Multi-messenger observations of a binary neutron star merger

On 2017 August 17 a binary neutron star coalescence candidate (later designated GW170817) with merger time 12:41:04 UTC was observed through gravitational waves by the Advanced LIGO and Advanced Virgo detectors. The Fermi Gamma-ray Burst Monitor independently detected a gamma-ray burst (GRB 170817A) with a time delay of ~1.7 s with respect to the merger time. From the gravitational-wave signal, the source was initially localized to a sky region of 31 deg2 at a luminosity distance of 40+8-8 Mpc and with component masses consistent with neutron stars. The component masses were later measured to be in the range 0.86 to 2.26 Mo. An extensive observing campaign was launched across the electromagnetic spectrum leading to the discovery of a bright optical transient (SSS17a, now with the IAU identification of AT 2017gfo) in NGC 4993 (at ~40 Mpc) less than 11 hours after the merger by the One- Meter, Two Hemisphere (1M2H) team using the 1 m Swope Telescope. The optical transient was independently detected by multiple teams within an hour. Subsequent observations targeted the object and its environment. Early ultraviolet observations revealed a blue transient that faded within 48 hours. Optical and infrared observations showed a redward evolution over ~10 days. Following early non-detections, X-ray and radio emission were discovered at the transient’s position ~9 and ~16 days, respectively, after the merger. Both the X-ray and radio emission likely arise from a physical process that is distinct from the one that generates the UV/optical/near-infrared emission. No ultra-high-energy gamma-rays and no neutrino candidates consistent with the source were found in follow-up searches. These observations support the hypothesis that GW170817 was produced by the merger of two neutron stars in NGC4993 followed by a short gamma-ray burst (GRB 170817A) and a kilonova/macronova powered by the radioactive decay of r-process nuclei synthesized in the ejecta

Comparison of digitally assessed quality of posterior crown preparations with and without previous practice on patient-specific 3D printed teeth models

INTRODUCTION: 3D-printing technology can provide customizable simulations, but its effects on patient care quality have not been well studied. This study aimed to assess the impact of practicing with patient-specific 3D-printed teeth models on the quality of 'patients' dental preparations performed by students transitioning to clinical training. Accordingly, the quality of posterior crown preparations was evaluated by objectively analyzing digital scans and grades in two groups: the study group, which practiced beforehand with patient-specific 3D-printed teeth models, and the control group, which did not practice with these models. METHODS: All seventy-eight fourth-year dental students who had just finished their fixed prosthodontics course at the simulation laboratory with training on phantom heads and without previous clinical experience in crown preparations were invited to participate in the study. sixty-eight agreed to take part and were randomly divided into a study group that practiced crown preparations on 3D-printed models of their own 'patient's teeth and a control group that did not practice with 3D-printed models and started their clinical work straightforward after simulation training. Students completed validated perception questionnaires on self-confidence and clinical skills before and after the protocol, which were compared using a chi-squared test. Crown preparations performed on 3D-printed models and then on patients were digitally scanned and objectively graded by prepCheck® software for critical parameters, such as undercuts, taper, and occlusion reduction. Non-parametric tests were used to compare preparations on 3D-printed models and on patients performed by the study group and those on patients made by the control group. RESULTS: Initially, both groups reported similar perceptions of self-confidence and clinical skills levels. The study group significantly improved both aspects after the protocol. Analysis of the scanned preparations demonstrated that the study group removed less tooth structure from actual patients than from the initial 3D-printed models. In contrast, the control group showed excess occlusal clearance in their patients compared to the study group. CONCLUSIONS: Practicing patient-specific 3D-printed teeth before performing procedures clinically appears to enhance preparation quality and minimize unnecessary tooth reduction in early clinical experiences

Η χρήση της θεραπευτικής υποθερμίας σε ασθενείς με καρδιολογικά νοσήματα

Introduction: Cardiovascular disease is the leading cause of death worldwide. Therapeutic hypothermia is used as a type of treatment, usually for people who have had a heart attack. The application of therapeutic hypothermia is applied when the heart begins to function again. The use of therapeutic hypothermia is done by lowering the body temperature to 32 ° C - 34 ° C. This process usually takes about 24 hours. Aim: To investigate the evaluation of the relationship between therapeutic hypothermia and survival after cardiac arrest. Even if pre-hospital cooling leads to higher success rates and the survival and neurological outcome of survivors is improved Material and Method: Systematic research of literature in the databases PubMed, Cinahl. The procedure is based on the following words: "therapeutic hypothermia" or "induced hypothermia" or "cooling treatment" or "cardiac arrest" or "cardiac arrest" or "cardiopulmonary resuscitation" or "cardiopulmonary resuscitation" or "resuscitation" or "external cardiac resuscitation" "hospital review" or "literature review" or "literature review" or "post-analysis" or "systematic review" or "systematic review of the literature" "randomized controlled trials" or rct or "randomized controlled trials" or "control tests" or "randomized controlled trials" or "randomized controlled trials" or testing "or" randomized controlled trial "with the specific words" AND "," OR "," NOT "to the user of the potential discrimination. Results: The search led to 10 articles that met all the criteria. It has been found that there is no increase in heart rate recurrence rates. However, there appeared to be an increased incidence of pulmonary edema in hospitalized patients. Conclusion: : With the use of therapeutic hypothermia, it appeared that there was no statistically significant difference between the patients who were treated and those who were not.Εισαγωγή: Τα καρδιαγγειακά νοσήματα είναι η κυρίαρχη αιτία θανάτου διεθνώς. Η θεραπευτική υποθερμία χρησιμοποιείται ως ένας τύπος θεραπείας, συνήθως για άτομα που έχουν υποστεί καρδιακή. Η εφαρμογή της θεραπευτικής υποθερμίας εφαρμόζεται όταν αρχίσει ξανά η λειτουργία της καρδίας. Η χρήση της θεραπευτικής υποθερμίας γίνεται με τη θερμοκρασία του σώματος να μειώνεται γύρο στους 32 °C - 34 °C. Συνήθως η διαδικασία αυτή διάρκεια περίπου 24 ώρες. Σκοπός: Να διερευνηθεί αξιολόγηση της σχέσης μεταξύ της θεραπευτικής υποθερμίας και της επιβίωσης μετά από καρδιακή ανακοπή. Ακόμα αν η προ - νοσοκομειακή ψύξη οδηγεί σε υψηλότερα ποσοστά επιτυχίας και αν είναι βελτιωμένη η επιβίωση και το νευρολογικό αποτέλεσμα των επιζώντων. Υλικό και Μέθοδος: Έγινε συστηματική αναζήτηση βιβλιογραφίας στις βάσεις δεδομένων PubMed, Cinahl. Η αναζήτηση έγινε με βάση τις πάρακατω λέξιες κλειδιά: “therapeutic hypothermia” or “induced hypothermia” or “cooling therapy” “cardiac arrest” or “heart arrest” or “cardiopulmonary arrest” or “cardiopulmonary resuscitation” or “resuscitation” or “out of hospital cardiac arrest”“review of literature” or “literature review” or “meta-analysis” or “systematic review” or “systematic literature review” “randomized controlled trials” or rct or “randomised control trials” or “randomized clinical trial” or “randomized controlled study” με τις συνδετικές λέξεις «AND», «OR», «NOT» με όλους του πιθανούς συνδυασμούς. Αποτελέσματα: Η αναζήτηση οδήγησε σε 10 άρθρα που πληρούσαν όλα τα κριτήρια. Διαπιστώθηκε ότι δεν υπάρχει αύξηση στα ποσοστά επανεμφάνισης καρδιακού επεισοδίου. Φάνηκε όμως να υπάρχει ένα αυξημένο ποσοστό εμφάνισης πνευμονικού οιδήματος σε ασθενείς που νοσηλευόνταν. Συμπέρασμα: Με τη χρήση της θεραπευτικής υποθερμίας φάνηκε ότι δεν υπάρχει στατιστικά σημαντική διαφορά στους ασθενείς που τους εφαρμόστηκε και σε αυτούς που δεν εφαρμόστηκε.Complete

Adjuvant anastrozole versus exemestane versus letrozole, upfront or after 2 years of tamoxifen, in endocrine-sensitive breast cancer (FATA-GIM3): a randomised, phase 3 trial

Background: Uncertainty exists about the optimal schedule of adjuvant treatment of breast cancer with aromatase inhibitors and, to our knowledge, no trial has directly compared the three aromatase inhibitors anastrozole, exemestane, and letrozole. We investigated the schedule and type of aromatase inhibitors to be used as adjuvant treatment for hormone receptor-positive early breast cancer. Methods: FATA-GIM3 is a multicentre, open-label, randomised, phase 3 trial of six different treatments in postmenopausal women with hormone receptor-positive early breast cancer. Eligible patients had histologically confirmed invasive hormone receptor-positive breast cancer that had been completely removed by surgery, any pathological tumour size, and axillary nodal status. Key exclusion criteria were hormone replacement therapy, recurrent or metastatic disease, previous treatment with tamoxifen, and another malignancy in the previous 10 years. Patients were randomly assigned in an equal ratio to one of six treatment groups: oral anastrozole (1 mg per day), exemestane (25 mg per day), or letrozole (2\ub75 mg per day) tablets upfront for 5 years (upfront strategy) or oral tamoxifen (20 mg per day) for 2 years followed by oral administration of one of the three aromatase inhibitors for 3 years (switch strategy). Randomisation was done by a computerised minimisation procedure stratified for oestrogen receptor, progesterone receptor, and HER2 status; previous chemotherapy; and pathological nodal status. Neither the patients nor the physicians were masked to treatment allocation. The primary endpoint was disease-free survival. The minimum cutoff to declare superiority of the upfront strategy over the switch strategy was assumed to be a 2% difference in disease-free survival at 5 years. Primary efficacy analyses were done by intention to treat; safety analyses included all patients for whom at least one safety case report form had been completed. Follow-up is ongoing. This trial is registered with the European Clinical Trials Database, number 2006-004018-42, and ClinicalTrials.gov, number NCT00541086. Findings: Between March 9, 2007, and July 31, 2012, 3697 patients were enrolled into the study. After a median follow-up of 60 months (IQR 46\u201372), 401 disease-free survival events were reported, including 211 (11%) of 1850 patients allocated to the switch strategy and 190 (10%) of 1847 patients allocated to upfront treatment. 5-year disease-free survival was 88\ub75% (95% CI 86\ub77\u201390\ub70) with the switch strategy and 89\ub78% (88\ub72\u201391\ub72) with upfront treatment (hazard ratio 0\ub789, 95% CI 0\ub773\u20131\ub708; p=0\ub723). 5-year disease-free survival was 90\ub70% (95% CI 87\ub79\u201391\ub77) with anastrozole (124 events), 88\ub70% (85\ub78\u201389\ub79) with exemestane (148 events), and 89\ub74% (87\ub73 to 91\ub71) with letrozole (129 events; p=0\ub724). No unexpected serious adverse reactions or treatment-related deaths occurred. Musculoskeletal side-effects were the most frequent grade 3\u20134 events, reported in 130 (7%) of 1761 patients who received the switch strategy and 128 (7%) of 1766 patients who received upfront treatment. Grade 1 musculoskeletal events were more frequent with the upfront schedule than with the switch schedule (924 [52%] of 1766 patients vs 745 [42%] of 1761 patients). All other grade 3\u20134 adverse events occurred in less than 2% of patients in either group. Interpretation: 5 years of treatment with aromatase inhibitors was not superior to 2 years of tamoxifen followed by 3 years of aromatase inhibitors. None of the three aromatase inhibitors was superior to the others in terms of efficacy. Therefore, patient preference, tolerability, and financial constraints should be considered when deciding the optimal treatment approach in this setting. Funding: Italian Drug Agency

Multiple Myeloma Treatment in Real-world Clinical Practice: Results of a Prospective, Multinational, Noninterventional Study

Multiple myeloma (MM) remains an incurable disease, with little information available on its management in real-world clinical practice. The results of the present prospective, noninterventional observational study revealed great diversity in the treatment regimens used to treat MM. Our results also provide data to inform health economic, pharmacoepidemiologic, and outcomes research, providing a framework for the design of protocols to improve the outcomes of patients with MM. Background: The present prospective, multinational, noninterventional study aimed to document and describe real-world treatment regimens and disease progression in multiple myeloma (MM) patients. Patients and Methods: Adult patients initiating any new MM therapy from October 2010 to October 2012 were eligible. A multistage patient/site recruitment model was applied to minimize the selection bias; enrollment was stratified by country, region, and practice type. The patient medical and disease features, treatment history, and remission status were recorded at baseline, and prospective data on treatment, efficacy, and safety were collected electronically every 3 months. Results: A total of 2358 patients were enrolled. Of these patients, 775 and 1583 did and did not undergo stem cell transplantation (SCT) at any time during treatment, respectively. Of the patients in the SCT and non-SCT groups, 49%, 21%, 14%, and 15% and 57%, 20%, 12% and 10% were enrolled at treatment line 1, 2, 3, and ≥ 4, respectively. In the SCT and non-SCT groups, 45% and 54% of the patients had received bortezomib-based therapy without thalidomide/lenalidomide, 12% and 18% had received thalidomide/lenalidomide-based therapy without bortezomib, and 30% and 4% had received bortezomib plus thalidomide/lenalidomide-based therapy as frontline treatment, respectively. The corresponding proportions of SCT and non-SCT patients in lines 2, 3, and ≥ 4 were 45% and 37%, 30% and 37%, and 12% and 3%, 33% and 27%, 35% and 32%, and 8% and 2%, and 27% and 27%, 27% and 23%, and 6% and 4%, respectively. In the SCT and non-SCT patients, the overall response rate was 86% to 97% and 64% to 85% in line 1, 74% to 78% and 59% to 68% in line 2, 55% to 83% and 48% to 60% in line 3, and 49% to 65% and 36% and 45% in line 4, respectively, for regimens that included bortezomib and/or thalidomide/lenalidomide. Conclusion: The results of our prospective study have revealed great diversity in the treatment regimens used to manage MM in real-life practice. This diversity was linked to factors such as novel agent accessibility and evolving treatment recommendations. Our results provide insight into associated clinical benefits. © 2018 The Author

Multi-messenger Observations of a Binary Neutron Star Merger

International audienceOn 2017 August 17 a binary neutron star coalescence candidate (later designated GW170817) with merger time 12:41:04 UTC was observed through gravitational waves by the Advanced LIGO and Advanced Virgo detectors. The Fermi Gamma-ray Burst Monitor independently detected a gamma-ray burst (GRB 170817A) with a time delay of $\sim 1.7\,{\rm{s}}$ with respect to the merger time. From the gravitational-wave signal, the source was initially localized to a sky region of 31 deg(2) at a luminosity distance of ${40}_{-8}^{+8}$ Mpc and with component masses consistent with neutron stars. The component masses were later measured to be in the range 0.86 to 2.26 $\,{M}_{\odot }$. An extensive observing campaign was launched across the electromagnetic spectrum leading to the discovery of a bright optical transient (SSS17a, now with the IAU identification of AT 2017gfo) in NGC 4993 (at $\sim 40\,{\rm{Mpc}}$) less than 11 hours after the merger by the One-Meter, Two Hemisphere (1M2H) team using the 1 m Swope Telescope. The optical transient was independently detected by multiple teams within an hour. Subsequent observations targeted the object and its environment. Early ultraviolet observations revealed a blue transient that faded within 48 hours. Optical and infrared observations showed a redward evolution over ∼10 days. Following early non-detections, X-ray and radio emission were discovered at the transient’s position $\sim 9$ and $\sim 16$ days, respectively, after the merger. Both the X-ray and radio emission likely arise from a physical process that is distinct from the one that generates the UV/optical/near-infrared emission. No ultra-high-energy gamma-rays and no neutrino candidates consistent with the source were found in follow-up searches. These observations support the hypothesis that GW170817 was produced by the merger of two neutron stars in NGC 4993 followed by a short gamma-ray burst (GRB 170817A) and a kilonova/macronova powered by the radioactive decay of r-process nuclei synthesized in the ejecta