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Efficacy and safety profile of exenatide once weekly compared with insulin once daily in Japanese patients with type 2 diabetes treated with oral antidiabetes drug(s): results from a 26-week, randomized, open-label, parallel-group, multicenter, noninferiority study. A comparison of twice-daily exenatide and biphasic insulin aspart in patients with type 2 diabetes who were suboptimally controlled with sulfonylurea and metformin: a non-inferiority study. Efficacy and safety of pramlintide injection adjunct to insulin therapy in patients with type 1 diabetes mellitus: a systematic review and meta-analysis. Long-term effects of exenatide therapy over 82 weeks on glycemic control and weight in over-weight metformin-treated patients with type 2 diabetes mellitus. Exenatide elicits sustained glycemic control and progressive reduction of body weight in patients with type 2 diabetes inadequately controlled by sulfonylureas with or without metformin. Prandial options to advance basal Insulin glargine therapy: testing lixisenatide plus basal insulin versus insulin glulisine either as basal-plus or basal-bolus in type 2 diabetes: the GetGoal Duo-2 trial. Beneficial effects of once-daily lixisenatide on overall and postprandial glycemic levels without significant excess of hypoglycemia in type 2 diabetes inadequately controlled on a sulfonylurea with or without metformin (GetGoal-S). Efficacy and safety of lixisenatide once daily versus exenatide twice daily in type 2 diabetes inadequately controlled on metformin: a 24-week, randomized, open-label, active-controlled study (GetGoal-X). Patient-reported outcomes in a trial of exenatide and insulin glargine for the treatment of type 2 diabetes. The effect of adding exenatide to a thiazolidinedione in suboptimally controlled type 2 diabetes. They have been studied as monotherapy and in combination with other antidiabetic agents. Qtern (dapagliflozin/saxagliptin) was approved in February 2017; efficacy and safety were observed as add-on therapy with saxagliptin in patients on dapagliflozin plus metformin at 24 weeks (Matthaei et al 2015b) and at 52 weeks (Matthaei et al 2016); with dapagliflozin added to saxagliptin plus metformin at 24 weeks (Mathieu et al 2015) and 52 weeks (Mathieu et al 2016); and with saxagliptin plus dapagliflozin addition vs the single addition of saxagliptin or dapagliflozin to metformin at 24 weeks (Rosenstock et al 2015a, Rosenstock et al 2019). In patients inadequately controlled with metformin, ertugliflozin plus sitagliptin was more effective in glycemic control at weeks 26 and 52 as compared to individual components alone (Pratley et al 2018). This study was completed in December 2019; results are not yet available (ClinicalTrials. Findings in patients with diabetes were similar to those in patients without diabetes. Early combination therapy can be considered in some patients at treatment initiation to extend the time to treatment failure (level A). Canagliflozin has also been shown to be associated with a decrease in bone mineral density at the hip, but not the femoral neck, lumbar spine, or distal radius, with a significant increase in fractures of arms and legs but not the spine. Saxagliptin-containing products have the following contraindications: History of a serious hypersensitivity reaction including anaphylaxis, angioedema or exfoliative skin conditions.

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The following is a brief overview, while the tools themselves can be found in the Appendices. Pain often disrupts sleep in chronic pain patients, and the resulting insomnia may increase pain intensity and reduce the pain threshold. Remember that these are management tools, not definitive tests to determine deception or illicit use. The time limits of detection, tests to order, and "expected results" are listed in Appendix H. Patient-Provider Communication Patient treatment agreements Many providers wish to have conditions of treatment clearly stated in a written document prior to prescribing. Material risk notice the Oregon Medical Board states that a material risk notice needs to be signed by the patient whenever opioids are prescribed chronically. Medical risks of long-term opioid use Many patients are not familiar with the wide range of medical risks of long-term opioid use. Assessing Progress Graded pain and function scale the goal of opioid treatment is to improve function, both physical and emotional. This screening tool can help guide referrals to tobacco cessation programs, addictions and recovery programs, domestic violence prevention and mental health programs. Opioid withdrawal attenuation cocktail this is a list of medications that can be used to help manage "withdrawal symptoms" in patients who are being tapered down or off of their opioids. Patient and community resources this is a local southern Oregon resource guide, including addiction and residential services, populations served, as well as insurances accepted. Common chronic pain conditions in developed and developing countries: gender and age differences and comorbidity with depression-anxiety disorders. Evidence of a disposition toward fearfulness and vulnerability to posttraumatic stress in dysfunctional pain patients. Predictors of posttraumatic stress disorder symptom severity level in chronic low back pain patients. A preliminary examination of treatment for posttraumatic stress disorder in chronic pain patients: A case study. Predicting aberrant behaviors in opioid-treated patients: Preliminary validation of the opioid risk tool. How often have you been concerned that people will judge you for taking pain medication? How often have you been in an argument that was so out of control that someone got hurt? Tried hard not to think about it or went out of your way to avoid situations that reminded you of it?

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Similarly, Drinker and Drinker (1928) found elevated levels of zinc in the gall bladder, kidney, and pancreas of cats, rabbits, and rats exposed to airborne zinc oxide. Retention is reflective of deposition of zinc oxide in the lung rather than systemic absorption (Hirano et al. Species differences in retention have been observed; guinea pigs, rats, and rabbits retained 20, 12, and 5%, respectively, following nose-only exposure to 11. In humans, the highest concentrations of zinc have been found in bone, muscle, prostate, liver, and kidneys (Schroeder et al. Approximately 98% of serum zinc is bound to proteins; 85% is bound to albumin, 12% to "2-macroglobulin, and the remainder to amino acids (Giroux et al. In 8 erythrocytes, zinc is predominantly found as a component of carbonic anhydrase (87%) and Cu, Zn-superoxide dismutase (5. While small increases in tissue zinc levels relative to controls were reported, only occasionally were the differences statistically significant, and no pattern with increasing tissue zinc with time was noted. Exposure to 1200 ppm had no significant effect on tissue zinc levels relative to controls; the amount of stable zinc in liver, kidney, and bone was increased at 2400 ppm and higher, but reached a plateau (2400-7200 ppm; approximately 200-625 mg/kg-day). Exposure at the highest level (8400 ppm) caused additional increases in liver, kidney, and bone, as well as an increase in zinc level in the heart. Similar results for the accumulation of zinc in organs have been found in mice (He et al. In a series of animal experiments carried out by Drinker and Drinker (1928), the fate of inhaled zinc oxide from the lungs of animals (cats, rabbits and rats) was assessed. Increased zinc levels were found in the lungs, pancreas, liver, kidney, and gall bladder. It can also form soluble chelation complexes with amino acids and multidentate organic acids such as ethylenediaminetetraacetic acid. Oberleas (1996) found that the pancreas secretes into the 9 duodenum two to four times the amount of zinc that is typically consumed in an average day; most of this secreted zinc is reabsorbed. In humans, approximately 14% of the eliminated zinc was excreted in urine; when zinc intake was increased, urinary excretion accounted for 25% of the eliminated zinc (Wastney et al. The rate at which zinc is excreted is dependant on both current zinc intake and past zinc intake, probably via an effect on body stores (Johnson et al. However, no toxicokinetic models have been developed for zinc in either human or animal species. A list of key enzymes containing zinc or affected by zinc status are provided in Table 4-1. Zinc has three functions in these metalloenzymes: participation in catalytic functions, maintenance of structural stability, and regulatory functions (Vallee and Falchuk, 1993; Walsh et al. The configurations include the zinc finger, the most common zinc motif, and the zinc thiolate cluster (Walsh et al. Other physiological roles of zinc include enhancement of the affinity of growth hormone for its binding receptors, modulation of synaptic transmissions by interacting with specific sites on ionotrophic neurotransmitter receptor proteins, and induction of metallothionein (Walsh et al. The clinical manifestations of severe zinc deficiency, seen in individuals with an inborn error of zinc absorption or in patients receiving total parenteral nutrition lacking in adequate zinc, include bullous pustular dermatitis, diarrhea, alopecia, mental disturbances, and impaired cell-mediated immunity resulting in intercurrent infections.

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He was elected as Professor honoris causa by Saints Cyril and Methodius University, Skopje, Republic of Macedonia, in 2008. Dr Drueke is also an editorial board member for Journal of the American Society of Nephrology and Kidney International, a reviewer for numerous other journals, and the author of more than 450 peer-reviewed articles. He completed his fellowship at the University of Michigan and is an executive committee member for the Global Bone and Mineral Initiative. In 2004, Dr Block was awarded the Academic Publications Award by the University of Colorado. He was appointed to the Bone and Mineral Program at the Garvan Institute for Medical Research, where he completed his PhD studies on S115 biographic and disclosure information the molecular genetics and physiology of osteoporosis. He has been involved in writing evidence-based guidelines (the Caring for Australasians with Renal Impairment guidelines) and Cochrane reviews in the area of bone and mineral metabolism. He has served on the education committee of Kidney Health Australia, is the director of clinical renal research at Westmead Hospital, and is also a subject editor of the journal Nephrology. He is currently International Editor of the Clinical Journal of the American Society of Nephrology, and also serves as an editorial board member and reviewer for international journals. She completed fellowships in Internal Medicine and ~ Nephrology in Sao Paulo and in Renal Osteodystrophy at ^ Hopital Necker in Paris, France. Dr Jorgetti is a member of the Brazilian Society of Nephrology, Brazilian Society for Bone and Mineral Metabolism, and American Society for Bone and Mineral Research. She receives and analyzes bone biopsies from various Brazilian states as well as from other countries in Latin America. In addition, she has trained numerous doctors from Brazil and other countries who work in this area. Her interests include renal bone disease, mineral metabolism, and bone histomorphometry. He earned his medical degree at the University of Heidelberg and completed his internship and residency at the Department of Nephrology and Hypertension, University Hospital Steglitz, Free University Berlin. Dr Ketteler was a consultant (Nephrology/Internal Medicine) at the Department of Nephrology and Clinical Immunology, University Hospital Aachen, where he oversaw the Hemodialysis/Transplantation Unit. His major research interests include pathomechanisms of vascular calcifications in uremia, bone disease in renal transplant recipients, and the role of nitric oxide in experimental glomerulonephritis. He is a member of numerous professional societies and serves on the editorial board of the Journal of the American Society of Nephrology, Kidney International, Nephrology, Dialysis and Transplantation, and others. His research areas have included nephrolithiasis and also disorders of calcium, phosphorus, and vitamin D metabolism in infants, children, and adolescents. Dr Langman has published more than 170 articles, chapters, and reviews, and currently serves as Associate Editor of the American Journal of Nephrology, and on the editorial boards of Clinical Journal of the American Society of Nephrology, European Journal of Pediatrics, and Pediatric Nephrology.

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Of the total sample of 12,109 female veterans, 2,743 (23%) were deceased by the study end date of December 31, 2010, and the cause of death was available for 96. The adjusted total mortality and heart-disease-specific rates were lower in the female Vietnam veterans than in the U. The cancer mortality rate was approximately equal between the female Vietnam veterans group and both the U. Vietnam-veteran cohort provide direct information on the health and mortality status of female military personnel who served in Vietnam, the limitations of the results must be kept in mind. Specifically, female veterans likely experienced low herbicide exposure because they were not involved in applying herbicides or engaged in direct combat, and their in-country tours of duty were generally limited to 1 year and at fixed locations that were not in proximity to known defoliated areas. In summary, this analysis does not provide evidence of a higher risk of total or cause-specific mortality in female Vietnam-deployed veterans compared with non-deployed female Vietnam veterans and the U. Army veterans were identified from a list obtained by the Army and Joint Services Environmental Support Group; computerized lists were also provided by the Air Force, Navy, and Marine Corps. Of 5,230 eligible veterans, 4,390 with a documented tour of duty in Vietnam were alive on January 1, 1992. From a pool of 6,657 women whose military units did not serve in Vietnam, 4,390 veterans who were alive on January 1, 1992, were randomly selected as controls. After the research group excluded 250 veterans and 250 nonveterans who participated in a pilot study as well as those who could not be located (n = 370), who were deceased (n = 339), or who declined to participate (n = 775, 13% of Vietnam veterans and 17% of non-Vietnam veterans), 6,430 women completed a full telephone interview, and another 366 women completed only a short, written questionnaire. The information collected included demographic background, general health, lifestyle, menstrual history, pregnancy history, pregnancy outcomes, and military experience, including nursing occupation and combat exposure. Information on pregnancy risks and complications-including smoking, infections, medications, exposure to X-rays, occupational history, and exposure to anesthetic gases, ethylene oxide, herbicides, and pesticides-was collected for each pregnancy. For the comparison group, the first pregnancy after July 4, 1965, was designated as the index pregnancy. The study analyzed data on 3,392 Vietnam and 3,038 non-Vietnam veterans and on 1,665 Vietnam and 1,912 nonVietnam veteran index pregnancies. The authors attempted to "retrieve hospital records on all reported cancers as far back as 30 years. The authors did not provide specific data on diagnosis confirmation for the three sites other than the breast, but they stated that Vietnam status was not associated with a greater likelihood of finding confirmatory medical records. The legislation covers 18 birth defects, including cleft lip or palate, congenital heart disease, hypospadias, neural-tube defects, and Williams syndrome. Proportionate-Mortality Cohort Among the earliest reports on health outcomes in Vietnam veterans was a proportionate-mortality study by Breslin et al. The participants were Army and Marine Corps ground troops (all men) who served at any time from July 4, 1965, through March 1, 1973. From this list, 75,617 individuals were randomly selected for inclusion in the study.

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Erysipelothricosis in birds often has such an acute course that the animal dies before many appreciable pathologic lesions occur. The hemagglutinating activity is believed due to the high neuraminidase activity in virulent strains. Chronic erysipelothricosis leads to polyarthritis, synovitis, fibrosis and articular cartilage destruction. Vegetative valvular endocarditis frequently occurs, resulting in vasculitis, myocardial infarcts, destruction of valve endocardium, and splenic and renal infarcts. Infection and rapid proliferation is associated particularly with History: this captive ring-tailed lemur was housed in a Midwestern American zoo and first presented with labored breathing and was immobilized for a physical examination. The lemur recovered from anesthesia but continued to have labored breathing and lethargy. Gross Pathology: A 9 x 7 x 9 cm gelatinous mass was present in the pleural cavity, replacing and displacing most normal lung parenchyma. Within one of the fibrous cysts, there are several degenerating (mineralizing) cysticerci showing the scolex and invaginations of the thin bladder wall. There was no history or clinical pathology data to suggest this lemur is immunocompromised, but the perceived high frequency of cysticercosis in lemurs might indicate a predisposition in this exotic species which has presumably never been exposed to canid or felid parasites in their evolutionary history until very recently. Laparotomy revealed an intramural ulcerated mass close to the pyloric sphincter that was completely removed. The lesion affected the inner layers (mucosa and tunica muscularis) of the gastric wall and consisted of branching and anastomosing trabeculae of dense collagen separated by a densely cellular population of spindle-shaped cells (sclerosing fibroplasia). Scattered throughout the dense fibrous connective tissue are foci of large numbers of eosinophils and aggregates of brightly eosinophilic Splendore-Hoeppli material (at right). The fibroplasia contained variably dense infiltrates of eosinophils, mast cells, and fewer neutrophils, lymphocytes, and plasma cells. This animal had survived previous bouts of both aspiration pneumonia and congestive heart failure and was treated for both based on echocardiographic and radiographic findings. Gross Pathology: the animal exhibited marked symmetrical atrophy of the masticatory, paravertebral, and proximal limb muscles resulting in pronounced bony prominences. The proximal third of the stomach was displaced cranially into the thorax through a thick, fibrous, lax, tendinous portion of the diaphragm. Scattered myofibers contain abundant granular basophilic material (mineral) within the sarcoplasm. The cranial half of the stomach is present within the thorax consistent with a hiatal hernia. As the murine models fail to show severe clinical signs or cardiac lesions comparable to those observed in humans, these canine models fill an important niche in therapeutic studies. Examples of spontaneous muscular dystrophies that have been identified in animals are summarized in Table 1.

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Additional information available to the committees responsible for subsequent updates did not change these conclusions. Blood, urine, and two serially collected semen samples were obtained along with patient-provided information on smoking, food intake, physical activity, socioeconomic status, health status, and living conditions. Men who had total motility counts of less than 20 million were classified as subfertile. This study was limited by its very small sample size and by a failure to use all of the semen quality markers available. It also had a confusing sampling frame with cases and controls sampled first based on an unsuccessful conception within 12 months status, and then further divided by total motile count. The generalizability of results from fertility clinic patients to Vietnam veterans is also uncertain. Other congeners also showed consistently higher levels among the men in the infertile groups. The paper lacked many details on the recruitment of the men, the number of men was small, and no analysis of the impact of adjustment for other factors was presented. One hundred twenty-three men provided two semen samples a week apart, and 10 provided one sample. This report is based on a well-designed study, including a prospective follow-up and adjustment for multiple potential confounders. The study was not able to isolate possible in utero exposure and postnatal exposure. Moreover, its utility is limited by the fact that subjects were exposed to dioxins in a different period of their life (infancy, childhood, and adolescence) than the Vietnam veterans, and the generalizability of the results is open to question. Upon enrollment, in-person interviews were conducted with each male partner to ascertain health, demographic, and reproductive histories. A total of 35 semen parameters were measured, including five reflecting general characteristics (volume, straw distance [a motility marker], sperm concentration, total sperm count, and percent hypo-osmotic swollen [a marker of sperm quality]), 8 motility measures, 12 morphometry measures, 8 morphology measures, and 2 sperm chromatin stability assay measures. A total of 468 men had measured chemical concentrations and semen quality and were included in the analysis. When males with chemical concentrations in the fourth quartile were compared with those in the first quartile, significant associations (at the 0. Although the majority of the comparisons were null, the researchers did observe associations between each chemical class and each type of semen quality parameter, with results indicating both positive and negative associations with semen quality. Cases (n = 24) were men whose semen quality was considered low based on having at least an alteration in at least one semen quality parameter as compared with baseline values.


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