Need for information in a representative sample of outpatients with schizophrenia disorders

Background: providing adequate information and involving patients in treatment has become an essential component of mental health care. Despite this, research regarding the extent to which this need has been met in clinical services is still scarce. Aims: To investigate the need for information about psychiatric condition and treatment among outpatients with schizophrenia disorders and how this need is associated with service use, adjusting for sociodemographic and clinical characteristics. Methods: Need for information for information about condition and treatment was assessed using the corresponding domain in the Camberwell Assessment of Need (CAN), in a representative sample of 401 schizophrenia outpatients in Santos, Brazil. Hierarchical logistic regression was used to investigate the association of information as a reported need and as an unmet need with service use variables, adjusting for sociodemographic and clinical characteristics. Results: Need for information was reported by 214 (53.4%) patients, being met in 101 (25.2%) and unmet in 113 (28.2%). Hierarchical regression indicated a significant association of a reported need with higher age of onset, family monitoring medication use last year and lower education level, which was the only associated with an unmet need. Conclusion: Information was a commonly reported need and which was often unmet, showing no significant association with service use. Greater attention should be given by mental health services to information provision

Genotypic and phenotypic spectrum of pyridoxine-dependent epilepsy (ALDH7A1 deficiency)

Pyridoxine-dependent epilepsy was recently shown to be due to mutations in the ALDH7A1 gene, which encodes antiquitin, an enzyme that catalyses the nicotinamide adenine dinucleotide-dependent dehydrogenation of L-{alpha}-aminoadipic semialdehyde/L-{Delta}1-piperideine 6-carboxylate. However, whilst this is a highly treatable disorder, there is general uncertainty about when to consider this diagnosis and how to test for it. This study aimed to evaluate the use of measurement of urine L-{alpha}-aminoadipic semialdehyde/creatinine ratio and mutation analysis of ALDH7A1 (antiquitin) in investigation of patients with suspected or clinically proven pyridoxine-dependent epilepsy and to characterize further the phenotypic spectrum of antiquitin deficiency. Urinary L-{alpha}-aminoadipic semialdehyde concentration was determined by liquid chromatography tandem mass spectrometry. When this was above the normal range, DNA sequencing of the ALDH7A1 gene was performed. Clinicians were asked to complete questionnaires on clinical, biochemical, magnetic resonance imaging and electroencephalography features of patients. The clinical spectrum of antiquitin deficiency extended from ventriculomegaly detected on foetal ultrasound, through abnormal foetal movements and a multisystem neonatal disorder, to the onset of seizures and autistic features after the first year of life. Our relatively large series suggested that clinical diagnosis of pyridoxine dependent epilepsy can be challenging because: (i) there may be some response to antiepileptic drugs; (ii) in infants with multisystem pathology, the response to pyridoxine may not be instant and obvious; and (iii) structural brain abnormalities may co-exist and be considered sufficient cause of epilepsy, whereas the fits may be a consequence of antiquitin deficiency and are then responsive to pyridoxine. These findings support the use of biochemical and DNA tests for antiquitin deficiency and a clinical trial of pyridoxine in infants and children with epilepsy across a broad range of clinical scenarios

Multi-site binding of epigallocatechin gallate to human serum albumin measured by NMR and isothermal titration calorimetry

The affinity of epigallocatechin gallate (EGCG) for human serum albumin (HSA) was measured in physiological conditions using NMR and isothermal titration calorimetry (ITC). NMR estimated the Ka (self-dissociation constant) of EGCG as 50 mM. NMR showed two binding events: strong (n1=1.8 ± 0.2; Kd1 =19 ± 12 μM) and weak (n2∼20; Kd2 =40 ± 20 mM). ITC also showed two binding events: strong (n1=2.5 ± 0.03; Kd1 =21.6 ± 4.0 μM) and weak (n2=9 ± 1; Kd2 =22 ± 4 mM). The two techniques are consistent, with an unexpectedly high number of bound EGCG. The strong binding is consistent with binding in the two Sudlow pockets. These results imply that almost all EGCG is transported in the blood bound to albumin and explains the wide tissue distribution and chemical stability of EGCG in vivo

iGlarLixi reduces residual hyperglycemia in Japanese patients with type 2 diabetes uncontrolled on basal insulin: A post‐hoc analysis of the LixiLan JP‐L trial

IntroductionTreatments for type 2 diabetes targeting baseline glucose levels but not postprandial glucose can result in normalized fasting blood glucose but suboptimal overall glycemic control (high glycated hemoglobin): residual hyperglycemia. In Japanese patients with type 2 diabetes the predominant pathophysiology is a lower insulin secretory capacity, and residual hyperglycemia is common with basal insulin treatment. Single-injection, fixed-ratio combinations of glucagon-like peptide-1 receptor agonists and basal insulin have been developed. iGlarLixi (insulin glargine 100 units/mL [iGlar]: lixisenatide ratio of 1 unit:1 µg) is for specific use in Japan. Post-hoc analysis of the LixiLan JP-L trial (NCT02752412) compared the effect of iGlarLixi with iGlar on this specific subpopulation with residual hyperglycemia.Materials and MethodsOutcomes at week 26 (based on the last observation carried forward) were assessed in patients in the modified intent-to-treat population with baseline residual hyperglycemia.ResultsOverall, 83 (32.5%) patients in the iGlarLixi group and 79 (30.7%) patients in the iGlar group had baseline residual hyperglycemia. The proportion of patients with residual hyperglycemia at week 26 decreased to 15.7% in the iGlarLixi group, and increased to 36.9% in the iGlar group. Patients in the iGlarLixi group had significantly greater reductions in glycated hemoglobin compared with the iGlar group (−0.72% difference between groups; P < 0.0001).ConclusionsNew data from this post-hoc analysis of the JP-L trial show that treatment with the fixed-ratio combination iGlarLixi reduced the proportion of Japanese patients with residual hyperglycemia from baseline to week 26 and significantly reduced glycated hemoglobin vs similar doses of iGlar alone

Genotypic and phenotypic spectrum of pyridoxine-dependent epilepsy (ALDH7A1 deficiency)

Pyridoxine-dependent epilepsy was recently shown to be due to mutations in the ALDH7A1 gene, which encodes antiquitin, an enzyme that catalyses the nicotinamide adenine dinucleotide-dependent dehydrogenation of l-α-aminoadipic semialdehyde/l-Δ1-piperideine 6-carboxylate. However, whilst this is a highly treatable disorder, there is general uncertainty about when to consider this diagnosis and how to test for it. This study aimed to evaluate the use of measurement of urine l-α-aminoadipic semialdehyde/creatinine ratio and mutation analysis of ALDH7A1 (antiquitin) in investigation of patients with suspected or clinically proven pyridoxine-dependent epilepsy and to characterize further the phenotypic spectrum of antiquitin deficiency. Urinary l-α-aminoadipic semialdehyde concentration was determined by liquid chromatography tandem mass spectrometry. When this was above the normal range, DNA sequencing of the ALDH7A1 gene was performed. Clinicians were asked to complete questionnaires on clinical, biochemical, magnetic resonance imaging and electroencephalography features of patients. The clinical spectrum of antiquitin deficiency extended from ventriculomegaly detected on foetal ultrasound, through abnormal foetal movements and a multisystem neonatal disorder, to the onset of seizures and autistic features after the first year of life. Our relatively large series suggested that clinical diagnosis of pyridoxine dependent epilepsy can be challenging because: (i) there may be some response to antiepileptic drugs; (ii) in infants with multisystem pathology, the response to pyridoxine may not be instant and obvious; and (iii) structural brain abnormalities may co-exist and be considered sufficient cause of epilepsy, whereas the fits may be a consequence of antiquitin deficiency and are then responsive to pyridoxine. These findings support the use of biochemical and DNA tests for antiquitin deficiency and a clinical trial of pyridoxine in infants and children with epilepsy across a broad range of clinical scenario

Rapid development of spiral garnets during subduction zone metamorphism revealed from high-resolution Sm-Nd garnet geochronology

Multiple studies have applied zoned garnet geochronology to place temporal constraints on the rates of metamorphism and deformation during orogenesis. We report new high-resolution isotope dilution–thermal ionization mass spectrometry Sm-Nd isochron ages on concentric growth zones from microstructurally and thermodynamically characterized garnets from the Betic Cordillera, southern Spain. Our ages for the garnet core (13.64 ± 0.31 Ma), mantle (13.41 ± 0.37 Ma), and rim (13.34 ± 0.45 Ma) indicate rapid garnet growth and are consistent with published garnet ages interpreted to reflect high-pressure metamorphism in the region. Thermodynamic analysis indicates garnets grew during subduction at ∼1.5–2.0 GPa and 570–600 °C. The core to rim duration of spiral garnet growth was just a few hundred thousand years. While other zoned garnet studies have shown similar rapid growth in subduction zone settings, this is the first documentation of such rapid growth of a spiral garnet. Combining this garnet growth duration with the magnitude of spiral inclusion trail curvature, we compute a strain rate of ∼10−13 s−1, an order of magnitude faster than all previous spiral garnet studies. We interpret that these spiral garnets recorded a rapid pulse of deformation and strain during the final stages of subduction and incipient exhumation.Spanish grants CGL2015–65602-R (AEI-FEDER), P18-RT-3275, and B-RNM-301-UGR18 (Junta de Andaucía/FEDER)U.S. National Science Foundation grants PIRE-1545903 and EAR-194665

The state of the Martian climate

60°N was +2.0°C, relative to the 1981–2010 average value (Fig. 5.1). This marks a new high for the record. The average annual surface air temperature (SAT) anomaly for 2016 for land stations north of starting in 1900, and is a significant increase over the previous highest value of +1.2°C, which was observed in 2007, 2011, and 2015. Average global annual temperatures also showed record values in 2015 and 2016. Currently, the Arctic is warming at more than twice the rate of lower latitudes

Options for managing alkaline steel slag leachate: A life cycle assessment

Management of steel slag (a major by-product of the steel industry) includes the treatment of highly alkaline leachate (pH > 11.5) from rainwater infiltration of slag deposits to prevent adverse impact upon surface or ground waters. This study aims to compare different treatment options for steel slag leachate through a life cycle assessment (LCA). Five options were compared: active treatment by acid dosing (A-H2SO4), active treatment by carbon dioxide dosing (A-CO2), active treatment by calcium chloride dosing (A-CaCl2), passive treatment by cascade and reedbeds with pumping (P-P), and passive treatment by cascade and reedbeds in a gravity-driven configuration (P-G). The functional unit was 1 m3 of treated leachate with pH < 9, considering 24 h and 365 days of operating, maintenance operations every year, and service life of 20 years. Inventory data were obtained from project designers, commercial suppliers, laboratory data and field tests. The environmental impacts were calculated in OpenLCA using the ELCD database and ILCD 2011 method, covering twelve impact categories. The A-CaCl2 option scored worse than all other treatments for all considered environmental impact categories. Regarding human toxicity, A-CaCl2 impact was 1260 times higher than the lowest impact option (A-CO2) for carcinogenics and 53 times higher for non-carcinogenics (A-H2SO4). For climate change, the lowest impact was calculated for P-G < P-P < A-H2SO4 < A-CO2 < A-CaCl2, while for particulate matter/respiratory inorganics, the options ranked as follows P-G < P-P < A-CO2 < A-H2SO4 < A-CaCl2. The major contributor to these impact categories was the Solvay process to produce CaCl2. Higher uncertainty was associated with the categories particulate matter formation, climate change and human toxicity, as they are driven by indirect emissions from electricity and chemicals production. Both passive treatment options had better environmental performance than the active treatment options. Potential design measures to enhance environmental performance of the treatments regarding metal removal and recovery are discussed and could inform operational management at active and legacy steel slag disposal sites

Cost-Effectiveness of iGlarLixi in People with Type 2 Diabetes Mellitus Suboptimally Controlled on Basal Insulin Plus Metformin in the UK

Introduction: A cost-effectiveness analysis was conducted comparing a fixed-ratio combination (FRC) of insulin glargine 100 units/mL plus lixisenatide (iGlarLixi) versus the FRC of insulin degludec plus liraglutide (iDegLira) and the free-combination comparators insulin glargine plus dulaglutide (iGlar plus Dula) and basal insulin plus liraglutide (BI plus Lira).Methods: The IQVIA Core Diabetes Model was used to estimate lifetime costs and outcomes for a cohort of patients with type 2 diabetes mellitus (T2DM) from the UK healthcare perspective. Initial clinical data for iGlarLixi were based on the randomized, controlled LixiLan-L trial and the relative treatment effects for comparators were based on an indirect treatment comparison using data from the AWARD-9 (iGlar plus Dula), LIRA ADD2 BASAL (BI plus Lira), and DUAL V (iDegLira) trials. Costs were derived from publicly available sources. Lifetime costs (in British Pound Sterling [£]) and quality-adjusted life-years (QALYs) were predicted; net monetary benefit (NMB) for iGlarLixi versus comparators was derived using a willingness-to-pay threshold of £20,000. Extensive scenario and sensitivity analyses were conducted.Results: Estimated costs were lowest with iGlarLixi (£31,295) compared with iGlar plus Dula (£38,790), iDegLira (£40,179), and BI plus Lira (£42,467). Total QALYs gained were identical with iGlarLixi and iDegLira (8.438), and comparable with iGlar plus Dula (8.439) and BI plus Lira (8.466). NMB for iGlarLixi was positive versus all comparators (£10,603.86 vs. BI plus Lira; £7,466.24 vs. iGlar plus Dula; £8.874.11 vs. iDegLira).Conclusion: In patients with T2DM with suboptimal glycemic control on basal insulin, iGlarLixi provides very similar outcomes and substantial cost savings, compared with other fixed and free combinations of insulins plus glucagon-like peptide-1 receptor agonists.</p