Pirfenidone in idiopathic pulmonary fibrosis:expert panel discussion on the management of drug-related adverse events

Pirfenidone is currently the only approved therapy for idiopathic pulmonary fibrosis, following studies demonstrating that treatment reduces the decline in lung function and improves progression-free survival. Although generally well tolerated, a minority of patients discontinue therapy due to gastrointestinal and skin-related adverse events (AEs). This review summarizes recommendations based on existing guidelines, research evidence, and consensus opinions of expert authors, with the aim of providing practicing physicians with the specific clinical information needed to educate the patient and better manage pirfenidone-related AEs with continued pirfenidone treatment. The main recommendations to help prevent and/or mitigate gastrointestinal and skin-related AEs include taking pirfenidone during (or after) a meal, avoiding sun exposure, wearing protective clothing, and applying a broad-spectrum sunscreen with high ultraviolet (UV) A and UVB protection. These measures can help optimize AE management, which is key to maintaining patients on an optimal treatment dose.Correction in: Advances in Therapy, Volume 31, Issue 5, pp 575-576 , doi: 10.1007/s12325-014-0118-8</p

Keratinocytes can modulate and directly initiate nociceptive responses

How thermal, mechanical and chemical stimuli applied to the skin are transduced into signals transmitted by peripheral neurons to the CNS is an area of intense study. Several studies indicate that transduction mechanisms are intrinsic to cutaneous neurons and that epidermal keratinocytes only modulate this transduction. Using mice expressing channelrhodopsin (ChR2) in keratinocytes we show that blue light activation of the epidermis alone can produce action potentials (APs) in multiple types of cutaneous sensory neurons including SA1, A-HTMR, CM, CH, CMC, CMH and CMHC fiber types. In loss of function studies, yellow light stimulation of keratinocytes that express halorhodopsin reduced AP generation in response to naturalistic stimuli. These findings support the idea that intrinsic sensory transduction mechanisms in epidermal keratinocytes can directly elicit AP firing in nociceptive as well as tactile sensory afferents and suggest a significantly expanded role for the epidermis in sensory processing

Prostaglandin D2-supplemented “functional eicosanoid testing and typing” assay with peripheral blood leukocytes as a new tool in the diagnosis of systemic mast cell activation disease: an explorative diagnostic study

Background: Systemic mast cell activation disease (MCAD) is characterized by an enhanced release of mast cell-derived mediators, including eicosanoids, which induce a broad spectrum of clinical symptoms. Accordingly, the diagnostic algorithm of MCAD presupposes the proof of increased mast cell mediator release, but only a few mediators are currently established as routine laboratory parameters. We thus initiated an explorative study to evaluate in vitro typing of individual eicosanoid pattern of peripheral blood leukocytes (PBLs) as a new diagnostic tool in MCAD. Methods: Using the “functional eicosanoid testing and typing” (FET) assay, we investigated the balance (i.e. the complex pattern of formation, release and mutual interaction) of prostaglandin E2 (PGE2) and peptido-leukotrienes (pLT) release from PBLs of 22 MCAD patients and 20 healthy individuals. FET algorithms thereby consider both basal and arachidonic acid (AA)-, acetylsalicylic acid (ASA)-, and substance P (SP)-triggered release of PGE2 and pLT. The FET assay was further supplemented by analyzing prostaglandin D2 (PGD2), as mast cell-specific eicosanoid. Results: We observed marked PGE2-pLT imbalances for PBLs of MCAD patients, as indicated by a markedly enhanced mean FET value of 1.75 ± 0.356 (range: 1.14–2.36), compared to 0.53 ± 0.119 (range: 0.36-0.75) for healthy individuals. In addition, mean PGD2 release from PBLs of MCAD patients was significantly, 6.6-fold higher than from PBLs of healthy individuals (946 ± 302.2 pg/ml versus 142 ± 47.8 pg/ml; P < 0.001). In contrast to healthy individuals, PGD2 release from PBLs of MCAD patients was markedly triggered by SP (mean: 1896 ± 389.7 pg/ml; P < 0.001), whereas AA and ASA caused individually varying effects on both PGD2 and pLT release. Conclusions: The new in-vitro FET assay, supplemented with analysis of PGD2, demonstrated that the individual patterns of eicosanoid release from PBLs can unambiguously distinguish MCAD patients from healthy individuals. Notably, in our analyses, the FET value and both basal and triggered PGD2 levels were not significantly affected by MCAD-specific medication. Thus, this approach may serve as an in-vitro diagnostic tool to estimate mast cell activity and to support individualized therapeutic decision processes for patients suffering from MCAD

Ekologisk restaurering av skog i boreala Sverige : bristanalys, åtgärdsförslag och skötsel av död ved på Vitberget, Lycksele

Sweden's boreal forest has suffered from radical human caused changes since the beginning of industrialisation. Ecological qualities, such as large trees, dead trees, and deciduous trees, have been removed from the forest. Natural processes, like fire, have been suppressed leading to ecosystem degradation, even in the forest reserves. Many species that directly or indirectly depend upon natural structures are disfavoured and the restoration need is evident. In this study, the present status of a Swedish boreal forest is analysed in a biodiversity restoration context. Based on ecological qualities of a historic reference state, a restoration gap analysis is produced. Methods to recreate lost ecological qualities are discussed. Also, the efficiency of four methods to kill trees and thus increase deadwood, is tested. These methods are: clobbering, girdling, topping with explosives and inoculation of wood-rotting fungi. A gap-analysis is one way to view forest degradation and measure its deviation from the reference state. Ecological qualities are relatively high in this area as compared to the region as a whole, mainly because of recent logging in the region. However, if compared with the reference state, the area has lost a great deal of ecological qualities due to human activity. To be successful, strategies for restoring a degraded forest should ultimately have a landscape level approach. Therefore, restoration of ecological qualities not only includes reserves but also production forests. In production forests, forest management should be adapted to the natural functioning of the ecosystem. Fire is the most important natural process in this ecosystem. Fire-reintroduction and management is the primary goal in the restoration process. Although, it should be complemented by other methods. Clobbering and girdling were the most time-efficient methods to kill trees and did not substantially differ from each other. Topping and inoculation were much less time-efficient. They are also more technically complicated and thus more costly. Due to lack of dead wood in the forest, clobbering, girdling and topping are recommended methods to be used at this time. Whereas, inoculation of wood-rotting funge should be more thoroughly tested. Larger studies, with repeated sample plots in different stand types, must be implemented to gather more data for precise management recommendations. Because of dramatic losses of old growth characters during the last centuries, it is imperative that restoration of old-growth characters is accomplished as well as retaining residual old-growth characters

Preconditions and barriers to support patient autonomy in palliative home care : a qualitative study from a nursing perspective

SAMMANFATTNING Bakgrund: Sjuksköterskor inom palliativ hemsjukvård förväntas idag arbeta med ett personcentrerat förhållningssätt gentemot patienterna. Genom att skapa en relation präglad av omtanke och värme med patienten kan sjuksköterskan tillgodose patientens såväl yttre som inre behov och sörja för ett värdigt liv. Att stötta patientens autonomi ses som en av de viktigaste uppgifterna för sjuksköterskor inom palliativ hemsjukvård. Emellertid är autonomi ett komplext begrepp. Aspekter relaterade till beslutsfattande, delaktighet, självständighet, relationer och känsla av värdighet bör beaktas i förhållande till patientens autonomi. Patienten ska involveras i vården och har rätt att vara delaktig i beslutsfattande, men vårdorganisationen är inte alltid anpassad till detta. Förmågan till beslutsfattande bland patienterna är också individuell och viljan att vara delaktig varierar. Därtill är svårt sjuka patienter ofta beroende av andra för att kunna hantera sin vardag. Syfte: Att beskriva sjuksköterskors upplevelser av hinder och förutsättningar för att stötta patienters autonomi i en palliativ hemsjukvårdskontext. Metod: En kvalitativ induktiv studie med deskriptiv design utfördes och data samlades in medelst fokusgrupper på en avancerad hemsjukvårdsenhet i Stockholm mellan februari och mars 2015. Data analyserades med manifest innehållsanalys. Resultat: Studien visar att sjuksköterskor inom palliativ hemsjukvård identifierar ett flertal hinder och förutsättningar för att stötta patientens autonomi. Fyra kategorier identifierades i resultatet: Patienten, Sjuksköterskan, Organisationen samt Palliativ vård. Resultatet beskriver hur patientens individuella egenskaper, verktyg och resurser samt relationer till andra avgör till vilken grad patienten kan vara autonom. Den enskilda sjuksköterskans kompetens och förmåga att skapa trygghet i relationen med patienten, genom att ta ansvar, ge fullgod och anpassad information och arbeta personcentrerat, skapar förutsättningar för patientens autonomi i vardagen och i förhållande till sjukvården. Därtill är sjuksköterskan i sin tur beroende av en organisation som understödjer personcentrerad vård och underlättar etisk medvetenhet och samsyn i palliativ vårdfilosofi. Slutsats: De slutsatser som kan dras av resultatet är att sjuksköterskor inom palliativ hemsjukvård anser att patientens autonomi är beroende av patientens individualitet och relationer till andra, sjuksköterskans relationsskapande och samordnande kompetenser, vårdenhetens organisation och resursfördelning samt i viss mån sjukvårdspersonalens kunskap om och följsamhet till den palliativa vårdens grunder