Incidence and duration of side effects and those rated as bothersome with selective serotonin reuptake inhibitor treatment for depression: patient report versus physician estimate

BACKGROUND: Selective serotonin reuptake inhibitors (SSRIs) are widely used as the first-line treatment for depression. Information regarding their side effects is mostly based on controlled clinical trials. METHOD: Patients who received an SSRI for a new or recurrent case of depression (ICD-9 code 296.2 or 311) between December 15, 1999, and May 31, 2000 were interviewed by telephone 75 to 105 days after initiation of SSRI therapy. Using closed-ended questions, investigators asked patients if they experienced any of 17 side effects commonly associated with SSRIs, how bothersome they were, and what their duration was. Prescribing physicians completed a written survey providing their estimates about frequency of side effects associated with SSRIs and how bothersome those side effects are. RESULTS: Of 401 patients who completed the phone interview, 344 patients (86%) reported at least 1 side effect, and 219 patients (55%) experienced 1 or more bothersome side effect(s). The most common bothersome side effects were sexual dysfunction and drowsiness (17% each). While most side effects first occurred within the first 2 weeks of treatment, the majority of patients were still experiencing the same side effects at the time of interview, most notably blurred vision (85%) and sexual dysfunction (83%). Overall, physicians (N = 137) significantly underestimated the occurrence of the 17 side effects explored, and they tended to underrate how bothersome those side effects were to their patients. CONCLUSION: Side effects associated with SSRIs are common and bothersome to patients. Treatment-emergent side effects tend to persist during the first 3 months of treatment.     

Urinary oxalate excretion increases in home parenteral nutrition patients on a higher intravenous ascorbic acid dose

BACKGROUND: Vitamin C can be metabolized to oxalate. Case reports have suggested an association between IV vitamin C and urinary oxalate excretion. Recently, the US Food and Drug Administration required the dose of vitamin C in IV multivitamin preparations to be increased from 100 mg to 200 mg/d. We compared the urinary oxalate excretion level in stable home total parenteral nutrition (TPN) patients receiving both doses of vitamin C. METHODS: Each participant provided a 24-hour urine sample for oxalate determination on the vitamin C dose (100 mg/d), and again after at least 1 month on the increased vitamin C dose (200 mg/d). A 2-day diet diary was completed covering the day before and the day of the urine collection and was analyzed for oxalate and vitamin C content. Comparisons were made using Student paired t test and Wilcoxon signed rank. RESULTS: Thirteen patients (7 males/6 females) aged 63.1 +/- 12.2 years who had no history of nephrolithiasis and had received TPN for 55.9 +/- 78.8 months were enrolled. The most common indication for TPN was short bowel syndrome (38.5%). Eight patients had an intact colon. Urinary oxalate excretion increased on the 200-mg vitamin C dose, from 0.34 +/- 0.13 to 0.44 +/- 0.17 mmol/d (mean increase = 0.10 mmol/d; p = .04; 95% confidence interval 0.004 to 0.19 mmol/d). Oral intake of vitamin C and oxalate did not differ between the 2 collection periods. CONCLUSIONS: In therapeutically used doses, IV vitamin C increases urinary oxalate excretion, potentially predisposing susceptible individuals to nephrolithiasis. This factor should be considered in patients receiving home TPN.     

Effectiveness of heptavalent pneumococcal conjugate vaccine in children younger than five years of age for prevention of pneumonia

OBJECTIVE: To determine the effectiveness of the Wyeth heptavalent pneumococcal conjugate vaccine against clinical and radiograph-confirmed pneumonia in children. METHODS: The heptavalent CRM(197) pneumococcal conjugate vaccine (PCV) was given to infants at 2, 4, 6 and 12 to 15 months of age in a randomized, double blind trial. Children were randomized to receive either the CRM(197) PCV (vaccine group) or the meningococcal type C CRM(197) conjugate vaccine (control group). The primary outcome of this trial was invasive pneumococcal disease. In addition children with the clinical diagnosis of pneumonia in the study population were identified through review of automated inpatient, emergency and outpatient databases. The subset of the cohort of these children who had chest radiographs obtained at the time of diagnosis was identified, and the original reading of their radiographs by the radiologist was obtained from automated databases. Rates of clinically diagnosed pneumonia, of pneumonia with a radiograph obtained regardless of result, of pneumonia with positive radiograph (consolidation, empyema or parenchymal infiltrate) and of pneumonia with only perihilar infiltrates were compared between vaccinated and nonvaccinated groups. In addition risk of disease pneumonia was evaluated by race and ethnicity. RESULTS: The incidence of a first pneumonia episode in the control group was 55.9 per 1000 person-years. A radiograph was obtained in 61% of episodes, a positive radiograph in 21% and perihilar findings in an additional 5%. In per protocol follow-up of children given PCV, first episodes of all clinically diagnosed pneumonia were reduced by 4.3% [95% confidence interval (CI), -3.5, 11.5%, = 0.27], episodes with a radiograph were reduced by 9.8% (CI 0.1, 18.5%, < 0.05) and episodes with a positive radiograph were reduced by 20.5% (CI 4.4, 34.0, = 0.02). In the intent to treat analysis including all episodes after randomization, episodes with a positive radiograph were reduced by 17.7%, =.01). The greatest impact was in the first year of life with a 32.2% reduction and a 23.4% reduction in the first 2 years, but only a 9.1% reduction in children >2 years of age. Asians, blacks and Hispanics were at higher risk of pneumonia than were whites, but there was no evidence of ethnic variation in PCV effectiveness. Ten of the 11 cases of pneumococcal pneumonia with a positive blood culture were in the control group. CONCLUSION: The pneumococcal conjugate vaccine tested was effective in reducing the risk of pneumonia in young children.     

Rework the workload

Kindred Healthcare, Inc., the nation's largest full-service network of long-term acute care hospitals, initiated a 3-year strategic plan to re-evaluate its workload management system. Here, follow the project's most important and difficult phase--designing and implementing the patient classification system.     

Sch-66336 (sarasar) and other benzocycloheptapyridyl farnesyl protein transferase inhibitors: discovery,biology and clinical observations

Farnesyl Protein Transferase as a target for therapeutic intervention is currently under investigation in human clinical trials. Sch-66336 (sarasar), a benzocycloheptapyridyl Farnesyl Transferase Inhibitor (FTI), has been found to be effective in cellular proliferation assays and in in vivo oncology models both as a single agent and in combination with other anti-cancer agents. Clinically, early evidence is being generated that suggests efficacy in humans, particularly in patients with leukemia. Herein, we review the biology of FPT, the discovery of Sch-66336 and other benzocycloheptapyridyl FTIs, and the clinical evaluation of Sch-66336 for the treatment of leukemia and solid tumors.     

An exposure prevention rating method for intervention needs assessment and effectiveness evaluation

This article describes a new method for (1) systematically prioritizing needs for intervention on hazardous substance exposures in manufacturing work sites, and (2) evaluating intervention effectiveness. We developed a checklist containing six unique sets of yes/no variables organized in a 2 x 3 matrix of exposure potential versus protection (two columns) at the levels of materials, processes, and human interface (three rows). The three levels correspond to a simplified hierarchy of controls. Each of the six sets of indicator variables was reduced to a high/moderate/low rating. Ratings from the matrix were then combined to generate a single overall exposure prevention rating for each area. Reflecting the hierarchy of controls, material factors were weighted highest, followed by process, and then human interface. The checklist was filled out by an industrial hygienist while conducting a walk-through inspection (N = 131 manufacturing processes/areas in 17 large work sites). One area or process per manufacturing department was assessed and rated. Based on the resulting Exposure Prevention ratings, we concluded that exposures were well controlled in the majority of areas assessed (64% with rating of 1 or 2 on a 6-point scale), that there is some room for improvement in 26 percent of areas (rating of 3 or 4), and that roughly 10 percent of the areas assessed are urgently in need of intervention (rated as 5 or 6). A second hygienist independently assessed a subset of areas to evaluate inter-rater reliability. The reliability of the overall exposure prevention ratings was excellent (weighted kappa = 0.84). The rating scheme has good discriminatory power and reliability and shows promise as a broadly applicable and inexpensive tool for intervention needs assessment and effectiveness evaluation. Validation studies are needed as a next step. This assessment method complements quantitative exposure assessment with an upstream prevention focus.     

Early Results after Laparoscopic Gastric Bypass: EEA vs GIA Stapled Gastrojejunal Anastomosis

Background: Various surgical techniques have been successfully applied to isolated Roux-en-Y gastric bypass (RYGBP). Many surgeons rely on stapling devices for the gastrojejunal (GJ) anastomosis. Early follow-up results were compared for two laparoscopic techniques for GJ anastomosis: circular end-to-end (EEA) and linear cutting (GIA) staplers. Methods: Medical charts were retrospectively reviewed of all patients who had undergone stapled GJ anastomosis for isolated RYGBP over a 2-year period. The jejunal limb used for GJ anastomosis was fashioned at 1 cm / unit body mass index (BMI). Patients were grouped by GJ anastomotic technique, EEA or GIA, and the results compared. Results: 61 patients underwent RYGBP (EEA=32; GIA=29), with no differences in preoperative BMI or co-morbidities. Mean (±SD) operative time was shorter for the GIA group (EEA=180±56.1 minutes; GIA=145.3±27.9 minutes, P=0.003). There were 2 early re-operations in the GIA group for anastomotic leaks. Postoperative complications were not statistically different; however, there was an increased incidence of wound infections in the EEA group vs the GIA group (21.9% vs 6.9%, P=0.08). Follow-up at 6-8 months revealed an average percent excess weight loss of 46.7%±12.2% for EEA and 51.4%±10.7% for GIA (P=0.25). Length of stay, total hospital costs and operating-room costs were similar (P=0.34, 0.53 and 0.96 respectively). Conclusion: Operative time was significantly shorter in the GIA group. Complications, length of stay, weight loss and costs were similar between the groups. Selection of anastomotic technique may be based on surgeon preference, operative time, and potential for serious complications.