Impact of modern systemic therapies and clinical markers on treatment outcome for metastatic melanoma in a real-world setting.

BACKGROUND: The survival in metastatic melanoma has dramatically improved after the introduction of immune checkpoint- (ICIs) and MAPKinase inhibitors (MAPKis). OBJECTIVE: Our aim was to describe therapy response and survival in a real-world population as well as to assess the associations between clinical variables and therapy outcome for patients with metastatic melanoma receiving first-line ICIs or MAPKis. METHODS: A total of 252 patients with metastatic (stage IV) melanoma were prospectively followed between 1 January 2010 and 3 December 2017 with follow-up until 31 March 2019, at the Karolinska University Hospital, Sweden. Hazard ratios (HRs) for progression-free survival (PFS) and overall survival (OS) were analysed with Cox regression, and logistic regression was used to estimate odds ratios (ORs) for therapy response. RESULTS: Patients receiving ICIs (n = 138) experienced longer PFS compared to patients that received MAPKis (n = 114; median PFS for ICIs was 6.8 months, and median PFS for MAPKis was 5.3 months). In the multivariable analyses of clinical markers, increasing M-stage (OR 0.65; 95% CI 0.45-0.94; P = 0.022) and male sex (OR 0.41; 95% CI 0.19-0.90; P = 0.027) were significantly associated with lower response to ICIs. Lower baseline albumin levels (OR 0.90; 95% CI 0.83-0.98; P = 0.019) and male sex (OR 0.33; 95% CI 0.12-0.93; P = 0.036) were related with lower response to MAPKis. For ICIs, increasing M-stage (HR 1.34; 95% CI 1.07-1.68; P = 0.010), increasing LDH (HR 1.73; 95% CI 1.19-2.50; P = 0.004) and decreasing albumin (HR 1.06; 95% CI 1.01-1.10; P = 0.011) were significantly associated lower PFS in the adjusted model. The corresponding markers for MAPKis were increasing LDH (HR 1.44; 95% CI 1.08-1.92; P = 0.013) and decreasing albumin (HR 1.05; 95% CI 1.02-1.09; P = 0.005) for PFS. CONCLUSION: ICIs and MAPKis were effective in this real-world population, and we could confirm the importance of previously reported clinical prognostic markers. Albumin values may be associated with therapy outcome but need further validation.

Economic motives to use a participatory design approach in the development of public-health information systems.

Within public health, there is a tradition of co-operation between researchers and communities in planning and implementation of health promotion programs. As a consequence, public-health organizations are characterized by having complex multidisciplinary structure and dynamic organizational goals. In this paper, we discuss the economic impacts from the use of Participatory Design for development of public-health information systems. Creation of systems that have both utility and usability is suggested to be highlighted as the central goal. The identified pre-requisites for a positive impact are that the new system should be of high quality, appropriate to the nature of the health promotion tasks, and to how activities are coordinated and integrated both between and within the stakeholder groups involved. We argue further that a method that minimizes the information asymmetry in the development process is necessary for avoiding market failures 1. The conclusion is that participatory design will diminish transaction costs, will help to avoid sunk costs, and will contribute to rich efficient use of human and economic resources in public-health organizations.

Pre-operative fasting guidelines: an update.

Liberal pre-operative fasting routines have been implemented in most countries. In general, clear fluids are allowed up to 2 h before anaesthesia, and light meals up to 6 h. The same recommendations apply for children and pregnant women not in labour. In children <6 months, most recommendations now allow breast- or formula milk feeding up to 4 h before anaesthesia. Recently, the concept of pre-operative oral nutrition using a special carbohydrate-rich beverage has also gained support and been shown not to increase gastric fluid volume or acidity. Based on the available literature, our Task Force has produced new consensus-based Scandinavian guidelines for pre-operative fasting. What is still not clear is to what extent the new liberal fasting routines should apply to patients with functional dyspepsia or systematic diseases such as diabetes mellitus. Other still controversial areas include the need for and effect of fasting in emergency patients, women in labour and in association with procedures done under 'deep sedation'. We think more research on the effect of various fasting regimes in subpopulations of patients is needed before we can move one step further towards completely evidence-based pre-operative fasting guidelines.

Comparison of eltanolone and thiopental in anaesthesia for termination of pregnancy.

Eltanolone, a new steroid hypnotic, was compared to thiopental in short anaesthesia. Sixty unpremedicated, Asa 1-2 women were randomized to receive eltanolone 0.6 (group E1) or 0.8 mg.kg-1 (group E2) or thiopental 4 mg.kg-1 (group T) for induction of anaesthesia. One minute before induction glycopyrrolate 0.2 mg and alfentanil 15 micrograms.kg-1 i.v. were administered. If induction failed, additional boluses of the test drug were given. Anaesthesia was maintained with 67% nitrous oxide in oxygen, and additional bolus doses of the test drug were given in a standardized fashion, if needed. Recovery was assessed by a research nurse blinded to the agent used. Mean +/- s.d. induction doss were 0.7 +/- 0.1 mg.kg-1 (group E1), 0.8 +/- 0.1 mg.kg-1 (group E2) and 4.0 +/- 0.0 mg.kg-1 (group T). Induction time was prolonged in the group E1 compared to the other two groups (P < 0.05). Side effects were few in all groups, but involuntary muscle movements or hypertonus occurred in 23% of the patients in the eltanolone and in 3% in the thiopental groups (n.s). Early recovery (eye opening, orientation and sitting) was slower in both eltanolone groups compared to the thiopental group (P < 0.01). No differences between the groups were found in toleration of oral fluids, walking, voiding, postoperative analgesic requirements or postoperative nausea and vomiting.(ABSTRACT TRUNCATED AT 250 WORDS)

Pre-operative fasting guidelines: an update

Liberal pre-operative fasting routines have been implemented in most countries. In general, clear fluids are allowed up to 2 h before anaesthesia, and light meals up to 6 h. The same recommendations apply for children and pregnant women not in labour. In children <6 months, most recommendations now allow breast- or formula milk feeding up to 4 h before anaesthesia.Recently, the concept of pre-operative oral nutrition using a special carbohydrate-rich beverage has also gained support and been shown not to increase gastric fluid volume or acidity. Based on the available literature, our Task Force has produced new consensus-based Scandinavian guidelines for pre-operative fasting. What is still not clear is to what extent the new liberal fasting routines should apply to patients with functional dyspepsia or systematic diseases such as diabetes mellitus. Other still controversial areas include the need for and effect of fasting in emergency patients, women in labour and in association with procedures done under ‘deep sedation’. We think more research on the effect of various fasting regimes in subpopulations of patients is needed before we can move one step further towards completely evidence-based pre-operative fasting guidelines.