A novel initiation codon mutation in the ribosomal protein S17 gene (RPS17) in a patient with Diamond‐Blackfan anemia

Diamond‐Blackfan anemia (DBA) is an inherited bone marrow failure syndrome characterized by pure red cell aplasia, various congenital anomalies, and cancer predisposition. We report a novel mutation in the RPS17 gene in a Korean patient with DBA. The mutation occurred in the translation initiation codon, changing Atg to Gtg (c.1A>G), thus disrupting the natural start of the RPS17 protein biosynthesis. This is the third case of DBA from a RPS17 mutation in the literature and is the second case of a RPS17 mutation in the translation initiation codon, following c.2T>G. Pediatr Blood Cancer 2010;54:629–631. © 2009 Wiley‐Liss, Inc.     

Trimethoprim‐induced immune hemolytic anemia in a pediatric oncology patient presenting as an acute hemolytic transfusion reaction

A 10‐year‐old male with acute leukemia presented with post‐chemotherapy anemia. During red cell transfusion, he developed hemoglobinuria. Transfusion reaction workup was negative. Drug‐induced immune hemolytic anemia was suspected because of positive direct antiglobulin test, negative eluate, and microspherocytes on smear pre‐ and post‐transfusion. Drug studies using the indirect antiglobulin test were strongly positive with trimethoprim and trimethoprim–sulfamethoxazole but negative with sulfamethoxazole. The patient recovered after discontinuing the drug, with no recurrence in 2 years. Other causes of anemia should be considered in patients with worse‐than‐expected anemia after chemotherapy. Furthermore, hemolysis during transfusion is not always a transfusion reaction. Pediatr Blood Cancer. 2010;55:1201–1203. © 2010 Wiley‐Liss, Inc.     

Alogliptin Use in Elderly People: A Pooled Analysis from Phase 2 and 3 Studies

OBJECTIVES: To compare the efficacy and safety of alogliptin, a dipeptidyl peptidase-4 (DPP-4) enzyme inhibitor, in elderly (≥65) and younger (<65) patients with type 2 diabetes mellitus.
DESIGN: Pooled analysis of six randomized, double-blind, placebo-controlled studies of alogliptin.
PARTICIPANTS: Patients aged 18 to 80 with type 2 diabetes mellitus and inadequate glycemic control.
INTERVENTIONS: Elderly (mean age 70.0; n=455) and younger (mean age 51.8; n=1,911) patients received alogliptin 12.5 mg (n=922), alogliptin 25 mg (n=910), or placebo (n=534) for 26 weeks (12 weeks in a Phase 2 study). The studies evaluated alogliptin as monotherapy and coadministered with pioglitazone, glyburide, metformin, or insulin.
MEASUREMENTS: Efficacy endpoints included change from baseline in glycosylated hemoglobin (HbA1c), fasting plasma glucose (FPG), weight, and lipid values. Safety variables included hypoglycemic events, adverse events, and blood pressure.
RESULTS: Least-squares mean HbA1c decreased from baseline by 0.7% and 0.8% in elderly patients receiving alogliptin 12.5 and 25 mg, respectively, and 0.5% and 0.6%, respectively, in younger patients ( P <.001 for both alogliptin doses vs placebo for both age groups P =.70 for 12.5 mg and .68 for 25 mg for differences between age groups). Results were similar for FPG. Incidence of hypoglycemia was 8.3% or less in all alogliptin groups (≤10.5% for placebo), with no apparent difference between elderly and younger patients. Changes in weight were negligible in all treatment groups in both age categories. The safety profiles of alogliptin were similar in the age and dose groups.
CONCLUSION: Alogliptin was effective and well tolerated in the elderly patients enrolled in these studies. Improvements in HbA1c were similar to those seen in younger patients, and no increase in the risk of hypoglycemia, weight gain, or other adverse events was apparent in elderly patients.     

Adaptation and validation of the Portuguese version of the Lithium Knowledge Test (LKT) of bipolar patients treated with lithium: cross-over study

Objective

Adherence problems are a common feature among bipolar patients. A recent study showed that lithium knowledge was the main difference between adherent and non adherents bipolar patients. The Lithium Knowledge Test (LKT), a brief questionnaire, was developed as a means of identifying aspects of patients' practical and pharmacological knowledge which are important if therapy is to be safe and effective. The original English version is validated in psychiatric population, but a validated Portuguese one is not yet available.

Methods

One hundred six patients selected were diagnosed with bipolar disorder (I or II) according to DSM-IV criteria and had to be on lithium treatment for at least one month. The LKT was administered on only one occasion. We analysed the internal consis tency, concurrent validity, sensitivity and specificity of the LKT for the detection of the knowledge about lithium treatment of bipolar patients.

Results

The internal consistency, evaluated by Cronbach's alpha was 0.596. The mean of total score LKT by bipolar patients was 9.0 (SD: 0.75) for men and 8.74 (SD: 0.44) for women. Concurrent validity based on plasma lithium concentration showed a significant correlation between the total LKT score and plasma lithium (r = 0,232; p = 0.020). The sensitivity was 84% and specificity was 81%.

Conclusion

LKT is a rapid, reliable instrument which appears to be as effective as a lengthier standard interview with a lithium clinic doctor, and which has a high level of acceptability to lithium patients. We found that the psychometric assessment of the Portuguese version of LKT showed good internal consistency, sensitivity and specificity.

     

Validation of the Portuguese version of the Lithium Attitudes Questionnaire (LAQ) in bipolar patients treated with lithium: cross-over study

Background

Poor adherence to lithium is very common in bipolar patients and it is a frequent cause of recurrence during prophylactic treatment. Several reports suggest that attitudes of bipolar patients interfere with adherence to lithium. The Lithium Attitudes Questionnaire (LAQ) is a brief questionnaire developed as a means of identifying and grouping the problems patients commonly have with taking lithium regularly. The original version is validated in patients, but a validated version in Portuguese is not yet available.

Methods

One-hundred six patients with bipolar disorder (DSM-IV criteria) criteria under lithium treatment for at least one month were assessed using LAQ. LAQ is a brief questionnaire administered under interview conditions, which includes 19 items rating attitudes towards prophylactic lithium treatment. We analysed the internal consistency, concurrent validity, sensitivity and specificity of the Portuguese version of LAQ.

Results

The internal consistency, evaluated by Cronbach's alpha was 0.78. The mean total LAQ score was 4.1. Concurrent validity was confirmed by a negative correlation between plasma lithium concentration and total LAQ score (r = -0,198; p = 0.048). We analysed the scale's discriminative capacity revealing a sensitivity of 69% and a specificity of 71% in the identification of negative attitudes of bipolar patients.

Conclusion

The psychometric assessment of the Portuguese version of LAQ showed good internal consistency, sensitivity and specificity. The results were similar to the original version in relation to attitudes of bipolar patients towards lithium therapy.

     

Lower mitotic activity in BRCA1/2-associated primary breast cancers occurring after risk-reducing salpingo-oophorectomy

Risk-reducing salpingo-oophorectomy (RRSO) is associated with 50% reduction of BRCA1/2-associated breast cancer (BC) risk, possibly through decreased growth activity. In this pilot study, tumor characteristics and growth rates of BRCA1/2-associated primary BCs (PBCs) detected after RRSO were compared with those of PBCs originating without RRSO. From a cohort of 271 women with BRCA1/2-associated screen detected BC, we selected 20 patients with PBC detected ≥12 months after RRSO (RRSO group). Controls were 36 BRCA1/2 mutation carriers with PBC detected without RRSO (non-RRSO group) matched for age at diagnosis (± 2.5 y) and for BRCA1 or BRCA2 mutation. Pathology samples were revised for histological subtype, tumor differentiation grade, mitotic activity index (MAI), estrogen receptor (ER), progesterone receptor (PR), and HER2 status. Tumor growth rates, expressed as tumor volume doubling times (DT), were calculated from revised magnetic resonance and mammographic images. Median age at PBC diagnosis was 52 y (range 35–67). PBCs after RRSO had lower MAIs (12 vs. 22 mitotic counts/2 mm, P = 0.02), were smaller (11 vs. 17 mm, P = 0.01), and tend to be PR-positive more often than PBCs without RRSO (38% vs. 13%, P = 0.07). Differentiation grade, ER, and HER2 status were not different. Median DT was 124 d (range 89–193) in the RRSO group and 93 days (range 54–253) in the non-RRSO group (P = 0.47). BC occurring after RRSO in BRCA mutation carriers features a lower MAI, suggesting a less aggressive biological phenotype. When confirmed in larger series, this may have consequences for BC screening protocols after RRSO.     

The efficacy of prophylactic intravenous antibiotics in elective foot and ankle surgery

A retrospective chart review of 555 patients who received elective foot and ankle surgeries between 1995 and 2001 at 1 outpatient podiatric hospital clinic was performed to evaluate the efficacy of preoperative intravenous antibiotic use. Only those patients who were having elective foot or ankle surgery for the first time, were being followed up at the hospital's outpatient clinic, and had a nontraumatic cause for their surgery were included in this study. A wound was considered infected when purulent material from the wound sites was noted and an organism(s) was cultured. A wound complication was defined as a superficial dehiscence, edema, erythema, or stitch abscess. Three hundred six (55.1%) patients received a preoperative antibiotic and 249 (44.9%) patients did not. Of the 306 patients who received a preoperative antibiotic, 9 (1.6%) acquired a postoperative wound infection, whereas 8 (1.4%) of the 249 patients who did not receive preoperative antibiotics acquired a postoperative infection. A logistic regression model and chi square tests of association were used to determine if preoperative antibiotic use, age, gender, type of surgical procedure, operative time, tourniquet use, past medical history, and internal fixation were predictive of or associated with postoperative wound infection or complication. None of the study factors was predictive of postoperative wound infection or complication (P >.01). Preoperative antibiotic use was associated with surgical category and internal fixation use (P <.001) but not postoperative wound infection or complication (P >.01). The results suggest that prophylactic intravenous antibiotic use in routine elective foot and ankle surgery is not warranted.