Cost-Effectiveness of Alendronate in the Treatment of Osteoporosis in Denmark - An Economic Evaluation Based on the Fracture Intervention Trial

Background: The Fracture Intervention Trial (FIT) showed that the bisphosphonate alendronate reduces the risk of fractures in women with low bone mass in the United States. Objective: To estimate the cost-effectiveness (cost per life-year gained and cost per quality-adjusted life-year, QALY, gained) of treating osteoporotic women in Denmark with alendronate, compared with no treatment. Design: A Markov model earlier used in the economic evaluation for Sweden was adapted using epidemiological and cost data for Denmark. In the base-case alendronate was assumed to have a fracture-risk reducing effect for ten years; a treatment duration period of 5 years followed by a 5-year period where the effect declined linearly to zero. Results: Treating a 71-year old (the mean age in the vertebral arm of the FIT) osteoporotic woman with one prior vertebral fracture with alendronate was found to be associated with a cost of DKK 52,311 per QALY gained. The cost-effectiveness ratio when treating a 69-year old woman with low bone mass and without previous vertebral fractures was higher (DKK 205,816) but still within the limits of what can be considered good value for money. Conclusions: The results of this study indicate that treatment with alendronate in Denmark is cost-effective, provided the treatment is targeted towards high-risk patients corresponding to the patient groups in the FIT study.osteoporosis; cost-effectiveness; quality of life; Markov models; acceptability curve

Cost-utility analysis of Interferon Beta-1b in the treatment of different types of Multiple Sclerosis

Background Economic evaluation of treatments in multiple sclerosis (MS) presents a challenge. The disease affects a number of different body functions and leads to severe disability over time, without however a strong effect on mortality. At onset, the majority of patients will have relapsing-remitting disease (RRMS) and will then convert to secondary-progressive disease (SPMS) overtime. However, the course of the disease is unpredictable, and the conversion to SPMS can take place at different times since onset and at different levels of disability for different patients. Relapses appear to occur with the same frequency at all levels of disability, but will diminish over time. The effectiveness of treatments can be measured in different ways such as disease activity, the number and the severity of relapses or the progression of functional disability, regardless of the type of MS. However, improvements in outcome achieved over a short term may have an effect on the disease in the longer term, and effectiveness data from clinical trials must therefore be extrapolated to the longer term, using modelling techniques. This requires good epidemiological data on the natural course of the disease, where disease progression is expressed with the same measures as in the clinical trials. Also to perform economic evaluations, a global outcome measure is required to capture the impact of treatments on the disease and the most frequently used such measure is quality-adjusted life years (QALYs). However, for QALYs to be used in cost-effectiveness analysis of MS, they must be related to a measure of the disease and disease progression. The Expanded Disability Status Scale (EDSS) provides a good measure of the disease and has been widely used in epidemiological studies and clinical trials, in all types of MS. Lastly, detailed economic data that can be related to the different levels of disability (EDSS) are required. Objective We have earlier proposed a basic framework for cost-effectiveness modelling in MS, and the original model has been updated, as new data have become available. The current study proposes a further development of the modelling technique and estimates the cost-effectiveness of treatment with interferon b-1b (IFNB-1b) in a defined patient population with active disease, both RRMS and SPMS, from a societal perspective in Sweden. Methods The framework of the earlier Markov model is used, where states are defined according to EDSS. Transition probabilities for the first years in the model are calculated from clinical trial data, and for the extrapolation from a large epidemiological database on the natural history of MS. In view of the fact that the number of relapses at given levels of disability did not differ between patients with RRMS or SPMS in any of the three datasets used in this analysis, and that conversion from RRMS to SPMS did not occur at well defined levels of disability, we combined data from two large clinical trials in RRMS and SPMS. Patients were selected on whether or not they had active disease at enrolment, defined as an increase in the EDSS by at least 1 point (0.5 points for scores between EDSS 6 and 7) or at least 2 relapses in the preceding 2 years. This allows simulating treatment start at any stage and for any type of the disease and estimating long-term consequences within the same model. The combination of the two types of MS is further supported by the fact that it has been shown in 3 observational studies that costs and quality of life at given EDSS levels are not different for patients with different types of the disease. Transition probabilities between the Markov states are estimated for both the clinical trial and the natural history cohorts using an ordered probit model. Transitions thus depend on several factors, including what state a patient is in, whether or not she/he has a relapse, age, age at onset of the disease, time since onset of the disease, age at treatment start. The base case simulations use mean costs and mean utilities in each state from a large observational study in Sweden. However, the model allows calculating acceptability curves, i.e. the probability with which the cost effectiveness ratio of a treatment scenario is below given levels of willingness-to-pay for a QALY, using the entire distribution of costs and utilities at each EDSS level. Costs and benefits are discounted with 3%. Results The base case assumes treatment with IFNB-1b during 36 months, with no further effect when treatment is stopped, and includes both patients with active RRMS and SPMS. Sensitivity analysis is presented for treatment during 54 months. The annual cost of IFNB-1b treatment was 102 587 SEK plus 1600 SEK for special monitoring, and was adjusted for compliance in the clinical trial. In the base-case treatment adds 13 000 to costs over 10 years, and the cost per QALY gained is 71 400 SEK. When the time horizon is increased to 15-25 years, treatment dominates no treatment (higher utility and lower cost). With treatment during 54 months, the cost per QALY is 353 800 SEK, all costs included. When treatment is started early, the cost-effectiveness ratio is higher, e.g. 643 100 SEK in state 2, as patients in these states progress only very slowly. In the net benefit approach, there is a 80% probability that the treatment initiated in states 3 or 4 (EDSS 4.0-5.5) is cost-effective, if the willingness to pay for a QALY is 400 000 to 600 000 SEK. At that level of willingness to pay, the probability in state 2 is 45%. Conclusions With this new model, which combines active RRMS and SPMS, the effect of early treatment on the long-term outcome can be estimated for the first time using patient-level clinical data for RRMS and SPMS, as well as natural history data. The combination of the two types of MS into one model is supported by the finding that, at given levels of EDSS, there was no difference in the number of annual relapses in the three clinical datasets used, nor in the mean cost and mean utilities in the observational study. The model is more flexible than previous models, as it includes individual patient demographics and the entire distribution of costs and utilities in the different states. It thus represents a valuable tool to estimate the cost-effectiveness of treating different patient groups with IFNB-1b.MS; Cost-effectiveness

Surgical Treatment and Major Complications within the First Year of Life in Newborns with Long-Gap Esophageal Atresia Gross Type a and B – a Systematic Review

Background The surgical repair of long-gap esophageal atresia (LGEA) is still a challenge and there is no consensus on the preferred method of reconstruction. We performed a systematic review of the surgical treatment of LGEA Gross type A and B with the primary aim to compare the postoperative complications related to the different methods within the first postoperative year. Methods Systematic literature review on the surgical repair of LGEA Gross type A and B within the first year of life published from January 01, 1996 to November 01, 2016. Results We included 57 articles involving a total of 326 patients of whom 289 had a Gross type A LGEA. Delayed primary anastomosis (DPA) was the most applied surgical method (68.4%) in both types, followed by gastric pull-up (GPU) (8.3%). Anastomotic stricture (53.7%), gastro-esophageal reflux (GER) (32.2%) and anastomotic leakage (22.7%) were the most common postoperative complications, with stricture and GER occurring more often after DPA (61.9% and 40.8% respectively) compared to other methods (pPeer reviewe

Serum levels of perfluorinated compounds and sperm Y:X chromosome ratio in two European populations and in Inuit from Greenland.

This study investigated whether perfluorooctanoic acid (PFOA) and perfluorooctanesulfonate (PFOS), which exhibit reproductive toxicity in experimental animals, affect sperm sex chromosome ratio. The Y:X ratio was determined by fluorescence in situ hybridization. Serum concentrations of PFOA and PFOS were measured in 607 men from Greenland, Poland and Ukraine using liquid chromatography-tandem mass spectrometry. Data was analyzed by linear and nonlinear regression. We observed no associations between PFOA and Y:X ratio (p=0.845 in a linear model, p=0.296 in a nonlinear model). A positive nonlinear association between PFOS and Y:X ratio was observed (p=0.016), with no association in a linear model (p=0.118). Analyzing the populations separately, a negative trend between categorized PFOS exposure and Y:X ratio was observed for the Inuit (B=-0.002, p=0.044). In conclusion, there was a negative trend between Y:X ratio and PFOS in the Inuit, while there was no association between PFOA and the Y:X ratio in adult men

The worldwide costs of dementia in 2019

Introduction: Dementia is a leading cause of death and disability globally. Estimating total societal costs demonstrates the wide impact of dementia and its main direct and indirect economic components. Methods: We constructed a global cost model for dementia, presenting costs as cumulated global and regional costs. Results: In 2019, the annual global societal costs of dementia were estimated at US $1313.4 billion for 55.2 million people with dementia, corresponding to US$23,796 per person with dementia. Of the total, US $213.2 billion (16$448.7 billion (34%) direct social sector costs (including long-term care), and US $651.4 billion (50$1313.4 in 2019. Sixty-one percent of people with dementia live in low-and middle-income countries, whereas 74% of the costs occur in high-income countries. The impact of informal care accounts for about 50% of the global costs. The development of a long-term care infrastructure is a great challenge for low-and middle-income countries. There is a great need for more cost studies, particularly in low- and middle-income countries. Discussions of a framework for global cost comparisons are needed

The 2022 symposium on dementia and brain aging in low‐ and middle‐income countries: Highlights on research, diagnosis, care, and impact

Two of every three persons living with dementia reside in low‐ and middle‐income countries (LMICs). The projected increase in global dementia rates is expected to affect LMICs disproportionately. However, the majority of global dementia care costs occur in high‐income countries (HICs), with dementia research predominantly focusing on HICs. This imbalance necessitates LMIC‐focused research to ensure that characterization of dementia accurately reflects the involvement and specificities of diverse populations. Development of effective preventive, diagnostic, and therapeutic approaches for dementia in LMICs requires targeted, personalized, and harmonized efforts. Our article represents timely discussions at the 2022 Symposium on Dementia and Brain Aging in LMICs that identified the foremost opportunities to advance dementia research, differential diagnosis, use of neuropsychometric tools, awareness, and treatment options. We highlight key topics discussed at the meeting and provide future recommendations to foster a more equitable landscape for dementia prevention, diagnosis, care, policy, and management in LMICs. Highlights: Two‐thirds of persons with dementia live in LMICs, yet research and costs are skewed toward HICs. LMICs expect dementia prevalence to more than double, accompanied by socioeconomic disparities. The 2022 Symposium on Dementia in LMICs addressed advances in research, diagnosis, prevention, and policy. The Nairobi Declaration urges global action to enhance dementia outcomes in LMICs

Long-gap esophageal atresia - The development of an experimental model of esophageal regeneration in vivo as an attempt to improve clinical outcome

Background: A subset (~8-15%) of the patients born with esophageal atresia (EA) suffer from a lack of esophageal tissue, which makes a primary anastomosis difficult to achieve. This is most common in patients born without a distal fistula between the trachea and the distal esophageal segment. Purpose: To investigate the clinical course and outcome in patients born with long-gap esophageal atresia (LGEA) in the western region of Sweden and to develop an experimental model of guided tissue regeneration in the intrathoracic esophagus. Methods: A retrospective study of 16 consecutive patients born with LGEA between 1995 and 2010 was performed. The patients had been followed according to a structured program at one and seven years of age. The experimental studies had been performed in growing piglets, where 3 cm of the intrathoracic esophagus had been replaced with a silicone stented Biodesign® mesh. The piglets were provided with a gastrostomy through a small midline laparotomy. Factors influencing the clinical and histological outcome had been recorded. In Paper II, six piglets underwent surgery, in Paper III, ten and, in Paper IV, six. Results: No mortality was seen in the patients with LGEA. The mean age at definitive surgery was 147 days. The patients were small for gestational age. Eleven of sixteen (70%) had a delayed primary anastomosis as a definitive procedure, three had a gastroplasty and two underwent a colonic interposition. After surgery, anastomotic leakage was seen in seven of 16 (45%) patients and stricture developed in 11 of 16 (70%). At follow-up, some catch-up in weight was seen at seven years of age, but no catch-up in stature was seen. Spirometry performed at one and seven years of age showed obstruction or restriction in 9 of 14 (55%) measurements. The spirometry findings did not indicate any further need for surgery. Multiple breath washout was within the normal range in 11 of 15 (75%) measurements at one and seven years of age. Three of four (75%) of the patients with a pathological lung clearance index (LCI) at multiple breath washout required further surgery to prevent pulmonary damage due to aspiration. All patients either underwent surgery or were receiving continuous medical treatment for gastroesophageal reflux, and 7 of 16 (45%) had gastrostomy at the end of the study period. All patients were able to drink orally, but two of 16 (13%) were unable to eat solid foods. In the first experimental study (Paper II), six animals lived for one to 17 weeks after surgery. Four animals were alive for at least four weeks and in two of them (50%) the stent was lost prior to four weeks. Piglets that lived longer than four weeks had recurrent stricture and required dilation. Histology showed connective tissue and intense angiogenesis in three piglets. In two of them, living four and 17 weeks respectively after surgery, the bridging area contained islets of immature-looking cells in the submucosa. The remaining three piglets only had inflammatory cells and fibrosis in the bridging area. In Paper III, the piglets lived for three to 10 days after surgery. Three of 10 (30%) animals were sacrificed prior to plan due to mediastinitis. The surgical method was developed in such a way that the bridging graft could be sewn without leakage. If there was no significant leakage, the bridging graft was macroscopically surrounded by a tissue tube that connected the native esophageal edges. Histology showed connective tissue and inflammatory cells with intense angiogenesis in the bridging area. In addition, a thin layer of smooth muscle cells was seen around the bridging graft. In the piglets with significant leakage, there was an aggressive inflammatory pattern, with macrophages in the native muscle layers and islets of lymphocytes in the bridging area. In Paper IV, all the piglets survived until sacrifice 20 days after surgery. In two of six (33%) piglets, there was stent loss prior to sacrifice. In the animals with a retained stent, the tissue tube between the native muscle edges was easily dissected macroscopically. If the stent was lost, the bridging area was narrow and attached to the surrounding tissues with firm adhesions. Histology in the piglets with a retained stent showed that the bridging area was organized in three layers with islets of smooth muscle cells organized in two layers in the wall. CD163-positive, M2 machrophages were seen close to the lumen. In those animals in which the stent was lost, the organization into three layers could not be seen. There were no M2 macrophages in the specimen, but calprotectin-positive, M1 macrophages could be seen throughout the wall of the bridging area. Conclusion: Patients in our study born with LGEA required long hospitalization and suffered from symptoms related to gatroesophageal reflux during childhood. These individuals were small for gestational age. Some catch-up in weight was seen at seven years of age, but no catch-up in stature was seen. Multiple breath washout might be a valuable tool for the early detection of aspiration into the lungs in this patient group. The experimental model for replacing a part of the intrathoracic esophagus in growing piglets showed that a remodeling inflammatory pattern, accumulation of muscle cells and a structured overall organization in the wall of the bridging graft can be achieved under favorable conditions. Leakage in the anastomoses and stent loss prior to 20 days changed the inflammatory profile and gave rise to scar tissue formation and stricture. Future studies are needed in order to see whether these differences account for a regenerative healing process, with functional tissue reforming in the esophagus

Reducering av rumsresonanser med hjälp av stämda membranabsorbenter

The purpose with this project is to give insight about the theory behind, and the usage of, membrane absorption. This was done in an effort to reduce a particular acoustical problem regarding a room mode which resonated strongly in my music studio and was causing trouble within the low frequencies. In this essay I go through the history, theory, making-of and results of said absorption technique, and explore the possibilities of it working as a relatively cheap and space efficient solution to problems regarding standing waves. The results were positive considering the low budget. The standing wave decay time was almost halved and the frequency response improved, which proves the capability of this type of absorption