Dosing practices and risk factors for bleeding in patients receiving enoxaparin for the treatment of an acute coronary syndrome

OBJECTIVES: To describe dosing practices and to identify risk factors for bleeding in patients with an acute coronary syndrome (ACS) who received treatment with enoxaparin. DESIGN: Retrospective chart review. SETTING: Coronary care unit of a tertiary-care teaching hospital. PATIENTS: Patients with a discharge diagnosis of an ACS who received at least one dose of enoxaparin, 1 mg/kg, were eligible for this study. Enoxaparin dosing practices, factors that might influence the safety of enoxaparin administration, and bleeding events were documented. Multivariable regression analysis was used to identify independent predictors of bleeding in this clinical setting. RESULTS: Of 208 patients with an ACS who received enoxaparin, 48 patients (23%) received a dose that was > 10% or < 10% of the recommended 1 mg/kg dose, 18 patients (9%) did not have body weight documentation to guide enoxaparin dosing, and 17 patients (8%) had significant renal impairment (serum creatinine > 150 micromol/L), with the potential for bioaccumulation of enoxaparin. There were 35 bleeding events (17%), of which 8 events (4%) were major. Risk factors for any bleeding (major or minor) were increasing patient age (odds ratio [OR], 1.57; 95% confidence interval [CI], 1.13 to 2.20), coadministered nonsteroidal anti-inflammatory or antiplatelet drug therapy (OR, 2.38; 95% CI, 1.06 to 5.38), and number of enoxaparin doses (OR, 2.15; 95% CI, 1.25 to 3.68). Risk factors for major bleeding were increasing patient age (OR, 2.56; 95% CI, 1.05 to 6.28) and coadministered clopidogrel (OR, 7.70; 95% CI, 1.16 to 51.9). CONCLUSION: In this clinical practice assessment of patients with an ACS, the use of enoxaparin was suboptimal, with the potential to increase bleeding complications. Coadministered clopidogrel, other drugs that affect hemostasis, and increasing age conferred an increased bleeding risk.     

Thyroid tumors invading the larynx and trachea

Thyroid tumors may involve the airway. Eight patients with such invasion are reported; five with invasion of the larynx and three of the trachea. The symptoms varied: five of the eight patients had stridor and hemoptysis, one had hoarseness, and two had no symptoms at all. Endoscopic and radiologic examinations were performed in all patients including computed tomography in six. Six patients underwent total thyroidectomy and two patients, one with paraganglioma and one with hemangiopericytoma, had a hemithyroidectomy. Three patients had a total laryngectomy, one a partial laryngectomy and one a laryngofissure procedure. Tracheal resection was performed in two patients and one had laser excision of the endotracheal tumor involvement. Three patients received postoperative external irradiation. Six of the eight patients are alive with follow-up of 39 to 85 months.     

Malignancy grading and cytophotometric evaluation of T1 lip carcinomas

Histological malignancy grading using the score system set out by Jakobsson et al. in combination with static DNA cytofluorometry was applied to 20 T1 squamous cell carcinomas of the lower lip, 11 with and 9 without lymph node metastases. The mean malignancy score was 18.0 for tumours with metastases and 13.0 for those without (P less than 0.05, chi square test). Nuclear polymorphism, mode of invasion, vascular invasion, and cellular response were the single factors with the strongest influence. All but 3 carcinomas were DNA diploid, but DNA ploidy and proliferative activity (S-phase) yielded no prognostic information. However, hypertetraploid cells were found in all DNA diploid carcinomas with metastases, but in only half of those without (P less than 0.05).     

DNA pattern in oral cavity carcinomas in relation to clinical stage and histological grading

Cytofluorometric DNA analysis was performed in 88 squamous cell carcinomas of the oral cavity. 48% (42/88) of the tumours were DNA non-diploid. The frequency of DNA non-diploid tumours seemed to correlate with the increasing size of the tumour, and the decrease of histological grading, and certainly with the presence of lymph node metastases (p less than 0.001). DNA non-diploid tumours often had shorter duration of symptoms. The S-phase level seemed to increase the less differentiated the tumour but did not correlate either to tumour size or to duration of symptoms. Polyploid nuclei were more common in poorly differentiated tumours (9/10) as compared to well differentiated ones (17/33) (p less than 0.05) and seemed to be more common in tumours with metastases (20/26) than in those without (40/62).     

Inhaled corticosteroids and mortality in COPD

STUDY OBJECTIVES: To assess the influence of inhaled corticosteroids (ICSs) on mortality in COPD patients, which is currently a controversial topic. SETTING: Manitoba Health maintains a population-wide research database that includes pharmaceutical information. Design and patients: We examined mortality in people 90 to 365 days after hospital discharge for COPD, comparing those persons who received inhaled steroids within 90 days of hospital discharge with those who did not. Cox proportional hazards models were used with adjustments for other respiratory drugs, comorbidities, and physician visits before and after hospital discharge. We also compared mortality in patients who received inhaled steroids with those who received other respiratory drugs, but not inhaled steroids, and those who received neither. Using nested case control analysis, we examined the time of receipt of inhaled steroids in relation to fatal events. RESULTS: In people > 65 years of age, inhaled steroids were associated with a 25% reduction in mortality between 90 and 365 days after hospital discharge, while mortality increased with bronchodilator use, physician visits, age, and comorbidities. The exclusion of people who had also received a diagnosis of asthma or had received inhaled steroids before hospitalization did not change the result. Inhaled steroids were associated with an even larger mortality reduction in people aged 35 to 64 years. People who received bronchodilators but no steroids had higher mortality than people who received no bronchodilators or received both bronchodilators and inhaled steroids. The reduction in all-cause mortality was largely due to the decreased number of cardiovascular deaths. The receipt of inhaled steroids within 30 days of death was protective, but this was not the case for greater time intervals. CONCLUSIONS: Therapy with ICSs reduced mortality in COPD patients; the effect was particularly notable for cardiovascular death and was short term in that it was dependent on recent exposure.     

Preoperative Irradiation in Oral Cavity Carcinoma: A study with special reference to DNA pattern, histological response and prognosis

The relation between DNA pattern and response to preoperative radiotherapy was studied in 51 patients with oral squamous cell carcinomas operated 4 weeks after irradiation. Small tumors (T1 and T2) showed more pronounced response to radiotherapy than larger ones (T3 and T4), as did DNA aneuploid tumors. Eight of 11 DNA aneuploid tumors showed no remaining tumor in the operation specimen, compared to 6 of 21 DNA polyploid and 2 of 19 DNA diploid tumors. None of 16 patients without demonstrable remaining cancer in the operation specimen had local recurrence. The presence of lymph node metastases was the most important prognostic factor.     

Squamous cell carcinoma of the oral cavity. A review of 176 cases with application of malignancy grading and DNA measurements

This retrospective study comprised 176 patients with squamous cell carcinoma of the oral cavity treated at The Link?ping University Hospital over a 19-year period. Clinical parameters, microscopic malignancy grading (according to Jakobsson et al. and Glanz and Eichhorn), DNA cytofluorometry, analysis of therapeutic modalities and statistics regarding survival and prognosis are reported. The mean age was 70 years with a male: female ratio of 1.3:1 One hundred and four patients had T1 or T2 tumours and 109 an N0 neck. Cervical lymph node metastases were more frequent in patients with larger tumours (T3 + T4) than in those with smaller (T1 + T2) (P less than 0.01), in tumours with a high malignancy grading compared to those with a low (P less than 0.05) and in DNA non-diploid tumours compared to diploid ones (P less than 0.001). The aneuploid tumours responded better to preoperative radiotherapy than did diploid (P less than 0.01) or polyploid (P less than 0.05) tumours. Eighty-nine per cent of the recurrences occurred within 1 year of initial therapy. Secondary treatment was successful in 15 of 37 (41%) patients in whom the tumour recurred either at the primary site or in regional lymph nodes, but only in 1 of 8 (12%) with recurrences in both locations. Surgery alone or combined with radiotherapy resulted in equivalent survival rates for tumours in stages I and II. In advanced stages combined radiotherapy and surgery gave better survival figures than either modality alone (P less than 0.01; Kaplan-Meier). The presence of lymph node metastases (P less than 0.001), tumour size (P less than 0.01) and tumour ploidy (P less than 0.005) were the only clinical and histological parameters that significantly influenced survival (Cox regression analysis). Twenty-four patients developed a secondary primary malignancy; 21 of these were located in the aerodigestive tract.     

DNA ploidy in oral cavity carcinomas,with special reference to prognosis

Single-cell DNA cytofluorometry was performed on paraffin-em bedded tissue of 140 patients with squamous cell carcinomas of the oral cavity. Half of the tumors (71 of 140) were DNA nondip loid. Well-differentiated carcinomas were more often DNA dip loid than moderately well-differentiated ones (P<0.001; chi square). The aneuploid tumors responded better to preoperative radiotherapy than did the DNA diploid (P<0.001) and polyploid tumors (P<0.05; chi-square). Using the multivariate Cox's re gression analysis multiploid type tumor, age of the patients and presence of lymph node metastases were the only significant factors influencing survival. DNA diploid tumors in stages I and II had a better prognosis than DNA nondiploid (P<0.01; Kaplan-Meier). The reverse was true for stages III and IV, where DNA nondiploid tumors had a better prognosis (P<0.05; Kaplan-Meier). Tumor stages (P<0.001; Kaplan-Meier) and especially lymph node metastases (P<0.0005; Kaplan-Meier) were major prognostic factors. Tumor DNA ploidy may be a complement to clinical and morphologic parameters as a prognostic predictor in squamous cell carcinoma of the oral cavity.