| 1. |
- Sullivan, Richard, et al.
(författare)
-
Delivering affordable cancer care in high-income countries
- 2011
-
Ingår i: The Lancet Oncology. - London : Lancet Oncology. - 1470-2045 .- 1474-5488. ; 12:10, s. 933-980
-
Tidskriftsartikel (refereegranskat)abstract
- The burden of cancer is growing, and the disease is becoming a major economic expenditure for all developed countries. In 2008, the worldwide cost of cancer due to premature death and disability (not including direct medical costs) was estimated to be US$895 billion. This is not simply due to an increase in absolute numbers, but also the rate of increase of expenditure on cancer. What are the drivers and solutions to the so-called cancer-cost curve in developed countries? How are we going to afford to deliver high quality and equitable care? Here, expert opinion from health-care professionals, policy makers, and cancer survivors has been gathered to address the barriers and solutions to delivering affordable cancer care. Although many of the drivers and themes are specific to a particular field-eg, the huge development costs for cancer medicines-there is strong concordance running through each contribution. Several drivers of cost, such as over-use, rapid expansion, and shortening life cycles of cancer technologies (such as medicines and imaging modalities), and the lack of suitable clinical research and integrated health economic studies, have converged with more defensive medical practice, a less informed regulatory system, a lack of evidence-based sociopolitical debate, and a declining degree of fairness for all patients with cancer. Urgent solutions range from re-engineering of the macroeconomic basis of cancer costs (eg, value-based approaches to bend the cost curve and allow cost-saving technologies), greater education of policy makers, and an informed and transparent regulatory system. A radical shift in cancer policy is also required. Political toleration of unfairness in access to affordable cancer treatment is unacceptable. The cancer profession and industry should take responsibility and not accept a substandard evidence base and an ethos of very small benefit at whatever cost; rather, we need delivery of fair prices and real value from new technologies.
|
|
| 2. |
- Henriksson, Otto, 1976-, et al.
(författare)
-
Protection against cold in prehospital care : evaporative heat loss reduction by wet clothing removal or the addition of a vapour barrier - a thermal manikin study
- 2012
-
Ingår i: Prehospital and Disaster Medicine. - 1049-023X .- 1945-1938. ; 26:6, s. 1-6
-
Tidskriftsartikel (refereegranskat)abstract
- Introduction: In the prehospital care of a cold and wet person, early application of adequate insulation is of utmost importance to reduce cold stress, limit body core cooling, and prevent deterioration of the patient’s condition. Most prehospital guidelines on protection against cold recommend the removal of wet clothing prior to insulation, and some also recommend the use of a waterproof vapor barrier to reduce evaporative heat loss. However, there is little scientific evidence of the effectiveness of these measures.Objective: Using a thermal manikin with wet clothing, this study was conducted to determine the effect of wet clothing removal or the addition of a vapor barrier on thermal insulation and evaporative heat loss using different amounts of insulation in both warm and cold ambient conditions.Methods: A thermal manikin dressed in wet clothing was set up in accordance with the European Standard for assessing requirements of sleeping bags, modified for wet heat loss determination, and the climatic chamber was set to -15 degrees Celsius (°C) for cold conditions and +10°C for warm conditions. Three different insulation ensembles, one, two or seven woollen blankets, were chosen to provide different levels of insulation. Five different test conditions were evaluated for all three levels of insulation ensembles: (1) dry underwear; (2) dry underwear with a vapor barrier; (3) wet underwear; (4) wet underwear with a vapor barrier; and (5) no underwear. Dry and wet heat loss and thermal resistance were determined from continuous monitoring of ambient air temperature, manikin surface temperature, heat flux and evaporative mass loss rate.Results: Independent of insulation thickness or ambient temperature, the removal of wet clothing or the addition of a vapor barrier resulted in a reduction in total heat loss of 19-42%. The absolute heat loss reduction was greater, however, and thus clinically more important in cold environments when little insulation is available. A similar reduction in total heat loss was also achieved by increasing the insulation from one to two blankets or from two to seven blankets.Conclusion: Wet clothing removal or the addition of a vapor barrier effectively reduced evaporative heat loss and might thus be of great importance in prehospital rescue scenarios in cold environments with limited insulation available, such as in mass-casualty situations or during protracted evacuations in harsh conditions.
|
|
| 3. |
- Lundgren, Peter, 1977-
(författare)
-
Protection and treatment of hypothermia in prehospital trauma care : with emphasis on active warming
- 2012
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Background: In prehospital trauma care active warming is recommended to aid in protection from further cooling. However, scientific evidence of the effectiveness of active warming in a clinical setting is scarce. Also, evaluating the effectiveness of active warming, especially in harsh ambient conditions, by objective measures, is difficult. Objective: To evaluate the effectiveness of field applicabe heat sources (I) and to evaluate active warming intervention in a prehospital clinical setting (II and III). To evaluate reliability and validity of the Cold Discomfort Scale (CDS), a subjective judgement scale for assessment of the thermal state of patients in a cold environment (IV). Methods: In a laboratory trial, non-shivering hypothermic subjects (n=5), were cooled in 8 ºC water followed by spontaneous warming, a charcoal heater, two flexible hot-water bags or two chemical heat pads, all applied to the chest and upper back (I). Oesophageal temperature, skin temperature, heat flux, oxygen consumption, respiratory rate and, heart rate were measured. In two clinical randomized trials, shivering patients during road and air ambulance transport (II) and during field treatment (III) were randomized to either passive warming alone (n=22 and n=9) or to passive warming with the addition of a chemical heat pad (n=26 and n=11). Body core temperature, respiratory rate, heart rate, blood pressure (II) and the patients’ subjective sensation of thermal comfort (II and III) were measured. In a laboratory trial, shivering subjects were exposed to – 20 ºC (n=22). The CDS was evaluated regarding reliability, defined as test-retest stability, and criterion validity, defined as the ability to detect changes in cold discomfort due to changes in cumulative cold stress (IV). Results: In non-shivering hypothermic subjects postcooling afterdrop was significantly less for the chemical heat pads, but not for the hot water bags and the charcoal heater, compared to spontaneous warming (I). Temperature drop during the entire warming phase was significantly less for all the heat sources respectively, compared to spontaneous warming (I). During road and air ambulance transport, ear canal temperature was significantly increased and cold discomfort significantly decreased, both in patients assigned to passive warming only, and in patients assigned to additional active warming (II). During field treatment, cold discomfort was significantly reduced in patients assigned to additional active warming, but remained the same in patients assigned to passive warming only (III). Weighted kappa coefficient, describing test-retest stability, was 0.84 (IV). CDS ratings were significantly increased during each 30 minutes interval (IV). Conclusion: In non-shivering hypothermic subjects, heat sources were effective to attenuate afterdrop, when providing high heat content over a large surface area and effective to continue to increase body core temperature when providing sustained high heat content. In shivering trauma patients, adequate passive warming were sufficient treatment to prevent afterdrop, to slowly increase body core temperature, and to reduce cold discomfort. If inadequate passive warming, additional active warming was required to reduce cold discomfort. The CDS, a subjective judgement scale for assessment of the thermal state of patients in a cold environment seemed to be reliable regarding test-retest stability and valid regarding ability to detect change in cumulative cold stress.
|
|
| 4. |
- Lundgren, Peter, et al.
(författare)
-
The effect of active warming in prehospital trauma care during road and air ambulance transportation : a clinical randomized trial
- 2011
-
Ingår i: Scandinavian Journal of Trauma, Resuscitation and Emergency Medicine. - : BioMed Central. - 1757-7241. ; 19:59
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Prevention and treatment of hypothermia by active warming in prehospital trauma care is recommended but scientifical evidence of its effectiveness in a clinical setting is scarce. The objective of this study was to evaluate the effect of additional active warming during road or air ambulance transportation of trauma patients. Methods: Patients were assigned to either passive warming with blankets or passive warming with blankets with the addition of an active warming intervention using a large chemical heat pad applied to the upper torso. Ear canal temperature, subjective sensation of cold discomfort and vital signs were monitored. Results: Mean core temperatures increased from35.1°C(95% CI; 34.7–35.5 °C) to36.0°C(95% CI; 35.7–36.3 °C) (p<0.05) in patients assigned to passive warming only (n=22) and from35.6°C(95% CI; 35.2–36.0 °C) to36.4°C(95% CI; 36.1–36.7°C) (p<0.05) in patients assigned to additional active warming (n=26) with no significant differences between the groups. Cold discomfort decreased in 2/3 of patients assigned to passive warming only and in all patients assigned to additional active warming, the difference in cold discomfort change being statistically significant (p<0.05). Patients assigned to additional active warming also presented a statistically significant decrease in heart rate and respiratory frequency (p<0.05). Conclusions: In mildly hypothermic trauma patients, with preserved shivering capacity, adequate passive warming is an effective treatment to establish a slow rewarming rate and to reduce cold discomfort during prehospital transportation. However, the addition of active warming using a chemical heat pad applied to the torso will significantly improve thermal comfort even further and might also reduce the cold induced stress response.
|
|
| 5. |
- Lundgren, Peter, 1977-, et al.
(författare)
-
Validity and reliability of the Cold Discomfort Scale : a subjective judgement scale for the assessment of patient thermal state in a cold environment.
- 2014
-
Ingår i: Journal of clinical monitoring and computing. - : Springer Science and Business Media LLC. - 1387-1307 .- 1573-2614. ; 28:3, s. 287-291
-
Tidskriftsartikel (refereegranskat)abstract
- Complementary measures for the assessment of patient thermoregulatory state, such as subjective judgement scales, might be of considerable importance in field rescue scenarios where objective measures such as body core temperature, skin temperature, and oxygen consumption are difficult to obtain. The objective of this study was to evaluate, in healthy subjects, the reliability of the Cold Discomfort Scale (CDS), a subjective judgement scale for the assessment of patient thermal state in cold environments, defined as test-retest stability, and criterion validity, defined as the ability to detect a difference in cumulative cold stress over time. Twenty-two healthy subjects performed two consecutive trials (test-retest). Dressed in light clothing, the subjects remained in a climatic chamber set to -20 °C for 60 min. CDS ratings were obtained every 5 min. Reliability was analysed by test-retest stability using weighted kappa coefficient that was 0.84 including all the 5-min interval measurements. When analysed separately at each 5-min interval the weighted kappa coefficients were was 0.48-0.86. Criterion validity was analysed by comparing median CDS ratings of a moving time interval. The comparison revealed that CDS ratings were significantly increased for every interval of 10, 15, and 30 min (p < 0.001) but not for every interval of 5 min. In conclusion, in a prehospital scenario, subjective judgement scales might be a valuable measure for the assessment of patient thermal state. The results of this study indicated that, in concious patients, the CDS may be both reliable and valid for such purpose.
|
|
| 6. |
- Norlén, Olov
(författare)
-
Small Intestinal Neuroendocrine Tumor : A Rare Malignancy with Favorable Outcome
- 2013
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Small intestinal neuroendocrine tumor (SI-NET) is the most common small bowel tumor in Europe and USA, with an annual incidence of around 0.3-1.3/100000 persons. SI-NETs are the most common type of gastroenteropancreatic NETs (GEP-NETs), and they are known for their ability to produce hormones such as tachykinins and serotonin, as well as for their favorable long-term prognosis in comparison to gastrointestinal adenocarcinoma. The overall aim of the thesis was to investigate unknown or unclear aspects of SI-NET disease, in connection with prognosis, treatment and follow-up. Paper I confirmed several known negative prognostic factors and also showed, for the first time, that para-aortal lymph node metastases and peritoneal carcinomatosis were associated with worse survival by multivariable analyses. Locoregional surgery was associated with a low post-operative mortality, and a prolonged long-term survival by multivariable analysis. In Paper II we continued to investigate peritoneal carcinomatosis and found it be a risk factor not only for death, but also for emergency re-surgery. Furthermore, genetic analyses of samples from primary tumors in patients with and without peritoneal carcinomatosis showed a difference in the DNA between these two groups. In Paper III the outcome after liver surgery and/or radiofrequency ablation of liver metastases was investigated. To summarize, no difference in survival was seen in patients treated with surgery/radiofrequency ablation in comparison with matched controls. However, a superior radiological response of liver metasases and lower U-5-HIAA values were seen in patients subjected to liver surgery and/or radiofrequency ablation compared to matched controls. Paper IV compared ultrasonography, computed tomography and 11C-5HTP-PET in the follow-up after radiofrequency ablation of NET liver metastases. The study concluded that 11C-5HTP-PET depicted all residual tumors after RFA and that it, if used, should be combined with computed tomography for easier interpretation, as RFA areas are not clearly distinguishable with 11C-5HTP-PET alone. Paper V studied gallstone complications after somatostatin analog treatment in SI-NET patients, and concluded that there was a rather high risk to be subjected to a cholecystectomy due to biliary colic, cholecystitis, cholangitis or pancreatitis after primary surgery in somatostatin analog treated patients.
|
|
| 7. |
- Agnarsdóttir, Margrét, 1970-
(författare)
-
Biomarker Discovery in Cutaneous Malignant Melanoma : A Study Based on Tissue Microarrays and Immunohistochemistry
- 2011
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The incidence of cutaneous malignant melanoma has increased dramatically in Caucasians the last few decades, an increase that is partly explained by altered sun exposure habits. For the individual patient, with a localized disease, the tumor thickness of the excised lesion is the most important prognostic factor. However, there is a need to identify characteristics that can place patients in certain risk groups. In this study, the protein expression of multiple proteins in malignant melanoma tumors was studied, with the aim of identifying potential new candidate biomarkers. Representative samples from melanoma tissues were assembled in a tissue microarray format and protein expression was detected using immunohistochemistry. Multiple cohorts were used and for a subset of proteins the expression was also analyzed in melanocytes in normal skin and in benign nevi. The immunohistochemical staining was evaluated manually and for part of the proteins also with an automated algorithm. The protein expression of STX7 was described for the first time in tumors of the melanocytic lineage. Stronger expression of STX7 and SOX10 was seen in superficial spreading melanomas compared with nodular malignant melanomas. An inverse relationship between STX7 expression and T-stage was seen and between SOX10 expression and T-stage and Ki-67, respectively. In a population-based cohort the expression of MITF was analyzed and found to be associated with prognosis. Twenty-one potential biomarkers were analyzed using bioinformatics tools and a protein signature was identified which had a prognostic value independent of T-stage. The protein driving this signature was RBM3, a protein not previously described in malignant melanoma. Other markers included in the signature were MITF, SOX10 and Ki-67. In conclusion, the protein expression of numerous potential biomarkers was extensively studied and a new prognostic protein panel was identified which can be of value for risk stratification.
|
|
| 8. |
- Billing, Ola, 1981-, et al.
(författare)
-
A directed RNAi screen based on larval growth arrest reveals new modifiers of C. elegans insulin signaling
- 2012
-
Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 7:4, s. e34507-
-
Tidskriftsartikel (refereegranskat)abstract
- Genes regulating Caenorhabditis elegans insulin/IGF signaling (IIS) have largely been identified on the basis of their involvement in dauer development or longevity. A third IIS phenotype is the first larval stage (L1) diapause, which is also influenced by asna-1, a regulator of DAF-28/insulin secretion. We reasoned that new regulators of IIS strength might be identified in screens based on the L1 diapause and the asna-1 phenotype. Eighty-six genes were selected for analysis by virtue of their predicted interaction with ASNA-1 and screened for asna-1-like larval arrest. ykt-6, mrps-2, mrps-10 and mrpl-43 were identified as genes which, when inactivated, caused larval arrest without any associated feeding defects. Several tests indicated that IIS strength was weaker and that insulin secretion was defective in these animals. This study highlights the role of the Golgi network and the mitochondria in insulin secretion and provides a new list of genes that modulate IIS in C. elegans.
|
|
| 9. |
- Billing, Ola, 1981-, et al.
(författare)
-
Mitochondrial function is required for secretion of DAF-28/insulin in C. elegans.
- 2011
-
Ingår i: PLOS ONE. - : Public Library of Science. - 1932-6203. ; 6:1, s. e14507-
-
Tidskriftsartikel (refereegranskat)abstract
- While insulin signaling has been extensively studied in Caenorhabditis elegans in the context of ageing and stress response, less is known about the factors underlying the secretion of insulin ligands upstream of the insulin receptor. Activation of the receptor governs the decision whether to progress through the reproductive lifecycle or to arrest growth and enter hibernation. We find that animals with reduced levels of the mitochondrial outer membrane translocase homologue TOMM-40 arrest growth as larvae and have decreased insulin signaling strength. TOMM-40 acts as a mitochondrial translocase in C. elegans and in its absence animals fail to import a mitochondrial protein reporter across the mitochondrial membrane(s). Inactivation of TOMM-40 evokes the mitochondrial unfolded protein response and causes a collapse of the proton gradient across the inner mitochondrial membrane. Consequently these broadly dysfunctional mitochondria render an inability to couple food abundance to secretion of DAF-28/insulin. The secretion defect is not general in nature since two other neuropeptides, ANF::GFP and INS-22::VENUS, are secreted normally. RNAi against two other putative members of the TOMM complex give similar phenotypes, implying that DAF-28 secretion is sensitive to mitochondrial dysfunction in general. We conclude that mitochondrial function is required for C. elegans to secrete DAF-28/insulin when food is abundant. This modulation of secretion likely represents an additional level of control over DAF-28/insulin function.
|
|
| 10. |
- Bodén, Ida, 1977-, et al.
(författare)
-
In vivo skin measurements with a novel probe head for simultaneous skin impedance and near-infrared spectroscopy
- 2011
-
Ingår i: Skin research and technology. - : Wiley. - 0909-752X .- 1600-0846. ; 17:4, s. 494-504
-
Tidskriftsartikel (refereegranskat)abstract
- Background/purpose: Near-infrared (NIR) spectroscopy and skin impedance (IMP) measurements are useful techniques for objective diagnostics of various skin diseases. Here, we present a combined probe head for simultaneous, time-saving NIR spectroscopy and skin impedance measurements. The probe also ensures that both measurements are performed under equal conditions and at the same skin location.Methods: Finite element method simulations were performed for evaluation of the impedance. In vivo skin measurements were performed and combined NIR and impedance spectra were analysed by means of multivariate methods with respect to body location, age and gender. The classification rate was determined by a planar discriminant analysis. Reproducibility was investigated by calculation of scatter values and statistical significance between overlapping groups was assessed by the calculation of intra-model distances, q.Results: The novel probe yielded rapid reproducible results and was easy to manage. Significant differences between skin locations and to a lesser extent age groups and gender were demonstrated.Conclusion: With the novel probe, statistically significant differences between overlapping classes in score plots can be confirmed by calculating intra-model distances. The influence of molecular differences in the skin at different body locations is larger than the influence of gender or age and therefore relevant reference measurements are discussed.
|
|
