The Effect of Alendronate on Subsidence After Lateral Transpsoas Interbody Fusion: A Preliminary Report.

BACKGROUND: Success after lateral transpsoas interbody fusion (LLIF) partially depends on avoidance of subsidence to maintain spinal alignment, disc space height, and indirect neural decompression. Techniques for preventing subsidence have focused largely on surgical and biomechanical properties of spinal reconstruction; however, medical management may also affect subsidence rates as well. The purpose of this study is to examine the effect of alendronate on minimally invasive LLIF patients with regard to radiographic and catastrophic subsidence. METHODS: We followed 26 patients who had LLIF at the L4-5 level (13 on alendronate, 13 control) and 22 patients at the L3-4 level (10 on alendronate, 12 control). Radiographs were reviewed to obtain measurements of subsidence at the 4 corners of the cage at 3 follow-up time points (2-3, 5-8, and 10-12 months). A Tobit mixed model was used to confirm the results. RESULTS: We found no relationship between alendronate and subsidence for L3-4 fusion. At L4-5 we observed increased subsidence in the control group compared to the alendronate group (difference = 0.07 cm, 95% confidence interval [CI]: -0.01, 0.16, P = .08). There was a decrease in subsidence noted for the alendronate group for each time period (differences: 2-3: -0.06 cm, 95% CI: -0.28, 0.15], P = .27; 5-8: -0.14 cm, 95% CI: -0.36, .08, P = .10; 10-12: -0.21 cm, 95% CI: -0.48, .04, P = .05). CONCLUSIONS: A clear reduction in subsidence was found with the use of postoperative alendronate in patients undergoing L4-5 LLIF. Alendronate had a significant decrease in subsidence at L4-5 after 10-12 months as compared to the control group. Additionally, no patients treated with alendronate had catastrophic subsidence. These data suggest the need for further study of alendronate in the prevention of subsidence after LLIF. LEVEL OF EVIDENCE: 3.

Identifying the Risk of Swallowing-Related Pulmonary Complications in Older Patients With Hip Fracture.

To identify and potentially modify the risk of pulmonary complications in a group of older patients with hip fracture, the authors obtained speech and language pathology consultations for these patients. Then they performed a retrospective chart review of all patients 65 years and older who were admitted to their institution between June 2011 and July 2013 with acute hip fracture, were treated surgically, and had a speech and language pathology evaluation in the immediate perioperative period. The authors identified 52 patients who met the study criteria. According to the American Society of Anesthesiologists (ASA) classification system, at the time of surgery, 1 patient (2%) was classified as ASA I, 12 patients (23%) were ASA II, 26 (50%) were ASA III, and 12 (23%) were ASA IV. Based on a speech and language pathology evaluation, 22 patients (42%) were diagnosed with dysphagia. Statistical analysis showed that ASA III status and ASA IV status were meaningful predictors of dysphagia and that dysphagia itself was a strong risk factor for pulmonary aspiration, pneumonia, and aspiration pneumonitis. Evaluation by a speech and language pathologist, particularly of patients classified as ASA III or ASA IV, may be an efficient means of averting pulmonary morbidity that is common in older patients with hip fracture.

Cumulative impact of periodic top-down communications on infection prevention practices and outcomes in two units.

BACKGROUND: The problem of interest in this study is the challenge of consistent implementation of evidence-based infection prevention practices at the unit level, a challenge broadly characterized as "change implementation failure." The theoretical literature suggests that periodic top-down communications promoting tacit knowledge exchanges across professional subgroups may be effective for enabling change in health care organizations. However, gaps remain in understanding the mechanisms by which top-down communications enable practice change at the unit level. Our study sought to both validate the theoretical literature and address this gap. PURPOSE: Correspondingly, this study posed two research questions. (1) What is the impact of periodic "top-down" communications on practice change at the unit level? (2) What are the "unit-level" communication dynamics enabling practice changes? Whereas this article focuses on addressing the first question, the second question has been addressed in an earlier Health Care Management Review article (Rangachari et al., 2013). METHODS: A prospective study was conducted in two intensive care units at an academic health center. Both units had low baseline adherence to central line bundle (CLB) and higher-than-expected catheter-related bloodstream infections (CRBSIs). Periodic top-down communication interventions were conducted over 52 weeks to promote CLB adherence in both units. Simultaneously, the study examined (a) unit-level communication dynamics related to CLB through weekly "communication logs," completed by unit physicians, nurses, and managers, and (b) unit outcomes, that is, CLB adherence and CRBSI rates. FINDINGS: Both units showed increased adherence to CLB and significant, sustained declines in CRBSIs. Results showed that the interventions cumulatively had a significant negative (desired) impact on "catheter days," that is, central catheter use. PRACTICE IMPLICATIONS: Results help validate the theoretical literature and identify evidence-based management strategies for practice change at the unit level. They suggest that periodic top-down communications have the potential to modify interprofessional knowledge exchanges and enable practice change at the unit level, leading to significantly improved outcomes and reduced costs.

Comparative cytogenetic characterization of primary canine melanocytic lesions using array CGH and fluorescence in situ hybridization.

Melanocytic lesions originating from the oral mucosa or cutaneous epithelium are common in the general dog population, with up to 100,000 diagnoses each year in the USA. Oral melanoma is the most frequent canine neoplasm of the oral cavity, exhibiting a highly aggressive course. Cutaneous melanocytomas occur frequently, but rarely develop into a malignant form. Despite the differential prognosis, it has been assumed that subtypes of melanocytic lesions represent the same disease. To address the relative paucity of information about their genomic status, molecular cytogenetic analysis was performed on the three recognized subtypes of canine melanocytic lesions. Using array comparative genomic hybridization (aCGH) analysis, highly aberrant distinct copy number status across the tumor genome for both of the malignant melanoma subtypes was revealed. The most frequent aberrations included gain of dog chromosome (CFA) 13 and 17 and loss of CFA 22. Melanocytomas possessed fewer genome wide aberrations, yet showed a recurrent gain of CFA 20q15.3-17. A distinctive copy number profile, evident only in oral melanomas, displayed a sigmoidal pattern of copy number loss followed immediately by a gain, around CFA 30q14. Moreover, when assessed by fluorescence in situ hybridization (FISH), copy number aberrations of targeted genes, such as gain of c-MYC (80 % of cases) and loss of CDKN2A (68 % of cases), were observed. This study suggests that in concordance with what is known for human melanomas, canine melanomas of the oral mucosa and cutaneous epithelium are discrete and initiated by different molecular pathways.

The evolution of knowledge exchanges enabling successful practice change in two intensive care units.

BACKGROUND: Many hospitals are unable to consistently implement evidence-based practices. For example, implementation of the central line bundle (CLB), known to prevent catheter-related bloodstream infections (CRBSIs), is often challenging. This problem is broadly characterized as "change implementation failure." PURPOSE: The theoretical literature on organizational change has suggested that periodic top-down communications promoting tacit knowledge exchanges across professional subgroups may be effective for enabling learning and change in health care organizations. However, gaps remain in understanding the mechanisms by which top-down communications enable practice change at the unit level. Addressing these gaps could help identify evidence-based management strategies for successful practice change at the unit level. Our study sought to address this gap. METHODS: A prospective study was conducted in two intensive care units within an academic health center. Both units had low baseline adherence to CLB and higher-than-expected CRBSIs. Periodic top-down quality improvement communications were conducted over a 52-week period to promote CLB implementation in both units. Simultaneously, the study examined (a) the content and frequency of communication related to CLB through weekly "communication logs" completed by unit physicians, nurses, and managers and (b) unit outcomes, that is, CLB adherence rates through weekly chart reviews. FINDINGS: Both units experienced substantially improved outcomes, including increased adherence to CLB and statistically significant (sustained) declines in both CRBSIs and catheter days (i.e., central line use). Concurrently, both units indicated a statistically significant increase in "proactive" communications-that is, communications intended to reduce infection risk-between physicians and nurses over time. Further analysis revealed that, during the early phase of the study, "champions" emerged within each unit to initiate process improvements. PRACTICE IMPLICATIONS: The study helps identify evidence-based management strategies for successful practice change at the unit level. For example, it underscores the importance of (a) screening each unit for change champions and (b) enabling champions to emerge from within the unit to foster change implementation.

Genetic heterogeneity beyond CYP2C8*3 does not explain differential sensitivity to paclitaxel-induced neuropathy.

The development of paclitaxel-induced peripheral neuropathy (PIPN) is influenced by drug exposure and patient genetics. The purpose of this analysis was to expand on a previous reported association of CYP2C8*3 and PIPN risk by investigating additional polymorphisms in CYP2C8 and in hundreds of other genes potentially relevant to paclitaxel pharmacokinetics. Clinical data was collected prospectively in an observational registry of newly diagnosed breast cancer patients. Patients treated with paclitaxel-containing regimens were genotyped using the Affymetrix DMET™ Plus chip. Patients who carried the CYP2C8*2, *3, or *4 variant were collapsed into a low-metabolizer CYP2C8 phenotype for association with PIPN. Separately, all SNPs that surpassed quality control were assessed individually and as a composite of genetic ancestry for associations with PIPN. 412 paclitaxel-treated patients and 564 genetic markers were included in the analysis. The risk of PIPN was significantly greater in the CYP2C8 low-metabolizer group (HR = 1.722, p = 0.018); however, the influences of the *2 and *4 SNPs were not independently significant (*2: p = 0.847, *4: p = 0.408). One intronic SNP in ABCG1 (rs492338) surpassed the exploratory significance threshold for an association with PIPN in the Caucasian cohort (p = 0.0008) but not in the non-Caucasian replication group (p = 0.54). Substantial genetic variability was observed within self-reported racial groups but this genetic variability was not associated with risk of grade 2+ PIPN. The pharmacogenetic heterogeneity within a cohort of breast cancer patients is dramatic, though we did not find evidence that this heterogeneity directly influences the risk of PIPN beyond the contribution of CYP2C8*3.

Role of communication content and frequency in enabling evidence-based practices.

Many hospitals are unable to successfully implement evidence-based practices. For example, implementation of the central line bundle (CLB), proven to prevent catheter-related bloodstream infections (CRBSIs), is often challenging. This problem is broadly characterized as a "change implementation failure." A prospective study was conducted in 2 intensive care units (ICUs), a medical ICU (MICU) and a pediatric ICU (PICU), within an academic health center. Both units had low baseline adherence to CLB and higher-than-expected CRBSIs. The study sought to promote CLB implementation in both units through periodic quality improvement (QI) interventions over a 52-week period. Simultaneously, it examined (1) the content and frequency of communication related to CLB through weekly "communication logs" completed by physicians, nurses, and managers, and (2) outcomes, that is, CLB adherence rates through weekly medical record reviews. The aim of the study was 2-fold: (1) to examine associations between QI interventions and communication content and frequency at the unit level, and (2) to examine associations between communication content and frequency and outcomes at the unit level. The periodic QI interventions were expected to increase CLB adherence and reduce CRBSIs through their influence on communication content and frequency. A total of 2638 instances of communication were analyzed. Both units demonstrated a statistically significant increase in "proactive" communications-that is, communication intended to reduce infection risk between physicians and nurses over time. Proactive communications increased by 68% in the MICU (P < .05) and 61% in the PICU (P < .05). During the same timeframe, both units increased CLB adherence to 100%. Both units also demonstrated statistically significant declines in (1) catheter days: 34% decline in the MICU (P < .05) and 30% in the PICU (P < .05); and (2) CRBSI rates: 63% decline in the MICU (P < .05) and 100% in the PICU (P < .10). Direct costs savings from reduced CRBSIs in 1 year were estimated to be at least $840 000. Periodic QI interventions were effective in reframing interprofessional communication dynamics and enabling practice change. The prospective design provides insights into communication content and frequency associated with collective learning and culture change. The study identifies evidence-based management strategies for positive practice change at the unit level.

Evaluation of calling algorithms for array-CGH.

Copy number variation (CNV) detection has become an integral part many of genetic studies and new technologies promise to revolutionize our ability to detect and link them to disease. However, recent studies highlight discrepancies in the genome wide CNV profile when measured by different technologies and even by the same technology. Furthermore, the change point algorithms used to call CNVs can have substantial disagreement on the same data set. We focus this article on comparative genomic hybridization (CGH) arrays because this platform lends itself well to accurate statistical modeling. We describe some newer methodological developments in local statistics that are well suited for CNV detection and calling on CGH arrays. Then we use both simulation studies and public data to compare these new local methods with the global methods that currently dominate literature. These results offer suggestions for choosing a particular method and provide insight to the lack of reproducibility that has been seen in the field so far.

Metal-dependent reaction tuning with cyclopentylmetal reagents: application to the asymmetric synthesis of (+)-alpha-conhydrine and (S)-2-cyclopentyl-2-phenylglycolic acid.

The reaction profile of the cyclopentyl organometallic reagents with the aliphatic ketones can be tuned to reduction or addition by changing the metal atom. Cyclopentylmagnesium bromide (CPMB) reduces aromatic and aliphatic aldehydes and ketones to the corresponding alcohols without any C-C bond formation and shows good diastereoselectivity in the reduction of the substituted cyclic and polycyclic ketones as well as chiral alpha-oxygenated aliphatic ketones. However, in the presence of 10 mol % of ZnCl(2), the cyclopentylmagnesium halides follow a normal Grignard addition to the ketones to give tertiary alcohols with complete diastereoselectivity. The reductive as well as the addition protocols were used for the asymmetric synthesis of two medicinally important compounds, (+)-alpha-conhydrine and (S)-2-cyclopentyl-2-phenylglycolic acid.