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OBJECTIVES The objective of this study was to analyse antimicrobial prescriptions by veterinarians and to evaluate the appropriateness of use compared with prudent use guidelines. PRACTICES AND METHODS: Computerized records of prescriptions and treatments from eight mixed veterinary practices were analysed over a period of 2 years. A total of 61 212 antimicrobial treatments were recorded. Treatments were classified according to animal species treated, indication for treatment, route of administration and antimicrobial class used. For each treatment and antimicrobial substance, the prescribed dose was calculated. Dosage, antimicrobial classes and combinations of different classes used for different indications were compared with published recommendations. RESULTS From the total amount of 1590 kg of active antimicrobial substance, sulphonamides (594 kg), tetracyclines (335 kg), and penicillins and cephalosporins (290 kg) were the classes of which the largest quantity was prescribed. Penicillins and cephalosporins were most frequently prescribed (37% of treatments), followed by aminoglycosides (18%), tetracyclines (14%) and sulphonamides (11%). Sixty-one per cent of the amount of antimicrobials prescribed was used for the treatment of groups of animals via feed or water. Antimicrobial classes classified as highest priority for human medicine by an international group of experts were used in 9% of the prescriptions. The dosage corresponded to the manufacturer's recommendation in 45% of the analysed prescriptions. CONCLUSIONS Most prescriptions corresponded well to guidelines on prudent use of antimicrobials. Nevertheless, the large variation of prescriptions among different veterinarians indicates that the usage of critical antimicrobial substances and the amount of antimicrobials used for group medication without a specific indication could be further reduced.

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BACKGROUND Outcome data are limited in patients with ST-segment elevation acute myocardial infarction (STEMI) or other acute coronary syndromes (ACSs) who receive a drug-eluting stent (DES). Data suggest that first generation DES is associated with an increased risk of stent thrombosis when used in STEMI. Whether this observation persists with newer generation DES is unknown. The study objective was to analyze the two-year safety and effectiveness of Resolute™ zotarolimus-eluting stents (R-ZESs) implanted for STEMI, ACS without ST segment elevation (non-STEACS), and stable angina (SA). METHODS Data from the Resolute program (Resolute All Comers and Resolute International) were pooled and patients with R-ZES implantation were categorized by indication: STEMI (n=335), non-STEACS (n=1416), and SA (n=1260). RESULTS Mean age was 59.8±11.3 years (STEMI), 63.8±11.6 (non-STEACS), and 64.9±10.1 (SA). Fewer STEMI patients had diabetes (19.1% vs. 28.5% vs. 29.2%; P<0.001), prior MI (11.3% vs. 27.2% vs. 29.4%; P<0.001), or previous revascularization (11.3% vs. 27.9% vs. 37.6%; P<0.001). Two-year definite/probable stent thrombosis occurred in 2.4% (STEMI), 1.2% (non-STEACS) and 1.1% (SA) of patients with late/very late stent thrombosis (days 31-720) rates of 0.6% (STEMI and non-STEACS) and 0.4% (SA) (P=NS). The two-year mortality rate was 2.1% (STEMI), 4.8% (non-STEACS) and 3.7% (SA) (P=NS). Death or target vessel re-infarction occurred in 3.9% (STEMI), 8.7% (non-STEACS) and 7.3% (SA) (P=0.012). CONCLUSION R-ZES in STEMI and in other clinical presentations is effective and safe. Long term outcomes are favorable with an extremely rare incidence of late and very late stent thrombosis following R-ZES implantation across indications.

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AIMS To assess incidence rates (IRs) of and identify risk factors for incident severe hypoglycaemia in patients with type 2 diabetes newly treated with antidiabetic drugs. METHODS Using the UK-based General Practice Research Database, we performed a retrospective cohort study between 1994 and 2011 and a nested case-control analysis. Ten controls from the population at risk were matched to each case with a recorded severe hypoglycaemia during follow-up on general practice, years of history in the database and calendar time. Using multivariate conditional logistic regression analyses, we adjusted for potential confounders. RESULTS Of 130,761 patients with newly treated type 2 diabetes (mean age 61.7 ± 13.0 years), 690 (0.5%) had an incident episode of severe hypoglycaemia recorded [estimated IR 11.97 (95% confidence interval, CI, 11.11-12.90) per 10,000 person-years (PYs)]. The IR was markedly higher in insulin users [49.64 (95% CI, 44.08-55.89) per 10,000 PYs] than in patients not using insulin [8.03 (95% CI, 7.30-8.84) per 10,000 PYs]. Based on results of the nested case-control analysis increasing age [≥ 75 vs. 20-59 years; adjusted odds ratio (OR), 2.27; 95% CI, 1.65-3.12], cognitive impairment/dementia (adjusted OR, 2.00; 95% CI, 1.37-2.91), renal failure (adjusted OR, 1.34; 95% CI, 1.04-1.71), current use of sulphonylureas (adjusted OR, 4.45; 95% CI, 3.53-5.60) and current insulin use (adjusted OR, 11.83; 95% CI, 9.00-15.54) were all associated with an increased risk of severe hypoglycaemia. CONCLUSIONS Severe hypoglycaemia was recorded in 12 cases per 10,000 PYs. Risk factors for severe hypoglycaemia included increasing age, renal failure, cognitive impairment/dementia, and current use of insulin or sulphonylureas.

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BACKGROUND A large cohort study recently reported high pain scores after caesarean section (CS). The aim of this study was to analyse how pain after CS interferes with patients' activities and to identify possible causes of insufficient pain treatment. METHODS We analysed pain scores, pain-related interferences (with movement, deep breathing, mood and sleep), analgesic techniques, analgesic consumption, adverse effects and the wish to have received more analgesics during the first 24 h after surgery. To better evaluate the severity of impairment by pain, the results of CS patients were compared with those of patients undergoing hysterectomy. RESULTS CS patients (n = 811) were compared with patients undergoing abdominal, laparoscopic-assisted vaginal or vaginal hysterectomy (n = 2406, from 54 hospitals). Pain intensity, wish for more analgesics and most interference outcomes were significantly worse after CS compared with hysterectomies. CS patients with spinal or general anaesthesia and without patient-controlled analgesia (PCA) received significantly less opioids on the ward (62% without any opioid) compared with patients with PCA (p < 0.001). Patients with PCA reported pain-related interference with movement and deep breathing between 49% and 52% compared with patients without PCA (between 68% and 73%; p-values between 0.004 and 0.013; not statistically significant after correction for multiple testing). CONCLUSION In daily clinical practice, pain after CS is much higher than previously thought. Pain management was insufficient compared with patients undergoing hysterectomy. Unfavourable outcome was mainly associated with low opioid administration after CS. Contradictory pain treatment guidelines for patients undergoing CS and for breastfeeding mothers might contribute to reluctance of opioid administration in CS patients.

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INTRODUCTION The aim of this study was to evaluate the concordance of 2- and 3-dimensional radiography and histopathology in the diagnosis of periapical lesions. METHODS Patients were consecutively enrolled in this study provided that preoperative periapical radiography (PR) and cone-beam computed tomographic imaging of the tooth to be treated with apical surgery were performed. The periapical lesional tissue was histologically analyzed by 2 blinded examiners. The final histologic diagnosis was compared with the radiographic assessments of 4 blinded observers. The initial study material included 62 teeth in the same number of patients. RESULTS Four lesions had to be excluded during processing, resulting in a final number of 58 evaluated cases (31 women and 27 men, mean age = 55 years). The final histologic diagnosis of the periapical lesions included 55 granulomas (94.8%) and 3 cysts (5.2%). Histologic analysis of the tissue samples from the apical lesions exhibited an almost perfect agreement between the 2 experienced investigators with an overall agreement of 94.83% (kappa = 0.8011). Radiographic assessment overestimated cysts by 28.4% (cone-beam computed tomographic imaging) and 20.7% (periapical radiography), respectively. Comparing the correlation of the radiographic diagnosis of 4 observers with the final histologic diagnosis, 2-dimensional (kappa = 0.104) and 3-dimensional imaging (kappa = 0.111) provided only minimum agreement. CONCLUSIONS To establish a final diagnosis of an apical radiolucency, the tissue specimen should be evaluated histologically and specified as a granuloma (with/without epithelium) or a cyst. Analysis of 2-dimensional and 3-dimensional radiographic images alike results only in a tentative diagnosis that should be confirmed with biopsy.

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PURPOSE Recent advances in optogenetics and gene therapy have led to promising new treatment strategies for blindness caused by retinal photoreceptor loss. Preclinical studies often rely on the retinal degeneration 1 (rd1 or Pde6b(rd1)) retinitis pigmentosa (RP) mouse model. The rd1 founder mutation is present in more than 100 actively used mouse lines. Since secondary genetic traits are well-known to modify the phenotypic progression of photoreceptor degeneration in animal models and human patients with RP, negligence of the genetic background in the rd1 mouse model is unwarranted. Moreover, the success of various potential therapies, including optogenetic gene therapy and prosthetic implants, depends on the progress of retinal degeneration, which might differ between rd1 mice. To examine the prospect of phenotypic expressivity in the rd1 mouse model, we compared the progress of retinal degeneration in two common rd1 lines, C3H/HeOu and FVB/N. METHODS We followed retinal degeneration over 24 weeks in FVB/N, C3H/HeOu, and congenic Pde6b(+) seeing mouse lines, using a range of experimental techniques including extracellular recordings from retinal ganglion cells, PCR quantification of cone opsin and Pde6b transcripts, in vivo flash electroretinogram (ERG), and behavioral optokinetic reflex (OKR) recordings. RESULTS We demonstrated a substantial difference in the speed of retinal degeneration and accompanying loss of visual function between the two rd1 lines. Photoreceptor degeneration and loss of vision were faster with an earlier onset in the FVB/N mice compared to C3H/HeOu mice, whereas the performance of the Pde6b(+) mice did not differ significantly in any of the tests. By postnatal week 4, the FVB/N mice expressed significantly less cone opsin and Pde6b mRNA and had neither ERG nor OKR responses. At 12 weeks of age, the retinal ganglion cells of the FVB/N mice had lost all light responses. In contrast, 4-week-old C3H/HeOu mice still had ERG and OKR responses, and we still recorded light responses from C3H/HeOu retinal ganglion cells until the age of 24 weeks. These results show that genetic background plays an important role in the rd1 mouse pathology. CONCLUSIONS Analogous to human RP, the mouse genetic background strongly influences the rd1 phenotype. Thus, different rd1 mouse lines may follow different timelines of retinal degeneration, making exact knowledge of genetic background imperative in all studies that use rd1 models.

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OBJECTIVES This study sought to evaluate: 1) the effect of impaired renal function on long-term clinical outcomes in women undergoing percutaneous coronary intervention (PCI) with drug-eluting stent (DES); and 2) the safety and efficacy of new-generation compared with early-generation DES in women with chronic kidney disease (CKD). BACKGROUND The prevalence and effect of CKD in women undergoing PCI with DES is unclear. METHODS We pooled patient-level data for women enrolled in 26 randomized trials. The study population was categorized by creatinine clearance (CrCl) <45 ml/min, 45 to 59 ml/min, and ≥60 ml/min. The primary endpoint was the 3-year rate of major adverse cardiovascular events (MACE). Participants for whom baseline creatinine was missing were excluded from the analysis. RESULTS Of 4,217 women included in the pooled cohort treated with DES and for whom serum creatinine was available, 603 (14%) had a CrCl <45 ml/min, 811 (19%) had a CrCl 45 to 59 ml/min, and 2,803 (66%) had a CrCl ≥60 ml/min. A significant stepwise gradient in risk for MACE was observed with worsening renal function (26.6% vs. 15.8% vs. 12.9%; p < 0.01). Following multivariable adjustment, CrCl <45 ml/min was independently associated with a higher risk of MACE (adjusted hazard ratio: 1.56; 95% confidence interval: 1.23 to 1.98) and all-cause mortality (adjusted hazard ratio: 2.67; 95% confidence interval: 1.85 to 3.85). Compared with older-generation DES, the use of newer-generation DES was associated with a reduction in the risk of cardiac death, myocardial infarction, or stent thrombosis in women with CKD. The effect of new-generation DES on outcomes was uniform, between women with or without CKD, without evidence of interaction. CONCLUSIONS Among women undergoing PCI with DES, CKD is a common comorbidity associated with a strong and independent risk for MACE that is durable over 3 years. The benefits of newer-generation DES are uniform in women with or without CKD.