Clarithromycin (Biaxin)‐lenalidomide‐low‐dose dexamethasone (BiRd) versus lenalidomide‐low‐dose dexamethasone (Rd) for newly diagnosed myeloma

The objective of this case‐matched study was to compare the efficacy and toxicity of the addition of clarithromycin (Biaxin) to lenalidomide/low‐dose dexamethasone (BiRd) vs. lenalidomide/low‐dose dexamethasone (Rd) for newly diagnosed myeloma. Data from 72 patients treated at the New York Presbyterian Hospital‐Cornell Medical Center were retrospectively compared with an equal number of matched pair mates selected among patients seen at the Mayo Clinic who received Rd. Case matching was blinded and was performed according to age, gender, and transplant status. On intention‐to‐treat analysis, complete response (45.8% vs. 13.9%, P < 0.001) and very‐good‐partial‐response or better (73.6% vs. 33.3%, P < 0.001) were significantly higher with BiRd. Time‐to‐progression (median 48.3 vs. 27.5 months, P = 0.071), and progression‐free survival (median 48.3 vs. 27.5 months, P = 0.044) were higher with BiRd. There was a trend toward better OS with BiRd (3‐year OS: 89.7% vs. 73.0%, P = 0.170). Main grade 3–4 toxicities of BiRd were hematological, in particular thrombocytopenia (23.6% vs. 8.3%, P = 0.012). Infections (16.7% vs. 9.7%, P = 0.218) and dermatological toxicity (12.5% vs. 4.2%, P = 0.129) were higher with Rd. Results of this case‐matchedanalysis suggest that there is significant additive value when clarithromycin is added to Rd. Randomized phase III trials are needed to confirm these results. Am. J. Hematol., 2010. © 2010 Wiley‐Liss, Inc.     

Biopsy‐proven adenoviral diarrhea responding to low‐dose cidofovir

Abstract: We present a case of diarrhea secondary to biopsy‐proven adenovirus (ADV) infection after autologous peripheral hematopoietic stem cell transplant for multiple myeloma. The patient had a negative plasma polymerase chain reaction for ADV and a dramatic clinical response to low‐dose cidofovir. To our knowledge, this is the first report in an adult hematopoietic stem cell recipient of the use of low‐dose cidofovir to treat proven ADV gastrointestinal infection.     

Fixed‐dose vs free‐dose combinations for the management of hypertension—An analysis of 81 958 patients

Fixed‐dose combinations (FDC) have been developed to reduce the pill burden for hypertensive patients. Data on fixed‐dose or free‐dose (freeDC) ramipril/amlodipine (R/A) or candesartan/amlodipine (C/A) combination treatment initiation were assessed. 71 463 patients were prescribed R/A and 10 495 C/A. For both R/A and C/A, FDC patients were younger (both P < .001) and less comorbid. Prior MI (OR: 0.61 and 0.60), prior stroke (OR: 0.68 and 0.70) and CHD (OR: 0.68 and 0.64) were negatively associated with FDC use, whereas hyperlipidemia was positively associated (OR: 1.26 and 1.19). Use of antihypertensive comedication (OR: 0.78; OR: 0.55) and treatment discontinuation within 12 months (HR: 0.65 and 0.82) were less likely in FDC patients, who also showed superior adherence (mean MPR; both P < .001). Cost of the combination was higher for FDCs (both P < .001). FDCs improve persistence and adherence, although they are more commonly prescribed in patients with less cardiovascular disease.     

Complications of low‐dose,echo‐guided alcohol septal ablation

Background : Alcohol septal ablation (ASA) is a catheter‐based intervention that has been used as an alternative to surgical myectomy in highly symptomatic patients with hypertrophic obstructive cardiomyopathy (HOCM). Methods : This retrospective study was designed to evaluate the incidence of major complications in the mid‐term follow‐up of low‐dose (1–2.5 ml of ethanol), echo‐guided alcohol septal ablation. Results : A total of 101 consecutive patients (56 ± 15 years) with highly symptomatic HOCM were enrolled. At 6 months, there was a significant decrease in resting outflow gradient accompanied by reduction in basal septal diameter and improvement in symptoms (P < 0.01). Two patients (2%) experienced procedural ventricular tachycardias terminated by electrical cardioversion. A total of 87 patients (86%) underwent an uneventful postprocedural hospital stay. The postprocedural complete heart block occurred in 10 patients (10%), and subsequent permanent pacemaker was implanted in four cases (4%). Sustained ventricular arrhythmias requiring electrical cardioversion occurred in four patients (4%) within postprocedural hospital stay. Subsequently, ICD was not implanted in any of these cases. The patients were repeatedly examined by Holter ECG monitoring, and in the mid‐term follow‐up (6–50 months), they stayed asymptomatic and without any ventricular arrhythmias. Conclusion : This study demonstrates the same early incidence of complete heart block requiring permanent pacemaker implantation (4%) and sustained ventricular arrhythmias following low‐dose, echo‐guided ASA. © 2009 Wiley‐Liss, Inc.     

Predictors and outcomes of scleroderma renal crisis: The high‐dose versus low‐dose D‐penicillamine in early diffuse systemic sclerosis trial

Objective

The reported frequency of scleroderma M01‐R renal crisis (SRC) in diffuse systemic sclerosis (SSc; scleroderma) is 15–20%. Early use of angiotensin‐converting enzyme (ACE) inhibitors has markedly improved outcome. The present analysis reexamines the prognostic factors for and outcome of SRC in a prospective cohort of patients with early diffuse SSc.

Methods

We retrospectively evaluated the cohort of SSc patients who participated in the High‐Dose Versus Low‐Dose D‐Penicillamine in Early Diffuse SSc trial. Patients with diffuse cutaneous scleroderma were enrolled if their disease duration was <18 months. Because the trial failed to show a difference between treatment groups, the data were pooled.

Results

One hundred thirty‐four SSc patients entered the observation period a mean ± SD of 0.8 ± 0.3 years after onset of SSc. SRC occurred in 18 patients a mean ± SD of 0.9 ± 1.1 years after entry. During a mean ± SD 4.0 ± 1.1 years of followup after entry, 9 of the 18 patients died (mean ± SD 0.6 ± 0.9 years after SRC onset). Baseline characteristics that predicted SRC included a modified Rodnan skin thickness score of ≥20 (P < 0.01), enlarged cardiac silhouette on radiograph (P = 0.04), large joint contractures (wrist, elbow, knee) (P = 0.008), and prednisone use at entry (P = 0.01). Baseline characteristics that did not predict SRC included age, sex, race, Health Assessment Questionnaire score, fist closure, handspread, lung involvement, muscle weakness, erythrocyte sedimentation rate, and platelet count. In 5 of 10 subjects for whom at least 2 sequential skin scores were available, skin scores increased significantly (P = 0.012) in the 6 months before onset of SRC.

Conclusion

SRC occurred in 13% of patients soon (mean 11 months) after entry into the cohort. Predictors of SRC identified in this study included higher than average skin score, prednisone use at study entry, large joint contractures, and heart enlargement. Our data suggest, however, that low‐dose prednisone alone was not associated with the onset of SRC, except in the appropriate clinical setting. Although ACE inhibitors and dialysis are now readily available, SRC continues to be associated with poor survival (in this study, 50% of patients with SRC died).

     

Immunosuppressive therapy in lupus nephritis: The Euro‐Lupus Nephritis Trial,a randomized trial of low‐dose versus high‐dose intravenous cyclophosphamide

Objective

Glomerulonephritis is a severe manifestation of systemic lupus erythematosus (SLE) that is usually treated with an extended course of intravenous (IV) cyclophosphamide (CYC). Given the side effects of this regimen, we evaluated the efficacy and the toxicity of a course of low‐dose IV CYC prescribed as a remission‐inducing treatment, followed by azathioprine (AZA) as a remission‐maintaining treatment.

Methods

In this multicenter, prospective clinical trial (the Euro‐Lupus Nephritis Trial [ELNT]), we randomly assigned 90 SLE patients with proliferative glomerulonephritis to a high‐dose IV CYC regimen (6 monthly pulses and 2 quarterly pulses; doses increased according to the white blood cell count nadir) or a low‐dose IV CYC regimen (6 fortnightly pulses at a fixed dose of 500 mg), each of which was followed by AZA. Intent‐to‐treat analyses were performed.

Results

Followup continued for a median of 41.3 months in the low‐dose group and 41 months in the high‐dose group. Sixteen percent of those in the low‐dose group and 20% of those in the high‐dose group experienced treatment failure (not statistically significant by Kaplan‐Meier analysis). Levels of serum creatinine, albumin, C3, 24‐hour urinary protein, and the disease activity scores significantly improved in both groups during the first year of followup. Renal remission was achieved in 71% of the low‐dose group and 54% of the high‐dose group (not statistically significant). Renal flares were noted in 27% of the low‐dose group and 29% of the high‐dose group. Although episodes of severe infection were more than twice as frequent in the high‐dose group, the difference was not statistically significant.

Conclusion

The data from the ELNT indicate that in European SLE patients with proliferative lupus nephritis, a remission‐inducing regimen of low‐dose IV CYC (cumulative dose 3 gm) followed by AZA achieves clinical results comparable to those obtained with a high‐dose regimen.

     

Agonist substitution—a treatment alternative for high‐dose benzodiazepine‐dependent patients?

There is vast evidence for the superiority of agonist treatments (methadone, buprenorphine) over a withdrawal approach in opioid‐dependent populations. Little research, however, has been conducted on the same approach for the treatment of high‐dose benzodiazepine (BZD) dependence. Even large‐scale reviews and meta‐analyses discussing treatment strategies for benzodiazepine‐dependent patients focus solely upon approaches that aim at achieving abstinence, namely on complete BZD withdrawal. While the types of interventions differ (e.g. gradual benzodiazepine taper with a long or a short half‐life benzodiazepine, switching to non‐benzodiazepine anxiolytics or prescribing adjunctive medications such as antidepressants or anticonvulsants on an in‐ or out‐patient basis), the common aim of treatment still is total abstinence from benzodiazepines. However, the majority of patients suffering from high‐dose BZD dependence do not succeed with long‐term abstinence, irrespective of the procedure, and clinicians have been using BZD ‘substitution’ treatment in such cases for decades. Therefore, we suggest the evaluation of a substitution approach in this group, consisting of maintenance treatment with a slow‐onset, long‐acting BZD. Advantages of such a procedure may be improved health, less craving, fewer withdrawal complications, reduced anxiety, increased treatment retention, improvements in social functioning and less illegal activity. Cognitive impairments, the most problematic side effects of substitution treatment with benzodiazepines, could possibly be minimized by using an optimal agonist.