Efficacy, safety, and improved tolerability of travoprost BAK-free ophthalmic solution compared with prior prostaglandin therapy

J Charles Henry1, James H Peace2, Jeanette A Stewart3,4, William C Stewart3,41Little Rock Eye Clinic, Little Rock, AR, USA; 2Diabetic Eye Medical Clinic, Inglewood, CA, USA; 3PRN Pharmaceutical Research Network, LLC, Dallas,TX, USA; 4Carolina Eye Institute, University of South Carolina, School of Medicine, Columbia, SC, USAPurpose: To evaluate the efficacy, safety and tolerability of changing to travoprost BAK-free from prior prostaglandin therapy in patients with primary open-angle glaucoma or ocular hypertension.Design: Prospective, multi-center, historical control study.Methods: Patients treated with latanoprost or bimatoprost who needed alternative therapy due to tolerability issues were enrolled. Patients were surveyed using the Ocular Surface Disease Index (OSDI) to evaluate OSD symptoms prior to changing to travoprost BAK-free dosed once every evening. Patients were re-evaluated 3 months later.Results: In 691 patients, travoprost BAK-free demonstrated improved mean OSDI scores compared to either latanoprost or bimatoprost (p < 0.0001). Patients having any baseline OSD symptoms (n = 235) demonstrated significant improvement after switching to travoprost BAK-free (p < 0.0001). In 70.2% of these patients, symptoms were reduced in severity by at least 1 level. After changing medications to travoprost BAK-free, mean intraocular pressure (IOP) was significantly decreased (p < 0.0001). Overall, 72.4% preferred travoprost BAK-free (p < 0.0001, travoprost BAK-free vs prior therapy). Travoprost BAK-free demonstrated less conjunctival hyperemia than either prior therapy (p < 0.0001).Conclusions: Patients previously treated with a BAK-preserved prostaglandin analog who are changed to travoprost BAK-free have clinically and statistically significant improvement in their OSD symptoms, decreased hyperemia, and equal or better IOP control.Keywords: glaucoma, prostaglandin analog, travoprost, latanoprost, bimatoprost, preservative, benzalkonium chloride, ocular surface diseas

The Society for Immunotherapy of Cancer consensus statement on immunotherapy for the treatment of prostate carcinoma.

Prostate cancer is the most commonly diagnosed malignancy and second leading cause of cancer death among men in the United States. In recent years, several new agents, including cancer immunotherapies, have been approved or are currently being investigated in late-stage clinical trials for the management of advanced prostate cancer. Therefore, the Society for Immunotherapy of Cancer (SITC) convened a multidisciplinary panel, including physicians, nurses, and patient advocates, to develop consensus recommendations for the clinical application of immunotherapy for prostate cancer patients. To do so, a systematic literature search was performed to identify high-impact papers from 2006 until 2014 and was further supplemented with literature provided by the panel. Results from the consensus panel voting and discussion as well as the literature review were used to rate supporting evidence and generate recommendations for the use of immunotherapy in prostate cancer patients. Sipuleucel-T, an autologous dendritic cell vaccine, is the first and currently only immunotherapeutic agent approved for the clinical management of metastatic castrate resistant prostate cancer (mCRPC). The consensus panel utilized this model to discuss immunotherapy in the treatment of prostate cancer, issues related to patient selection, monitoring of patients during and post treatment, and sequence/combination with other anti-cancer treatments. Potential immunotherapies emerging from late-stage clinical trials are also discussed. As immunotherapy evolves as a therapeutic option for the treatment of prostate cancer, these recommendations will be updated accordingly

Drones y el orden legal internacional. Tecnología, estrategia y largas cadenas de acción

The main thesis of this article is that the increasing recourse to the use of unmanned aerial systems in asymmetric warfare and the beginning routinization of U.S. drone operations represent part of an evolutionary change in the spatial ordering of global politics -- Using a heuristic framework based on actor-network theory, it is argued that practices of panoptic observation and selective airstrikes, being in need of legal justification, contribute to a reterritorialization of asymmetric conflicts -- Under a new normative spatial regime, a legal condition of state immaturity is constructed, which establishes a zone of conditional sovereignty subject to transnational aerial policing -- At the same time, this process is neither a deterministic result of the new technology nor a deliberate effect of policies to which drones are merely neutral instruments -- Rather, military technology and political decisions both form part of a long chain of action which has evolved under the specific circumstances of recent military interventionsEste artículo propone que la creciente utilización de sistemas aéreos no tripulados y la rutinización de sus operaciones en guerras asimétricas representan parte de un cambio evolutivo en el ordenamiento espacial de la política global -- Utilizando un marco heurístico basado en la teoría del actor-red, se argumenta que las prácticas de observación panóptica y ataques aéreos selectivos, carentes aún de justificación legal, contribuyen a una reterritorialización de los conflictos asimétricos -- En virtud de un nuevo régimen normativo espacial, se construye una condición legal de inmadurez estatal que facilita el establecimiento de una zona de soberanía condicionada, sometida a la vigilancia aérea transnacional -- Al mismo tiempo, esté proceso no es resultado predeterminado de la nueva tecnología, ni efecto deliberado de decisiones políticas para las que los drones son solo instrumentos neutros -- Antes que ello, la tecnología militar y las decisiones políticas forman parte importante de una larga cadena de acción que se ha desarrollado en las circunstancias específicas de intervenciones militares más reciente

Genome Sequences of Mycobacteriophages Amgine, Amohnition, Bella96, Cain, DarthP, Hammy, Krueger, LastHope, Peanam, PhelpsODU, Phrank, SirPhilip, Slimphazie, and Unicorn

We report the genome sequences of 14 cluster K mycobacteriophages isolated using Mycobacterium smegmatis mc2155 as host. Four are closely related to subcluster K1 phages, and 10 are members of subcluster K6. The phage genomes span considerable sequence diversity, including multiple types of integrases and integration sites

Replication and single-cycle delivery of SARS-CoV-2 replicons

Molecular virology tools are critical for basic studies of the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) and for developing new therapeutics. There remains a need for experimental systems that do not rely on viruses capable of spread that could potentially be used in lower containment settings. Here, we develop spike-deleted SARS-CoV-2 self-replicating RNAs using a yeast-based reverse genetics system. These non-infectious self-replicating RNAs, or replicons, can be trans-complemented with viral glycoproteins to generate Replicon Delivery Particles (RDPs) for single-cycle delivery into a range of cell types. This SARS-CoV-2 replicon system represents a convenient and versatile platform for antiviral drug screening, neutralization assays, host factor validation, and characterizing viral variants

Impact of opioid-free analgesia on pain severity and patient satisfaction after discharge from surgery: multispecialty, prospective cohort study in 25 countries

Background: Balancing opioid stewardship and the need for adequate analgesia following discharge after surgery is challenging. This study aimed to compare the outcomes for patients discharged with opioid versus opioid-free analgesia after common surgical procedures.Methods: This international, multicentre, prospective cohort study collected data from patients undergoing common acute and elective general surgical, urological, gynaecological, and orthopaedic procedures. The primary outcomes were patient-reported time in severe pain measured on a numerical analogue scale from 0 to 100% and patient-reported satisfaction with pain relief during the first week following discharge. Data were collected by in-hospital chart review and patient telephone interview 1 week after discharge.Results: The study recruited 4273 patients from 144 centres in 25 countries; 1311 patients (30.7%) were prescribed opioid analgesia at discharge. Patients reported being in severe pain for 10 (i.q.r. 1-30)% of the first week after discharge and rated satisfaction with analgesia as 90 (i.q.r. 80-100) of 100. After adjustment for confounders, opioid analgesia on discharge was independently associated with increased pain severity (risk ratio 1.52, 95% c.i. 1.31 to 1.76; P < 0.001) and re-presentation to healthcare providers owing to side-effects of medication (OR 2.38, 95% c.i. 1.36 to 4.17; P = 0.004), but not with satisfaction with analgesia (beta coefficient 0.92, 95% c.i. -1.52 to 3.36; P = 0.468) compared with opioid-free analgesia. Although opioid prescribing varied greatly between high-income and low- and middle-income countries, patient-reported outcomes did not.Conclusion: Opioid analgesia prescription on surgical discharge is associated with a higher risk of re-presentation owing to side-effects of medication and increased patient-reported pain, but not with changes in patient-reported satisfaction. Opioid-free discharge analgesia should be adopted routinely

2022 Roadmap on integrated quantum photonics

AbstractIntegrated photonics will play a key role in quantum systems as they grow from few-qubit prototypes to tens of thousands of qubits. The underlying optical quantum technologies can only be realized through the integration of these components onto quantum photonic integrated circuits (QPICs) with accompanying electronics. In the last decade, remarkable advances in quantum photonic integration have enabled table-top experiments to be scaled down to prototype chips with improvements in efficiency, robustness, and key performance metrics. These advances have enabled integrated quantum photonic technologies combining up to 650 optical and electrical components onto a single chip that are capable of programmable quantum information processing, chip-to-chip networking, hybrid quantum system integration, and high-speed communications. In this roadmap article, we highlight the status, current and future challenges, and emerging technologies in several key research areas in integrated quantum photonics, including photonic platforms, quantum and classical light sources, quantum frequency conversion, integrated detectors, and applications in computing, communications, and sensing. With advances in materials, photonic design architectures, fabrication and integration processes, packaging, and testing and benchmarking, in the next decade we can expect a transition from single- and few-function prototypes to large-scale integration of multi-functional and reconfigurable devices that will have a transformative impact on quantum information science and engineering