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Advanced pain treatment

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https://www.readbyqxmd.com/read/28324649/sulfonamides-as-selective-nav1-7-inhibitors-optimizing-potency-pharmacokinetics-and-metabolic-properties-to-obtain-atropisomeric-quinolinone-am-0466-that-affords-robust-in-vivo-activity
#1
Russell F Graceffa, Alessandro A Boezio, Jessica Able, Steven Altmann, Loren M Berry, Christiane M Boezio, John R Butler, Margaret Y Chu-Moyer, Melanie Cooke, Erin F DiMauro, Thomas A Dineen, Elma Feric Bojic, Robert S Foti, Robert T Fremeau, Angel Guzman-Perez, Hua Gao, Hakan Gunaydin, Hongbing Huang, Liyue Huang, Christopher Ilch, Michael Jarosh, Thomas Kornecook, Charles R Kreiman, Daniel S La, Joseph Ligutti, Benjamin Charles Milgram, Min-Hwa Jasmine Lin, Isaac E Marx, Hanh Nho Nguyen, Emily A Peterson, Gwen Rescourio, John Roberts, Laurie B Schenkel, Roman Shimanovich, Brian Andrew Sparling, John Stellwagen, Kristin Taborn, Karina R Vaida, Jean Wang, John T S Yeoman, Violeta L Yu, Dawn Zhu, Bryan D Moyer, Matthew M Weiss
Due to its strong genetic validation, NaV1.7 has attracted significant interest as a target for the treatment of pain. We have previously reported on a number of structurally distinct bicyclic heteroarylsulfonamides as NaV1.7 inhibitors that demonstrate high levels of selectivity over other NaV isoforms. Herein, we report the discovery and optimization of a novel series of atropisomeric quinolinone sulfonamide inhibitors of NaV1.7, which demonstrate nanomolar inhibition of NaV1.7 and exhibit high levels of selectivity over other sodium channel isoforms...
March 21, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28317097/engagement-in-advance-care-planning-and-surrogates-knowledge-of-patients-treatment-goals
#2
Terri R Fried, Maria Zenoni, Lynne Iannone, John O'Leary, Brenda T Fenton
OBJECTIVES: A key objective of advance care planning (ACP) is improving surrogates' knowledge of patients' treatment goals. Little is known about whether ACP outside of a trial accomplishes this. The objective was to examine patient and surrogate reports of ACP engagement and associations with surrogate knowledge of goals. DESIGN: Cohort study SETTING: Primary care in a Veterans Affairs Medical Center. PARTICIPANTS: 350 community-dwelling veterans age ≥55 years and the individual they would choose to make medical decisions on their behalf, interviewed separately...
March 20, 2017: Journal of the American Geriatrics Society
https://www.readbyqxmd.com/read/28314688/nivolumab-treatment-for-oesophageal-squamous-cell-carcinoma-an-open-label-multicentre-phase-2-trial
#3
Toshihiro Kudo, Yasuo Hamamoto, Ken Kato, Takashi Ura, Takashi Kojima, Takahiro Tsushima, Shuichi Hironaka, Hiroki Hara, Taroh Satoh, Satoru Iwasa, Kei Muro, Hirofumi Yasui, Keiko Minashi, Kensei Yamaguchi, Atsushi Ohtsu, Yuichiro Doki, Yuko Kitagawa
BACKGROUND: Nivolumab is a human monoclonal IgG4 antibody that inhibits programmed cell death protein 1 (PD-1) expressed on activated T cells. We investigated the safety and activity of nivolumab in patients with treatment-refractory oesophageal cancer. METHODS: We did an open-label, single-arm, multicentre phase 2 study. Eligible patients had advanced squamous-cell carcinoma, adenosquamous-cell carcinoma, or adenocarcinoma of the oesophagus refractory or intolerant to fluoropyrimidine-based, platinum-based, and taxane-based chemotherapy...
March 14, 2017: Lancet Oncology
https://www.readbyqxmd.com/read/28303362/phase-i-ii-study-of-a-combination-of-capecitabine-cisplatin-and-intraperitoneal-docetaxel-xp-id-in-advanced-gastric-cancer-patients-with-peritoneal-metastasis
#4
Hyungwoo Cho, Min-Hee Ryu, Kyu-Pyo Kim, Baek-Yeol Ryoo, Sook Ryun Park, Bum Soo Kim, In-Seob Lee, Hee-Sung Kim, Moon-Won Yoo, Jeong Hwan Yook, Seong Tae Oh, Byung Sik Kim, Yoon-Koo Kang
BACKGROUND: This study was conducted to determine the recommended dose (RD) of intraperitoneal docetaxel (ID) in combination with systemic capecitabine and cisplatin (XP) and to evaluate its efficacy and safety at the RD in advanced gastric cancer (AGC) patients with peritoneal metastasis. METHODS: AGC patients with peritoneal metastasis received XP ID, which consists of 937.5 mg/m(2) of capecitabine twice daily on days 1-14, 60 mg/m(2) of intravenous cisplatin on day 1, and intraperitoneal docetaxel at 3 different dose levels (60, 80, or 100 mg/m(2)) on day 1, every 3 weeks...
March 16, 2017: Gastric Cancer
https://www.readbyqxmd.com/read/28300907/dermatologic-manifestations-of-infective-endocarditis
#5
Rafael Tomaz Gomes, Larissa Rezende Tiberto, Viviane Nardin Monte Bello, Margarete Aparecida Jacometo Lima, Gisele Alborghetti Nai, Marilda Aparecida Milanez Morgado de Abreu
Despite advances in diagnosis and treatment, infective endocarditis still shows considerable morbidity and mortality rates. The dermatological examination in patients with suspected infective endocarditis may prove very useful, as it might reveal suggestive abnormalities of this disease, such as Osler's nodes and Janeway lesions. Osler's nodes are painful, purple nodular lesions, usually found on the tips of fingers and toes. Janeway lesions, in turn, are painless erythematous macules that usually affect palms and soles...
September 2016: Anais Brasileiros de Dermatologia
https://www.readbyqxmd.com/read/28296770/evaluation-of-intrathecal-drug-delivery-system-for-intractable-pain-in-advanced-malignancies-a-prospective-cohort-study
#6
Shuyue Zheng, Liangliang He, Xiaohui Yang, Xiuhua Li, Zhanmin Yang
Pain is prevalent in advanced malignancies; however, some patients cannot get adequate pain relief by conservative routes of analgesic administration or experience serious side effects related to high dose of opioids. For those who have exhausted multimodal conservative analgesic, intrathecal drug delivery is an alternative intervention for truly effective pain management. The objective of this study was to evaluate the clinical efficacy and safety of intrathecal drug delivery system (IDDS) for the treatment of intractable pain in advanced cancer patients...
March 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/28295118/an-unusual-case-of-aorta-right-atrial-tunnel-with-windsock-aneurysm-imaging-diagnosis-and-treatment
#7
Shehzaadi Aneesah Khan, Leonie Scholtz, F Adriaan Snyders, Johan de Villiers
The first successfully diagnosed and treated case of aorta-right atrial tunnel was reported by Coto et al. in 1980. The most common cause of aorta-right atrial tunnel is a ruptured aneurysm of the sinus of Valsalva. Sinus of Valsalva aneurysms had been reported as early as 1840 by Thurnam; these were diagnosed at autopsy. With the advances in radiology, many cases of aorta-right atrial tunnel have been reported since then, each with its own subtle variations. We report on a unique case of aorta-right atrial tunnel with a windsock aneurysm in the right atrium...
March 15, 2017: Cardiovascular Journal of Africa
https://www.readbyqxmd.com/read/28294643/a-videofluoroscopy-based-tracking-algorithm-for-quantifying-the-time-course-of-human-intervertebral-displacements
#8
Christian Balkovec, Jim H Veldhuis, John W Baird, G Wayne Brodland, Stuart M McGill
The motions of individual intervertebral joints can affect spine motion, injury risk, deterioration, pain, treatment strategies, and clinical outcomes. Since standard kinematic methods do not provide precise time-course details about individual vertebrae and intervertebral motions, information that could be useful for scientific advancement and clinical assessment, we developed an iterative template matching algorithm to obtain this data from videofluoroscopy images. To assess the bias of our approach, vertebrae in an intact porcine spine were tracked and compared to the motions of high-contrast markers...
March 15, 2017: Computer Methods in Biomechanics and Biomedical Engineering
https://www.readbyqxmd.com/read/28292501/indian-health-service-pharmacists-engaged-in-opioid-safety-initiatives-and-expanding-access-to-naloxone
#9
Hillary Duvivier, Samantha Gustafson, Morgan Greutman, Tenzin Jangchup, Ashlee Knapp Harden, Aimee Reinhard, Keith Warshany
OBJECTIVE: To develop effective pharmacy-based interventions to mitigate harm from opioid use disorders. Programs include responsible opioid prescribing, expanded access to medication-assisted treatment (MAT), naloxone, and community interventions. SETTING: Clinical pharmacists practicing at Indian Health Service (IHS) locations in the Southwest, Midwest, and Great Lakes regions. These pharmacists serve culturally diverse American Indian populations throughout the United States and interface with tribal and federal programs to impact the opioid epidemic in Indian Country...
March 2017: Journal of the American Pharmacists Association: JAPhA
https://www.readbyqxmd.com/read/28291658/how-do-they-get-here-does-the-method-of-transportation-impact-salvage-for-patients-with-testicular-torsion
#10
D A Weiss, N Tsarouhas, M C Carr, A Kalmus, S A Zderic
INTRODUCTION: A growing number of patients are arriving at our tertiary care center for evaluation of possible testicular torsion using ambulance or helicopter transport. In many cases the parents arrive by car before the patient arrives. Are these advanced methods of medical transport worth the expense and risk in the case of suspected testicular torsion? OBJECTIVE: We evaluated the total number of patients presenting to our emergency room for suspected testicular torsion to see if the means of transport affected testicular survival...
January 23, 2017: Journal of Pediatric Urology
https://www.readbyqxmd.com/read/28290973/total-artificial-heart-implantation-as-a-bridge-to-heart-transplantation-in-an-active-duty-service-member-with-amyloid-cardiomyopathy
#11
Michael S Scully, Dylan E Wessman, James M McKee, Gregory M Francisco, Keshav R Nayak, Jon A Kobashigawa
INTRODUCTION: Cardiac involvement by light-chain (AL) amyloid occurs in up to 50% of patients with primary AL amyloidosis. The prognosis of amyloid heart disease is poor with 1-year survival rates of 35 to 40%. Historically, heart transplantation was considered controversial for patients with AL amyloid cardiomyopathy (CM) given the systemic nature of the disease and poor survival. We present a case report of an active duty service member diagnosed with advanced cardiac amyloid who underwent total artificial heart transplant as a bridge to heart transplant and eventual autologous stem cell transplant...
March 2017: Military Medicine
https://www.readbyqxmd.com/read/28289863/a-phase-ii-study-of-reolysin-%C3%A2-pelareorep-in-combination-with-carboplatin-and-paclitaxel-for-patients-with-advanced-malignant-melanoma
#12
Devalingam Mahalingam, Christos Fountzilas, Jennifer Moseley, Nicole Noronha, Hue Tran, Romit Chakrabarty, Giovanni Selvaggi, Matthew Coffey, Brad Thompson, John Sarantopoulos
REOLYSIN(®) (pelareorep) is an investigational new drug, consisting of a live, replication-competent, Reovirus Type 3 Dearing strain in a proprietary formulation. Several preclinical and clinical trials with REOLYSIN(®) on a wide range of cancer indications have demonstrated antineoplastic activity on cells with activated RAS-signaling pathway. Furthermore, long-term survival benefits were evident in post-treatment patients indicating a potential antitumor immune response triggered by REOLYSIN(®). Numerous mono and/or combination therapy studies with the agent showed a consistent safety profile...
March 13, 2017: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/28282277/role-of-stereotactic-body-radiotherapy-in-the-treatment-of-elderly-and-poor-performance-status-patients-with-pancreatic-cancer
#13
Lauren M Rosati, Joseph M Herman
Literature on the management of nonmetastatic pancreatic ductal adenocarcinoma in patients who are elderly or have poor performance status is sparse. The median survival of this unique cohort of patients is < 6 months, and most patients are only offered single-agent gemcitabine or supportive care. Recently, adding nanoparticle albumin-bound paclitaxel to gemcitabine was shown to improve survival of patients with metastatic disease with Eastern Cooperative Group performance status of 2. Although standard chemoradiotherapy provides long-term locoregional control in locally advanced pancreatic cancer, it is difficult for this group of patients to tolerate 6 weeks of therapy...
March 2017: Journal of Oncology Practice
https://www.readbyqxmd.com/read/28280980/emergencies-in-motoneuron-disease
#14
REVIEW
Josef Finsterer, Claudia Stöllberger
Genetic and acquired motor-neuron-disorders (MNDs) may undergo acute deterioration resulting in various emergency situations. This literature review aims at summarising and discussing current knowledge about emergencies in MNDs. Emergencies that have been reported in MND patients include: respiratory, bulbar, cardiac, septic, epileptic, psychiatric, pain-related, and traumatic emergencies. Emergencies due to respiratory insufficiency have the strongest impact on morbidity and mortality in MNDs. To optimise the management of emergencies in MNDs, it is recommended to discuss these topics with the patient prior to their occurrence...
March 9, 2017: Internal and Emergency Medicine
https://www.readbyqxmd.com/read/28278355/functional-and-structural-plasticity-in-the-primary-somatosensory-cortex-associated-with-chronic-pain
#15
REVIEW
Woojin Kim, Sun Kwang Kim, Junichi Nabekura
Tissue or nerve injury induces widespread plastic changes from the periphery and spinal cord up to the cortex, resulting in chronic pain. Although many clinicians and researchers have extensively studied altered nociceptive signaling and neural circuit plasticity at the spinal cord level, effective treatments to ameliorate chronic pain are still insufficient. For about the last two decades, the rapid development in macroscopic brain imaging studies on humans and animal models have revealed maladaptive plastic changes in the 'pain matrix' brain regions, which may subsequently contribute to chronic pain...
March 9, 2017: Journal of Neurochemistry
https://www.readbyqxmd.com/read/28277993/maggot-therapy-for-wound-care-in-iran-a-case-series-of-the-first-28-patients
#16
A Mirabzadeh, M J Ladani, B Imani, S A B Rosen, R A Sherman
OBJECTIVE: The need for improved wound care is receiving considerable attention in the Islamic Republic of Iran. Beginning in 2003, maggot therapy (MT) became part of Iran's effort to advance its wound care technology. The first cohort of patients treated with MT was analysed to evaluate the use of this treatment. METHOD: Patients treated with MT at three hospitals in Tehran were analysed retrospectively. Primary outcomes were time to wound debridement and time to wound healing...
March 2, 2017: Journal of Wound Care
https://www.readbyqxmd.com/read/28276971/new-drugs-for-pain-management-in-advanced-cancer-patients
#17
Sebastiano Mercadante
Advanced cancer patients represent a frail population, often requiring aggressive pain management, particularly in the late stage of disease, when untreated pain is one the most important causes of suffering. Areas covered: In the last decade, a series of new analgesics have been introduced in the market to offer additional options amongst existent drugs. The characteristics of these drugs, their efficacy and tolerability are examined on the basis of existent studies. Expert opinion: Although new analgesic preparations have been developed in recent years, no specific drug has provided a better analgesic performance in comparison with others...
March 5, 2017: Expert Opinion on Pharmacotherapy
https://www.readbyqxmd.com/read/28276651/realignment-surgery-for-malunited-ankle-fracture
#18
Chang-Jun Guo, Xing-Cheng Li, Mu Hu, Yang Xu, Xiang-Yang Xu
OBJECTIVE: To investigate the characteristics and the results of realignment surgery for the treatment of malunited ankle fracture. METHODS: Thirty-three patients with malunited fractures of the ankle who underwent reconstructive surgery at our hospital from January 2010 to January 2014 were reviewed. The tibial anterior surface angle (TAS), the tibiotalar tilt angle (TTA), the malleolar angle (MA), and the tibial lateral surface angle (TLS) were measured. Clinical assessment was performed with use of the American Orthopaedic Foot and Ankle Society (AOFAS) scale and visual analogue scale (VAS) scores, and the osteoarthritis stage was determined radiographically with the modified Takakura classification system...
March 9, 2017: Orthopaedic Surgery
https://www.readbyqxmd.com/read/28274851/emerging-therapeutic-targets-in-cancer-induced-bone-disease-a-focus-on-the-peripheral-type-2-cannabinoid-receptor
#19
REVIEW
Silvia Marino, Aymen I Idris
Skeletal complications are a common cause of morbidity in patients with primary bone cancer and bone metastases. The type 2 cannabinoid (Cnr2) receptor is implicated in cancer, bone metabolism and pain perception. Emerging data have uncovered the role of Cnr2 in the regulation of tumour-bone cell interactions and suggest that agents that target Cnr2 in the skeleton have potential efficacy in the reduction of skeletal complications associated with cancer. This review aims to provide an overview of findings relating to the role of Cnr2 receptor in the regulation of skeletal tumour growth, osteolysis and bone pain, and highlights the many unanswered questions and unmet needs...
March 6, 2017: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/28274395/attitudes-of-radiation-oncologists-toward-palliative-and-supportive-care-in-the-united-states-report-on-national-membership-survey-by-the-american-society-for-radiation-oncology-astro
#20
Randy L Wei, Malcolm D Mattes, James Yu, Adrienne Thrasher, Hui-Kuo Shu, Harald Paganetti, Jennifer De Los Santos, Bridget Koontz, Christopher Abraham, Tracy Balboni
PURPOSE: Radiation oncologists are frequently involved in providing palliative and supportive care (PSC) for patients with advanced cancers through delivery of palliative radiation. Whether they are confident in their ability to assess and initiate treatments for pain, nonpain, and psychosocial distress is unknown. The American Society for Radiation Oncology surveyed its practicing members in the United States on self-assessment of their primary PSC skills and access to continuing medical education on PSC...
March 2017: Practical Radiation Oncology
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