Effects of adjuvant chemotherapy in HER2-positive or triple-negative pT1ab breast cancers: a multi-institutional retrospective study

Previous studies have reported higher recurrence rates in T1a/b N0 breast cancers characterized by high-risk biology (HER2+ or triple-negative), but the benefits of adjuvant chemotherapy in these patients have not been established. This study was designed to determine whether recurrence risk is reduced with chemotherapy and to define a group of patients most appropriate for treatment based on retrospective data. We pooled cases from two multi-institutional databases spanning the period of 1996–2010. A propensity score model adjusted unbalanced confounders between the groups treated or untreated with adjuvant chemotherapy and, in case of HER2-positive disease, with trastuzumab. Competing risk analysis was utilized to study effects of chemotherapy on cancer recurrences in the matched populations. Among the 318 patients identified, 41 % received adjuvant chemotherapy and 54 % of HER2+ patients received it with trastuzumab. The cumulative risk of recurrence at 5 years was 7.3 %. Age less than 35 years and triple-negative status were the only significant prognostic factors. Overall, administration of chemotherapy was not associated with a significant decrease in the risk of recurrence (HR 0.93, p = 0.91). The rate of recurrence in HER2+ patients who received trastuzumab was lower but not statistically significant (HR 0.50, p = 0.63). Clinical characteristics are of limited prognostic value for stratifying risk of recurrence in very small, node-negative HER2+, or triple-negative cancers. While limited by the small number of events, our analysis does not support the increasingly prevalent practice of administering adjuvant chemotherapy in this population without more accurate prognostic and predictive factors.     

Lumbar disk protrusion rates of symptomatic patients using magnetic resonance imaging

ObjectiveThe purpose of this study was to determine the rate of disk protrusions detected via magnetic resonance imaging (MRI) in patients symptomatic for spine pain, radiculopathy, or other spine-related pain.MethodsA retrospective review of 1983 MRI scans was performed over a 2-year period on 1486 patients, each of whom was symptomatic for spine pain, radiculopathy, or other noncancer, spine-related pain. Of these patients, 761 were scanned in the recumbent position using low-field (0.3 T, Airis II, Hitachi, Twinsburg, Ohio) MRI, and 725 were scanned in an upright, sitting position using mid-field (0.6 T) open Upright MRI (Fonar, Melville, NY). In total, 986 serial scans were performed on patients in the recumbent position and 997 serial scans on patients in the weight-bearing position.ResultsOne or more disk protrusions were identified in 73.3% of scans performed in the sitting position and in 50.1% of scans performed in the recumbent position. Most disk protrusions occurred at L5-S1 (52.3% and 29.8%), L4-L5 (42.6% and 26.7%), and L3-L4 (26.7% and 13.1%) in upright and recumbent positions, respectively.ConclusionsThe disk protrusion rate in this group of patients ranged between 50.1% (recumbent) and 73.3% (weight-bearing). These rates are higher than rates reported in the medical literature for asymptomatic patients, a finding that supports the decision to further evaluate patients with persistent spine-related pain.     

Maternal Directiveness in Interactions with Mentally Handicapped Children: An Analytical Commentary

Maternal directiveness is portrayed as a negative interactional phenomenon in the mental retardation literature. Based on the speculation that a directive interactional style is causally related to poor developmental outcomes, the reduction of maternal directive behaviour is becoming a major thrust in early intervention work. This paper questions the characterization of directiveness as an inherently negative interactional phenomenon and highlights limitations in our current understanding of directiveness. Critical issues requiring attention in future research are identified and early interventionists cautioned that management of maternal directive behaviour must be founded on sound, empirically validated principles.     

Development and evaluation of natural gum-based extended release matrix tablets of two model drugs of different water solubilities by direct compression

The study was aimed at developing extended release matrix tablets of poorly water-soluble diclofenac sodium and highly water-soluble metformin hydrochloride by direct compression using cashew gum, xanthan gum and hydroxypropylmethylcellulose (HPMC) as release retardants. The suitability of light grade cashew gum as a direct compression excipient was studied using the SeDeM Diagram Expert System. Thirteen tablet formulations of diclofenac sodium (∼100 mg) and metformin hydrochloride (∼200 mg) were prepared with varying amounts of cashew gum, xanthan gum and HPMC by direct compression. The flow properties of blended powders and the uniformity of weight, crushing strength, friability, swelling index and drug content of compressed tablets were determined. In vitro drug release studies of the matrix tablets were conducted in phosphate buffer (diclofenac: pH 7.4; metformin: pH 6.8) and the kinetics of drug release was determined by fitting the release data to five kinetic models. Cashew gum was found to be suitable for direct compression, having a good compressibility index (ICG) value of 5.173. The diclofenac and metformin matrix tablets produced generally possessed fairly good physical properties. Tablet swelling and drug release in aqueous medium were dependent on the type and amount of release retarding polymer and the solubility of drug used. Extended release of diclofenac (∼24 h) and metformin (∼8–12 h) from the matrix tablets in aqueous medium was achieved using various blends of the polymers. Drug release from diclofenac tablets fitted zero order, first order or Higuchi model while release from metformin tablets followed Higuchi or Hixson-Crowell model. The mechanism of release of the two drugs was mostly through Fickian diffusion and anomalous non-Fickian diffusion. The study has demonstrated the potential of blended hydrophilic polymers in the design and optimization of extended release matrix tablets for soluble and poorly soluble drugs by direct compression.