The Cost Effectiveness of Levodopa-Carbidopa Intestinal Gel in the Treatment of Advanced Parkinson’s Disease in England

Background: Parkinson’s disease is a progressive neurodegenerative disease, which significantly impacts patients’ quality of life and is associated with high treatment and direct healthcare costs. In England, levodopa/carbidopa intestinal gel (LCIG) is indicated for the treatment of levodopa-responsive advanced Parkinson’s disease with troublesome motor fluctuations when available combinations of medicinal products are unsatisfactory. Objective: We aimed to determine the cost effectiveness of LCIG compared to the standard of care for patients with advanced Parkinson’s disease in England, using real-world data. Methods: A Markov model was adapted from previous published studies, using the perspective of the English National Health System and Personal and Social Services to evaluate the cost effectiveness of LCIG compared to standard of care in patients with advanced Parkinson’s disease over a 20-year time horizon. The model comprised 25 health states, defined by a combination of the Hoehn and Yahr scale, and waking time spent in OFF-time. The base case considered an initial cohort of patients with an Hoehn and Yahr score of ≥ 3, and > 4 h OFF-time. Standard of care comprised standard oral therapies, and a proportion of patients were assumed to be treated with subcutaneous apomorphine infusion or injection in addition to oral therapies. Efficacy inputs were based on LCIG clinical trials where possible. Resource use and utility values were based on results of a large-scale observational study, and costs were derived from the latest published UK data, valued at 2017 prices. The EuroQol five-dimensions-3-level (EQ-5D-3L) instrument was used to measure utilities. Costs and quality-adjusted life-years were discounted at 3.5%. Both deterministic and probabilistic sensitivity analyses were conducted. Results: Total costs and quality-adjusted life-years gained for LCIG vs standard of care were £586,832 vs £554,022, and 2.82 vs 1.43, respectively. The incremental cost-effectiveness ratio for LCIG compared to standard of care was £23,649/quality-adjusted life-year. Results were sensitive to the healthcare resource utilisation based on real-world data, and long-term efficacy of LCIG. Conclusions: The base-case incremental cost-effectiveness ratio was estimated to be within the acceptable thresholds for cost effectiveness considered for England

Soil carbon loss in warmed subarctic grasslands is rapid and restricted to topsoil

Global warming may lead to carbon transfers from soils to the atmosphere, yet this positive feedback to the climate system remains highly uncertain, especially in subsoils (Ilyina and Friedlingstein, 2016; Shi et al., 2018). Using natural geothermal soil warming gradients of up to +6.4 degrees C in subarctic grasslands (Sigurdsson et al., 2016), we show that soil organic carbon (SOC) stocks decline strongly and linearly with warming (-2.8 t ha(-1) degrees C-1). Comparison of SOC stock changes following medium-term (5 and 10 years) and long-term (> 50 years) warming revealed that all SOC stock reduction occurred within the first 5 years of warming, after which continued warming no longer reduced SOC stocks. This rapid equilibration of SOC observed in Andosol suggests a critical role for ecosystem adaptations to warming and could imply short-lived soil carbon-climate feedbacks. Our data further revealed that the soil C loss occurred in all aggregate size fractions and that SOC stock reduction was only visible in topsoil (0-10 cm). SOC stocks in subsoil (10-30 cm), where plant roots were absent, showed apparent conservation after > 50 years of warming. The observed depth-dependent warming responses indicate that explicit vertical resolution is a prerequisite for global models to accurately project future SOC stocks for this soil type and should be investigated for soils with other mineralogies

Laparoscopic management of achalasia

To access publisher full text version of this article. Please click on the hyperlink in Additional Links fieldCardiomyotomy for achalasia is one of the ideal procedures for the video endoscopic approach. Magnification of the operative field during laparoscopic surgery allows precise division of the muscle fibers with excellent results. The number of reports on cardiomyotomy performed with laparoscopic (and thoracoscopic) access is growing. They all show the same excellent results as for conventional (open) myotomy, with minimal morbidity, short hospital stay, and early return to routine activity

Gastric cancer in Iceland. What is the current status? Survival of 193 patients operated on for cure, 1980-1995.

OBJECTIVE: The incidence of gastric cancer has been decreasing in the last decades. Nevertheless, gastric cancer is still a substantial health problem in Iceland. The aim of this study was to analyze the survival of patients with gastric cancer operated on for cure. MATERIAL AND METHODS: We reviewed all medical files for above-mentioned patients, operated on at the National University Hospital in Reykjavik and the Quarter District Hospital of Akureyri during 1980-1995. The study was divided into three periods: 1980-1985, 1986-1990 and 1991-1995. The five-year survival for each study period and for the whole group was evaluated. RESULTS: The study group included 193 patients between the ages of 21-96 (median 71). The five-year survival for the whole group was 28% (26% 1980-1985, 22% 1986-1990, 35% 1991-1995). Despite longer survival during the last period, it was not statistically significant (p = 0.16). The major survival factor of gastric cancer was the stage of the disease at diagnosis. A greater number of patients were at stage IA during 1991-1995. The complication rate was rather high or 31% and the hospital mortality was 6.7%. CONCLUSION: The survival of patients with gastric cancer operated on for cure was low in Iceland but comparable to that in other countries. During the last years, the survival has been rising, and fortunately, more were diagnosed at a lower stage of the disease. These operations have a considerable risk and the hospital mortality was substantial

Urinary 2,8-dihydroxyadenine excretion in patients with adenine phosphoribosyltransferase deficiency, carriers and healthy control subjects.

To access publisher's full text version of this article click on the hyperlink belowBACKGROUND: Adenine phosphoribosyltransferase (APRT) deficiency is a rare autosomal recessive disorder of adenine metabolism that results in excessive urinary excretion of the poorly soluble 2,8-dihydroxyadenine (DHA), leading to kidney stones and chronic kidney disease. The purpose of this study was to assess urinary DHA excretion in patients with APRT deficiency, heterozygotes and healthy controls, using a recently developed ultra-performance liquid chromatography - tandem mass spectrometry (UPLC-MS/MS) assay. METHODS: Patients enrolled in the APRT Deficiency Registry and Biobank of the Rare Kidney Stone Consortium (http://www.rarekidneystones.org/) who had provided 24-h and first-morning void urine samples for DHA measurement were eligible for the study. Heterozygotes and healthy individuals served as controls. Wilcoxon-Mann-Whitney test was used to compare 24-h urinary DHA excretion between groups. Associations were examined using Spearman's correlation coefficient (rs). RESULTS: The median (range) 24-h urinary DHA excretion was 138 (64-292) mg/24 h and the DHA-to-creatinine (DHA/Cr) ratio in the first-morning void samples was 13 (4-37) mg/mmol in APRT deficiency patients who were not receiving xanthine oxidoreductase inhibitor therapy. The 24-h DHA excretion was highly correlated with the DHA/Cr ratio in first-morning void urine samples (rs = 0.84, p < .001). DHA was detected in all urine samples from untreated patients but not in any specimens from heterozygotes and healthy controls. CONCLUSIONS: High urinary DHA excretion was observed in patients with APRT deficiency, while urine DHA was undetectable in heterozygotes and healthy controls. Our results suggest that the UPLC-MS/MS assay can be used for diagnosis of APRT deficiency.Rare Kidney Stone Consortium, a part of the National Center for Advancing Translational Sciences (NCATS) Rare Diseases Clinical Research Network (RDCRN) United States Department of Health & Human Services National Institutes of Health (NIH) - USA NIH National Center for Advancing Translational Sciences (NCATS) United States Department of Health & Human Services National Institutes of Health (NIH) - USA NIH National Institute of Diabetes & Digestive & Kidney Diseases (NIDDK

Community adaptation to temperature explains abrupt soil bacterial community shift along a geothermal gradient on Iceland

Understanding how and why soil microbial communities respond to temperature changes is important for understanding the drivers of microbial distribution and abundance. Studying soil microbe responses to warming is often made difficult by concurrent warming effects on soil and vegetation and by a limited number of warming levels preventing the detection of non-linear effects. A unique area in Iceland, where soil temperatures have recently increased due to geothermic activity, created a stable warming gradient in both grassland (dominated by Agrostis capillaris) and forest (Picea sitchensis) vegetation. By sampling soils which had been subjected to four years of temperature elevation (ambient (MAT 5.2 °C) to +40 °C), we investigated the shape of the response of soil bacterial communities to warming, and their associated community temperature adaptation. We used 16S rRNA amplicon sequencing to profile bacterial communities, and bacterial growth-based assays (3H-Leu incorporation) to characterize community adaptation using a temperature sensitivity index (SI, log (growth at 40 °C/4 °C)). Despite highly dissimilar bacterial community composition between the grassland and forest, they adapted similarly to warming. SI was 0.6 (equivalent to a minimum temperature for growth of between −6 and −7 °C) in both control plots. Both diversity and community composition, as well as SI, showed similar threshold dynamics along the soil temperature gradient. There were no significant changes up to soil warming of 6–9 °C above ambient, beyond which all indices shifted in parallel, with SI increasing from 0.6 to 1.5. The consistency of these responses provide evidence for an important role for temperature as a direct driver of bacterial community shifts along soil temperature gradients