental stepwise framework. The study gathers information from service users, parents, families and mental health care professionals who have experience working with young people undergoing the transition process from eight European countries. Discussion: There is an urgent need for comprehensive measures that can assess transition across the CAMHS/AMHS boundary. This study protocol describes the process of development of two new transition measures: the TRAM and TROM. The TRAM has the potential to nurture better transitions as the findings can be summarised and provided to clinicians as a clinician-decision making support tool for identifying cases who need to transition and the TROM can be used to examine the outcomes of the transition process. Trial registration: MILESTONE study registration: ISRCTN83240263 Registered 23-July-2015 - ClinicalTrials.gov NCT03013595 Registered 6 January 2017

Quality Improvement: A guide for services

This guide provides information for clinicians from organisations and services participating in PCOC to use their reports and the suite of PCOC quality improvement tools for continuous improvement, and to demonstrate improvement in patient and family/carer outcomes

Structural and ultrastructural evaluation of the effects induced by IL-22 alone or in combination with psoriatic cytokines in an ex-vivo human skin model

IL-22 is a pro-inflammatory cytokine playing a crucial role in the pathogenesis of psoriasis, an autoimmune chronic inflammatory skin disease. The immunological activation during the progression of the psoriatic lesion is driven by IL-22 together with other cytokines, such as (TNF)-alpha and interleukin (IL)-17 [1]. The aim of our study was to evaluate the early, direct, and specific effect of IL-22 alone or in combination with TNF-alpha and IL-17 by immunofluorescence on i) the molecular composition of intercellular junctions (desmocollin (DSC)1, E-cadherin, and occludin), ii) keratin(K) 10 and 17 expression, iii) keratinocyte proliferation, and, by transmission electron microscopy (TEM), on the ultrastructural morphology of the skin. An innovative model of human skin culture standardized in our laboratory, in which a psoriatic microenvironment was reproduced, was used [2]. Skin explants obtained from plastic surgery of healthy 20-40 year-old women (n = 7) after informed consent were cultured overnight in Dulbecco's modified Eagle's medium, divided before adding IL-22 or a combination of the three cytokines, and harvested 24, 48, and 72 hours after cytokine incubation. Interestingly, keratinocyte proliferation was inhibited after exposure to the combination of cytokines while was not affected by IL-22 incubation. In both experimental groups, starting from T24, occludin immunostaining was non homogeneously distributed, K10 immunostaining gradually decreased in scattered clusters in the spinous layer, while K17 expression was induced and progressively increased with time in the suprabasal layers of epidermis. By TEM, after IL-22 incubation we observed keratin aggregates in the perinuclear cytoplasm of cells, while the combination of the three cytokines induced an enlargement of intercellular spaces. Altogether, our results suggest that IL-22 mainly affects keratinocyte terminal differentiation, whereas, for inducing an impairment in cell proliferation, a more complex psoriatic-like microenvironment is needed