Nizhny Novgorod Research Institute of Traumatology and Orthopedics

Three hundred forty-three multiple trauma patients with major pelvic ring disruption were studied and subdivided into four major groups by mechanism of injury: antero-posterior compression (APC), lateral compression (LC), vertical shear (VS), and combined mechanical injury (CMI). Acetabular fractures which did not disrupt the pelvic ring were excluded. The mode of injury was: MVA, 57.4%; motorcycle, 9.3%; fall, 9.3%; pedestrian, 17.8%; crush, 3.8%. The LC and APC groups were divided into Grades 1–3 of increasing severity. The pattern of organ injury: including brain, lung, liver, spleen, bowel, bladder, pelvic vascular injury (PVASI), retroperitoneal hematoma (RPH) and complications: circulatory shock, sepsis, ARDS, abnormal physiology, and 24-hr total fluid volume administration were all evaluated as a function of mortality (M). As LC grade increased from 1 to 3 there was increased % incidence of PVASI, RPH, shock, and 24-hr volume needs. However, the large incidence of brain, lung, and upper abdominal visceral injuries as causes of death in Grade 1 and 2 fell in LC3, with limitation of the LC3 injury pattern to the pelvis. As APC grade increased from 1 to 3 there was increased % injury to spleen, liver, bowel, PVASI with RPH, shock, sepsis, and ARDS, and large increases in volume needs, with important incidence of brain and lung injuries in all grades. Organ injury patterns and % M associated with vertical shear were similar to those with severe grades of APC, but CMI had an associated organ injury pattern similar to lower grades of APC and LC fractures. The pattern of injury in APC3 was correlated with the greatest 24-hour fluid requirements and with a rise in mortality as the APC grade rose. However, there were major differences in the causes of death in LC vs. APC injuries, with brain injury compounded by shock being significant contributors in LC. In contrast, in APC there were significant influences of shock, sepsis, and ARDS related to the massive torso forces delivered in APC, with large volume losses from visceral organs and pelvis of greater influence in APC, but brain injury was not a significant cause of death. These data indicate that the mechanical force type and severity of the pelvic fracture are the keys to the expected organ injury pattern, resuscitation needs, and mortality.

The Russian Academy of Sciences and Federal Space Agency, together with the participation of many international organizations, worked toward the launch of the RadioAstron orbiting space observatory with its onboard 10-m reflector radio telescope from the Baikonur cosmodrome on July 18, 2011. Together with some of the largest ground-based radio telescopes and a set of stations for tracking, collecting, and reducing the data obtained, this space radio telescope forms a multi-antenna ground-space radio interferometer with extremely long baselines, making it possible for the first time to study various objects in the Universe with angular resolutions a million times better than is possible with the human eye. The project is targeted at systematic studies of compact radio-emitting sources and their dynamics. Objects to be studied include supermassive black holes, accretion disks, and relativistic jets in active galactic nuclei, stellar-mass black holes, neutron stars and hypothetical quark stars, regions of formation of stars and planetary systems in our and other galaxies, interplanetary and interstellar plasma, and the gravitational field of the Earth. The results of ground-based and inflight tests of the space radio telescope carried out in both autonomous and ground-space interferometric regimes are reported. The derived characteristics are in agreement with the main requirements of the project. The astrophysical science program has begun.

Serum C-reactive protein (CRP) levels and erythrocyte sedimentation rates (ESR) were measured serially in 50 osteoarthritic patients treated with uncomplicated primary total hip arthroplasties (THAs) and also in 28 patients with painful hip for different periods after THA. The follow-up period was one year. In uncomplicated primary THA, the ESR was slightly elevated before surgery and was variable after surgery; some patients continued to have abnormally high ESRs one year after surgery. However, CRP was normal before surgery and after surgery showed a distinctive pattern that rapidly normalized within three weeks. In patients with a painful hip after THA, ESR was elevated in those with septic loosening and variable in those with mechanical loosening; however, the difference was not significant. ESR after successful revision THA was also variable. CRP was high in patients with septic loosening and normal in those with mechanical loosening. Normalization of CRP was rapid after control of infection or within three weeks of successful revision THA. Uneventful recovery after THA is indicated by normalization of CRP within three weeks, regardless of ESR. Measurement of both ESR and CRP is helpful in differentiating septic and mechanical loosening, detecting complications, and monitoring the effects of treatment, but CRP is more informative and sensitive than ESR for these purposes.

BACKGROUND/AIMS: Since the majority of skin diseases are known to be accompanied by structural alterations, research efforts are focused on the development of various novel diagnostic techniques capable of providing in vivo information on the skin structure. An essential parameter here is spatial resolution. In this paper we demonstrate the capabilities of optical coherence tomography (OCT) in detecting in vivo specific features of thin and thick skin. A particular focus is made on the identification of OCT patterns typical of certain pathological processes in skin, by performing parallel histological and tomographical studies. METHODS: To obtain images of the skin, we used a compact fiber OCT system developed at the Institute of Applied Physics of the Russian Academy of Sciences. A low coherence source (superluminescent diode) operated at a wavelength of 1280 nm; the output power was 0.5-2 mW. This power is low enough to conform to the ANSI safety standards for light exposure. The in-depth resolution limited by the spectral bandwidth (40-50 nm) of the probing light was approximately 20 &mgr;m. The lateral resolution determined by the probe light focusing ranged from 15 to 30 &mgr;m. In this series of experiments the maximum depth of imaging did not extend beyond 1.5 mm. Obtaining images of skin regions 2-6 mm long took 2-4 s. OCT capabilities for imaging normal skin of different localization and some skin diseases were studied in 12 healthy volunteers and 24 patients. RESULTS: OCT imaging of the skin can detect in vivo such general pathological reactions of the human body as active inflammation and necrosis. OCT is useful for in vivo diagnosis of some specific processes in the skin, including hyperkeratosis, parakeratosis and formation of intradermal cavities. OCT imaging is noninvasive and therefore allows frequent multifocal examination of skin without any adverse effects. OCT can perform monitoring of disease progress and recovery in the course of therapy. Morphometric studies, measurements of the depth and extension of skin pathology within the human body can be easily performed by OCT. CONCLUSIONS: OCT allows imaging of subsurface soft tissues with the spatial resolution of 15-20 &mgr;m, a resolution one order of magnitude higher than that provided by other clinically available noninvasive diagnostic techniques. An imaging depth of up to 1.5-2 mm, given by current OCT technology, is sufficient to examine the skin. Real time OCT imaging can provide information not only on the structure, but also on some specific features in the functional state, of tissues. OCT imaging is a noninvasive technique, i.e., OCT does not cause trauma and has no side effects since it utilizes radiation in the near infrared wavelength range at a power as low as 1 mW.

Long-distance intercellular electrical signals, including variation potential (VP) in higher plants, are a potential mechanism of coordinate functional responses in different plant cells under action of stressors. VP, which is caused by damaging factors (e.g., heating, crushing), is transient depolarization with an irregular shape. It can include a long-term depolarization and fast impulse depolarization ('AP-like' spikes). Mechanisms of VP generation and propagation are still under investigation. It is probable that VP is a local electrical response induced by propagation of hydraulic wave and (or) chemical agent. Both hypotheses are based on numerous experimental results but they predict VP velocities which are not in a good accordance with speed of variation potential propagation. Thus combination of hydraulic and chemical signals is the probable mechanism of VP propagation. VP generation is traditionally connected with transient H(+)-ATPase inactivation, but AP-like spikes are also connected with passive ions fluxes. Ca(2+) influx is a probable mechanism which triggers H(+)-ATPase inactivation and ions channels activation at VP.

OBJECTIVE: Surveillance of Barrett's esophagus is problematic, as high-grade dysplasia cannot be recognized endoscopically. Endoscopic ultrasound lacks the resolution to detect high-grade dysplasia. Optical coherence tomography (OCT) employs infrared light reflectance to provide in vivo tissue images at resolution far superior to endoscopic ultrasound, nearly at the level of histology. We have developed a catheter-based system well suited for study of the GI tract. The purpose of this study was to test this catheter-based OCT system and characterize the OCT appearance of normal squamous mucosa, gastric cardia, Barrett's esophagus, and carcinoma. METHODS: The OCT catheter was passed through the operating channel of the endoscope and placed in contact with the esophageal mucosa. Image acquisition occurred in approximately 3 s. OCT images were correlated with biopsy and/or resection specimens. RESULTS: OCT was used to construct 477 images of the esophagus and stomach in 69 patients. There were unique, distinct OCT appearances of squamous mucosa, gastric cardia, Barrett's esophagus, and carcinoma. Further, these OCT images were accurately recognized by observers unaware of their site of origin. CONCLUSIONS: OCT provides a highly detailed view of the GI wall, with clear delineation of a multiple layered structure. It is able to distinguish squamous mucosa, gastric cardia, Barrett's esophagus, and cancer. This technique holds great potential as an adjunct to the surveillance of patients with Barrett's esophagus, ulcerative pancolitis, and other premalignant conditions.

IMPORTANCE: The patents for the first approved treatments for relapsing-remitting multiple sclerosis are expiring, creating the opportunity to develop generic alternatives. OBJECTIVE: To evaluate in the Glatiramer Acetate Clinical Trial to Assess Equivalence With Copaxone (GATE) study whether generic glatiramer acetate (hereafter generic drug) is equivalent to the originator brand glatiramer acetate (hereafter brand drug) product, as measured by imaging and clinical end points, safety, and tolerability. DESIGN, SETTING, AND PARTICIPANTS: Randomized, multicenter, double-blind, active and placebo-controlled phase 3 trial. The setting included academic medical centers and clinical practices. Participants were patients with relapsing-remitting multiple sclerosis 18 to 55 years old with at least 1 relapse in the prior year and 1 to 15 gadolinium-enhancing brain magnetic resonance imaging lesions. They were randomized between December 7, 2011, and March 21, 2013. The last participant completed follow-up December 2, 2013. INTERVENTIONS: Participants were randomized 4.3:4.3:1 to receive generic glatiramer acetate (20 mg), brand glatiramer acetate (20 mg), or placebo by daily subcutaneous injection for 9 months. MAIN OUTCOMES AND MEASURES: The primary end point was the total number of gadolinium-enhancing lesions during months 7, 8, and 9. Additional end points included other magnetic resonance imaging parameters, annualized relapse rate, and Expanded Disability Status Scale score. Safety and tolerability were assessed by monitoring adverse events, injection site reactions, and laboratory test results. RESULTS: In total, 794 participants were randomized and treated with generic drug (n = 353), brand drug (n = 357), or placebo (n = 84). The estimated mean numbers of gadolinium-enhancing lesions with generic drug and brand drug were lower than with placebo (ratio, 0.488; 95% CI, 0.365-0.651; P < 001), confirming study sensitivity. For gadolinium-enhancing lesions, the estimated ratio of generic drug to brand drug was 1.095 (95% CI, 0.883-1.360), which was within the predefined equivalence margin of 0.727 to 1.375. The incidence, spectrum, and severity of reported adverse events, including injection site reactions, were similar in the generic drug and brand drug groups. CONCLUSIONS AND RELEVANCE: As treatment for relapsing-remitting multiple sclerosis, glatiramer acetate generic drug and brand drug had equivalent efficacy, safety, and tolerability. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01489254.

This Letter aims to demonstrate the ultrafast nature of laser produced betatron radiation and its potential for application experiments. An upper estimate of the betatron x-ray pulse duration has been obtained by performing a time-resolved x-ray diffraction experiment: The ultrafast nonthermal melting of a semiconductor crystal InSb has been used to trigger the betatron x-ray beam diffracted from the surface. An x-ray pulse duration of less than 1 ps at full width half-maximum FWHM has been measured with a best fit obtained for 100 fs FWHM.

STUDY DESIGN: A prospective, randomized study was used to compare 2 anesthesia/analgesia methods for reconstructive spine surgery. OBJECTIVE: To assess the efficacy and influence of 2 anesthetic methods on clinical outcome and stress response during reconstructive spine surgery. SUMMARY OF BACKGROUND DATA: Pain control is an important goal of the postoperative care after spinal surgery. Some prior studies have suggested that epidural anesthesia with or without postoperative epidural analgesia may blunt the surgical stress response after major surgery. This treatment approach has not been fully investigated for patients undergoing major spinal surgery. We hypothesized that the stress response after major spine surgery would be attenuated by continuous epidural anesthesia/analgesia with ropivacaine, fentanyl, and epinephrine. METHODS: Eighty-five patients were randomly allocated to 2 groups as follows: group E (n = 45) had epidural anesthesia and endotracheal anesthesia with sevoflurane during surgery and continuous epidural analgesia with ropivacaine, fentanyl, and epinephrine after surgery; group G (n = 40) had general anesthesia with sevoflurane and fentanyl and systemically administered opioids after surgery. Patient pain, nausea, mobility, and satisfaction were measured after surgery along with levels of cortisol, glucose, interleukin (IL)-1β, IL-6, and IL-10 during and after surgery. RESULTS: In group E, there were significantly less pain, less nausea, earlier mobility, and higher satisfaction than those in group G. Group E also experienced significantly less introperative and postoperative blood loss. Group E demonstrated lower levels of glucose, cortisol, IL-1β, IL-6, and IL-10 during the postoperative period. CONCLUSION: Combined epidural/general anesthesia and postoperative epidural analgesia produced better pain control, less bleeding, and a lower surgical stress response than general anesthesia with postoperative systemically administered narcotic analgesia. This technique deserves further study in the setting of major spinal surgery.

PURPOSE: The aim of this study was to determine the prevalence of a Segond avulsion fractures in acute ACL tears with ultrasound and to investigate whether other injuries can predict the avulsion. MATERIALS AND METHODS: One hundred thirty-eight ultrasound analyses of acute knee trauma were collected and scored for diagnosed injuries. The reports of patients with an ACL tear (N = 87) were evaluated to determine possible increased prevalence of Segond avulsion fracture with ultrasound. The associations between the diagnosed injuries and presence of a Segond avulsion were scored. The sports carried out at the time of injury were evaluated as possible prognostic factor. RESULTS: In 25/87 (29%) of the patients with an ACL tear, a Segond avulsion was observed in ultrasound. Lateral femoral condyle (LFC) impaction showed the strongest individual association with a Segond avulsion and was the best predicting variable. LFC impaction, sustained during low-risk pivoting sport, shows a stronger association with a Segond avulsion, as compared to LFC impaction sustained during high-risk pivoting sports. CONCLUSION: Ultrasound shows a higher prevalence of Segond avulsions as literature shows with MRI or radiography. LFC impaction is the best variable in predicting this type of avulsion. Ultrasound examination should be considered, if this fracture was not diagnosed with MRI or radiographic analysis. LEVEL OF EVIDENCE: IV.

Transparent objects are ubiquitous in human environments but, due to their special interaction with light, very few vision methods exist to identify them. We propose a new algorithm for recognition and pose estimation of rigid transparent objects which can deal with overlapping instances and cluttered environments. Using an active depth sensor for segmentation of the objects and 2d edge analysis for pose estimation, we are able to provide accurate identification and position. The proposed method is evaluated on a Microsoft Kinect and also on a PR2 robot. Results show that the algorithm is robust and accurate enough for robotic grasping and that it can be used in practical applications like table cleaning.

BACKGROUND: In many countries, gastric cancer is not diagnosed until an advanced stage. An Internet-based e-learning system to improve the ability of endoscopists to diagnose gastric cancer at an early stage was developed and was evaluated for its effectiveness. METHODS: The study was designed as a randomized controlled trial. After receiving a pre-test, participants were randomly allocated to either an e-learning or non-e-learning group. Only those in the e-learning group gained access to the e-learning system. Two months after the pre-test, both groups received a post-test. The primary endpoint was the difference between the two groups regarding the rate of improvement of their test results. FINDINGS: 515 endoscopists from 35 countries were assessed for eligibility, and 332 were enrolled in the study, with 166 allocated to each group. Of these, 151 participants in the e-learning group and 144 in the non-e-learning group were included in the analysis. The mean improvement rate (standard deviation) in the e-learning and non-e-learning groups was 1·24 (0·26) and 1·00 (0·16), respectively (P<0·001). INTERPRETATION: This global study clearly demonstrated the efficacy of an e-learning system to expand knowledge and provide invaluable experience regarding the endoscopic detection of early gastric cancer (R000012039).

Aim. To study the clinical course specifics of coronavirus disease 2019 (COVID-19) and comorbid conditions in COVID-19 survivors 3, 6, 12 months after recovery in the Eurasian region according to the AKTIV register. Material and methods. The AKTIV register was created at the initiative of the Eurasian Association of Therapists. The AKTIV register is divided into 2 parts: AKTIV 1 and AKTIV 2. The AKTIV 1 register currently includes 6300 patients, while in AKTIV 2 — 2770. Patients diagnosed with COVID-19 receiving in- and outpatient treatment have been anonymously included on the registry. The following 7 countries participated in the register: Russian Federation, Republic of Armenia, Republic of Belarus, Republic of Kazakhstan, Kyrgyz Republic, Republic of Moldova, Republic of Uzbekistan. This closed multicenter register with two nonoverlapping branches (in- and outpatient branch) provides 6 visits: 3 in-person visits during the acute period and 3 telephone calls after 3, 6, 12 months. Subject recruitment lasted from June 29, 2020 to October 29, 2020. Register will end on October 29, 2022. A total of 9 fragmentary analyzes of the registry data are planned. This fragment of the study presents the results of the post-hospitalization period in COVID-19 survivors after 3 and 6 months. Results. According to the AKTIV register, patients after COVID-19 are characterized by long-term persistent symptoms and frequent seeking for unscheduled medical care, including rehospitalizations. The most common causes of unplanned medical care are uncontrolled hypertension (HTN) and chronic coronary artery disease (CAD) and/or decompensated type 2 diabetes (T2D). During 3- and 6-month follow-up after hospitalization, 5,6% and 6,4% of patients were diagnosed with other diseases, which were more often presented by HTN, T2D, and CAD. The mortality rate of patients in the post-hospitalization period was 1,9% in the first 3 months and 0,2% for 4-6 months. The highest mortality rate was observed in the first 3 months in the group of patients with class II-IV heart failure, as well as in patients with cardiovascular diseases and cancer. In the pattern of death causes in the post-hospitalization period, following cardiovascular causes prevailed (31,8%): acute coronary syndrome, stroke, acute heart failure. Conclusion. According to the AKTIV register, the health status of patients after COVID-19 in a serious challenge for healthcare system, which requires planning adequate health system capacity to provide care to patients with COVID-19 in both acute and post-hospitalization period.

Childhood conduct disorder (CD) may originate in a stressful upbringing, and be associated with unusual physical or sexual development and thyroid dysfunction. We therefore explored circulating levels of hormones from adrenal, gonadal and growth hormone axes associated with stress, aggression and development in 28 CD patients and 13 age-matched healthy children (10-18 years old). The CD group had higher levels of dehydroepiandrosterone sulphate (DHEA-S), corticotropin (ACTH) and free tri-iodothyronine (fT(3)) if under 14 years. There were no differences for gonadal hormones or maturity ratings which were not associated with aggression. Smaller physical measures in CD children correlated with DHEA-S and growth factors (e.g. insulin-like growth factor I) increased ACTH and fT(3) correlated with restless-impulsive ratings, and DHEA-S with 'disruptive behaviour'. Imbalances in the adrenal and growth axes may have neurotropic repercussions in development.

New experimental results regarding "warm" water dimer spectra under equilibrium conditions are presented. An almost equidistant series of six peaks corresponding to the merged individual lines of the bound dimer with consecutive rotational quantum numbers is studied in the 188-258 GHz frequency range in water vapour over a broad range of pressures and temperatures relevant to the Earth's atmosphere. The series is a continuation of the sequence detected earlier at lower frequencies at room temperature. The signal-to-noise ratio of the observed spectra allowed investigating their evolution, when water vapour was diluted by atmospheric air with partial pressure from 0 up to 540 Torr. Analysis of the obtained spectra permitted determining the dimerization constant as well as the hydrogen bond dissociation energy and the dimer spectral parameters, including the average coefficient of collisional broadening of individual lines by water vapour and air. The manifestation of metastable states of the dimer in the observed spectra is assessed. The contribution of three possible pair states of water molecules to the second virial coefficient is evaluated over the broad range of temperatures. The work supports the significant role of the water dimer in atmospheric absorption and related processes.

BACKGROUND: Intrathecal neostigmine causes analgesia by inhibiting the breakdown of acetylcholine. Experimental data suggest that the production of endogenous nitric oxide is necessary for tonic cholinergic inhibition of spinal pain transmission. The purpose of this study was to determine whether association of transdermal nitroglycerine would enhance analgesia from a low dose of intrathecal neostigmine in patients undergoing gynecologic surgery during spinal anesthesia. METHODS: Forty-eight patients were randomized to one of four groups. Patients were premedicated with use of 0.05-0.1 mg/kg intravenous midazolam and received 15 mg bupivacaine plus 1 ml test drug intrathecally (saline or neostigmine, 5 microgram). Twenty to 30 min after the spinal puncture, a transdermal patch of either 5 mg nitroglycerin or placebo was applied. The control (Con) group received spinal saline and transdermal placebo. The neostigmine group received spinal neostigmine and transdermal placebo. The nitroglycerin group received spinal saline and a transdermal nitroglycerine patch. Finally, the neostigmine-nitroglycerin group received spinal neostigmine and transdermal nitroglycerine. Pain and adverse effects were evaluated using a 10-cm visual analog scale. RESULTS: Patients in the groups were similar regarding age, weight, height, and American Society of Anesthesiologists status. Sensory level to pin prick at 10 min, surgical duration, anesthetic duration, and visual analog scale score for pain at the time of administration of first rescue medication were statistically the same for all groups. The time to administration of first rescue analgesic (min) was longer in the neostigmine-nitroglycerin group (550 min; range, 458-1,440 min; median, 25-75th percentile) compared with the other groups (P < 0.001). The neostigmine-nitroglycerin group required fewer rescue analgesics in 24 h than did the control group (P < 0.0005), whereas the neostigmine group required less analgesics compared with the control group (P < 0.02). The incidence of perioperative adverse effects (nausea, vomiting, headache, back pain) was similar among groups (P > 0.05). CONCLUSION: Although neither intrathecal 5 microgram neostigmine alone nor transdermal nitroglycerine alone (5 mg/day) delayed the time to administration of first rescue analgesics, the combination of both provided an average of 14 h of effective postoperative analgesia after vaginoplasty, suggesting that transdermal nitroglycerin and the central cholinergic agent neostigmine may enhance each other's antinociceptive effects at the dose studied.

BACKGROUND: Approved botulinum toxin A products require reconstitution. AbobotulinumtoxinA solution for injection is a ready-to-use liquid formulation of abobotulinumtoxinA. OBJECTIVES: The objective of this study was to demonstrate the superior efficacy of abobotulinumtoxinA solution for injection to placebo and to test the noninferior efficacy of abobotulinumtoxinA solution for injection versus abobotulinumtoxinA (dry formulation) in cervical dystonia. METHODS: This was a phase-3, multicenter, prospective, double-blind, randomized, active, and placebo-controlled study (N = 369). Patients with cervical dystonia were randomized (3:3:1) to abobotulinumtoxinA solution for injection 500 U, abobotulinumtoxinA 500 U, or placebo. Following the double-blind phase, patients received abobotulinumtoxinA solution for injection, open-label, for up to 4 cycles. The primary outcome was change from baseline at week 4 of the Toronto Western Spasmodic Torticollis Rating Scale total score. Secondary measures included change from baseline or cycle baseline in Toronto Western Spasmodic Torticollis Rating Scale scores. RESULTS: At week 4, both products were superior to placebo (Toronto Western Spasmodic Torticollis Rating Scale total score least square mean decrease from baseline, abobotulinumtoxinA solution for injection 500 U -12.5, abobotulinumtoxinA 500 U -14.0, placebo -3.9; P < .0001 vs placebo). The noninferiority limit of 3 points in the Toronto Western Spasmodic Torticollis Rating Scale total score at week 4 was not met for abobotulinumtoxinA solution for injection versus abobotulinumtoxinA. Toronto Western Spasmodic Torticollis Rating Scale total score reductions were maintained for up to 4 cycles of abobotulinumtoxinA solution for injection open-label follow-up treatment. Safety profiles of abobotulinumtoxinA solution for injection and abobotulinumtoxinA were similar, with dysphagia and injection-site pain the most frequent drug-related adverse events. CONCLUSIONS: Although the predefined noninferiority criterion was not met, abobotulinumtoxinA solution for injection was similarly effective to freeze-dried abobotulinumtoxinA in reducing Toronto Western Spasmodic Torticollis Rating Scale total scores with a similar safety profile. AbobotulinumtoxinA solution for injection efficacy was maintained with chronic open-label treatment, and this novel formulation may add convenience as well as dosing accuracy to treatment with abobotulinumtoxinA. © 2016 International Parkinson and Movement Disorder Society.

BACKGROUND: Blonanserin is a second-generation antipsychotic used for the treatment of schizophrenia. This study determined the efficacy, safety and pharmacokinetics of a blonanserin transdermal patch in patients with acutely exacerbated schizophrenia. METHODS: This double-blind, multicenter, phase 3 study consisted of a 1-week observation period during which patients were treated with two patches of placebo, followed by a 6-week double-blind period where patients were randomized (1:1:1) to receive once-daily blonanserin 40 mg, blonanserin 80 mg, or placebo patches. The primary endpoint was the change from baseline in the total Positive and Negative Symptom Scale (PANSS) score. Safety assessments included treatment-emergent adverse events (TEAEs). RESULTS: Between December 2014 and October 2018, patients were recruited and randomly assigned to blonanserin 40 mg (n = 196), blonanserin 80 mg (n = 194), or placebo (n = 190); of these, 77.2% completed the study. Compared with placebo, blonanserin significantly improved PANSS total scores at 6 weeks (least square mean [LSM] difference vs placebo: -5.6 with blonanserin 40 mg; 95% confidence interval [CI] -9.6, -1.6; adjusted p = 0.007, and - 10.4 with blonanserin 80 mg; 95% CI -14.4, -6.4; adjusted p < 0.001). Blonanserin was well tolerated; the most common TEAEs reported were application-site erythema and pruritus, akathisia, tremor, and insomnia. CONCLUSIONS: Blonanserin transdermal patch improved the symptoms of acute schizophrenia with acceptable tolerability.

OBJECTIVES: Netakimab (NTK) is a humanised monoclonal antibody targeting interleukin-17A, previously investigated in a phase 1 trial in healthy volunteers. Here, we report the results of a phase 2 trial, conducted to assess safety and pharmacokinetics (PK), to establish a therapeutic dose of NTK in a target population of patients with active ankylosing spondylitis (AS). METHODS: 89 patients with active AS, despite non-steroidal anti-inflammatory (NSAID) drug treatment, were randomised to receive 40, 80 or 120 mg of subcutaneous NTK or placebo at weeks 0, 1, 2 and q2wk thereafter until week 12. The primary endpoint was to achieve a proportion of patients with ≥20% improvement in Assessment of Spondyloarthritis. RESULTS: Rates of ASAS20 response at week 16 for NTK with 95%CI for difference in ASAS20 rates NTK vs. placebo were 72.73% [1.69%;58.05%], 81.82% [12.36%;65.56%], 90.91% [23.71%;72.39%] at doses of 40, 80 and 120 mg. The response rate in the placebo arm was 42.86%. The pre-specified margin of clinically non-meaningful difference was 10%. Superiority to placebo was confirmed for doses 80 and 120 mg. The most frequent adverse events (AEs) were lymphocytosis, neutropenia, and asymptomatic bacteriuria. No dose-dependent toxicity or serious adverse events (SAEs) were observed. The most effective dose with the fastest response onset and favourable safety profile was 120 mg. CONCLUSIONS: The data obtained demonstrate the efficacy and favourable safety profile of NTK in active AS. Clinical development of NTK will be continued in a phase 3 trial aimed to evaluate the efficacy of 1-year treatment with NTK 120 mg in patients with AS.

A Hamiltonian system having a saddle-focus singular point with a transversal homoclinic orbit is considered. The bifurcations that occur upon a variation of the Hamiltonian are studied. Reconstructions of a symbolic system describing the hyperbolic set are investigated. Bifurcations linked with the appearance of Smale horseshoes are pointed out. The results are applied to a system determining traveling-wave solutions of the Landau-Lifshitz equation. Multisolitons with any number of humps can exist.