A Review of Automation and Sensors: Parameter Control of Thermal Treatments for Electrical Power Generation.

This review delves into the critical role of automation and sensor technologies in optimizing parameters for thermal treatments within electrical power generation. The demand for efficient and sustainable power generation has led to a significant reliance on thermal treatments in power plants. However, ensuring precise control over these treatments remains challenging, necessitating the integration of advanced automation and sensor systems. This paper evaluates the pivotal aspects of automation, emphasizing its capacity to streamline operations, enhance safety, and optimize energy efficiency in thermal treatment processes. Additionally, it highlights the indispensable role of sensors in monitoring and regulating crucial parameters, such as temperature, pressure, and flow rates. These sensors enable real-time data acquisition, facilitating immediate adjustments to maintain optimal operating conditions and prevent system failures. It explores the recent technological advancements, including machine learning algorithms and IoT integration, which have revolutionized automation and sensor capabilities in thermal treatment control. Incorporating these innovations has significantly improved the precision and adaptability of control systems, resulting in heightened performance and reduced environmental impact. This review underscores the imperative nature of automation and sensor technologies in thermal treatments for electrical power generation, emphasizing their pivotal role in enhancing operational efficiency, ensuring reliability, and advancing sustainability in power generation processes.

Efficacy and safety of MYL-1501D versus insulin glargine in people with type 1 diabetes mellitus: Results of the INSTRIDE 3 phase 3 switch study.

AIMS: To assess the efficacy, insulin dose, safety and immunogenicity when people with type 1 diabetes mellitus switched between MYL-1501D and reference insulin glargine (Lantus®; Sanofi-Aventis US LLC, Bridgewater, New Jersey). MATERIALS AND METHODS: Eligible participants from INSTRIDE 1 who completed 52 weeks of reference insulin glargine treatment were randomized 1:1 to the reference sequence (n = 63; reference insulin glargine for 36 weeks) or to the treatment-switching sequence (n = 64; MYL-1501D [weeks 0-12], reference insulin glargine [weeks 12-24] and MYL-1501D [weeks 24-36]). Change in glycated haemoglobin (HbA1c) from baseline to week 36 was the primary efficacy endpoint used to demonstrate equivalence between the two treatment sequences. Secondary endpoints included: change in fasting plasma glucose (FPG), self-monitored blood glucose (SMBG) and insulin dose; immunogenicity; and adverse events, including hypoglycaemia. RESULTS: Mean changes in HbA1c (least squares [LS] mean [SE]) from baseline to week 36 were -0.05 (0.032) and -0.06 (0.034) for the treatment-switching and reference sequences, respectively (LS mean difference 0.01 [95% CI -0.085 to 0.101]). Treatment sequences were comparable in terms of secondary endpoints, including FPG, SMBG and insulin dose, and the safety and immunogenicity profiles of the two sequences were similar. CONCLUSIONS: Switching participants between MYL-1501D and reference insulin glargine demonstrated equivalent efficacy and similar safety and immunogenicity, showing that people taking reference insulin glargine can safely switch to MYL-1501D.

Efficacy and safety of MYL-1501D versus insulin glargine in patients with type 2 diabetes after 24 weeks: Results of the phase III INSTRIDE 2 study.

AIMS: To assess the non-inferiority of MYL-1501D, a proposed biosimilar or follow-on biological agent to marketed insulin glargine, to reference insulin glargine (Lantus®; Sanofi-Aventis US LLC, Bridgewater, New Jersey) based on change in glycated hemoglobin (HbA1c). MATERIALS AND METHODS: INSTRIDE 2 was a multicentre, open-label, randomized, parallel-group, phase III non-inferiority study comparing the efficacy and safety of MYL-1501D with those of reference insulin glargine in insulin-naive and insulin-non-naive patients with type 2 diabetes mellitus receiving oral antidiabetic drugs (OADs). The primary efficacy endpoint was change in HbA1c from baseline to week 24. Secondary endpoints included metabolic readouts (eg, changes in fasting plasma glucose, insulin dosage, self-monitored blood glucose), immunogenicity and adverse events, including hypoglycaemia and nocturnal hypoglycaemic events. RESULTS: In all, 560 patients were randomized to MYL-1501D or insulin glargine in combination with OADs for 24 weeks. The mean change in HbA1c from baseline to week 24 was -0.60% (95% CI -0.78, -0.41) and - 0.66% (95% CI -0.84, -0.48) for MYL-1501D and reference insulin glargine, respectively. MYL-1501D was well tolerated and had a safety profile similar to that of reference insulin glargine. CONCLUSIONS: Demonstration of non-inferiority between MYL-1501D and reference insulin glargine for reduction of HbA1c during 24 weeks of treatment was achieved. The two treatment groups were similar in terms of secondary endpoints, including hypoglycaemia and nocturnal hypoglycaemia, local and systemic reactions, other safety variables, and immunogenicity.

Prevalence and triggers of anaphylactic events in schools.

BACKGROUND: Prevention and management of anaphylaxis in schools is an area of active interest as allergy and asthma rates in children continue to increase. A greater understanding of the prevalence and characteristics of anaphylaxis can help guide preventive and management strategies both within and outside of the school setting, with the goal of reducing morbidity and mortality. OBJECTIVE: This study was performed to elucidate the epidemiology of and management strategies for anaphylaxis in the school setting. METHODS: A cross-sectional, Web-based survey was administered to schools that participated in an initiative that provides stock epinephrine autoinjectors (EAIs) to qualifying U.S. schools. Representatives from participating schools completed a questionnaire regarding anaphylactic reactions that occurred during the 2014-2015 school year. Weighted analyses were performed to account for differential responses between schools that completed the survey and those that did not. RESULTS: A total of 12,275 of the 45,819 invited schools responded to the survey. The occurrence of one or more anaphylactic events was reported by 1358 schools. Most events (89.8% [1803/2008]) occurred in students. High school students accounted for the largest proportion of anaphylactic reactions among students (40.1% [723/1802]). Food was the most commonly identified anaphylaxis trigger across grade levels, seasons, and geographic regions. The trigger was unknown to the individual who experienced anaphylaxis in 21.8% of the events (436/1998). No known history of allergy or asthma was present in 24.5% (491/2001) and 51.3% (1026/2000) of affected individuals, respectively. Transportation to the hospital or clinic for further treatment and/or management was reported for 72.6% of the individuals with anaphylactic events (1450/1997). Results from the weighted analyses were similar to those of the unweighted analyses. CONCLUSION: Anaphylaxis occurred across grade levels and in individuals with or without known risk factors, which reinforced the need for school preparedness in both management of anaphylaxis and stocking of EAIs.

Using 1H low-field NMR relaxometry to detect the amounts of Robusta and Arabica varieties in coffee blends.

Low-field nuclear magnetic resonance (LF-NMR) is a method of widespread use in food research due to its non-destructive character and the relatively low cost of the instruments, allowing the determination of oil / fat contents and the achievement of images of different types of food materials, among other uses. In this work, 1H LF-NMR relaxometry was used to distinguish the contributions due to Arabica and Robusta coffee varieties present in coffee blends. As the method detects preferentially the NMR signals due to phases with high molecular mobility, which exhibit longer values of the 1H transverse relaxation time (T2), the difference in the oil contents associated with Arabica and Robusta coffee was the key factor responsible for the detection of the contributions due to each variety. The analysis presented in this work showed that the relative hydrogen index is a useful parameter to be used in quantitative analyses of the contents of each coffee variety present in the blends. The results illustrate the high potential of applicability of LF-NMR relaxometry as a screening tool for quality control and adulteration detection of coffee-related products.

The Characterization of Melanaphis sacchari Microbiota and Antibiotic Treatment Effect on Insects.

Insects are under constant selective pressure, which has resulted in adaptations to novel niches such as crops. This is the case of the pest Melanaphis sacchari, the sugarcane aphid, native to Africa and currently spreading worldwide. The aphid undergoes successful parthenogenesis, causing important damage to a variety of crops and leading to important economic losses for farmers. A natural M. sacchari population grown in sorghum was studied to identify its microbiome through the sequencing of its 16S rDNA metagenome. A high proportion of Proteobacteria, followed by Firmicutes, Bacteroidetes, and Actinobacteria, was observed. We also detected Wolbachia, which correlates with the asexual reproduction of its host. M. sacchari was challenged in a bioassay with the antibiotics oxytetracycline and streptomycin, resulting in a dose-dependent decay of its survival rate. The possibility of controlling this pest by altering its microbiota is proposed.

A randomized, double-blind study of 30 versus 20 mg dexmethylphenidate extended-release in children with attention-deficit/hyperactivity disorder: late-day symptom control.

The objective of this study was to evaluate the safety and efficacy of dexmethylphenidate extended-release (d-MPH-ER) 30 versus 20 mg in children with attention-deficit/hyperactivity disorder (ADHD) in a 12-hour laboratory classroom setting. In a randomized, double-blind, 3-period × 3-treatment, crossover study, children aged 6 to 12 years with Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition-diagnosed ADHD previously stabilized on MPH (40-60 mg/d) or D-MPH (20-30 mg/day) [corrected] were randomized to receive D-MPH-ER 20 mg/day, 30 mg/day, [corrected] or placebo for 7 days each. Primary efficacy measurements were change in the average SKAMP-Combined [corrected] score from predose to 10, 11, and 12 hours postdose [Avg(10-12)] between 30 mg [corrected] and 20 mg D-MPH-ER. Safety was assessed by adverse events, (AEs), [corrected] vital sign monitoring, and ECGs. [corrected] A total of 165 children were randomized, and 162 included in the intent-to-treat analysis. Mean Avg (10-12) change from pre-dose [corrected] in SKAMP-Combined score was significantly greater for D-MPH-ER 30 mg (-4.47) compared with D-MPH-ER 20 mg (-2.02; P = 0.002). Most common adverse events (≥ 3% in any group) were decreased appetite (6.1%, 4.9%, and 0%), headache (4.3%, 4.3%, and 1.9%), abdominal pain (3.7%, 3.1%, and 3.1%), and tachycardia (1.2%, 3.1%, and 0.6%) for D-MPH-ER 30 mg, D-MPH-ER 20 mg, and placebo, respectively). Significantly greater improvement in ADHD symptoms was noted with D-MPH-ER 30 mg compared with D-MPH-ER 20 mg at hours 10 through 12. Tolerability was comparable between doses. Dexmethylphenidate extended-release 30-mg dose may provide further benefit to patients who do not maintain optimal symptom control later in the day with D-MPH-ER 20 mg.

Adalimumab Biosimilars in the Treatment of Rheumatoid Arthritis: A Systematic Review of the Evidence for Biosimilarity.

Although treatment with biologic disease-modifying antirheumatic drugs (bDMARDs) has significantly improved clinical outcomes in patients with rheumatoid arthritis (RA), many patients do not have access to these treatments. As cost-effective alternatives to their reference products (RPs), biosimilars provide an opportunity to increase access to bDMARDs. The European Medicines Agency and the US Food and Drug Administration have detailed pathways for the approval of biosimilars based on establishing the similarity of the biosimilar to the RP in terms of structure and function, pharmacokinetics (PK), efficacy, safety, and immunogenicity. A number of biosimilars of adalimumab, infliximab, etanercept, and rituximab RPs have been approved in the United States and/or European Union. This article is focused on the seven adalimumab biosimilars. A review of the data for the biosimilars FKB327, ABP 501, BI 695501, GP2017, MSB11022, PF-06410293, and SB5 confirm that these products are highly similar to the adalimumab RP with regard to structure, physicochemical and biological properties, PK, safety, immunogenicity, and efficacy in the treatment of RA and other chronic immune-mediated, inflammatory conditions. Data from several switching studies showed no changes in efficacy, safety, trough serum drug concentration, or immunogenicity between the biosimilars and their RP.Trial registration: ClinicalTrials.gov identifiers: NCT02260791, NCT02405780, NCT01970475, NCT02137226, NCT02045979, NCT02744755, NCT02144714, NCT02167139, NCT03014947, NCT02114931, NCT02640612, NCT02167139, NCT03052322, NCT02480153. EudraCT numbers: 2012-005140-23, 2012-000785-37, 2013-003722-84, 2015-000579-28, 2014-002879-29, 2014-000662-21, 2013-004654-13, 2015-002634-41, 2014-005229-11, 2016-002852-26, 2014-000352-29.

Biologic disease-modifying antirheumatic drugs (bDMARDs) improve outcomes for patients with rheumatoid arthritis (RA); however, many patients do not have access to these treatments. Biosimilars offer a cost-effective alternative to their reference product (RP) and provide the opportunity to increase access to bDMARDs. This article reviews available data regarding the pharmacokinetics (PK), safety, immunogenicity, and effectiveness of the adalimumab RP and its biosimilars (FKB327, ABP 501, BI 695501, GP2017, MSB11022, PF-06410293, and SB5) in the treatment of RA. Based on the published literature, we concluded that these products are similar to the adalimumab RP in terms of their structure, physicochemical and biological properties, and PK. We also found that these biosimilars have similar safety and effectiveness to the adalimumab RP in the treatment of patients with RA. In addition, switching between a biosimilar and the adalimumab RP resulted in no impact on safety, effectiveness, serum concentrations, or immunogenicity.

Physicochemical analysis and biological characterization of FKB327 as a biosimilar to adalimumab.

FKB327 was approved by the European Medicines Agency as a biosimilar to European-authorized adalimumab (Humira® ; AbbVie Inc). Adalimumab is a monoclonal antibody, binding and inhibiting tumor necrosis factor (TNF)-α with use indicated for several immune-mediated, chronic, and inflammatory disorders. The approval is based on high similarity in the physicochemical properties between FKB327 and adalimumab. The objective of this study is to assess the biological similarity, with regard to Fab- and Fc-associated functions, and describe the relationship between physicochemical and biological characterization and functional activity. State-of-the-art orthogonal techniques were implemented to assess the structure and function of FKB327. Peptide mapping with liquid chromatography and mass spectrometry, capillary electrophoresis-sodium dodecyl sulfate, ultraviolet circular dichroism, size-exclusion high-performance liquid chromatography (HPLC), and cation exchange HPLC were the techniques used to assess structure. Functional activity was assessed with enzyme-linked immunosorbent assay, surface plasmon resonance, and cell-based assays. The polypeptide sequence of FKB327 was identical to that of adalimumab. FKB327 also was demonstrated to have a similar secondary and tertiary structure to adalimumab. Posttranslational heterogeneities, along with size and charge variants, were not clinically meaningful. FKB327 binds to TNF-α, FcγR, the neonatal Fc receptor, and C1q, and induces apoptosis, antibody-dependent cellular cytotoxicity, and complement-dependent cytotoxicity. The binding and activity of FKB327 were similar to that of adalimumab. FKB327 shares similar structure and activity with adalimumab. Based on characterization of physicochemical and biological properties, FKB327 is expected to have a similar safety, immunogenicity, and efficacy profile to adalimumab.

Long-term safety, immunogenicity and efficacy comparing FKB327 with the adalimumab reference product in patients with active rheumatoid arthritis: data from randomised double-blind and open-label extension studies.

BACKGROUND/OBJECTIVE: FKB327 is a biosimilar of the antitumour necrosis factor adalimumab reference product (RP). A randomised, double-blind (DB) phase 3 study compared the efficacy of FKB327 with the RP in patients with active rheumatoid arthritis (RA) inadequately controlled with methotrexate (MTX). A subsequent randomised open-label extension (OLE) study with treatment switching assessed long-term safety, efficacy, pharmacokinetics and immunogenicity of FKB327 compared with the RP. METHODS: Patients with moderate-to-severe, active RA on a stable dose of MTX were randomised 1:1 to receive FKB327 or the RP (40 mg subcutaneously every other week) for 24 weeks. Patients who completed the DB study were enrolled in the OLE and rerandomised 2:1 to receive FKB327 or the RP; two-thirds continued on the same treatment and one-third switched for 30 weeks. All patients received FKB327 through Week 76. Long-term efficacy, safety and immunogenicity were assessed. RESULTS: Of 728 patients in the DB study, 645 were enrolled in the FKB327-OLE study. The American College of Rheumatology (ACR)20 response rates for all treatment groups at Week 30 in the OLE ranged from 83.2% to 85.9%. ACR20 response rates remained stable for all patients regardless of single- or double-switching treatment and were similar for all treatment sequences through Week 76. The safety profile and incidence of antidrug antibodies were comparable across sequences. CONCLUSION: Efficacy, safety and immunogenicity were similar among patients with RA treated with FKB327 or the RP for up to 2 years, and were not affected by single- or double-switching treatment.

Immunogenicity of an adalimumab biosimilar, FKB327, and its reference product in patients with rheumatoid arthritis.

AIM: This study, FKB327-003, is a phase 3, open-label extension (OLE) study comparing the long-term immunogenicity of an adalimumab biosimilar, FKB327 (F), with the reference product (RP). METHODS: In the OLE, patients completing 24 weeks of an initial randomized, double-blind (DB) study (Period 1) with clinical response and no safety concerns were rerandomized to F or RP, so that two-thirds of patients remained on the same treatment and one-third switched to the alternate treatment for weeks 24 through 54 (OLE weeks 0-30; Period 2), then all received F through week 100 (OLE week 76; Period 3). Treatment sequences were F-F-F (no switch), RP-F-F and RP-RP-F (single switch), and F-RP-F (double switch). Patients who entered the OLE study were evaluated for immunogenicity across switching sequences. RESULTS: The proportion of patients with positive antidrug antibody (ADA) status at the end of Period 1 was 61.7% and 60.0% for F and RP, respectively. The proportion of patients with positive ADA status did not increase throughout Period 1, and was similar for F and RP at all time points. At the end of Period 3, the proportion of patients with positive ADA status was lower in all treatment sequences, at 51.1%, 54.4%, 48.1%, and 42.5% for F-F-F, F-RP-F, RP-F-F, and RP-RP-F, respectively. CONCLUSION: The RP and F showed comparable immunogenicity characteristics after long-term administration. Development of ADAs with the RP and F was similar, and was not impacted by switching and double switching between F and RP treatment.

Egg Parasitoids Survey of Spodoptera frugiperda (Smith) (Lepidoptera: Noctuidae) in Maize and Sorghum in Central Mexico.

Spodoptera frugiperda (Smith) is the main maize pest in America and was recently detected as an invasive pest in some countries in Asia and Africa. Among its natural enemies presented in Mexico, Trichogramma pretiosum Riley is the only egg parasitoid used in Integrated Pest Management (IPM) programs regardless of its effectiveness. A search for natural enemies of S. frugiperda was then carried out to determine whether this parasitoid has been established, and to detect native egg parasitoids or predators associated with this pest. The sentinel technique (egg masses) was used, and then placed in maize and sorghum fields in the state of Guanajuato, Mexico. Trichogramma atopovirilia Oatman and Platner, an egg parasitoid, and Chelonus insularis Cresson egg-larva parasitoid were recovered from field surveys. Among the natural enemies that preyed on eggs of S. frugiperda, we found mites of the genus Balaustium, and Dermaptera of the genus Doru, both species in great abundance. Laboratory tests were performed to compare the potential parasitism of T. atopovirilia against T. pretiosum. T. atopovirilia obtained 70.14% parasitism while T. pretiosum, 29.23%. In field cages, three doses of the parasitoids were tested. Total parasitism did not exceed 8% in any of the two species, but T. atopovirilia parasitized a greater number of hosts using two and three parasitoids per pest egg. Then, the use of Trichogramma species needs to be reevaluated in biological control programs against S. frugiperda.

Differential Susceptibility of Bagrada hilaris (Hemiptera: Pentatomidae) to Different Species of Fungal Pathogens.

Bagrada hilaris Burmeister (Hemiptera: Pentatomidae) is a pest of Palearctic origin. Its presence in the United States was first reported in 2008 and in Mexico in 2014; it affects brassica crops. There are practically no reports of natural enemies of B. hilaris in America. Entomopathogenic fungi are strong candidates for microbial control of this pest. Evaluating the susceptibility of this pest to fungi that are native to the region where they will be used is a sensible first step to finding candidate biological control agents. The aim of our research was to select potential microbial agents to control B. hilaris. Eleven isolates of Beauveria bassiana, Beauveria pseudobassiana, Metarhizium anisopliae, and Isaria fumosorosea were evaluated to determine the susceptibility of B. hilaris. Isolates of B. bassiana caused the highest mortality due to infection (100%) compared with the other isolates. The I. fumosorosea isolate caused the lowest percent mortality (56%). The two B. bassiana isolates Bb88 and AP3 were more virulent than M. anisopliae isolate Ma129. The sex of the insect had no effect on infection levels achieved by B. bassiana isolates Bb88 and AP3. The results of our study contribute valuable information for the development of fungal species with potential to manage B. hilaris populations. Field studies are the next step in order to develop these isolates as biological control agents of B. hilaris.

Cytogenetic assessment of methylphenidate treatment in pediatric patients treated for attention deficit hyperactivity disorder.

Methylphenidate (MPH, Ritalin), has been prescribed to treat attention deficit/hyperactivity disorder (ADHD) since its approval by the FDA over 50 years ago. Diagnoses of pediatric patients with ADHD and the administration of MPH to treat the symptoms have increased in prevalence in recent years. A 2005 study by El-Zein et al. reported statistically significant increases in cytogenetic anomalies including chromosomal aberrations (CA), micronuclei (MN) and sister chromatid exchanges (SCEs) in peripheral blood lymphocytes cultured from pediatric patients treated for 3 months with MPH. These findings led to wide-spread concern regarding the potential for genotoxic risks associated with prolonged administration of MPH. The study described in the present paper was designed to repeat the El-Zein effort with a much larger sample size. The subjects (N = 109) were randomized into two groups: one treated with MPH as well as behavior therapy, the other was a control group that received behavior therapy only. We evaluated CAs, MN, and SCEs in peripheral blood lymphocytes in samples obtained prior to therapy and after 3 months of treatment with MPH. The data were analyzed using a Poisson regression model with a generalized estimating equation method adjusted for several covariates including time, treatment-by-time interaction, sex, and age group. The log(e) rate ratios of the MPH plus behavior therapy and behavior therapy groups were compared. The frequencies of CAs, MN, and SCEs were not increased in the MPH plus behavior therapy group when compared to the behavior therapy group only (p = 0.53, 0.28, 0.81, respectively). These results provide evidence in a large cohort that MPH does not induce cytogenetic anomalies in children, in contrast to the findings of the El-Zein study.

Long-term effectiveness and safety of dexmethylphenidate extended-release capsules in adult ADHD.

OBJECTIVE: This study evaluates dexmethylphenidate extended release (d-MPH-ER) in adults with ADHD. METHOD: Following a 5-week, randomized, controlled, fixed-dose study of d-MPH-ER 20 to 40 mg/d, 170 adults entered a 6-month open-label extension (OLE) to assess long-term safety, with flexible dosing of 20 to 40 mg/d. Exploratory effectiveness outcomes included change from Week 5 on ADHD Rating Scale (ADHD-RS) and proportion of responders on Clinical Global Impressions-Improvement (CGI-I) scale. RESULTS: 103 patients completed OLE, and effectiveness was evaluable in 102 patients. d-MPH-ER was well tolerated; the most common adverse events (>15%) were headache, insomnia, and decreased appetite. Mean improvements in ADHD-RS score were -10.2 for patients switched from placebo to d-MPH-ER (n = 20) and -8.4 for those maintained on d-MPH-ER (n = 82). Respective CGI-I responder rates were 95.0% and 95.1%. CONCLUSION: Once-daily d-MPH-ER 20 to 40 mg is safe and effective for long-term treatment of adult ADHD.

A phase 1, randomized, open-label, single-dose study to assess the relative bioavailability of a subcutaneous dose of FKB327 when administered using a prefilled syringe, a prefilled auto-injector, or a vial with disposable syringe in healthy subjects.

BACKGROUND/OBJECTIVE: FKB327 is a biosimilar of the adalimumab reference product (RP). The primary objective was to assess the relative bioavailability of FKB327 after a single subcutaneous (SC) dose via prefilled syringe (PFS), auto-injector (AI), or vial with a disposable syringe (vial), in healthy subjects. METHODS: This randomized, open-label, parallel-group, single SC-dose study was conducted in 195 healthy male and female subjects who were randomized 1:1:1 to receive FKB327 40 mg via PFS, AI, or vial. The primary pharmacokinetic (PK) parameters, areas under the serum concentration-time curve to the last detectable value (AUC0-t) and extrapolated to infinity (AUC0-∞), and maximum concentration (Cmax), were compared. Relative bioavailability was established if the ratio of geometric least squares (LS) means of the test product was within the predefined bioequivalence (BE) range of 0.80 to 1.25 of the RP for each comparison. Safety and immunogenicity were assessed. RESULTS: The mean serum FKB327 concentration-time profiles appeared similar across all 3 presentations. AUC0-t, AUC0-∞, and Cmax were within the predefined BE range for PFS compared with vial, suggesting comparable bioavailability. AUC0-∞ and Cmax of AI compared with vial and PFS were fully contained within BE range, although the upper limit of 90% confidence intervals of the geometric LS means ratios for AUC0-t was slightly high. Treatment-emergent adverse events in all 3 groups were mild, with no new safety concern with FKB327 identified. Similar immunogenicity was observed among administrations. CONCLUSION: Among all 3 delivery methods, PK characteristics, safety profiles, and immunogenicity were similar. TRIAL REGISTRATION: EU Clinical Trials Registry EudraCTN2014-004469-26, registered October 14, 2014.

A randomized, double-blind, crossover study of once-daily dexmethylphenidate in children with attention-deficit hyperactivity disorder: rapid onset of effect.

BACKGROUND: Long-acting methylphenidate formulations provide control of attention-deficit hyperactivity disorder (ADHD) symptoms for up to 12 hours; however, not all formulations have rapid onset of therapeutic effect, which is essential for providing symptom control during morning hours. The primary objective of this randomized, double-blind, crossover study was to assess the efficacy of dexmethylphenidate extended release (ER) versus placebo by measuring the change from pre-dose to 0.5 hours post-dose on the Swanson, Kotkin, Agler, M-Flynn and Pelham (SKAMP) rating scale. METHODS: Eighty-six children (6-12 years) with ADHD diagnosed using the DSM-IV criteria were randomized to receive dexmethylphenidate ER 20 mg/day or placebo, sequentially, for 7 days, with the final dose administered in a laboratory classroom setting on day 7 of each treatment period. The primary efficacy comparison was change in the SKAMP-Combined score from pre-dose to 0.5 hours post-dose, with additional secondary assessments at 1, 2, 4, 6 and 8 hours post-dose. Secondary efficacy measures included change from pre-dose at all timepoints in the SKAMP-Attention and SKAMP-Deportment, Math Test-Attempted and Math Test-Correct scores, and change from baseline on the Conners' ADHD/DSM-IV Scale for Parents (CADS-P). In an exploratory analysis, a daily diary card was completed by parents on the children's in-home behaviour before school. Safety was assessed by occurrence of adverse events, monitoring of vital signs and interpretation of ECGs. RESULTS: Significant improvements were noted at 0.5 hours and at all timepoints post-dose throughout the 8-hour laboratory classroom day for dexmethylphenidate ER vs placebo in the primary outcome measure of the SKAMP-Combined scores (p < 0.001), as well as SKAMP-Attention, SKAMP-Deportment, Math Test-Attempted and Math Test-Correct scores (p < 0.05). The changes from baseline in CADS-P scores were significantly greater with dexmethylphenidate ER than placebo (-16.382 vs -4.622; p < 0.001). Responses to all diary questions indicated significant improvement with dexmethylphenidate ER treatment versus placebo (all p < 0.001). The most common adverse events were abdominal pain (dexmethylphenidate ER 3.5%; placebo 4.7%), headache (dexmethylphenidate ER 3.5%; placebo 2.3%) and increased appetite (dexmethylphenidate ER 0%; placebo 3.5%). CONCLUSION: Compared with placebo, once-daily dexmethylphenidate ER 20 mg provided rapid and significant improvement at 0.5 hours post-dose in attention, deportment and academic performance, which was sustained for 8 hours post-dose. Overall, once-daily dexmethylphenidate ER 20 mg was well tolerated. In an analysis of parental assessment of diary responses, children appeared more organized, and morning preparation for school was smoother and less frustrating with once-daily dexmethylphenidate ER compared with placebo.

Dexmethylphenidate extended-release capsules in children with attention-deficit/hyperactivity disorder.

OBJECTIVE: This study compared once-daily dexmethylphenidate extended release (D-MPH-ER) 20 mg/day and placebo over 12 hours in children ages 6 to 12 with attention-deficit/hyperactivity disorder (ADHD) in a laboratory classroom setting. METHOD: All of the children were stabilized for > or =2 weeks on a total dose (nearest equivalent) MPH 40 mg/day or immediate-release D-MPH 20 mg/day before screening. After a practice day, they received 6 days of D-MPH-ER 20 mg/day or placebo at home, returning on day 7 for one dose. Subjects were evaluated at predose and postdose hours 0.5, 1, 3, 4, 5, 7, 9, 10, 11, and 12 and then crossed over to the other treatment arm using the identical protocol. The primary efficacy variable was the change from predose in Swanson, Kotkin, Agler, M-Flynn, and Pelham rating scale (SKAMP) combined score from 1 to 12 hours. Secondary efficacy variables included SKAMP combined score at 0.5 hours, SKAMP subscale scores, and math test results over 12 hours. RESULTS: Sixty-eight children were randomized, with 67 completing the study. Onset of action was indicated by a significant difference between D-MPH-ER and placebo at 0.5 hour on the SKAMP combined score (p = .001). For efficacy measures, differences from placebo were significant at all points between 0.5 and 12 hours (p < .001 top = .013). CONCLUSIONS: D-MPH-ER provided sustained improvement in attention, deportment, and academic productivity throughout the 12-hour laboratory day.

Barriers to the Administration of Epinephrine in Schools.

BACKGROUND: Anaphylaxis is a serious and growing concern in the school setting as the prevalence of food allergies and food-induced severe allergic reactions continues to increase. METHODS: A cross-sectional, web-based survey was conducted regarding anaphylactic events that occurred during the 2014-2015 school year. Eligible schools were enrolled in the EPIPEN4SCHOOLS® program (Mylan Specialty L.P., Canonsburg, PA), which provides free epinephrine auto-injectors to qualifying US schools. Participating schools completed a 29-item survey on anaphylactic event occurrence and treatment, epinephrine stock, school policies regarding anaphylaxis, school staff training, and school nursing coverage. RESULTS: Responses were provided by 12,275 schools. Epinephrine was administered on school property for 63.7% of reported anaphylactic events (1272/1998). In 38.5% (235/610) of events for which epinephrine was not used, antihistamines were cited as the reason. Only 59.4% of schools cited epinephrine as their standard first-line therapy for anaphylaxis. School nurses were most likely to be trained in anaphylaxis recognition and permitted to administer epinephrine; however, just 53.6% of schools had a full-time nurse on staff. CONCLUSIONS: Process-related barriers to the appropriate use of epinephrine go beyond access to medication. Widespread staff training and review of school policies are needed to ensure that anaphylaxis is appropriately managed in schools.

Pulmonary Ultrasound in Patients with Heart Failure - Systematic Review.

Pulmonary congestion is an important clinical finding in patients with heart failure (HF). Physical examination and chest X-ray have limited accuracy in detecting congestion. Pulmonary ultrasound (PU) has been incorporated into clinical practice in the evaluation of pulmonary congestion. This paper aimed to perform a systematic review of the use of PU in patients with HF, in different scenarios. A search was performed in the MEDLINE and LILACS databases in February 2017 involving articles published between 2006 and 2016. We found 26 articles in the present review, 11 of which in the emergency setting and 7 in the outpatient setting, with diagnostic and prognosis defined value and poorly studied therapeutic value. PU increased accuracy by 90% as compared to physical examination and chest X-ray for the diagnosis of congestion, being more sensitive and precocious. The skill of the PU performer did not interfere with diagnostic accuracy. The presence of B-lines ≥ 15 correlated with high BNP values (≥ 500) and E/e' ratio ≥ 15, with prognostic impact in IC patients at hospital discharge and those followed up on an outpatient basis. In conclusion, when assessing pulmonary congestion in HF, PU has an incremental value in the diagnostic and prognostic approach in all scenarios studied.