Description of an Evidence-Based Elective in Complementary and Alternative Medicine

This paper describes a new elective course in complementary and alternative medicine (CAM) for second or third year Doctor of Pharmacy students. Prior to this elective, students received approximately 10 contact hours of lecture primarily focusing on herbal products. This CAM course included different types of CAM therapies including Oriental medicine, acupuncture, massage, homeopathy and naturopathy, energy therapies, mind-body, and biological products. A session on research techniques and the difficulties of doing research in CAM topics was held early in the course. All material provided was evidence-based. Students were required to make an oral presentation and write a short referenced paper on a CAM topic of their choice. The hands on demonstration and practice of massage techniques and the acupuncture demonstration were the best received sessions

Protective effect of prostacyclin on postischemic acute renal failure in the rat

Protective effect of prostacyclin on postischemic acute renal failure in the rat. Infusion of prostacyclin (PGI2) reportedly attenuates renal ischemic injury in the dog and the rat. In the dog, PGI2 is a potent renal vasodilator; in the rat a direct action on the renal vasculature is not always apparent. To determine whether or not the protective effect of PGI2 on postichemic ARF was hemodynamically mediated, studies were performed in uninephrectomized Sprague–Dawley rats before and after a 40 minute period of complete renal artery occlusion. In response to the preischemic infusion of PGI2 for 30 minutes at 160 ng/kg body wt/min i.v. (N = 7), MAP and RBF fell to 86 ± 7% (P < 0.0001) and 84 ± 9% (P < 0.05) of baseline values, respectively. RVR initially declined to 81 ± 9% of baseline values (P < 0.025) but returned to 102 ± 13% of baseline values prior to the period of ischemia. Following the period of ischemia, reflow of blood in the rats receiving PGI2 was delayed when compared to rats not receiving PGI2 (N = 1). RBF returned to only 76 ± 19% of the initial values in PGI2-treated rats (P < 0.01) but to 90 ± 12% of the initial values in rats receiving buffer alone (NS). Observations made during the ensuing 48 hours in animals treated with either 80 (N = 8) or 160 ng/kg/body wt/min (N = 7) for 30 minutes before and four hours after the period of ischemia indicated that renal function improved to a greater extent in the PGI2-treated animals than in buffer–treated animals (N = 15) as judged by significantly–greater mean values of V, UOsm, UCr and CCr. On the second day after ischemia, CInwas significantly greater in PGI2-treated animals than in the postischemic animals receiving buffer alone (77 ± 45 vs. 33 ± 20 µl/min/100 g body wt; P < 0.05) despite the fact that no differences were found in the mean values of RBF (3.59 ± 1.08 vs. 3.43 ± 0.32 ml/min/100 body wt. Blinded analysis of the histological sections revealed significantly less evidence of tublar epithelial cell necrosis in the PGI2-treated animals (P < 0.005). The data indicate that the protective effect of PGI2 on the renal response to ischemic injury in the Sprague–Dawley rat is not related to changes in RBF or RVR. Instead, the beneficial effect of PGI2may be a result of cytoprotective properties as has been demonstrated in other tissues

Measured energy expenditure of tube-fed patients with severe neurodevelopment disabilities

Objective: To determine measured resting energy expenditure (REE) of nonambulatory tube-fed patients with severe neurological neurodevelopmental disabilities. Methods: Twenty patients were prospectively studied. Only steady state indirect calorimetry measurements were taken. All measurements were conducted using a canopy system. Nutritional needs were met entirely by enteral feedings via a permanent ostomy. Results: REE was widely distributed from 16 kcals/kg/day to 39 kcals/kg/day. The mean REE (888 ±176 kcals/day) of the patients was significantly (p \u3c 0.01) lower than predicted as estimated by the Harris-Benedict equations (1081 ± 155 kcals/day) and World Health Organization equations (1194 ± 167 kcals/day). Fat-free mass (FFM) was the best parameter for predicting REE. Two predictive equations were developed that are not significantly biased and more precise (≤ 15% error) than conventional predictive formulas. Conclusion: Conventional formulas for estimating energy expenditure are inaccurate and generally overestimate measured energy expenditure of nonambulatory patients with severe developmental disabilities

Enhancement of peritoneal dialysis clearance with docusate sodium

A study was done in rabbits to determine the effect of docusate sodium (DSS) on the peritoneal clearance of creatinine and urea. Following a series of control exchanges with a commercially available peritoneal dialysis solution, three animals in each of four groups received DSS (0.005%, 0.01%, 0.02%, or 0.04%) in a single exchange, followed by 10 subsequent exchanges of control fluid. Creatinine and urea clearances were measured for each exchange. Comparison of post-DSS clearances (exchanges 5 through 15) with pre-DSS baseline values (exchanges 1 through 4) showed a mean percent increase in creatinine clearance that was proportional to the concentration and ranged from 74% to 244% above baseline. Similarly, urea clearance increased by 79 to 166%. The effect on both creatinine and urea clearance persisted through the completion of the dialysis procedure. No animals showed signs of toxicity from DSS. The mechanism of the DSS effect on clearance is unknown. Although studies are needed to delineate the mechanism of the effect and to identify potential toxic effects, the results of this study indicate that DSS has a significant effect on clearance of both creatinine and urea

Comparison of arterial plasma amino acid concentrations in rats fed ad lib oral chow or parenteral nutrition via intravenous or gastric infusion

Abstract from the 22nd Clinical Congress of the American Society for Parenteral and Enteral Nutrition, Orlando, FL, January 18-21, 1998

Sequential group trial to determine gastrointestinal site of absorption and systemic exposure of azathioprine

Azathioprine (AZA) is used in the treatment of patients with refractory inflammatory bowel disease; however, its use is limited because of systemic toxicity associated with long-term use. Ileocecal delivery of AZA might be advantageous if local intestinal therapeutic effects could be provided with decreased systemic side effects. Decreased cecal systemic absorption would allow higher dosages of AZA to be administered. A two-phase study was performed to compare the systemic exposure of AZA and 6-mercaptopurine (6-MP) following administration of AZA into the stomach, jejunum, and cecum and to compare the systemic exposure to AZA and 6-MP following administration of three different dosages of AZA into the cecum. In phase I, six healthy male volunteers received three 50 mg sequential doses of AZA via an oral tube directly placed into the stomach, jejunum, and cecum, respectively. In phase II, six healthy male volunteers received three different dosages (50, 300, 600 mg of AZA) into the cecum. Plasma concentrations of AZA and 6-MP at various times were quantified and area under the plasma concentration-time curve (AUC) and mean residence time (MRT) were determined. No significant differences in the AUC of AZA were seen at the different sites. The AUC of 6-MP following administration of AZA into the jejunum (67.0 ± 30.1 ng × hr/ml) was higher compared to the stomach (39.9 ± 38.1 ng/hr/ml) and cecum (29.2 ± 10.9 ng × hr/ml). Jejunal absorption was 68% higher than absorption from the stomach and 129% higher than that of the cecum. Gastric absorption was 27% higher than that of the cecum. Increased dosages given into the cecum resulted in increased AUCs of AZA and 6-MP. The AUCs of AZA following 50, 300, and 600 mg dosages were 16.9 ± 7.4, 52.3 ± 67.2, and 132 ± 151 ng × hr/ml, respectively, and the AUCs of 6-MP were 22.2 ± 14.9, 63.4 ± 50.6, and 104 ± 115 ng × hr/ml, respectively. Systemic exposure to 6-MP is reduced following administration of AZA into the cecum, most likely secondary to reduced absorption of 6-MP from the colon. Higher dosages of AZA presented to the cecum do result in increased systemic absorption, but may still allow more drug to be administered with less toxicity than the same dose received orally

Measured energy expenditure of nonambulatory patients with severe neurodevelopmental disabilities

Abstract from American College of Clinical Pharmacy 1997 Annual Meeting, Phoenix, AZ, November 9-12, 1997

The SAMI Galaxy Survey: kinematic alignments of early-type galaxies in A119 and A168

We investigate the kinematic alignments of luminous early-type galaxies (M r ≤ −19.5 mag) in A119 and A168 using the kinematic position angles (${{\rm{PA}}}_{{\rm{kin}}}$) from the Sydney-AAO Multi-object Integral-field spectrograph (SAMI) survey data, motivated by the implication of the galaxy spin alignment in a cosmological context. To increase the size of our sample for statistical significance, we also use the photometric position angles (${{\rm{PA}}}_{{\rm{phot}}}$) for galaxies that have not been observed by SAMI, if their ellipticities are higher than 0.15. Our luminous early-type galaxies tend to prefer the specific position angles in both clusters, confirming the results of Kim et al., who recently found the kinematic alignment of early-type galaxies in the Virgo cluster based on the ATLAS 3D integral-field spectroscopic data. This alignment signal is more prominent for galaxies in the projected phase-space regions dominated by infalling populations. Furthermore, the alignment angles are closely related to the directions of the filamentary structures around clusters. The results lead us to conclude that many cluster early-type galaxies are likely to be accreted along filaments while maintaining their spin axes, which are predetermined before cluster infall

Report from Working Group 3: Beyond the standard model physics at the HL-LHC and HE-LHC

This is the third out of five chapters of the final report [1] of the Workshop on Physics at HL-LHC, and perspectives on HE-LHC [2]. It is devoted to the study of the potential, in the search for Beyond the Standard Model (BSM) physics, of the High Luminosity (HL) phase of the LHC, defined as $3$ ab$^{-1}$ of data taken at a centre-of-mass energy of 14 TeV, and of a possible future upgrade, the High Energy (HE) LHC, defined as $15$ ab$^{-1}$ of data at a centre-of-mass energy of 27 TeV. We consider a large variety of new physics models, both in a simplified model fashion and in a more model-dependent one. A long list of contributions from the theory and experimental (ATLAS, CMS, LHCb) communities have been collected and merged together to give a complete, wide, and consistent view of future prospects for BSM physics at the considered colliders. On top of the usual standard candles, such as supersymmetric simplified models and resonances, considered for the evaluation of future collider potentials, this report contains results on dark matter and dark sectors, long lived particles, leptoquarks, sterile neutrinos, axion-like particles, heavy scalars, vector-like quarks, and more. Particular attention is placed, especially in the study of the HL-LHC prospects, to the detector upgrades, the assessment of the future systematic uncertainties, and new experimental techniques. The general conclusion is that the HL-LHC, on top of allowing to extend the present LHC mass and coupling reach by $20-50\%$ on most new physics scenarios, will also be able to constrain, and potentially discover, new physics that is presently unconstrained. Moreover, compared to the HL-LHC, the reach in most observables will, generally more than double at the HE-LHC, which may represent a good candidate future facility for a final test of TeV-scale new physics

Atrasentan and renal events in patients with type 2 diabetes and chronic kidney disease (SONAR): a double-blind, randomised, placebo-controlled trial

Background: Short-term treatment for people with type 2 diabetes using a low dose of the selective endothelin A receptor antagonist atrasentan reduces albuminuria without causing significant sodium retention. We report the long-term effects of treatment with atrasentan on major renal outcomes. Methods: We did this double-blind, randomised, placebo-controlled trial at 689 sites in 41 countries. We enrolled adults aged 18–85 years with type 2 diabetes, estimated glomerular filtration rate (eGFR)25–75 mL/min per 1·73 m 2 of body surface area, and a urine albumin-to-creatinine ratio (UACR)of 300–5000 mg/g who had received maximum labelled or tolerated renin–angiotensin system inhibition for at least 4 weeks. Participants were given atrasentan 0·75 mg orally daily during an enrichment period before random group assignment. Those with a UACR decrease of at least 30% with no substantial fluid retention during the enrichment period (responders)were included in the double-blind treatment period. Responders were randomly assigned to receive either atrasentan 0·75 mg orally daily or placebo. All patients and investigators were masked to treatment assignment. The primary endpoint was a composite of doubling of serum creatinine (sustained for ≥30 days)or end-stage kidney disease (eGFR <15 mL/min per 1·73 m 2 sustained for ≥90 days, chronic dialysis for ≥90 days, kidney transplantation, or death from kidney failure)in the intention-to-treat population of all responders. Safety was assessed in all patients who received at least one dose of their assigned study treatment. The study is registered with ClinicalTrials.gov, number NCT01858532. Findings: Between May 17, 2013, and July 13, 2017, 11 087 patients were screened; 5117 entered the enrichment period, and 4711 completed the enrichment period. Of these, 2648 patients were responders and were randomly assigned to the atrasentan group (n=1325)or placebo group (n=1323). Median follow-up was 2·2 years (IQR 1·4–2·9). 79 (6·0%)of 1325 patients in the atrasentan group and 105 (7·9%)of 1323 in the placebo group had a primary composite renal endpoint event (hazard ratio [HR]0·65 [95% CI 0·49–0·88]; p=0·0047). Fluid retention and anaemia adverse events, which have been previously attributed to endothelin receptor antagonists, were more frequent in the atrasentan group than in the placebo group. Hospital admission for heart failure occurred in 47 (3·5%)of 1325 patients in the atrasentan group and 34 (2·6%)of 1323 patients in the placebo group (HR 1·33 [95% CI 0·85–2·07]; p=0·208). 58 (4·4%)patients in the atrasentan group and 52 (3·9%)in the placebo group died (HR 1·09 [95% CI 0·75–1·59]; p=0·65). Interpretation: Atrasentan reduced the risk of renal events in patients with diabetes and chronic kidney disease who were selected to optimise efficacy and safety. These data support a potential role for selective endothelin receptor antagonists in protecting renal function in patients with type 2 diabetes at high risk of developing end-stage kidney disease. Funding: AbbVie