Effects of hypothermia and rewarming on cardiovascular autonomic control in vivo.

Rewarming from accidental hypothermia is associated with cardiovascular dysfunction that complicates rewarming and contributes to a high mortality rate. We investigated autonomic cardiovascular control, as well as the separate effects of cooling, hypothermia, and rewarming on hemodynamic function, aiming to provide knowledge of the pathophysiology causing such complications in these patients. A rat model designed for circulatory studies during cooling, hypothermia (15°C), and rewarming was used. Spectral analysis of diastolic arterial pressure and heart rate allowed assessment of the autonomic nervous system. Hemodynamic variables were monitored using a conductance catheter in the left ventricle and a pressure transducer connected to the left femoral artery. Sympathetic cardiovascular control was reduced after rewarming. Stroke volume increased during cooling but decreased during stable hypothermia and did not normalize during rewarming. Despite autonomic dysfunction, total peripheral resistance increased during cooling and did not normalize after rewarming. The present data show that sympathetic cardiovascular control is reduced by hypothermia and rewarming. A simultaneous systolic dysfunction is seen in rewarmed animals, caused by reduced filling of the left ventricle and impaired contractile function, in the presence of normal diastolic function. These findings show that dysfunction of the efferent sympathetic nervous system could be instrumental in development of rewarming shock. NEW & NOTEWORTHY The present study shows impaired autonomic control of cardiovascular function after rewarming from severe hypothermia. In victims of accidental hypothermia, rewarming shock is a much feared and lethal complication. The pathophysiology causing such cardiovascular collapse appears complex. Our findings indicate that dysfunction of the autonomic nervous system is an important part of the pathophysiology. Thus the present study gives novel information, important for further development of treatment strategies in this patient group.

Health Economics and Radium-223 (Xofigo®) in the Treatment of Metastatic Castration-Resistant Prostate Cancer (mCRPC): A Case History and a Systematic Review of the Literature.

OBJECTIVES: Prostate cancer (PC) is the most common cancer in Western countries. Recent advances in the treatment of metastatic castration resistant prostate cancer (mCRPC) have caused significant pressure on health care budgets. We aimed to exemplify this dilemma presenting an example, radium-223 (Xofigo®), and review the literature. METHODS: A 74-year-old man diagnosed with mCRPC was referred to our department in October 2014 for radium-223 therapy. We faced the following dilemma: is radium-223 standard therapy? Is it cost-effective? Medline was searched employing the following search criteria: "radium-223", "alpharadin", "Xofigo" and "prostate". Exclusion and inclusion criteria were applied. Guidelines and cost-effectiveness analyses were focused. We also searched the websites of ASCO, ESMO and ISPOR. The web was searched, using Yahoo and Google search engines, for Health Technology Assessments (HTAs). RESULTS: 181 publications were identified in the Medline database. Only four studies included the word "cost", three "economics" and none "budget" in heading or abstract. None of the publications were thorough of cost analysis (cost-effectiveness, cost-utility, cost-minimizing or cost-of-illness analysis). Six HTAs and eight national guidelines were identified. The cost per quality adjusted life years was indicated €80.000-94,000. HTAs concluded reimbursement being not recommendable or no ultimate statement could be made. One pointed towards a limited use with caution. CONCLUSION: Guidelines were based on data from randomized clinical trials (RCTs). Health economics was not considered when guidelines were made. Most HTAs concluded this therapy not cost-effective or there was insufficient data for final conclusions. Licensing and reimbursement processes should be run simultaneously.

PET-CT in the sub-arctic region of Norway 2010-2013. At the edge of what is possible?

BACKGROUND: It is challenging to obtain a similar access to positron emission tomography/computed tomography (PET-CT) within the whole region served. In the subarctic and arctic region of Norway, significant distances, weather conditions and seasonable darkness have been challenging when the health care provider has aimed for a high quality PET-CT service with similar availability to all inhabitants. METHODS: The PET-CT service at the University Hospital of North Norway (UNN) was established in May 2010. The glucose analogue tracer fluorine-18 fluorodeoxyglucose (FDG) was delivered from Helsinki, Finland. An ambulatory PET-CT scanner was initially employed and a permanent local one was introduced in October 2011. In March 2014, we analysed retrospectively all data on the PET-CT exams performed at the Section of Nuclear Medicine, Department of Radiology during a 32 months time period 2010-13. The following patient data were recorded: gender, age, diagnosis, residence and distance of travelling. There were in total 796 exams in 706 patients. RESULTS: Four hundred sixty-one PET-CT exams per million inhabitants were, on average, performed per year. Lung cancer (32.7%), malignant melanoma (11.3%), colorectal cancer (10.9%) and lymphoma (9.7%) constituted two-thirds of all exams. Three-fourths were males and the median age was 63.5 years (range 15.2-91.4 years). The access to PET-CT exam varied within the region. The southern county (Nordland) experienced a significantly less access (p < 0.0001) to the regional service. Except for malignant melanoma, this finding was observed in all major cancer subgroups. In colorectal cancer and lymphoma a lower consumption of PET-CT was also observed in the northeastern county (Finnmark). Patients' mean distance of travelling by car (one way) was 373 km (median 313 km, range 5-936 km). CONCLUSION: PET-CT was not similarly available within the region. Especially, inhabitants in the southern county experienced less access to the regional service. National and regional standards of care, new scanners and improved collaboration between hospital trusts may alter this situation.

[Nuclear medicine examination in heart failure patients]. / Nukleaermedisinsk utredning av pasienter med hjertesvikt.

BACKGROUND: Recently, cardiac resynchronization therapy, by using biventricular pacemakers, has become implemented in the treatment of patients with severe heart failure. However, using the classical inclusion criteria, 30 % of patients treated with resynchronization do not improve symptoms or activity level. Phase analysis of radionuclide ventriculography gives information about pattern of ventricular contraction and may detect dyssynchrony. The method may therefore be used to select patients with dyssynctrony to resynchronization therapy. In this study we have investigated the amount of dyssynchrony, by using phase analysis of radionuclide ventriculography, in men and women as a function of left ventricular ejection fraction. MATERIAL AND METHODS: The study is based on 1 266 radionuclide ventriculographies performed at Section of Nuclear Medicine, University Hospital North-Norway, during 1998 - 2006. The relationship between left ventricular ejection fraction and number of patients with ventricular dyssynchrony was investigated. 90 patients with no known heart problems were considered as reference values for synchrony data. RESULTS: The phase analysis showed that 35 % of the women and 34 % of the men with left ventricular ejection fraction below 35 % had both inter- and intra-ventricular dyssynchrony. INTERPRETATION: Today's criteria for including patients to resynchonizing therapy are not good enough. Phase analysis of radionuclide ventriculography of patients with left ventricular ejection fraction below 35 % shows that one third of the patients have both inter- and intra- ventricular dyssynchrony. These patients might be responders to resynchronization therapy.