Nedocromil sodium is a pyranoquinoline dicarboxylic acid derivative, formulated in a metered-dose inhaler. Because nedocromil sodium has in vitro and in vivo anti-inflammatory properties, it was evaluated in a group of steroid-dependent patients with asthma to observe how well it might be tolerated and for evidence of any beneficial effects. In a double-blind, group-comparative study, 127 patients received nedocromil sodium and 61 received placebo, administered as two puffs of 2 mg, four times per day, for 12 weeks. Ten patients developed adverse reactions, seven receiving active drug and three patients receiving placebo. Two patients of each group withdrew because of worsening asthma. Despite selecting patients whose asthma was stable, when they were receiving established therapeutic regimens that included steroids and bronchodilators, it was found that diary-card symptom scores, morning and evening peak expiratory flow rate values, and inhaled beta-agonist usage all demonstrated slight but significant benefit with addition of nedocromil sodium. It is concluded that the inhaled, anti-inflammatory agent, nedocromil sodium, may be added to asthma-treatment regimens with the reasonable expectation of further modest symptomatic benefit.
5-hydroxytryptamine-3 receptor antagonist with or without short-course dexamethasone in the prophylaxis of radiation induced emesis: a placebo-controlled randomized trial of the National Cancer Institute of Canada Clinical Trials Group (SC19).
To evaluate the effectiveness of prophylactic dexamethasone for the control of radiation induced emesis (RIE) when added to ondansetron during days 1 to 5 of fractionated radiotherapy. The study had two hypotheses: ondansetron and dexamethasone could provide superior control of RIE over ondansetron alone during the prophylactic period and; the combination could provide sustained control of RIE during subsequent fractions of radiotherapy.
Between May 2001 to Jan 2004, 211 patients receiving radiotherapy (> or = 15 fractions) to the upper abdomen were randomly assigned to receive ondansetron 8 mg bid with either dexamethasone 4 mg daily or placebo during fractions 1 to 5. Rescue antiemetics were provided.
During the prophylactic period there was a trend for improved complete control of nausea in the dexamethasone arm (50% v 38%; P = .06) while complete and partial control of emesis, average nausea score, and use of rescue medications were similar in the two groups. During the overall study period patients receiving dexamethasone had better complete control of emesis (23% v 12%; P = .02) and a lower average nausea score (0.28 v 0.39; P = .03); there was a trend towards less use of rescue medications with dexamethasone (70% v 80%; P = .09); other outcomes were similar on the two arms. Quality of life analysis showed a significant difference in appetite.
The addition of dexamethasone to ondansetron as prophylaxis provides a modest improvement in protection against RIE during moderately emetogenic fractionated radiotherapy. It is a potentially useful addition to 5-hydroxytryptamine-3 receptor antagonists in this setting.
In patients treated with cytotoxic drugs granulocytopenia and septicemia are commonly seen. In this 10-year survey 324 blood culture isolates from 184 patients with hematological diseases and septicemia were studied. The distribution of microbiological diagnoses in patients with hematological diseases as well as acute leukemia 1980-1986 was significantly different (p less than 0.01) from an unselected blood culture material from the same period. The differences are mainly seen between Enterobacteriaceae other than Escherichia coli, Pseudomonas aeruginosa and staphylococci. The microbiological spectrum for patients with hematological disease 1987-1989 was also significantly different (p less than 0.05) from the spectrum of the same group of patients 1980-1986 due to higher frequencies of coagulase-negative staphylococci and alpha-streptococci and lower frequency of E. coli in the latter period. 40% of the isolates were gram-positive cocci during the first period and increased to 50% during the second period. The susceptibility testing indicates that trimethoprim/sulfonamide is not as good a choice as ciprofloxacin or norfloxacin for oral antibiotic prophylaxis. For intravenous therapy imipenem/cilastatin or the combinations of an aminoglycoside/piperacillin or aminoglycoside/third generation cephalosporin have advantages over aminoglycoside/trimethoprim/sulfa in combination. However, addition of isoxazolylpenicillin or vancomycin now seems necessary to cover the increasing part of gram-positive bacteria causing septicemia in patients with hematological disease.
A 26-week, prospective, open-label, uncontrolled, multicenter study to evaluate the effect of an escalating-dose regimen of trandolapril on change in blood pressure in treatment-naive and concurrently treated adult hypertensive subjects (TRAIL).
This study evaluated the effectiveness of an escalating-dose regimen of trandolapril in subjects with stage 1 or stage 2 hypertension.
This was a 26-week, prospective, open-label,multicenter study in Canadian primary care centers. Subjects with hypertension who were treatment naive or whose disease was uncontrolled on current first-line antihypertensive monotherapy were treated with trandolapril for 26 weeks alone or in addition to their current treatment. Uncontrolled hypertension was defined as systolic/diastolic blood pressure (SBP/DBP) >or=140/90 mm Hg in subjects with no other risk factors or >or=130/80 mm Hg in subjects with diabetes or kidney disease. Trandolapril therapy was initiated at 1 mg/d and was titrated as required to 2 or 4 mg at 4 and 9 weeks after initiation of treatment, respectively, in those not achieving BP targets. At 14 weeks after treatment initiation, subjects not achieving BP targets could receive a combination of trandolapril 4 mg plus a calcium channel blocker (verapamil 240 mg) with or without a diuretic. Primary outcome was the percentage of patients reaching target BP after 14 weeks.
A total of 1683 subjects from 192 general practice clinics across Canada completed the 14-week trandolapril dose-optimization phase, and 1650 completed the full 26-week follow-up. Mean (SD) age was 56.6 (12.6) years, and 49.2% of the subjects were men. At baseline, 82.4% (1359/1650) of subjects were antihypertensive-treatment naive. At the trial end, 73.4% (95% CI, 70.9-75.9) of subjects achieved a target level of SBP/DBP
The impact of an ARB, with or without hydrochlorothiazide (HCTZ), on glycaemic factors and the risk for developing diabetes in hypertensive patients with the metabolic syndrome have not been fully assessed. This was a 52-week multicentre, prospective, phase-IV, open-label, cohort study of losartan or losartan/HCTZ in hypertensive patients with metabolic syndrome. All subjects were treated initially with losartan 50?mg?day(-1). Those not achieving target blood pressure (BP
Prosthetic joint infection (PJI) is a leading cause of early revision after total knee arthroplasty (TKA). Open debridement with exchange of tibial insert allows treatment of infection with retention of fixed components. We investigated the success rate of this procedure in the treatment of knee PJIs in a nationwide material, and determined whether the results were affected by microbiology, antibiotic treatment, or timing of debridement.
145 primary TKAs revised for the first time, due to infection, with debridement and exchange of the tibial insert were identified in the Swedish Knee Arthroplasty Register (SKAR). Staphylococcus aureus was the most common pathogen (37%) followed by coagulase-negative staphylococci (CNS) (23%). Failure was defined as death before the end of antibiotic treatment, revision of major components due to infection, life-long antibiotic treatment, or chronic infection.
The overall healing rate was 75%. The type of infecting pathogen did not statistically significantly affect outcome. Staphylococcal infections treated without a combination of antibiotics including rifampin had a higher failure rate than those treated with rifampin (RR = 4, 95% CI: 2-10). In the 16 cases with more than 3 weeks of symptoms before treatment, the healing rate was 62%, as compared to 77% in the other cases (p = 0.2). The few patients with a revision model of prosthesis at primary operation had a high failure rate (5 of 8).
Good results can be achieved by open debridement with exchange of tibial insert. It is important to use an antibiotic combination including rifampin in staphylococcal infections.
To provide updated, evidence-based recommendations for the management of hypertension in adults.
For patients who require pharmacological therapy for hypertension, a number of antihypertensive agents may be used. Randomized trials evaluating first-line therapy with diuretics, beta-blockers, angiotensin-converting enzyme (ACE) inhibitors, calcium channel blockers (CCBs), alpha-blockers, centrally acting agents or angiotensin receptor antagonists were reviewed. Also, randomized trials evaluating other agents, such as statins or acetylsalicylic acid, in patients with hypertension were reviewed. Changes in cardiovascular morbidity and mortality were the primary outcomes of interest. In addition, other relevant outcomes such as development of end-stage renal disease or changes in blood pressure were examined where appropriate.
MEDLINE searches were conducted from November 2001 to October 2003 to update the 2001 Recommendations for the management of hypertension. Reference lists were scanned, experts were contacted, and the personal files of the subgroup members and authors were used to identify additional published studies. All relevant articles were reviewed and appraised independently, using prespecified levels of evidence by content and methodology experts.
This document contains detailed recommendations and supporting evidence on treatment thresholds, target blood pressures and choice of agents for hypertensive patients with or without comorbidities. Lifestyle modifications are a key component of any antiatherosclerotic management strategy and detailed recommendations are contained in a separate document. Key recommendations for pharmacotherapy include the following: treatment thresholds and targets should take into account each individual's global atherosclerotic risk, target organ damage and comorbidities, with particular attention to systolic blood pressure; blood pressure should be lowered to 140/90 mmHg or less in all patients, and 130/80 mmHg or less in those with diabetes mellitus or renal disease (125/75 mmHg or less in those with nondiabetic renal disease and more than 1 g of proteinuria per day); most adults with hypertension require more than one agent to achieve target blood pressures; for adults without compelling indications for other agents, initial therapy should include thiazide diuretics; other agents appropriate for first-line therapy for diastolic hypertension with or without systolic hypertension include beta-blockers (in those younger than 60 years), ACE inhibitors (in non-Blacks), long-acting dihydropyridine CCBs or angiotensin receptor antagonists; other agents appropriate for first-line therapy for isolated systolic hypertension include long-acting dihydropyridine CCBs or angiotensin receptor antagonists; certain comorbidities provide compelling indications for first-line use of other agents: in patients with angina, recent myocardial infarction or heart failure, beta-blockers and ACE inhibitors are recommended as first-line therapy; in patients with diabetes mellitus, ACE inhibitors or angiotensin receptor antagonists (or thiazides in patients with diabetes mellitus without albuminuria) are appropriate first-line therapies; and in patients with mild to moderate nondiabetic renal disease, ACE inhibitors are recommended; all hypertensive patients should have their fasting lipids screened and those with dyslipidemia should be treated using the thresholds, targets and agents as per the Recommendations for the management of dyslipidemia and the prevention of cardiovascular disease; and selected patients with hypertension should also receive statin and/or acetylsalicylic acid therapy.
All recommendations were graded according to the strength of the evidence and voted on by the Canadian Hypertension Education Program Evidence-Based Recommendations Task Force. Individuals with irreconcilable competing interests (declared by all members, compiled and circulated before the meeting) relative to any specific recommendation were excluded from voting on that recommendation. Only recommendations achieving at least 70% consensus are reported here. These guidelines will continue to be updated annually.
Abatacept is a co-stimulation blocker that inhibits T-cell activation and interrupts the process leading to inflammation in rheumatoid arthritis. Patients with severe arthritis who took abatacept with at least one other disease-modifying antirheumatic drug in six and 12-month clinical trials demonstrated statistically significant improvement in tender, swollen joints and other clinical measures compared with placebo. Mild to moderate adverse events included headache, nasopharyngitis, hypertension and back pain. The adverse events were similar to those seen in placebo groups. Abatacept should not be used in combination with other biologic agents because of reported increased rates of serious adverse events, including serious infections. With its different mechanism of action, abatacept may be an alternative add-on therapy for patients with an inadequate response to other arthritis therapies.
OBJECT: The authors prospectively studied the occurrence of clinical and nonclinical electroencephalographically verified seizures during treatment with an intracranial pressure (ICP)-targeted protocol in patients with traumatic brain injury (TBI). METHODS: All patients treated for TBI at the Department of Neurosurgery, University Hospital Umeå, Sweden, were eligible for the study. The inclusion was consecutive and based on the availability of the electroencephalographic (EEG) monitoring equipment. Patients were included irrespective of pupil size, pupil reaction, or level of consciousness as long as their first measured cerebral perfusion pressure was > 10 mm Hg. The patients were treated in a protocol-guided manner with an ICP-targeted treatment based on the Lund concept. The patients were continuously sedated with midazolam, fentanyl, propofol, or thiopental, or combinations thereof. Five-lead continuous EEG monitoring was performed with the electrodes at F3, F4, P3, P4, and a midline reference. Sensitivity was set at 100 muV per cm and filter settings 0.5-70 Hz. Amplitude-integrated EEG recording and relative band power trends were displayed. The trends were analyzed offline by trained clinical neurophysiologists. RESULTS: Forty-seven patients (mean age 40 years) were studied. Their median Glasgow Coma Scale score at the time of sedation and intubation was 6 (range 3-15). In 8.5% of the patients clinical seizures were observed before sedation and intubation. Continuous EEG monitoring was performed for a total of 7334 hours. During this time neither EEG nor clinical seizures were observed. CONCLUSIONS: Our protocol-guided ICP targeted treatment seems to protect patients with severe TBI from clinical and subclinical seizures and thus reduces the risk of secondary brain injury.
Eight patients with Acanthamoeba keratitis were diagnosed and treated at our clinic between February 1991 and February 1993. Five of these were contact lens wearers, two had suffered recent corneal trauma and one had recently undergone penetrating keratoplasty. The diagnoses were based on both culture and histological examination of biopsy material in three cases, on culture alone in two cases and on histological examination alone in three cases. In all but one primary treatment was Propamidine isethionate and Neomycin/Polymyxin B topically and Ketoconazole orally. Because of poor healing three patients additionally received Paromomycin and Miconazole or Clotrimazol topically; two of these were further treated with Polyhexamethylene biguanide topically. The interval from initial symptoms to accurate diagnoses varied from one to eleven months. In one patient the eye could not be saved; in the remaining patients visual acuity after healing ranged from hand movements to 1.0.