M. Ahinee Amamoo

Change in Proteinuria After Adding Aldosterone Blockers to ACE Inhibitors or Angiotensin Receptor Blockers in CKD: A Systematic Review

BACKGROUND The use of mineralocorticoid receptor blockers (MRBs) in patients with chronic kidney disease is growing, but data for efficacy in decreasing proteinuria are limited by a relative paucity of studies, many of which are small and uncontrolled. STUDY DESIGN We performed a systematic review using the MEDLINE database (inception to November 1, 2006), abstracts from national meetings, and selected reference lists. SETTING & POPULATION Adult patients with chronic kidney disease and proteinuria. SELECTION CRITERIA FOR STUDIES English-language studies investigating the use of MRBs added to long-term angiotensin-converting enzyme (ACE)-inhibitor and/or angiotensin receptor blocker (ARB) therapy in adult patients with proteinuric kidney disease. INTERVENTION MRBs as additive therapy to conventional renin-angiotensin-aldosterone system blockade in patients with chronic kidney disease. OUTCOMES Changes in proteinuria as the primary outcome; rates of hyperkalemia, changes in blood pressure, and changes in glomerular filtration rate as secondary outcomes. RESULTS 15 studies met inclusion criteria for our review; 4 were parallel-group randomized controlled trials, 4 were crossover randomized controlled trials, 2 were pilot studies, and 5 were case series. When MRBs were added to ACE-inhibitor and/or ARB therapy, the reported proteinuria decreases from baseline ranged from 15% to 54%, with most estimates in the 30% to 40% range. Hyperkalemic events were significant in only 1 of 8 randomized controlled trials. MRB therapy was associated with statistically significant decreases in blood pressure and glomerular filtration rate in approximately 40% and 25% of included studies, respectively. LIMITATIONS Reported results were insufficient for meta-analysis, with only 2 studies reporting sufficient data to calculate SEs of their published estimates. We were unable to locate studies that showed no effect of MRB treatment over placebo, raising concern for publication bias. CONCLUSIONS Although data suggest that adding MRBs to ACE-inhibitor and/or ARB therapy yields significant decreases in proteinuria without adverse effects of hyperkalemia and impaired renal function, routine use of MRBs as additive therapy in patients with chronic kidney disease cannot be recommended yet. However, the findings of this review promote interesting hypotheses for future study.

Prevention of delayed chemotherapy-induced nausea and vomiting after moderately high to highly emetogenic chemotherapy : Comparison of ondansetron, prochlorperazine, and dexamethasone

The purpose of this article is to assess the comparative antiemetic efficacy of prochlorperazine, ondansetron, and dexamethasone in the prevention of delayed chemotherapy-induced nausea and vomiting (CINV) after moderately high to highly emetogenic chemotherapy. Cancer patients (n = 232) receiving moderately high to highly emetogenic chemotherapy were randomized to 1 of 3 treatments: 15 mg prochlorperazine spansules twice daily; 8 mg ondansetron tablets twice daily; or 8 mg dexamethasone tablets twice daily on days 2 through 5. All patients received 24 mg ondansetron and 20 mg dexamethasone orally before chemotherapy. Daily assessment (days 1 through 5) included the number of episodes of retching and vomiting, severity of nausea, restlessness, difficulty concentrating and fatigue, treatment satisfaction, and overall quality of life (measured using a 10-cm VAS). The Functional Living Index-Emesis (FLIE) was completed on day 5. Other side effects attributed to antiemetic therapy were recorded daily. For acute CINV, total control, defined as no vomiting, retching, nausea <1 cm on a 10-cm visual analog scale, and no administration of rescue medications, was achieved in 78% in the overall group and was not significantly different in the patients randomized to the 3 treatment arms for delayed CINV. Delayed CINV was reported by 43% to 57% of patients, with the highest incidence reported on day 3. For delayed CINV, patients receiving prochlorperazine reported the lowest average nausea score on days 2 to 5, whereas patients receiving ondansetron reported the highest nausea score (P = 0.05). No statistically significant differences in CINV or side effects of antiemetic therapy were noted between treatment groups on days 2 to 5. For patients similar to those included in this study, there does not appear to be a clinically important difference in efficacy, adverse effects, or treatment satisfaction among dexamethasone, prochlorperazine, and ondansetron in the doses used in these delayed CINV regimens on days 2 to 5 in this study.

Factors Predicting Successful Needle-Localized Breast Biopsy

RATIONALE AND OBJECTIVES The purpose of this study was to identify factors that predict successful removal of nonpalpable breast lesions with mammography-guided needle-localized breast biopsy. MATERIALS AND METHODS Of the 455 consecutive patients referred for needle-localized breast biopsy of one or more nonpalpable breast lesions between January 1990 and December 1994, 272 (59.8%) had sufficiently complete data to be included in this study. Medical charts, pathology laboratory reports, wire-placement mammograms, and radiographs of specimens from each patient were retrospectively reviewed to evaluate the effect of the following factors on the success of the procedure: distance from the lesion to the localizing wire, breast density, breast size, specimen volume, and lesion volume. All radiographs were independently evaluated by two radiologists who are experts in breast imaging. RESULTS Needle-localized breast biopsy was successful in 254 (93.3%) of 272 lesions. Placement of the localization wire within 5 mm of the breast lesion was a significant predictor of successful lesion removal (P = .007). Results from logistic regression analysis showed that needle-localized breast biopsy failure was associated with increased wire distance (P = .0006), decreased breast size (P = .02), and decreased specimen volume (P = .03). CONCLUSION Needle localization wires should be placed within 5 mm of mammographically visible lesions to increase the probability of successful lesion excision.

Corticosteroid Therapy for Henoch Schönlein Purpura

Weiss et al’s1 meta-analysis concludes that several weeks of corticosteroid use decreases the risk of longterm renal disease in children presenting with Henoch Schonlein purpura (HSP). They base this conclusion on a combined odds ratio ([OR]: 0.43; 95% confidence interval (CI): [0.19 – 0.96]) of 3 placebo-controlled or prospective trials. We disagree with their conclusion on the basis of selection bias in the studies reported, differences in duration of follow-up, as well as new data from a prospective study presented by Dudley et al2 at the 2007 American Society of Nephrology meeting that reported no differences in development of renal disease between those receiving prednisolone and placebo (OR: 1.32; 95% CI: [0.59 –2.94]). Extrapolating the results of the analyzed trials to the practice of the primary care pediatrician may not be wise, because the children reported were either hospitalized for HSP or presented to a tertiary care level emergency department. It is reasonable to assume that they, on average, were sicker and may have had more severe involvement than the child with HSP presenting to a primary care practice. Methodologic issues that raise concern about the validity of Weiss et al’s1 meta-analysis include differences in treatment regimens and follow-up duration. Follow-up periods for each study were quite different with Ronkainen et al3 who reported 6 months of follow-up compared with 1 year for the Mollica et al4 and Huber et al5 trials. Also, the Mollica et al4 study, which was designed as an incidence trial compared with the prevalence design of the other 3 studies, included 2 patients who developed renal disease 1 year after their HSP diagnosis but are not taken into account by Weiss et al1 in their metanalysis. If we exclude Mollica et al4 from the meta-analysis and add the Dudley et al2 study, we measure a new combined OR: 0.89; 95% CI (0.52–1.54). However, if the Dudley et al and Mollica et al2,4 studies are included, we measure a combined OR: 0.77; 95% CI (0.44 –1.39) (Fig 1). Both of the combined OR reported indicate a trend toward supporting steroids in patients with HSP, but neither are statistically significant because the CIs cross the null. Weiss et al1 in their sensitivity analysis for future studies estimate that 5%–20% of untreated patients with HSP will develop persistent renal involvement. This is a large overestimate because long-term studies of unselected patients with HSP show less than a 2% prevalence of persistent renal involvement.6 The relatively small subgroup of HSP patients who may benefit from corticosteroids includes those who present with renal involvement and probably those with severe abdominal symptoms requiring medical attention.4,6,7 In summary, we feel the data does not currently exist, however, to recommend the routine use of corticosteroids to prevent renal disease in children with uncomplicated HSP, and that if steroids are to be used for these children, it should be only in the context of a controlled trial.

Barriers to women's participation in inter-conceptional care: a cross-sectional analysis

BackgroundWe describe participation rates in a special interconceptional care program that addressed all commonly known barriers to care, and identify predictors of the observed levels of participation in this preventive care service.MethodsA secondary analysis of data from women in the intervention arm of an interconceptional care clinical trial in Philadelphia (n = 442). Gelberg-Andersen Behavioral Model for Vulnerable Populations to Health Services (herein called Andersen model) was used as a theoretical base. We used a multinomial logit model to analyze the factors influencing womens level of participation in this enhanced interconceptional care program.ResultsAlthough common barriers were addressed, there was variable participation in the interconceptional interventions. The Andersen model did not explain the variation in interconceptional care participation (Wald ch sq = 49, p = 0.45). Enabling factors (p = 0.058), older maternal age (p = 0.03) and smoking (p = < 0.0001) were independently associated with participation.ConclusionsActively removing common barriers to care does not guarantee the long-term and consistent participation of vulnerable women in preventive care. There are unknown factors beyond known barriers that affect participation in interconceptional care. New paradigms are needed to identify the additional factors that serve as barriers to participation in preventive care for vulnerable women.

Phase II study of low-dose infusional 5-fluorouracil and paclitaxel (Taxol) given every 2 weeks in metastatic breast cancer.

Twenty-one patients with recurrent or metastatic breast cancer were treated with paclitaxel (Taxol) as a 1-hour infusion on day 1 only of a 14-day cycle. This treatment was followed by 5-fluorouracil (5-FU) via a portable home pump, through a central venous catheter at 350 mg/m2 per day over 24 hours for a total of 96 hours, on days 1 to 5 and again on days 8 to 12. Based on reported phase I trials in other organ system cancers, the first 5 patients were treated with paclitaxel at 150 mg/m2 every 2 weeks, but this was associated with excessive toxicity. Subsequent patients received paclitaxel at 135 mg/m2. The FACT-B scale was used to assess quality of life for patients on entry of the study and after three cycles. Treatment was well tolerated, with no grade III or IV hematologic toxicities. Grade III nonhematologic toxicities comprised one patient with fatigue, one with mucositis, and one with diarrhea. Grade IV nonhematologic toxicities included 1 hypersensitivity reaction to paclitaxel. Four of the 16 patients (25%) had pump-related problems resulting in disrupted 5-FU dosing in the home setting. The patients had the following responses to the treatment: complete response 0 (0%), partial response 6 (37.5%), stable disease 4 (25%), progression 4 (25%), unassessable 2 (12.5%)—1 anaphylaxis and 1 thrombocytopenia; overall response rate 6 of 16 (0.37; 95% CI, of 0.57). The median duration of survival was 14 months, 95% CI (5.6–18.24). The FACT-B was assessed in 14 patients at baseline and in 8 patients after 3 cycles. Quality of Life improved in 6 patients, no patients remained stable, and worsened in 2 patients. Biweekly paclitaxel with weekly 4-day continuous infusion 5-FU was associated with minimal toxicity but did not meet the target response rate of 60%. This response rate does not justify use of a complex home infusion of 5-FU.