Real-world evidence from a European cohort study of patients with treatment resistant depression: Healthcare resource utilization.

BACKGROUND: Treatment resistant depression (TRD) is diagnosed when patients experiencing a major depressive episode fail to respond to ≥2 treatments. Along with substantial indirect costs, patients with TRD have higher healthcare resource utilization (HCRU) than other patients with depression. However, research on the economic impact of this HCRU, and differences according to response to treatment, is lacking. METHODS: This multicenter, observational study documented HCRU among patients with TRD in European clinical practice initiating new antidepressant treatments. Data regarding access to outpatient consultations and other healthcare resources for the first 6 months, collected using a questionnaire, were analyzed qualitatively according to response and remission status. The economic impact of HCRU, estimated using European costing data, was analyzed quantitatively. RESULTS: Among 411 patients, average HCRU was higher in non-responders, attending five times more general practitioner (GP) consultations and spending longer in hospital (1.7 versus 1.1 days) than responders. Greater differences were observed according to remission status, with non-remitters attending seven times more GP consultations and spending approximately three times longer in hospital (1.7 versus 0.6 days) than remitters. Consequently, the estimated economic impacts of non-responders and non-remitters were significantly greater than those of responders and remitters, respectively. LIMITATIONS: Key limitations are small cohort size, absence of control groups and generalizability to different healthcare systems. CONCLUSION: Patients with TRD, particularly those not achieving remission, have considerable HCRU, with associated economic impact. The costs of unmet TRD treatment needs are thus substantial, and treatment success is fundamental to reduce individual needs and societal costs.

The burden of caring for adults with depression and suicidal ideation in five large European countries: analysis from the 2020 National Health and Wellness Survey.

BACKGROUND: Suicidal ideation (SI) affects approximately 30-40% of those with major depressive disorder (MDD). To date, studies have examined the substantial humanistic and economic burden to caregivers of persons with MDD, however little is known of the impact of caring for persons with MDD when SI is present. This study examined the additional burden imposed on caregivers for persons with unipolar depression and SI in five major European countries. METHODS: A retrospective, cross-sectional analysis was conducted in five European countries using 2020 Europe National Health Wellness Survey (France, Germany, Italy, Spain and the United Kingdom) to compare differences in health and economic outcomes between caregivers of adults with unipolar depression and SI (CAUD-SI) and caregivers of adults with unipolar depression without SI (CAUD-nSI). The outcomes assessed included health-related quality of life (HRQoL; Medical Outcomes Study Short Form [SF-12v2]), health status (Short-Form 6 Dimension [SF-6D], EuroQol 5-Dimension 5-Level [EQ-5D-5L]), Work productivity and activity impairment (WPAI) and healthcare resource utilization (HRU). Linear mixed models and generalized linear mixed models adjusted for covariates were used to compare the two groups on outcomes of interest. RESULTS: Of 62,319 respondents, 0.89% (n = 554) were CAUD-SI and 1.34% (n = 837) were CAUD-nSI. In adjusted models, CAUD-SI reported greater humanistic burden than CAUD-nSI, with lower HRQoL (PCS: 42.7 vs. 45.0, p < 0.001 and MCS: 37.5 vs. 38.9, p = 0.007) and health status (SF-6D: 0.57 vs 0.60, p < 0.001 and EQ-5D-5L: 0.58 vs 0.66, p < 001). CAUD-SI respondents reported significantly higher economic burden than CAUD-nSI respondents for WPAI (percent activity impairment: 64.9% vs. 52.5%, p = 0.026) and HRU (provider visits: 10.0 vs. 7.9, p < 0.001, emergency room visits: 1.49 vs. 0.73, p < 0.001 and hospitalizations: 1.03 vs. 0.52, p < 0.001). CONCLUSION: In five European countries, caregivers of adults with depression and SI experience additional humanistic and economic burden than caregivers of adults with depression and no SI. Distinguishing caregiver groupings and their unique burden provide important insights for providing targeted support and interventions for both the patient and caregiver.

Discrimination of honey of different floral origins by a combination of various chemical parameters.

Honey is a high value food commodity with recognized nutraceutical properties. A primary driver of the value of honey is its floral origin. The feasibility of applying multivariate data analysis to various chemical parameters for the discrimination of honeys was explored. This approach was applied to four authentic honeys with different floral origins (rata, kamahi, clover and manuka) obtained from producers in New Zealand. Results from elemental profiling, stable isotope analysis, metabolomics (UPLC-QToF MS), and NIR, FT-IR, and Raman spectroscopic fingerprinting were analyzed. Orthogonal partial least square discriminant analysis (OPLS-DA) was used to determine which technique or combination of techniques provided the best classification and prediction abilities. Good prediction values were achieved using metabolite data (for all four honeys, Q(2)=0.52; for manuka and clover, Q(2)=0.76) and the trace element/isotopic data (for manuka and clover, Q(2)=0.65), while the other chemical parameters showed promise when combined (for manuka and clover, Q(2)=0.43).

Low-energy electron attachment to the dichlorodifluoromethane (CCl2F2) molecule.

Results from a joint experimental study of electron attachment to dichlorodifluoromethane (CCl(2)F(2)) molecules in the gas phase are reported. In a high resolution electron beam experiment involving two versions of the laser photoelectron attachment method, the relative cross section for formation of the dominant anion Cl(-) was measured over the energy range 0.001-1.8 eV at the gas temperature T(G) = 300 K. It exhibits cusp structure at thresholds for vibrational excitation of the nu(3)(a(1)) mode due to interaction with the attachment channels. With reference to the thermal attachment rate coefficient k(T = 300 K) = 2.2(8) x 10(-9) cm(3) s(-1) (fitted average from several data), a new highly resolved absolute attachment cross section for T(G) = 300 K was determined. Partial cross sections for formation of the anions Cl(-), Cl(2)(-), F(-), ClF(-), and CCl(2)F(-) were measured over the range 0-12 eV, using three different electron beam experiments of medium energy resolution. The dependence of the attachment rate coefficient k(T(e);T(G) = 300 K) on electron temperature T(e) was calculated over the range 50-15 000 K, based on a newly constructed total cross section for anion formation at T(G) = 300 K. R-matrix calculations for Cl(-) production have been carried out for comparison with the experimental data. The R-matrix results are in line with the main experimental observations and predict the dependence of the DEA cross section on the initial vibrational level nu(3)() and on the vibrational temperature. Furthermore, the cross section for vibrational excitation of the nu(3) mode has been computed.

Ultrastructural observations on oral ingestion and trans-tegumental uptake of clorsulon by the liver fluke, Fasciola hepatica.

Three experiments have been carried out in vitro to determine the effect of oral and trans-tegumental uptake of clorsulon on the fine structure of the tegument and gut of Fasciola hepatica. Changes were assessed by transmission electron microscopy. In the first experiment, the flukes were ligatured to prevent the oral ingestion of drug and treated for 24 h in clorsulon (10 microg/ml). Limited swelling of the basal infolds was observed in the tegumental syncytium. Swollen mitochondria were present in the syncytium, the underlying tegumental cells and in the gastrodermal cells. Swelling and vesiculation of the cisternae of the granular endoplasmic reticulum (ger) was evident in the gastrodermal cells, together with a reduction in secretory activity. In the second experiment, flukes were fed for 24 h on red blood cells isolated from rats dosed with clorsulon at 12.5 mg/kg body weight; this experiment was designed to prevent the exposure of the tegumental surface to the drug. There was severe swelling of the basal infolds in the tegumental syncytium and swelling of mitochondria in the syncytium, tegumental cells and gastrodermal cells. In the tegumental cells there was a decrease in the number of Golgi complexes as well. A number of changes were evident in the gastrodermal cells: swelling of the ger cisternae, an increase in the number of autophagic vacuoles, a reduction in the number of secretory bodies and disruption of the lamellae projecting from the surface of the cells. In the third experiment, flukes were incubated for 24 h in clorsulon (10 microg/ml), with both absorptive surfaces being available for drug uptake. There was severe swelling of the basal infolds in the tegumental syncytium and large autophagic vacuoles were present. Swollen mitochondria were a feature of the tegument, tegumental cells and gastrodermal cells, as were swollen cisternae of ger in the tegumental and gastrodermal cells. Fewer Golgi complexes were observed in the tegumental cells and in the gastrodermal cells there were fewer secretory bodies and an increased number of autophagic vacuoles. Overall, the gastrodermal cells were more severely affected than the tegument. Greater disruption of the tegument occurred when the oral route of uptake was available. The results support those of previous studies which point to oral uptake of clorsulon being the major route of entry into the fluke.

A scanning electron microscope study on the route of entry of clorsulon into the liver fluke, Fasciola hepatica.

Three experiments were carried out in vitro to determine the roles of the tegument and gut of Fasciola hepatica in the uptake of the flukicidal drug, clorsulon. Changes to the two surfaces were assessed by scanning electron microscopy. In the first experiment, the flukes were ligatured to prevent the oral ingestion of drug and treated for 24 h in clorsulon (10 microg/ml). The gastrodermal surface remained normal and few changes to the tegumental surface were observed. In the second experiment, flukes were fed for 24 h on red blood cells isolated from rats dosed with clorsulon at 12.5 mg/kg body weight; this experiment was designed to prevent the exposure of the tegumental surface to the drug. The gastrodermal surface was severely disrupted and the gut lamellae were disorganised and necrotic. Swelling of the tegument and blebbing on the tegumental surface were evident, but the changes were not severe. More severe swelling of the tegument was observed in the third experiment, in which flukes were incubated for 24 h in clorsulon (10 microg/ml), with both absorptive surfaces being available for drug uptake. The gastrodermal surface was badly disrupted and the gut lamellae were disorganised and necrotic. Taking the results of the three experiments together, the gastrodermal surface was more affected than the tegument and the greatest disruption to the two surfaces was seen when both routes of entry were available to the fluke. The data support a previous study which indicated that entry of clorsulon into the fluke in vivo is principally by the oral ingestion of drug bound to the red blood cells.

Determination of clenbuterol residues in bovine urine by optical immunobiosensor assay.

Clenbuterol (CBL) is an orally active beta2-adrenoceptor agonist which has been used in veterinary medicine as a broncodilator and an agent of uterine relaxation. It has however become better known as a drug used illegally to promote growth in farm animals. A rapid and sensitive biosensor assay was developed to detect CBL residues in bovine urine. The method involved a simple extraction procedure using tert-butyl methyl ether followed by analysis on the biosensor with results obtained against a buffer calibration curve. The assay allowed up to 88 samples to be analyzed per working day, with each cycle on the biosensor taking approximately 7 min to complete. The limit of detection (LOD) was determined as 0.27 ng/mL using 20 EU reference blank urine samples. The intra-assay Sr ranged from 4.7-7.6% for 3 control samples while the interassay Sr ranged from 9.2-12.7%. The recovery was found to be approximately 95%. A series of incurred urine samples were assayed and the results compared by Enzyme immunoassay (EIA), radio-immunoassay (RIA), and gas chromatography/mass spectrometry (GC/MS) analysis. Urine samples taken from local abattoirs were also analyzed by the biosensor method and by EIA analysis. The antibody used in the biosensor test exhibited high cross reactivity with at least 7 other beta-agonists allowing detection of these compounds at less than 1 ng/mL in bovine urine.

Evaluation of an immunobiosensor for the on-site testing of veterinary drug residues at an abattoir. Screening for sulfamethazine in pigs.

A study was conducted to determine the feasibility of performing "on-site" screening for sulfamethazine (SMT), at an abattoir, using a rapid immunobiosensor method. This involved transfer of the biosensor technology and an assay developed in the laboratory, to the cold, humid conditions of a modern pig-processing factory. A pre-determined threshold limit of 0.4 microgram ml-1 SMT in bile was used to identify the likelihood that corresponding tissue samples contained SMT concentrations in excess of the European maximum permissible residue limit of 0.1 mg kg-1. Bile samples containing SMT concentrations above the threshold limit were deemed positive and the corresponding kidney and muscle samples were sent to the laboratory for HPLC analysis. The robustness of the biosensor instrumentation in the harsh operating conditions was monitored throughout the project. The performance of the assay, on-site, was assessed by the regular inclusion of QA samples and by the submission of control 'SMT-positive' pigs to the abattoir. Sampling procedures, identification and traceability were also under scrutiny. During the project, 337 (9.35%) of the total kill were tested for SMT residues, representing 75% of all producers submitting pigs for slaughter. Twelve animals, including the ten controls, gave positive bile results. HPLC analysis confirmed SMT residues in all 12 kidneys (11 in excess of the permissible level). Ten muscle samples also contained violative SMT levels. Throughout the project, the biosensor performed reliably, with no adverse reaction of any mechanical or electrical components. The SMT assay also performed reliably. This is the first report of a biosensor being used for 'on-site' drug screening.