The Calm App as an Adjunct to Physical Therapy for Chronic Neck and Shoulder Pain

Background: As Physical Therapists tasked with treating chronic pain to combat the opioid epidemic it becomes necessary to treat both the physical and psychological aspects of pain in the outpatient clinic. Integrating a guided meditation application can be an effective way for Physical Therapists to integrate mindfulness training into their treatment plan. Purpose: The purpose of this case is to describe the integration of a meditation application in combination with a graded exercise program as part of the Physical Therapy treatment plan for chronic neck and shoulder pain. Case Description: A 66-year-old female presented to physical therapy for treatment of her long-standing neck and shoulder pain. The patient has a history of multiple motor vehicle accidents (MVA) along with an extensive list of comorbidities including cancer, anxiety disorder, and psychogenic non-epileptic seizures (PNES). Outcomes: The QuickDASH and Neck Disability Index(NDI) where used to evaluate shoulder and neck physical function and both showed significant improvement after 6 weeks of treatment. Subjective reports of fatigue, and stress were assessed at each treatment session. Discussion: While not a substitute for skilled clinical psychological intervention, a meditation application may be a way to integrate mindfulness practice, with Physical Therapy interventions, as a home program for patients with chronic pain

Lesinurad, a novel, oral compound for gout, acts to decrease serum uric acid through inhibition of urate transporters in the kidney.

BackgroundExcess body burden of uric acid promotes gout. Diminished renal clearance of uric acid causes hyperuricemia in most patients with gout, and the renal urate transporter (URAT)1 is important for regulation of serum uric acid (sUA) levels. The URAT1 inhibitors probenecid and benzbromarone are used as gout therapies; however, their use is limited by drug-drug interactions and off-target toxicity, respectively. Here, we define the mechanism of action of lesinurad (Zurampic®; RDEA594), a novel URAT1 inhibitor, recently approved in the USA and Europe for treatment of chronic gout.MethodssUA levels, fractional excretion of uric acid (FEUA), lesinurad plasma levels, and urinary excretion of lesinurad were measured in healthy volunteers treated with lesinurad. In addition, lesinurad, probenecid, and benzbromarone were compared in vitro for effects on urate transporters and the organic anion transporters (OAT)1 and OAT3, changes in mitochondrial membrane potential, and human peroxisome proliferator-activated receptor gamma (PPARγ) activity.ResultsAfter 6 hours, a single 200-mg dose of lesinurad elevated FEUA 3.6-fold (p < 0.001) and reduced sUA levels by 33 % (p < 0.001). At concentrations achieved in the clinic, lesinurad inhibited activity of URAT1 and OAT4 in vitro, did not inhibit GLUT9, and had no effect on ABCG2. Lesinurad also showed a low risk for mitochondrial toxicity and PPARγ induction compared to benzbromarone. Unlike probenecid, lesinurad did not inhibit OAT1 or OAT3 in the clinical setting.ConclusionThe pharmacodynamic effects and in vitro activity of lesinurad are consistent with inhibition of URAT1 and OAT4, major apical transporters for uric acid. Lesinurad also has a favorable selectivity and safety profile, consistent with an important role in sUA-lowering therapy for patients with gout

Cancer patient preferences for communication of prognosis in the metastatic setting

PURPOSE: To identify preferences for and predictors of prognostic information among patients with incurable metastatic cancer. PATIENTS AND METHODS: One hundred twenty-six metastatic cancer patients seeing 30 oncologists at 12 outpatient clinics in New South Wales, Australia, participated in the study. Patients were diagnosed with incurable metastatic disease within 6 weeks to 6 months of recruitment. Patients completed a survey eliciting their preferences for prognostic information, including type, quantity, mode, and timing of presentation; anxiety and depression levels; and information and involvement preferences. RESULTS: More than 95% of patients wanted information about side effects, symptoms, and treatment options. The majority wanted to know longest survival time with treatment (85%), 5-year survival rates (80%), and average survival (81%). Words and numbers were preferred over pie charts or graphs. Fifty-nine percent (59%) wanted to discuss expected survival when first diagnosed with metastatic disease. Thirty-eight percent and 44% wanted to negotiate when expected survival and dying, respectively, were discussed. Patients with higher depression scores were more likely to want to know shortest time to live without treatment (P = .047) and average survival (P = .049). Lower depression levels were significantly associated with never wanting to discuss expected survival (P = .03). Patients with an expected survival of years were more likely to want to discuss life expectancy when first diagnosed with metastases (P = .02). CONCLUSION: Most metastatic cancer patients want detailed prognostic information but prefer to negotiate the extent, format, and timing of the information they receive from their oncologists.<br /

Continued inhibition of structural damage over 2 years in patients with rheumatoid arthritis treated with rituximab in combination with methotrexate

Background Rituximab inhibited structural damage at 1 year in patients with rheumatoid arthritis (RA) who had had a previous inadequate response to tumour necrosis factor (TNF) inhibitors. Objective To assess structural damage progression through 2 years. Methods Intention-to-treat patients with one post-baseline radiograph (rituximab n = 281; placebo n = 187) received background methotrexate (MTX) and were randomised to rituximab (2 x 1000 mg infusions, 2 weeks apart) or placebo; patients were eligible for rituximab re-treatment every 6 months. By week 104, 82% of the placebo population had received >= 1 dose of rituximab. Radiographic end points included the change in total Sharp score (TSS), erosion and joint space narrowing scores at week 104. Results At week 104, significantly lower changes in TSS (1.14 vs 2.81; p < 0.0001), erosion score (0.72 vs 1.80; p < 0.0001) and joint space narrowing scores (0.42 vs 1.00; p < 0.0009) were observed with rituximab plus MTX vs placebo plus MTX. Within the rituximab group, 87% who had no progression of joint damage at 1 year remained non-progressive at 2 years. Conclusions Rituximab plus MTX demonstrated significant and sustained effects on joint damage progression in patients with RA and a previously inadequate response to TNF inhibitor

Costimulation blockade with Belatacept in renal transplantation

Background: Renal transplantation is the standard of care for patients with end-stage renal disease. Although maintenance immunosuppression with calcineurin inhibitors yields excellent one-year survival, it is associated over the long term with high rates of death and graft loss, owing in part to the adverse renal, cardiovascular, and metabolic effects of these agents. The use of potentially less toxic agents, such as belatacept, a selective blocker of T-cell activation, may improve outcomes. Methods: We randomly assigned renal-transplant recipients to receive an intensive or a less-intensive regimen of belatacept or cyclosporine. All patients received induction therapy with basiliximab, mycophenolate mofetil, and corticosteroids. The primary objective was to demonstrate the noninferiority of belatacept over cyclosporine in the incidence of acute rejection at six months (with an upper bound of the 95 percent confidence interval around the treatment difference of less than 20 percent). Results: At six months, the incidence of acute rejection was similar among the groups: 7 percent for intensive belatacept, 6 percent for less-intensive belatacept, and 8 percent for cyclosporine. At 12 months, the glomerular filtration rate was significantly higher with both intensive and less-intensive belatacept than it was with cyclosporine (66.3, 62.1, and 53.5 ml per minute per 1.73 m2, respectively), and chronic allograft nephropathy was less common with both regimens of belatacept than with cyclosporine (29 percent, 20 percent, and 44 percent, respectively). Lipid levels and blood-pressure values were similar or slightly lower in the belatacept groups, despite the greater use of lipid-lowering and antihypertensive medications in the cyclosporine group. Conclusions: Belatacept, an investigational selective costimulation blocker, did not appear to be inferior to cyclosporine as a means of preventing acute rejection after renal transplantation. Belatacept may preserve the glomerular filtration rate and reduce the rate of chronic allograft nephropathy

Maximizing the value of Solar System data through Planetary Spatial Data Infrastructures

Planetary spatial data returned by spacecraft, including images and higher-order products such as mosaics, controlled basemaps, and digital elevation models (DEMs), are of critical importance to NASA, its commercial partners and other space agencies. Planetary spatial data are an essential component of basic scientific research and sustained planetary exploration and operations. The Planetary Data System (PDS) is performing the essential job of archiving and serving these data, mostly in raw or calibrated form, with less support for higher-order, more ready-to-use products. However, many planetary spatial data remain not readily accessible to and/or usable by the general science user because particular skills and tools are necessary to process and interpret them from the raw initial state. There is a critical need for planetary spatial data to be more accessible and usable to researchers and stakeholders. A Planetary Spatial Data Infrastructure (PSDI) is a collection of data, tools, standards, policies, and the people that use and engage with them. A PSDI comprises an overarching support system for planetary spatial data. PSDIs (1) establish effective plans for data acquisition; (2) create and make available higher-order products; and (3) consider long-term planning for correct data acquisition, processing and serving (including funding). We recommend that Planetary Spatial Data Infrastructures be created for all bodies and key regions in the Solar System. NASA, with guidance from the planetary science community, should follow established data format standards to build foundational and framework products and use those to build and apply PDSIs to all bodies. Establishment of PSDIs is critical in the coming decade for several locations under active or imminent exploration, and for all others for future planning and current scientific analysis.Comment: 8 pages, 0 figures. White paper submitted to the Planetary Science and Astrobiology Decadal Survey 2023-203

Emricasan (IDN-6556) Lowers Portal Pressure in Patients with Compensated Cirrhosis and Severe Portal Hypertension

Caspases play a central role in apoptosis, inflammation and fibrosis. They produce hemodynamically-active, pro-inflammatory microparticles that cause intrahepatic inflammation, vasoconstriction and extrahepatic splanchnic vasodilation. Emricasan is a pan-caspase inhibitor that lowers portal hypertension (PH) and improves survival in murine models of cirrhosis. This exploratory study assessed whether emricasan lowers PH in patients with compensated cirrhosis. This multicenter, open-label study enrolled 23 subjects with compensated cirrhosis and PH (HVPG >5 mmHg). Emricasan 25 mg BID was given for 28 days. HVPG measurements were standardized and performed before and after emricasan. A single expert read all HVPG tracings.Median age was 59 (range 49-80); 70% were male. Cirrhosis etiologies were NASH and HCV. Subjects were Child class A (87%) with median MELD score of 8 (range 6-15). Twelve had severe PH (HVPG?12mmHg). Overall, there was no significant change in HVPG after emricasan (mean [SD] -1.1[4.57] mmHg). HVPG decreased significantly (mean [SD] -3.7[4.05] mmHg; p=0.003) in those with severe PH. 4/12 had a ?20% decrease; 8/12 had a ?10% decrease; and 2/12 HVPG decreased below 12mmHg. There were no significant changes in blood pressure or heart rate. AST/ALT decreased significantly in the entire group and in severe PH. Serum cCK18 and caspase-3/7 decreased significantly. Emricasan was well-tolerated. One subject discontinued for non-serious adverse events.Emricasan administered for 28 days decreased HVPG in patients with compensated cirrhosis and severe PH. An effect upon portal venous inflow is likely and concomitant decreases in AST/ALT suggest an intrahepatic anti-inflammatory effect

15th Annual Environmental Law Institute

Materials from the 15th Annual Environmental Law Institute held by UK/CLE in March 1999

Discussing prognosis with older people with musculoskeletal pain: a cross-sectional study in general practice

<p>Abstract</p> <p>Background</p> <p>Prognosis has been described as an important but neglected branch of clinical science. While patients' views have been sought in the context of life-threatening illness, similar research is lacking for patients presenting with common, non-life-threatening musculoskeletal complaints. The aim of this study was to gauge whether and why older patients with musculoskeletal pain think prognostic information is important, and how often they felt prognosis was discussed in the general practice consultation.</p> <p>Methods</p> <p>A cross-sectional survey of consecutive patients aged 50 years of over presenting with non-inflammatory musculoskeletal pain to 5 Central Cheshire general practices. The frequency of responses to the prognostic questions were described and the association with sociodemographic, presenting pain complaint, and psychosocial variables explored using logistic regression.</p> <p>Results</p> <p>502 participants (77%) responded to the postal questionnaire. 165 (33%) participants reported discussing prognosis in the consultation with their GP. Discussions about prognosis were more often reported by male patients (OR 1.72, 95% CI 1.09, 2.71) and those for whom this was their first consultation (OR 1.81, 95% CI 1.16, 2.80). 402 (82%) participants thought that prognostic information was important. This was highest among those currently in paid employment (OR 2.95, 95% CI 1.33, 6.57). The reasons patients gave for believing prognostic information was important included 'knowing for the sake of knowing' and planning future activity. Reasons for not believing prognostic information to be important included the belief that progression of pain was inevitable and that nothing could be done to help.</p> <p>Conclusion</p> <p>Prognostic information is thought to be important amongst older people with musculoskeletal pain yet discussions occur infrequently in primary care. Barriers to effective prognostic communication and the exact information needs of patients are still unknown and warrant further research.</p