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 Analysis of Commercially Available Kratom Products in Richmond, Virginia

Kratom is a novel psychoactive substance that has gained popularity within the past ten years. Originating from Southeast Asia, the leaves of the Mitragyna speciosa tree contain two principal alkaloids, mitragynine and 7-hydroxymitragynine, that play a key role in opioid-like effects. Twenty-nine kratom products were obtained from tobacco shops in the Richmond, Virginia area, including powders, teas, capsules, extracts, and a carbonated beverage. Samples were analyzed using Direct Analysis in Real Time-Mass Spectrometry (DART-MS) for kratom alkaloids, labeled ingredients, and other possible organic compounds. Inductively Coupled Plasma-Optical Emission Spectroscopy (ICP-OES) was used to quantitate aluminum, arsenic, copper, iron, magnesium, nickel, and lead with yttrium as the internal standard. Mitragynine and 7-hydroxymitragynine were present in every kratom sample. Kratom tea samples were found to have up to 20 times the tolerable upper intake of manganese. Overexposure to manganese can lead to Parkinsonian symptoms including tremors, dystonia, and facial muscle spasms. Gas Chromatography-Mass Spectrometry (GC-MS) was used to qualitatively confirm the presence of alkaloids and differentiate diastereomers. One non-kratom product was analyzed and was found to contain phenibut, an anxiolytic and nootropic substance. Phenibut was not listed on the label of this product. This work contributes to bring attention to the absence of quality control standards on kratom manufacturers as well as proper labeling of products sold at smoke and tobacco shops, prompting a public health concern due to the association of toxic metal levels in commercial kratom products.https://scholarscompass.vcu.edu/gradposters/1175/thumbnail.jp

A Study of the Safety and Efficacy of Travoprost 0.004%/Timolol 0.5% Ophthalmic Solution Compared to Latanoprost 0.005% and Timolol 0.5% Dosed Concomitantly in Patients with Open-Angle Glaucoma or Ocular Hypertension

Background/Aims: To compare the intraocular pressure (IOP)-lowering efficacy of travoprost 0.004%/timolol 0.5% in fixed combination with the unfixed combination of latanoprost 0.005% and timolol 0.5% in open-angle glaucoma or ocular hypertension patients with IOP levels below 18 mmHg on the unfixed combination of latanoprost 0.005% and timolol 0.5%. Methods: Following a 30-day open-label run-in with latanoprost QD PM and timolol QD AM, subjects with intraocular pressure below 18 mmHg were randomized to continue concomitant latanoprost QD PM and timolol QD AM or switch to travoprost 0.004%/timolol 0.5% QD AM and vehicle QD PM in masked fashion and were followed for 3 months. The primary efficacy endpoint was mean IOP reduction from baseline. Results: There were no clinically relevant or statistically significant differences in mean IOP, mean IOP change from baseline, or percentage IOP change from baseline between the two treatment groups. Between-group differences in mean IOP were within ±0.3 mmHg at all time points (p ≥ 0.384), and between-group differences in mean IOP change from baseline were within ±0.4 mmHg at all time points. Overall, 88% of patients whose IOP was less than 18 mmHg on the unfixed combination of latanoprost and timolol remained well controlled on the same regimen in the masked portion of the study, compared with 92% who remained well controlled after switching to travoprost/timolol. Conclusion: Travoprost 0.004%/timolol 0.5% administered once daily and concomitant administration of timolol 0.5% and latanoprost 0.005% produce similar maintenance of IOP-lowering effect in patients who were previously well controlled on concomitant administration of latanoprost and timolol. Patients who are well controlled on latanoprost and timolol concomitant therapy can be switched to once-daily therapy with travoprost 0.004%/timolol 0.5% with no expected compromise in the safety and efficacy of their treatment

A study of the safety and efficacy of travoprost 0.004%/timolol 0.5% ophthalmic solution compared to latanoprost 0.005% and timolol 0.5% dosed concomitantly in patients with open-angle glaucoma or ocular hypertension

Douglas J Rhee1, James H Peace2, Sushanta Mallick3, Theresa A Landry3, Michael VW Bergamini3, and the Study Group*1Massachusetts Eye and Ear Infirmary, Harvard University, Boston, MA, USA; 2Diabetic Eye Medical Clinic, Inglewood, CA, USA; 3Alcon Laboratories, Inc., Ft. Worth, TX, USA; *Study Group members listed in AppendixBackground/Aims: To compare the intraocular pressure (IOP)-lowering efficacy of travoprost 0.004%/timolol 0.5% in fixed combination with the unfixed combination of latanoprost 0.005% and timolol 0.5% in open-angle glaucoma or ocular hypertension patients with IOP levels below 18 mmHg on the unfixed combination of latanoprost 0.005% and timolol 0.5%.Methods: Following a 30-day open-label run-in with latanoprost QD PM and timolol QD AM, subjects with intraocular pressure below 18 mmHg were randomized to continue concomitant latanoprost QD PM and timolol QD AM or switch to travoprost 0.004%/timolol 0.5% QD AM and vehicle QD PM in masked fashion and were followed for 3 months. The primary efficacy endpoint was mean IOP reduction from baseline.Results: There were no clinically relevant or statistically significant differences in mean IOP, mean IOP change from baseline, or percentage IOP change from baseline between the two treatment groups. Between-group differences in mean IOP were within ±0.3 mmHg at all time points (p ≥ 0.384), and between-group differences in mean IOP change from baseline were within ±0.4 mmHg at all time points. Overall, 88% of patients whose IOP was less than 18 mmHg on the unfixed combination of latanoprost and timolol remained well controlled on the same regimen in the masked portion of the study, compared with 92% who remained well controlled after switching to travoprost/timolol.Conclusion: Travoprost 0.004%/timolol 0.5% administered once daily and concomitant administration of timolol 0.5% and latanoprost 0.005% produce similar maintenance of IOP-lowering effect in patients who were previously well controlled on concomitant administration of latanoprost and timolol. Patients who are well controlled on latanoprost and timolol concomitant therapy can be switched to once-daily therapy with travoprost 0.004%/timolol 0.5% with no expected compromise in the safety and efficacy of their treatment.Keywords: travoprost, timolol, glaucoma, intraocular pressure, fixed combinatio

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

The Iceland Microcontinent and a continental Greenland-Iceland-Faroe Ridge

The breakup of Laurasia to form the Northeast Atlantic Realm was the culmination of a long period of tectonic unrest extending back to the Late Palaeozoic. Breakup was prolonged and complex and disintegrated an inhomogeneous collage of cratons sutured by cross-cutting orogens. Volcanic rifted margins formed, which are blanketed by lavas and underlain variously by magma-inflated, extended continental crust and mafic high-velocity lower crust of ambiguous and probably partly continental provenance. New rifts formed by diachronous propagation along old zones of weakness. North of the Greenland-Iceland-Faroe Ridge the newly forming rift propagated south along the Caledonian suture. South of the Greenland-Iceland-Faroe Ridge it propagated north through the North Atlantic Craton along an axis displaced ~ 150 km to the west of the northern rift. Both propagators stalled where the confluence of the Nagssugtoqidian and Caledonian orogens formed a transverse barrier. Thereafter, the ~ 400-km-wide latitudinal zone between the stalled rift tips extended in a distributed, unstable manner along multiple axes of extension that frequently migrated or jumped laterally with shearing occurring between them in diffuse transfer zones. This style of deformation continues to the present day. It is the surface expression of underlying magma-assisted stretching of ductile mid- and lower continental crust which comprises the Icelandic-type lower crust that underlies the Greenland-Iceland-Faroe Ridge. This, and probably also one or more full-crustal-thickness microcontinents incorporated in the Ridge, are capped by surface lavas. The Greenland-Iceland-Faroe Ridge thus has a similar structure to some zones of seaward-dipping reflectors. The contemporaneous melt layer corresponds to the 3–10 km thick Icelandic-type upper crust plus magma emplaced in the ~ 10–30-km-thick Icelandic-type lower crust. This model can account for seismic and gravity data that are inconsistent with a gabbroic composition for Icelandic-type lower crust, and petrological data that show no reasonable temperature or source composition could generate the full ~ 40-km thickness of Icelandic-type crust observed. Numerical modeling confirms that extension of the continental crust can continue for many tens of Myr by lower-crustal flow from beneath the adjacent continents. Petrological estimates of the maximum potential temperature of the source of Icelandic lavas are up to 1450 °C, no more than ~ 100 °C hotter than MORB source. The geochemistry is compatible with a source comprising hydrous peridotite/pyroxenite with a component of continental mid- and lower crust. The fusible petrology, high source volatile contents, and frequent formation of new rifts can account for the true ~ 15–20 km melt thickness at the moderate temperatures observed. A continuous swathe of magma-inflated continental material beneath the 1200-km-wide Greenland-Iceland-Faroe Ridge implies that full continental breakup has not yet occurred at this latitude. Ongoing tectonic instability on the Ridge is manifest in long-term tectonic disequilibrium on the adjacent rifted margins and on the Reykjanes Ridge, where southerly migrating propagators that initiate at Iceland are associated with diachronous swathes of unusually thick oceanic crust. Magmatic volumes in the NE Atlantic Realm have likely been overestimated and the concept of a monogenetic North Atlantic Igneous Province needs to be reappraised. A model of complex, piecemeal breakup controlled by pre-existing structures that produces anomalous volcanism at barriers to rift propagation and distributes continental material in the growing oceans fits other oceanic regions including the Davis Strait and the South Atlantic and West Indian oceans

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