The incidence of cutaneous melanoma (hereafter melanoma) has increased dramatically among fair-skinned populations worldwide. In Norway, melanoma is the most rapidly growing type of cancer, with a 47% increase among women and 57% among men in 2000-2016. Intermittent ultraviolet exposure early in life and phenotypic characteristics like a fair complexion, freckles and nevi are established risk factors, yet the aetiology of melanoma is multifactorial. Certain prescription drugs may have carcinogenic side effects on the risk of melanoma. Some cardiovascular, antidepressant and immunosuppressive drugs can influence certain biological processes that modulate photosensitivity and immunoregulation. We aim to study whether these drugs are related to melanoma risk.
A population-based matched case-control study will be conducted using nation-wide registry data. Cases will consist of all first primary, histologically verified melanoma cases diagnosed between 2007 and 2015 identified in the Cancer Registry of Norway (14 000 cases). Ten melanoma-free controls per case (on date of case melanoma diagnosis) will be matched based on sex and year of birth from the National Registry of Norway. For the period 2004-2015, and by using the unique personal identification numbers assigned to all Norwegian citizens, the case-control data set will be linked to the Norwegian Prescription Database for information on drugs dispensed prior to the melanoma diagnosis, and to the Medical Birth Registry of Norway for data regarding the number of child births. Conditional logistic regression will be used to estimate associations between drug use and melanoma risk, taking potential confounding factors into account.
The project is approved by the Regional Committee for Medical Research Ethics in Norway and by the Norwegian Data Protection Authority. The study is funded by the Southeastern Norway Regional Health Authority. Results will be published in peer-reviewed journals and disseminated further through scientific conferences, news media and relevant patient interest groups.

Cangrelor is an intravenous P2Y12 receptor antagonist approved for use during percutaneous coronary intervention (PCI) to reduce ischemic events associated with new stent placement and has been used off-label at reduced doses guided by platelet function testing as a \"bridge\" from discontinuation of oral P2Y12 receptor antagonists to surgical procedures when the long-term effects of oral agents are undesirable.
To describe the dosing, laboratory monitoring, and clinical outcomes of a series of patients who received cangrelor as a \"bridging\" antiplatelet agent.
This study is a retrospective analysis of all patients within the study center with coronary stents who received cangrelor as a bridge to surgical procedure and had VerifyNow monitoring during treatment.
A total of 11 patients were identified for inclusion. The median cangrelor dose was 0.5 µg/kg/min (interquartile range = 0.5-0.5) and was maintained in 7 of 11 patients. Doses ranged from 0.25 to 2 µg/kg/min during therapy, and 81.6% of VerifyNow results assessed were within goal range (⩽208 P2Y12 reaction units). Bleeding complications during therapy occurred in 3 patients, all of whom were receiving concomitant heparin infusions, and no stent thrombosis was reported. Conclusion and Relevance: Low-dose cangrelor may represent an effective option for bridging antiplatelet therapy in patients with coronary stents. This study demonstrated that the majority of patients received adequate platelet inhibition without any incidence of stent thrombosis on 0.5 µg/kg/min using the VerifyNow assay to monitor platelet inhibition, which represents a lower dose than previously reported in the literature.

OBJECTIVE: To assess the required characteristics (cost, sensitivity and specificity) of a pharmacogenomic test for being a cost-effective prevention of angiotensin-converting enzyme inhibitors induced angioedema. Furthermore, we assessed the influence of only testing high-risk populations.
METHODS: A decision tree was used.
RESULTS: With a willingness-to-pay threshold of €20,000 and €80,000 per quality adjusted life year, a 100% sensitive and specific test may have a maximum cost of €1.30 and €1.95, respectively. When only genotyping high-risk populations, the maximum test price would be €5.03 and €7.55, respectively.
CONCLUSIONS: This theoretical pharmacogenomic test is only cost-effective at high specificity, high sensitivity and a low price. Only testing high-risk populations yields more realistic maximum test prices for cost-effectiveness of the intervention.

Cardiovascular patients frequently use herbal medicinal products, in order to contribute to the improvement of their chronic condition without medical intervention. However, they are likely to suffer from adverse effects from natural products and herb-drug interactions. In this work we present the results collected from a public campaign \"Learning Health, among Plants and Medicines\", carried out by the Observatory of Herb-Drug Interactions (www.oipm.uc.pt), to alert cardiovascular patients and healthcare providers for the potential occurrence of herb-drug interactions with cardiovascular therapy. From the data received, it was highlighted the prevalence of certain natural products used by many cardiovascular patients in Portugal, particularly goji berries, green tea, mangosteen and rooibos that have significant cardiovascular effects. For this reason their intake should be carefully monitored in these patients. This prevalence of consumption suggests a pattern in their use in Portugal and a prevention of herb-drug interactions should be carried out by the health professionals. The ending results also indicate that there is still a lack of knowledge about the possible risks of herbal products intake, which may adversely affect the health of any patient. Thus becomes clear the value of the role of health professionals in the screening of such interactions.

BACKGROUND: The purpose of this study is to describe a case where methylene blue improved hemodynamics in a poisoned patient.
METHODS: This is a single case report where a poisoned patient developed vasodilatory shock following ingestion of atenolol, amlodipine, and valsartan. Shock persisted after multiple therapies including vasopressors, high-dose insulin, hemodialysis, and 20% intravenous fat emulsion. Methylene blue (2 mg/kg IV over 30 min) was administered in the ICU with temporal improvement as measured by pulmonary artery catheter hemodynamic data pre- and post-methylene blue administration. Within 1 h of methylene blue administration, systemic vascular resistance improved (240 dyn s/cm5 increased to 1204 dyn s/cm5), and vasopressor requirements decreased with maintenance of mean arterial pressure 60 mmHg.
CONCLUSIONS: Methylene blue may improve hemodynamics in drug-induced vasodilatory shock and should be considered in critically ill patients poisoned with vasodilatory medications refractory to standard therapies.

OBJECTIVE: The external validity of trial results of new cardiovascular drugs is limited, because the short-term studies are performed with relatively small, highly selected populations. Using qualitative methods, we examined the clinical relevance of under-representation of subgroups of patients, and the underlying arguments.
METHODS: Interviews with 47 physicians and pharmacists involved in the pre- or post-marketing evaluation of cardiovascular drugs, addressing the issue in general and for two new drugs, losartan and atorvastatin, in particular.
RESULTS: The respondents were generally familiar with the under-representation of elderly patients, female patients, and patients with comorbidity in pre-marketing trials, but less familiar with details of representation in the cases of losartan and atorvastatin. In particular under-representation of patients with comorbidity was considered relevant. Arguments to confirm or refute the relevance referred to trial methodology, applicability of trial results or aspects of patient treatment. Conditional arguments referred to the aim of the trial, population size, therapeutic drug class or the timing of trials prior to or after drug registration.
CONCLUSIONS: To optimise the connection between pre-marketing clinical research and practice, trials should focus more on patient groups relevant to medical practice. If such research is not feasible prior to registration, it should be conducted afterwards. Drug information should allow practitioners to determine variations in the relative effects between subpopulations.

BACKGROUND: Pharmaceutical expenditure has grown by 16% per annum in China, enhanced by incentives for physicians and hospitals. Hospital pharmacies dispense 80% of medicines in China, accounting for 46% of total hospital expenditure. Principal measures to moderate drug expenditure growth include pricing initiatives as limited demand-side measures.
OBJECTIVE: Assess current utilization and expenditure including traditional Chinese medicines (TCMs) between 2006 and 2012.
METHODS: Uncontrolled retrospective study of medicines to treat cardiovascular and cerebrovascular diseases in one of the largest hospitals in southwest China.
RESULTS: Utilization increased 3.3-fold for cerebrovascular medicines, greatest for TCMs, with expenditure increasing 4.85-fold. Low prices for generics were seen, similar to Europe. However, there was variable utilization of generics at 29-31% of total product volumes in recent years. There continued to be irrationality in prescribing with high use of TCMs, and the utilization of different medicines dropping significantly once they achieved low prices.
CONCLUSIONS: Prices still have an appreciable impact on utilization in China. Potential measures similar to those implemented among western European countries could improve prescribing rationality and conserve resources.