Objectifying the conjunctival provocation test: photography-based rating and digital analysis.

BACKGROUND: Patients with allergic rhinoconjunctivitis are susceptible to both nasal and ocular symptoms. The conjunctival provocation test (CPT) is an established diagnostic procedure used in allergic rhinoconjunctivitis, particularly to document a patient's current reactivity to allergens. To date, there are no international guidelines defining the CPT. No approved evaluation method exists for interpreting CPT results. This paper aims to establish the digital analysis of macroimages as an objective, validated and standardized method for interpreting CPT results. METHODS: In a clinical immunotherapy trial with 155 patients, treatment progress was documented based on the CPT. Local investigators used a symptom score to grade tearing, reddening and the patients' subjective perception of symptoms (mucosal irritation). A central observer rated conjunctival hyperemia via digital photography. Digital image analysis software was utilized to determine conjunctival hyperemia. RESULTS: Spearman's correlation between the local investigators' and the central observer's ratings was r = 0.729 (p < 0.001); the percentage of total agreement was 48% (based on 739 photos). Digital image analysis (based on 48 photos) had a high percentage of total agreement with the central observer's ratings (69%) but a low percentage of total agreement with the investigators' ratings (38%). The corresponding correlations were r = 0.264 and 0.064, respectively. CONCLUSION: Photography-based rating by a central observer may represent a valuable supplement to the local investigator's assessment for making an objective evaluation of CPT results. Digital image analysis possesses the potential of being an objective evaluation method compared to the wide-spread subjective evaluation by the investigators.

[From heparin to apixaban: anticoagulants cut both ways?]. / Vom Heparin zum Apixaban: Was bringen die "neuen Antikoagulanzien"?

BACKGROUND: Regarding anticoagulant therapies there has been a remarkable shift in recent years. The objective of this brief overview is to provide relevant information and guidelines on the advantages and disadvantages of novel anticoagulants addressing specifically the surgical disciplines. Hitherto, conventional anticoagulant therapy in patients with a high thrombosis risk was largely limited to heparins and vitamin-K antagonists (VKA). Their modes of action, the difficulties in managing VKAs (e.g., bridging therapy) and the risk of HIT (heparin-induced thrombocytopenia) associated with heparins are briefly discussed. Novel anticoagulants supposedly eliminate these obstacles. Fondaparinux (Arixtra®) is a fully synthetic pentasaccharide which acts like a heparin but has an increased half life. Fondaparinux has a diminished risk of HIT. However, no specific antidote is currently available for Fondaparinux. The novel oral anticoagulants (NOAC) dabigatran etexilat (Pradaxa®), rivaroxaban (Xarelto®) and apixaban (Eliquis®), also known as "direct" anticoagulants, act independently from antithrombin by inhibiting thrombin, as in the case of dabigatran, or by inhibiting factor Xa, as in the case of rivaroxaban and apixaban. It is assumed that they are suitable for long-term use and do not require laboratory monitoring. Nevertheless, clinical experience is very limited and caution rather than quick conclusions is necessary. Two major drawbacks are on the one hand the risk of drug accumulation in kidney and/or liver disease and, on the other hand, the lack of specific antidotes. In addition, interactions with other medication may have unexpected effects on serum drug levels. Therefore, the analysis of drug levels in the plasma may become necessary in subgroups of patients. DISCUSSION AND CONCLUSION: Studies establishing clear recommendations for the desirable and measurable reference range are needed. Similarly, evidence-based recommendations regarding perioperative prevention of thrombosis are required ("bridging": yes or no?). Irrespective of these issues, the authors predict a further expansion of the use of NOACs.

Further fractionation and co-promoting activity of the large molecular weight components of aqueous tobacco extracts.

Earlier studies showed that aqueous extracts of tobacco exhibit tumor promoting activity. The activity required the simultaneous presence of two agents, one of which was methanol soluble and the other, methanol insoluble. In this study, the 80% methanol insoluble fraction was further fractionated using dialysis through controlled pore membranes. Each resulting sub-fraction was then combined with the methanol soluble fraction and tested as a promoting stimulus in mice treated with 7,12-dimethylbenz[a]anthracene. The subfraction (D) with a presumptive molecular weight greater than 13,000 produced a significantly higher tumor incidence and tumor yield together with a significantly shorter latent period than the other subfractions. D contained about 12% of the total 80% methanol insoluble material. All of the other subfractions exhibited significant but less pronounced co-promoting activity.