Paul G. Cuddy

The effects of sucralfate suspension and diphenhydramine syrup plus kaolin-pectin on radiotherapy-induced mucositis.

A prospective, double-blind study compared the effectiveness of sucralfate suspension with diphenhydramine syrup plus kaolin-pectin in reducing severity and pain of radiation-induced oropharyngeal mucositis. Fourteen patients who received at least 4600 cGy to the oral cavity used one of the mouth rinses four times a day, beginning at 1600 cGy. Data were collected on daily perceived pain and helpfulness of mouth rinse, weekly mucositis grade, weight change, and interruption of therapy. Analysis of data revealed no statistically significant differences between the two groups in any parameter. A retrospective review of 15 patients who had received at least 4600 cGy radiation to the oropharynx but had not used a daily mouth-coating rinse, was compared with the study group. Comparison of the two groups suggested that consistent daily oral hygiene and use of a mouth-coating agent will result in less pain and may reduce weight loss and interruption of radiation because of severe mucositis.

PEG site infections: the emergence of methicillin resistant Staphylococcus aureus as a major pathogen

OBJECTIVE:We reviewed the records of 126 patients who underwent PEG insertion during a 36-month period to determine the etiology of an observed increase in PEG-related infections.METHODS:Charts were reviewed to determine predictive factors of infection, the occurrence of infection, and culture results of infected sites. Insertion was performed in all cases using a standard sterile, pull-through technique. Infections were defined as having at least two of the following conditions: peristomal erythema, induration, and purulent discharge.RESULTS:PEG infections occurred in 22 patients. During the first 12-month interval, 0 of 25 patients (0%) had PEG-related infections; during the second 12-month interval, four of 37 patients (10.8%); and during the third 12-month interval, 18 of 64 patients (28.1%) (p < 0.05). Cultures from 14 of 22 peristomal infections grew methicillin resistant Staphylococcus aureus (nine), pseudomonads (three), and other organisms (two). One hundred twenty-four of 126 patients received prophylactic antibiotics or were receiving concomitant antibiotics. Of the infected patients, 21 of 22 (95.5%) received prophylaxis, and 11 of 22 (50%) were receiving concomitant antibiotics before PEG. In the noninfected group, 78 of 104 (75%) received prophylaxis, and 47 of 104 (45.2%) received concomitant antibiotics.CONCLUSIONS:Methicillin resistant Staphylococcus aureus is emerging as a major pathogen in PEG site infections. Further prospective studies are needed to establish whether current prophylactic antibiotic recommendations are adequate.

A double-blind placebo controlled trial of oral midazolam as premedication before flexible sigmoidoscopy

Objective:We aimed to determine the efficacy of oral midazolam as premedication to improve tolerance of flexible sigmoidoscopy.Methods:Ninety-nine patients were randomized to receive 7.5 mg of oral midazolam solution mixed with apple juice or placebo (apple juice), 20 min before sigmoidoscopy. Patients’ anxiety and pain experienced before sedation, before the procedure, and during the procedure were assessed using a 10-cm visual analog scale (VAS) by both patients and physicians (0 = no pain, anxiety, 10 = severe pain, anxiety). Extent of sedation, amnesia, overall tolerance, adequacy of sedation, and willingness to repeat the procedure were assessed, and changes in vital signs and oximetries were recorded.Results:Fifty-one patients received midazolam and 48 patients received placebo. Patients reported less pain and anxiety (VAS 2.56, 1.64) compared with placebo (VAS 4.62, 4.16) during the procedure (p < 0.005, p < 0.0005). Physicians observed less pain and anxiety (VAS 2.19, 1.52) with midazolam than placebo (VAS 5.00, 3.97) during the procedure (p < 0.0001, p < 0.0001). A significantly greater number of patients judged tolerance of the procedure to be “excellent” using midazolam (p < 0.005) compared with placebo. A majority of patients in both groups was willing to repeat the procedure if recommended. Two patients in the midazolam group had transient asymptomatic hypotension during sigmoidoscopy, but no patients were observed to have desaturation by oximetry.Conclusions:Oral midazolam significantly reduces anxiety and pain during flexible sigmoidoscopy as assessed by both patients and physicians. Oral midazolam is a safe and effective premedication before flexible sigmoidoscopy in patients who require or prefer sedation.

PREDICTING THE PATIENT AT LOW RISK FOR LYMPH NODE METASTASIS WITH LOCALIZED PROSTATE CANCER: AN ANALYSIS OF FOUR STATISTICAL MODELS

PURPOSE Statistical models using preoperative Prostate-Specific Antigen, Gleason primary grade or score of the biopsy specimen, and clinical stage have been developed to predict those patients with clinically localized prostate cancer at low risk for lymph node metastasis. It has been recommended that these patients do not require pelvic lymph node dissections. Four such models were evaluated to assess their accuracy in identifying this subgroup of patients. METHODS AND MATERIALS We reviewed the records of 214 patients with clinically localized prostate cancer who underwent pelvic lymph node dissections. Data from these patients were entered into the four models. RESULTS Lymph node metastasis was detected in 14% of patients. The results showed the following for each of the proposed models respectively: 78, 50, 76, and 42% of the patients were identified as low risk and, hence, would be spared pelvic lymph node dissections. The false negative rates are 13 (7.8%), 5 (4.6%), 14 (8.6%), and 1 (1.1%). Sensitivities are 56.7, 83.3, 53.3, and 96.7%. CONCLUSIONS While the pelvic lymph node dissection is the most accurate method of detecting occult nodal metastasis, statistical models can identify a cohort of low risk patients that may be spared lymphadenectomy.

Fluoroquinolone Treatment of Community-Acquired Pneumonia: A Meta-Analysis

OBJECTIVE: To determine the role of newer fluoroquinolones (FQs) for adults with community-acquired pneumonia (CAP) whose level of illness allows treatment with an oral antibiotic. METHODS: Meta-analysis of randomized controlled trials comparing a macrolide, β-lactam, or doxycycline antibiotic with a newer oral FQ for the treatment of CAP. RESULTS: Patients (5118), most of whom were <60 years of age and free of coexisting diseases, were enrolled in 13 studies comparing an oral macrolide or β-lactam antibiotic with an FQ for the treatment of CAP. No previous study compared doxycycline with an FQ. In the intention-to-treat (ITT) population, no trial demonstrated significant differences between FQs or alternative therapies. Summary estimates showed a statistically significant advantage in favor of the FQs in both the ITT (OR 1.22; 95% CI 1.02 to 1.47; p = 0.03) and evaluable populations (OR 1.37; 95% CI 1.11 to 1.68; p = 0.003). The number needed to treat for an FQ advantage was 33 (95% CI 17 to 362) in the ITT population and 37 (95% CI 22 to 121) in the evaluable population. Treatment failures represented slow symptom resolution; no deaths were reported. CONCLUSIONS: The newer oral FQs showed modest therapeutic benefit compared with the studied alternative antibiotics in adults with CAP. Based on the number needed to treat from the ITT population as a measure of treatment effect, clinicians must decide whether treating 33 patients with an FQ to prevent a single therapeutic failure with another studied antibiotic warrants use of an agent from that class for an illness with a generally favorable outcome regardless of antibiotic selection, and at a time when FQ resistance may be increasing.

Evaluating the medical literature part I: Abstract, introduction, methods

In this installment on critical evaluation of medical literature, we have discussed the Abstract, Introduction, and Methods sections. A great deal of information is placed in the methodology section of any paper. To critically evaluate a research publication, one must evaluate the methodology, for evaluation of the results of an investigation is meaningless if the methodology is unsound.

Elevation of Serum Aluminum in Humans on a Two-Day Sucralfate Regimen

Serum aluminum concentrations were determined in ten healthy subjects treated with phenytoin 500 mg and with sucralfate and phenytoin in a crossover fashion. Each subject received four 1,000‐mg sucralfate tablets between 8 am and 10 pm one day before the study, and this was repeated during the study day. A total of eight doses of sucralfate was administered over the two‐day period. Serum samples were drawn at 0, 2, 4, 8, 12, 24, 32, and 48 hours after administration. The areas under the serum aluminum concentration‐time curves before and after sucralfate (mean ± SD) were 496.0 ± 80.9 and 770.9 ± 146.6 hr‐ng/mL, respectively. This increase is statistically significant (P < .01), indicating that serum aluminum levels are elevated even after two days of treatment with sucralfate. The results from this study are not in agreement with the only other report on this subject.

Effect of sucralfate on phenytoin bioavailability.

The mechanism of action of the antiulcer agent, sucralfate, involves drug binding to proteins, pepsin, and bile salts. The potential for sucralfate to bind to, and inhibit the oral absorption of, concurrently-administered drugs has been studied for very few agents. Phenytoin bioavailability was studied following a single dose of phenytoin 500 mg po in nine normal subjects during a control period and when given with sucralfate. Area under the serum concentration-time curve was compared at 48 hours (AUC48) and 120 hours (AUC120) using observed and extrapolated data. The phenytoin AUC48 was reduced from 173.6 ± 22.6 mg • h L to 157.1 ± 19.6 mg • h L ( p < 0.02 ) , and the phenytoin AUC120 was reduced from 200.5 ± 31.9 mg • h L to 185.0 ± 26.8 mg • h L ( p < 0.05 ) , when sucralfate was administered. Because AUC comparisons for drugs with nonlinear elimination kinetics may reflect changes in rate, as well as extent, of absorption, these small changes in AUC may not reflect a change in the fraction of dose absorbed. However, our results suggest that sucralfate does affect phenytoin absorption. Further studies may be useful in determining the precise nature and clinical importance of this interaction.

Evaluating the medical literature, Part III: Results and discussion

This series has addressed the basic segments of a research publication and discussed critical considerations that a reader should make as he progresses through the segments. The questions listed in Figure 3 may be helpful to guide the reader through the evaluation process.

Benzathine Penicillin G in the Treatment of Neurosyphilis

The definition, pathogenesis, incidence, diagnosis, and treatment of neurosyphilis are discussed. Controlled trials of benzathine penicillin in the treatment of neurosyphilis are reviewed, as are recent case reports of benzathine penicillin failures. Although few well-controlled studies exist to document conclusively the efficacy of benzathine penicillin in the treatment of neurosyphilis, its use is recommended in selected situations.