Home-Based Titration with Duodenal Infusion of Levodopa-Carbidopa Intestinal Gel in People with Parkinson's Disease: An Observational Feasibility Study.

Background: Testing and titration of the right levodopa equivalent dose are usually performed during a hospital admission. However, optimal dose titration in people with Parkinson's disease (PwPs) may depend on home environment, emotional stress, and physical activity of everyday life. Objective: Firstly, to evaluate the feasibility and safety of a home-based LCIG titration program and patients'/caregivers' satisfaction. Secondly, to identify barriers and facilitators for home-based titration. Method: This study assesses the feasibility and safety of home-based titration of levodopa duodenal infusions with the use of self-reported evaluation questionnaires with open-ended questions included, registration of total time used, and number of contacts/visits. A telemedicine solution was used to remotely monitor the patients, adjust treatment, and provide support and guidance to patients and caregivers. Results: Ten of 12 PwPs (5 females and 7 males) completed the total titration program. Eight of the 12 PwPs were dependent on help. These 8 PwPs also had a high burden of nonmotor symptoms (NMS). Cognitive impairments varied in severity (range 16-30). Time spent with home visits was on average 93.4 minutes (ranging from 35 to 180 minutes), and the length of the total titration (LCIG initiation to termination of titration) was on average 3.4 days with 2-5 (mean 3.2) contacts/visits with PD team members. The average score on the satisfaction evaluation questionnaires was lower in the caregiver group (mean 31.8) than the PwP outcome (mean 36.2). Conclusions: Telehealth-assisted home-based titration programs are feasible due to the length of the titration period, number of contacts, and time spent in PwPs' private homes, are rated satisfactory and safe by PwPs and caregivers, and may be a substitute for in-hospital treatment. Clinical recommendations including facilitators and barriers from a patient/caregiver perspective are displayed. This trial is registered with NCT4196647.

Can virtual-reality simulation ensure transthoracic echocardiography skills before trainees examine patients?

Objectives: This study aimed to develop and gather the validity evidence for a standardised simulation-based skills test in transthoracic echocardiography and to establish a credible pass/fail score. Methods: Experts developed a virtual-reality simulator test in cardiology, medical education and simulation-based education. Thirty-six physicians with different experiences in transthoracic echocardiography completed the test at Odense University Hospital, Denmark. The performances of novice, intermediate and experienced participants were compared using the Bonferroni post hoc test. Cronbach's alpha was used to determine the internal consistency reliability of the test. The consistency of performance was analysed using the intraclass correlation coefficient. A pass/fail score was established using the contrasting groups' standard-setting method. Results: We developed a test with high consistent reliability (Alpha = .81), 95% CI [.69, .89]. In both cases, the performers' level was consistent, fitting others at the same level of experience (intraclass correlation r(35)=.81, p<.001). A pass/fail score of 48/50 points was established based on the mean test score of novice and experienced physicians. Conclusions: We developed a standardised virtual-reality simulation-based test of echocardiography skills with the ability to distinguish between participants with different levels of transthoracic echocardiography experience. This test could direct a mastery learning training program where trainees practise until they reach the pre-defined level and secure a higher level of competency to ensure quality and safety for patients.

Effects of health related farm-level factors on skin size and quality in commercial mink (Neovison vison) production.

This study investigated the potential effects of management and health related factors on the productivity in the commercial mink production, during 2015-2018. Data were available from the database at Kopenhagen Fur, the national veterinary prescription database, VetStat, and the laboratory database at the Center for Diagnostics, Technological University of Denmark. A cross-sectional study, including 1.464 min. farms grouped into 1.187 epidemiological units, was applied. Data were analyzed in two models with different outcomes representing productivity on the mink farms, namely skin size and economical value (value sum) of the produced skin. The studied risk factors included use of vaccines and antibacterials, herd size, associated feed producer, purchases and sales of live animals, breeding results (litter size after weaning), Aleutian mink disease virus antibody (AMDV status) and stamping out, and laboratory test results. Vaccination against mink enteritis parvovirus and high breeding results were found to have a positive association with both outcomes, skin size and value sum. Both outcomes also varied significantly between farm clusters associated with different feed producers. Significant effects of antibacterial treatment were found, but the results were complex with both positive and negative associations with the outcome variables, depending on season and interactions with feed producer. Positive effects on antibacterial prescription on skin size were observed, except for farms associated with two small feed producers, known to have a variable microbiological feed quality. In farms receiving feed of very high quality, the positive effect of antibacterial prescription was marginal. CONCLUSIONS: The use of mink data has allowed us to assess the impact of feed quality as well as antibacterial prescription on productivity. The results showed a positive quantitative effect of vaccination against mink enteritis parvovirus on skin size and value, with an optimal effect by vaccination of the whole litter. Antibacterial prescription in the growth period, particularly around weaning, was found to have a positive quantitative effect on productivity in some farms, and the results suggest that the effect was associated with the feed quality. Use of antibacterials to counteract negative effects of low feed quality is not in accordance with principles for prudent use of antibacterials.

Anti-interleukin-21 antibody and liraglutide for the preservation of ß-cell function in adults with recent-onset type 1 diabetes: a randomised, double-blind, placebo-controlled, phase 2 trial.

BACKGROUND: Type 1 diabetes is characterised by progressive loss of functional ß-cell mass, necessitating insulin treatment. We aimed to investigate the hypothesis that combining anti-interleukin (IL)-21 antibody (for low-grade and transient immunomodulation) with liraglutide (to improve ß-cell function) could enable ß-cell survival with a reduced risk of complications compared with traditional immunomodulation. METHODS: This randomised, parallel-group, placebo-controlled, double-dummy, double-blind, phase 2 trial was done at 94 sites (university hospitals and medical centres) in 17 countries. Eligible participants were adults aged 18-45 years with recently diagnosed type 1 diabetes and residual ß-cell function. Individuals with unstable type 1 diabetes (defined by an episode of severe diabetic ketoacidosis within 2 weeks of enrolment) or active or latent chronic infections were excluded. Participants were randomly assigned (1:1:1:1), with stratification by baseline stimulated peak C-peptide concentration (mixed-meal tolerance test [MMTT]), to the combination of anti-IL-21 and liraglutide, anti-IL-21 alone, liraglutide alone, or placebo, all as an adjunct to insulin. Investigators, participants, and funder personnel were masked throughout the treatment period. The primary outcome was the change in MMTT-stimulated C-peptide concentration at week 54 (end of treatment) relative to baseline, measured via the area under the concentration-time curve (AUC) over a 4 h period for the full analysis set (intention-to-treat population consisting of all participants who were randomly assigned). After treatment cessation, participants were followed up for an additional 26-week off-treatment observation period. This trial is registered with ClinicalTrials.gov, NCT02443155. FINDINGS: Between Nov 10, 2015, and Feb 27, 2019, 553 adults were assessed for eligibility, of whom 308 were randomly assigned to receive either anti-IL-21 plus liraglutide, anti-IL-21, liraglutide, or placebo (77 assigned to each group). Compared with placebo (ratio to baseline 0·61, 39% decrease), the decrease in MMTT-stimulated C-peptide concentration from baseline to week 54 was significantly smaller with combination treatment (0·90, 10% decrease; estimated treatment ratio 1·48, 95% CI 1·16-1·89; p=0·0017), but not with anti-IL-21 alone (1·23, 0·97-1·57; p=0·093) or liraglutide alone (1·12, 0·87-1·42; p=0·38). Despite greater insulin use in the placebo group, the decrease in HbA1c (a key secondary outcome) at week 54 was greater with all active treatments (-0·50 percentage points) than with placebo (-0·10 percentage points), although the differences versus placebo were not significant. The effects diminished upon treatment cessation. Changes in immune cell subsets across groups were transient and mild (<10% change over time). The most frequently reported adverse events included gastrointestinal disorders, in keeping with the known side-effect profile of liraglutide. The rate of hypoglycaemic events did not differ significantly between active treatment groups and placebo, with an exception of a lower rate in the liraglutide group than in the placebo group during the treatment period. No events of diabetic ketoacidosis were observed. One participant died while on liraglutide (considered unlikely to be related to trial treatment) in connection with three reported adverse events (hypoglycaemic coma, pneumonia, and brain oedema). INTERPRETATION: The combination of anti-IL-21 and liraglutide could preserve ß-cell function in recently diagnosed type 1 diabetes. The efficacy of this combination appears to be similar to that seen in trials of other disease-modifying interventions in type 1 diabetes, but with a seemingly better safety profile. Efficacy and safety should be further evaluated in a phase 3 trial programme. FUNDING: Novo Nordisk.

Integrated parasite management: path to sustainable control of fishborne trematodes in aquaculture.

Fishborne zoonotic trematodes (FZT) are an emerging problem and there is now a consensus that, in addition to wild-caught fish, fish produced in aquaculture present a major food safety risk, especially in Southeast Asia where aquaculture is important economically. Current control programs target communities at risk through mass drug administration. However, we argue that treatment alone will not reduce the risk from eating infected fish and that sustainable effective control must adopt an integrated FZT control approach based on education, infrastructure improvements, and management practices that target critical control points in the aquaculture production cycle identified from a thorough understanding of FZT and host biology and epidemiology. We present recommendations for an integrated parasite management (IPM) program for aquaculture farms.

[Large liver cyst with compression of the inferior vena cava causing massive deep vein thrombosis].

A 69-year-old female was admitted to hospital on suspicion of left-sided deep vein thrombosis (DVT). DVT stretching to the distal part of the vena cava inferior (VCI) was confirmed on computed tomography and ultrasound which also revealed a large cyst with compression of VCI. The patient had no predisposition or risk factors to venous thromboembolic disease. The DVT was initially successfully treated with warfarin and aspiration of the cyst. However, it reappeared only 11 months later. Other treatment options are aspiration and ethanol sclerosis or surgery, laparoscopic as well as traditional.

Fish-borne trematodes in cultured Nile tilapia (Oreochromis niloticus) and wild-caught fish from Thailand.

Fish-borne zoonotic trematode (FZT) infections affect the health of more than 18 million people around the world, particularly in Asian countries. Nile tilapia (Oreochromis niloticus) is a white meat fish that has an increasing national and international market. The objective of this study was to determine the prevalence of FZT metacercarial infections in Nile tilapia from cage and pond aquaculture systems and in wild-caught fish from Suphan Buri, Nakhon Pathom and Chachoengsao provinces, Thailand. Fish were collected from four cages in Suphan Buri and four ponds in Nakhon Pathom provinces between September-October 2011 and April-May 2012 and wild-caught fish were collected in May 2012. All fish were examined for metacercariae by a pepsin digestion and metacercariae identified using morphological and molecular methods. During the first sampling of tilapia the prevalence of metacercariae in cage culture fish were 2.5% and 10% in pond culture fish. During the second sampling, metacercariae was found in 2.0% of tilapia from cage and none from the ponds. Of the 150 wild-caught fish, a total of 80 (53.3%) were found to be infected with metacercariae, mostly the zoonotic species Stellantchasmus falcatus, Haplorchis pumilio and Procerovum varium. The results revealed a low risk for FZT in Nile tilapia cultured in cage and pond aquaculture systems. However, the high prevalence of FZT in wild-caught fish indicates a high potential for spillover from wild reservoir hosts and underscores the need for vigilance and good management practices by the aquaculture sector.

Risks for fishborne zoonotic trematodes in tilapia production systems in Guangdong province, China.

Guangdong province is the most important region for tilapia culture in China. However, it is also an endemic region for fishborne zoonotic trematodes (FZT), which pose a risk to human food safety and health. A study was designed to assess the status of trematode parasite infections in tilapia aquaculture systems as an indicator of potential risks from FZT associated with consumption of tilapia. Tilapia from nursery and grow-out ponds were sampled from monoculture, polyculture and integrated aquaculture systems. The results from 388 tilapia examined revealed a very low prevalence (1.5%) of trematode infections (Heterophyidae and Echinostomatidae). Integrated systems using animal manure and latrine wastes as fertilizer did not show a higher prevalence of FZT. Because it was not clear whether the low risk of infection was attributable to existing effective pond management practices or a low risk of spillover of FZT from area sylvatic reservoir hosts, a survey of local wild-caught fish was conducted. Five species of FZT were discovered from a total of 271 wild-caught fish and a mean infection density of 4.0 metacercariae/100g; FZT discovered included intestinal flukes (Haplorchis spp., Procerovum varium, and Metagonimus spp.) and metacercariae tentatively identified as Clonorchis sinenesis. The common occurrence of FZT in wild-caught fish suggests that the presence of FZT in local wild animal reservoirs is substantial, and that although the current aquaculture management systems for tilapia are generally effective in preventing transmission of these parasites into tilapia production systems, the improvement of pond management practices and biosecurity must be maintained at a high level.

Effects of delayed compared with early umbilical cord clamping on maternal postpartum hemorrhage and cord blood gas sampling: a randomized trial.

OBJECTIVE: To investigate the effect of delayed cord clamping (DCC) compared with early cord clamping (ECC) on maternal postpartum hemorrhage (PPH) and umbilical cord blood gas sampling. DESIGN: Secondary analysis of a parallel-group, single-center, randomized controlled trial. SETTING: Swedish county hospital. POPULATION: 382 term deliveries after a low-risk pregnancy. METHODS: Deliveries were randomized to DCC (≥180 seconds, n = 193) or ECC (≤10 seconds, n = 189). Maternal blood loss was estimated by the midwife. Samples for blood gas analysis were taken from one umbilical artery and the umbilical vein, from the pulsating unclamped cord in the DCC group and from the double-clamped cord in the ECC group. Samples were classified as valid when the arterial-venous difference was -0.02 or less for pH and 0.5 kPa or more for pCO2 . Main outcome measures. PPH and proportion of valid blood gas samples. RESULTS: The differences between the DCC and ECC groups with regard to PPH (1.2%, p = 0.8) and severe PPH (-2.7%, p = 0.3) were small and non-significant. The proportion of valid blood gas samples was similar between the DCC (67%, n = 130) and ECC (74%, n = 139) groups, with 6% (95% confidence interval: -4%-16%, p = 0.2) fewer valid samples after DCC. CONCLUSIONS: Delayed cord clamping, compared with early, did not have a significant effect on maternal postpartum hemorrhage or on the proportion of valid blood gas samples. We conclude that delayed cord clamping is a feasible method from an obstetric perspective.

Practical Guidance on How to Handle Levodopa/Carbidopa Intestinal Gel Therapy of Advanced PD in a Movement Disorder Clinic.

Continuous dopaminergic delivery is recognized for the capacity to ameliorate symptoms in Parkinson's disease (PD). In advanced PD the short comings of orally administered Levodopa/Carbidopa include fluctuations resulting in unstable effect and dyskinesia. Levodopa/Carbidopa intestinal gel, LCIG, (Duodopa®, Abbott Laboratories) is delivered continuously through a percutaneous endoscopic gastrostomy with the inner tube placed in the duodenum by means of a device (CADD legacy Duodopa pump (CE 0473)). The therapy implies continuous dopaminergic delivery directly to the duodenum and is therefore unaffected by gastric emptying and represents a major adjuvant in the treatment of advanced PD with significant improvement in motor and non-motor symptoms. The aim of this paper is to suggest the prerequisites for a LCIG clinic and propose a feasible set-up and lean organization of a movement disorder clinic. Secondly, the paper proposes practical handling of patients in LCIG treatment for advanced PD based on experience and initiation of LCIG treatment and follow-up in forty patients.

Prevention and control of fish-borne zoonotic trematodes in fish nurseries, Vietnam.

Worldwide, >18 million persons were infected with fish-borne zoonotic trematodes in 2002. To evaluate the effectiveness of interventions for reducing prevalence and intensity of fish-borne zoonotic trematode infections in juvenile fish, we compared transmission rates at nurseries in the Red River Delta, northern Vietnam. Rates were significantly lower for nurseries that reduced snail populations and trematode egg contamination in ponds than for nurseries that did not. These interventions can be used in the development of programs for sustained control of zoonotic trematodes in farmed fish.

[Successful conservative therapy of chylopericardium after coronary artery by-pass grafting]. / Vellykket konservativ behandling af chylopericardium efter koronar bypassoperation.

Chylopericardium after thoracic duct injury is a rare but serious complication of thoracic surgery with mortality rates above 50% without intervention. Complications of chylopericardium are malnutrition, immunosuppression, electrolyte derangement and tamponade. This case describes a 67-year-old male who developed chylopericardium after coronary artery by-pass grafting and was successfully treated with conservative therapy consisting of pericardiocentesis and a low fat diet. If conservative therapy fails, thoracic surgery is almost always effective.

Relationship between snail population density and infection status of snails and fish with zoonotic trematodes in Vietnamese carp nurseries.

BACKGROUND: Fish-borne zoonotic trematodes (FZT) are a food safety and health concern in Vietnam. Humans and other final hosts acquire these parasites from eating raw or under-cooked fish with FZT metacercariae. Fish raised in ponds are exposed to cercariae shed by snail hosts that are common in fish farm ponds. Previous risk assessment on FZT transmission in the Red River Delta of Vietnam identified carp nursery ponds as major sites of transmission. In this study, we analyzed the association between snail population density and heterophyid trematode infection in snails with the rate of FZT transmission to juvenile fish raised in carp nurseries. METHODOLOGY/PRINCIPAL FINDINGS: Snail population density and prevalence of trematode (Heterophyidae) infections were determined in 48 carp nurseries producing Rohu juveniles, (Labeo rohita) in the Red River Delta area. Fish samples were examined at 3, 6 and 9 weeks after the juvenile fish were introduced into the ponds. There was a significant positive correlation between prevalence of FZT metacercariae in juvenile fish and density of infected snails. Thus, the odds of infection in juvenile fish were 4.36 and 11.32 times higher for ponds with medium and high density of snails, respectively, compared to ponds where no infected snails were found. Further, the intensity of fish FZT infections increased with the density of infected snails. Interestingly, however, some ponds with no or few infected snails were collected also had high prevalence and intensity of FZT in juvenile fish. This may be due to immigration of cercariae into the pond from external water sources. CONCLUSIONS/SIGNIFICANCE: The total number and density of potential host snails and density of host snails infected with heterophyid trematodes in the aquaculture pond is a useful predictor for infections in juvenile fish, although infection levels in juvenile fish can occur despite low density or absence infected snails. This suggests that intervention programs to control FZT infection of fish should include not only intra-pond snail control, but also include water sources of allochthonous cercariae, i.e. canals supplying water to ponds as well as snail habitats outside the pond such as rice fields and surrounding ponds.

Low physical activity accentuates the effect of the FTO rs9939609 polymorphism on body fat accumulation.

OBJECTIVE: Three independent studies have shown that variation in the fat mass and obesity-associated (FTO) gene associates with BMI and obesity. In the present study, the effect of FTO variation on metabolic traits including obesity, type 2 diabetes, and related quantitative phenotypes was examined. RESEARCH DESIGN AND METHODS: The FTO rs9939609 polymorphism was genotyped in a total of 17,508 Danes from five different study groups. RESULTS: In studies of 3,856 type 2 diabetic case subjects and 4,861 normal glucose-tolerant control subjects, the minor A-allele of rs9939609 associated with type 2 diabetes (odds ratio 1.13 [95% CI 1.06-1.20], P = 9 x 10(-5)). This association was abolished when adjusting for BMI (1.06 [0.97-1.16], P = 0.2). Among 17,162 middle-aged Danes, the A-allele associated with overweight (1.19 [1.13-1.24], P = 1 x 10(-12)) and obesity (1.27 [1.20-1.34], P = 2 x 10(-16)). Furthermore, obesity-related quantitative traits such as body weight, waist circumference, fat mass, and fasting serum leptin levels were significantly elevated in A-allele carriers. An interaction between the FTO rs9939609 genotype and physical activity (P = 0.007) was found, where physically inactive homozygous risk A-allele carriers had a 1.95 +/- 0.3 kg/m(2) increase in BMI compared with homozygous T-allele carriers. CONCLUSIONS: We validate that variation in FTO is associated with type 2 diabetes when not adjusted for BMI and with an overall increase in body fat mass. Furthermore, low physical activity seems to accentuate the effect of FTO rs9939609 on body fat accumulation.

Studies of association of variants near the HHEX, CDKN2A/B, and IGF2BP2 genes with type 2 diabetes and impaired insulin release in 10,705 Danish subjects: validation and extension of genome-wide association studies.

OBJECTIVE: In the present study, we aimed to validate the type 2 diabetes susceptibility alleles identified in six recent genome-wide association studies in the HHEX/KIF11/IDE (rs1111875), CDKN2A/B (rs10811661), and IGF2BP2 (rs4402960) loci, as well as the intergenic rs9300039 variant. Furthermore, we aimed to characterize quantitative metabolic risk phenotypes of the four variants. RESEARCH DESIGN AND METHODS: The variants were genotyped in the population-based Inter99 cohort (n = 5,970), the ADDITION Study (n = 1,626), a population-based sample of young healthy subjects (n = 377), and in additional type 2 diabetic case (n = 2,111) and glucose-tolerant (n = 521) subjects. The case-control studies involved a total of 4,089 type 2 diabetic patients and 5,043 glucose-tolerant control subjects. RESULTS: We validated association of variants near HHEX/KIF11/IDE, CDKN2A/B, and IGF2BP2 with type 2 diabetes. Interestingly, in middle-aged people, the rs1111875 C-allele of HHEX/KIF11/IDE strongly associated with lower acute insulin response during an oral glucose tolerance test (P = 6 x 10(-7)). In addition, decreased insulin release following intravenous tolbutamide injection was observed in young healthy subjects (P = 0.02). Also, a reduced insulin release was observed for the CDKN2A/B rs10811661 T-allele after both oral and intravenous glucose challenges (P = 0.001 and P = 0.009, respectively). CONCLUSIONS: We validate that variants in the proximity of the HHEX/KIF11/IDE, CDKN2A/B, and IFG2BP2 loci associate with type 2 diabetes. Importantly, variations within the HHEX/KIF11/IDE and CDKN2A/B loci confer impaired glucose- and tolbutamide-induced insulin release in middle-aged and young healthy subjects, suggesting a role for these variants in the pathogenesis of pancreatic beta-cell dysfunction.