Evaluating the Impact of Source-specific Order Sets for Sepsis on Empiric Antibiotic Selection in the Emergency Department.

This retrospective cohort study found that implementing source-specific antibiotic order sets for sepsis in the emergency department increased appropriate empiric antibiotic selection from 51% to 74% (P = .01).

Isolated Infraspinatus Myositis after Intramuscular Vaccine Administration.

Case: A 74-year-old female developed left shoulder pain after receiving an influenza vaccine. Her initial physical exam was suggestive of subacromial bursitis, and a corticosteroid injection into the subacromial space resulted in a 50% improvement in her pain. Subsequent MRI demonstrated myositis isolated to the infraspinatus muscle. She was successfully treated with anti-inflammatory medication and physical therapy. Conclusion: Shoulder injury related to vaccine administration (SIRVA) is a rare clinical complication, and myositis in the rotator cuff musculature has not been previously reported. Proper administration of intramuscular vaccinations should be emphasized to prevent injury to structures surrounding the shoulder joint.

A Combinatorial Optimization Framework for Scoring Students in University Admissions.

BACKGROUND AND OBJECTIVES: Selecting applications for college admission is critical for university operation and development. This paper leverages machine learning techniques to support enrollment management teams through data-informed decision-making in this otherwise laborious admissions processing. RESEARCH DESIGN AND MEASURES: Two aspects of university admissions are considered. An ensemble learning approach, through the SuperLearner algorithm, is used to predict student show (yield) rate. The goal is to improve prediction accuracy to minimize over- or under-enrollment. A combinatorial optimization framework is proposed to weigh academic performance and experiential factors for ranking and selecting students for admission. This framework uses simulated annealing, and an efficacy study is presented to evaluate performance. RESULTS: The proposed framework is illustrated for selecting an incoming class by optimizing predicted graduation rate and by developing an eligibility index. Each example presents a selection process under potential academic performance and experiential factor targets a university may place on an admitted class. R code is provided for higher education researchers and practitioners to apply the proposed methods in their own settings.

Effect of Lateral Retinacular Release on Medial Patellofemoral Ligament Reconstruction.

BACKGROUND: When performing a medial patellofemoral ligament (MPFL) reconstruction, surgeons may place the MPFL graft under higher than anatomic tension to minimize the chance of recurrent instability. PURPOSE: To investigate whether a lateral retinacular release (LRR) significantly decreases patellofemoral contact pressures after an overtensioned (OT) MPFL reconstruction. STUDY DESIGN: Controlled laboratory study. METHODS: Mean and peak pressure across the patellofemoral joint at 30°, 45°, and 60° of flexion was assessed in 14 cadaveric knee specimens with intact MPFL, transected MPFL, reconstructed MPFL with graft OT, and OT MPFL with LRR. The Wilcoxon signed rank test was used to determine differences across states, with W and C values calculated when possible. RESULTS: Mean pressure decreased significantly after MPFL transection compared with intact at 30° (456.9 ± 116.8 vs 410.9 ± 109.4 N, P = .006, W < 7) and 45° (404.9 ± 91.7 vs 369.4 ± 85.3 N, P = .005, W < 5) and increased significantly from intact to OT graft at 30° (456.9 ± 116.8 vs 563.0 ± 11.2 N, P = .003, W < 7), 45° (404.9 ± 91.7 vs 481.4 ± 14.8 N, P = .005, W < 5), and 60° (272.9 ± 139.0 vs 367.0 ± 53.7 N, P = .007, W < 3). Peak pressure increased significantly between intact and OT graft at 30° (1364.0 ± 478.2 vs 2094.4 ± 619.8 N, P = .002, W < 9), 45° (1224.7 ± 491.5 vs 1676.7 ± 779.1 N, P = .005, W < 5), and 60° (1117.7 ± 566.8 vs 1604.2 ± 772.9 N, W < 3). In knees with significantly increased mean pressure after overtensioning, mean pressure increased by 23.3% (11/14 knees) at 30°, 18.3% (10/14 knees) at 45°, and 35.0% (10/14 knees) at 60°. Peak pressure increased significantly by 35.3% (30°), 25.2% (45°), and 29.3% (60°). A significant decrease in mean pressure, toward but not to baseline, was observed between the OT and LRR states at 30° (563.0 ± 11.2 vs 501.5 ± 9.3 N, W < 7) and 60° (367.0 ± 53.7 vs 302.0 ± 13.8 N, W < 5) and a decrease in peak pressure at 30° (2094.4 ± 619.8 vs 1886.5 ± 655.3 N; W < 9). CONCLUSION: LRR led to a statistically significant decrease in pressure across the patellofemoral joint in knees that demonstrated increased contact pressures after an OT MPFL graft. CLINICAL RELEVANCE: LRR after an MPFL reconstruction in which the MPFL graft has been OT may help reduce patellofemoral contact pressures at the time of surgery.

Influence of developmental nicotine exposure on serotonergic control of breathing-related motor output.

Serotonin plays an important role in the development of brainstem circuits that control breathing. Here, we test the hypothesis that developmental nicotine exposure (DNE) alters the breathing-related motor response to serotonin (5HT). Pregnant rats were exposed to nicotine or saline, and brainstem-spinal cord preparations from 1- to 5-day-old pups were studied in a split-bath configuration, allowing drugs to be applied selectively to the medulla or spinal cord. The activity of the fourth cervical ventral nerve roots (C4VR), which contain axons of phrenic motoneurons, was recorded. We applied 5HT alone or together with antagonists of 5HT1A, 5HT2A, or 5HT7 receptor subtypes. In control preparations, 5HT applied to the medulla consistently reduced C4VR frequency and this reduction could not be blocked by any of the three antagonists. In DNE preparations, medullary 5HT caused a large and sustained frequency increase (10 min), followed by a sustained decrease. Notably, the transient increase in frequency could be blocked by the independent addition of any of the antagonists. Experiments with subtype-specific agonists suggest that the 5HT7 subtype may contribute to the increased frequency response in the DNE preparations. Changes in C4VR burst amplitude in response to brainstem 5HT were uninfluenced by DNE. Addition of 5HT to the caudal chamber modestly increased phasic and greatly increased tonic C4VR activity, but there were no effects of DNE. The data show that DNE alters serotonergic signaling within brainstem circuits that control respiratory frequency but does not functionally alter serotonin signaling in the phrenic motoneuron pool.

UGT1A1 Guided Cancer Therapy: Review of the Evidence and Considerations for Clinical Implementation.

Multi-gene assays often include UGT1A1 and, in certain instances, may report associated toxicity risks for irinotecan, belinostat, pazopanib, and nilotinib. However, guidance for incorporating UGT1A1 results into therapeutic decision-making is mostly lacking for these anticancer drugs. We summarized meta-analyses, genome-wide association studies, clinical trials, drug labels, and guidelines relating to the impact of UGT1A1 polymorphisms on irinotecan, belinostat, pazopanib, or nilotinib toxicities. For irinotecan, UGT1A1*28 was significantly associated with neutropenia and diarrhea, particularly with doses ≥ 180 mg/m2, supporting the use of UGT1A1 to guide irinotecan prescribing. The drug label for belinostat recommends a reduced starting dose of 750 mg/m2 for UGT1A1*28 homozygotes, though published studies supporting this recommendation are sparse. There was a correlation between UGT1A1 polymorphisms and pazopanib-induced hepatotoxicity, though further studies are needed to elucidate the role of UGT1A1-guided pazopanib dose adjustments. Limited studies have investigated the association between UGT1A1 polymorphisms and nilotinib-induced hepatotoxicity, with data currently insufficient for UGT1A1-guided nilotinib dose adjustments.

Repeated measures random forests (RMRF): Identifying factors associated with nocturnal hypoglycemia.

Nocturnal hypoglycemia is a common phenomenon among patients with diabetes and can lead to a broad range of adverse events and complications. Identifying factors associated with hypoglycemia can improve glucose control and patient care. We propose a repeated measures random forest (RMRF) algorithm that can handle nonlinear relationships and interactions and the correlated responses from patients evaluated over several nights. Simulation results show that our proposed algorithm captures the informative variable more often than naïvely assuming independence. RMRF also outperforms standard random forest and extremely randomized trees algorithms. We demonstrate scenarios where RMRF attains greater prediction accuracy than generalized linear models. We apply the RMRF algorithm to analyze a diabetes study with 2524 nights from 127 patients with type 1 diabetes. We find that nocturnal hypoglycemia is associated with HbA1c, bedtime blood glucose (BG), insulin on board, time system activated, exercise intensity, and daytime hypoglycemia. The RMRF can accurately classify nights at high risk of nocturnal hypoglycemia.

Developmental Nicotine Exposure Alters Synaptic Input to Hypoglossal Motoneurons and Is Associated with Altered Function of Upper Airway Muscles.

Nicotine exposure during the fetal and neonatal periods [developmental nicotine exposure (DNE)] is associated with ineffective upper airway protective reflexes in infants. This could be explained by desensitized chemoreceptors and/or mechanoreceptors, diminished neuromuscular transmission or altered synaptic transmission among central neurons, as each of these systems depend in part on cholinergic signaling through nicotinic AChRs (nAChRs). Here, we showed that DNE blunts the response of the genioglossus (GG) muscle to nasal airway occlusion in lightly anesthetized rat pups. The GG muscle helps keep the upper airway open and is innervated by hypoglossal motoneurons (XIIMNs). Experiments using the phrenic nerve-diaphragm preparation showed that DNE does not alter transmission across the neuromuscular junction. Accordingly, we used whole cell recordings from XIIMNs in brainstem slices to examine the influence of DNE on glutamatergic synaptic transmission under baseline conditions and in response to an acute nicotine challenge. DNE did not alter excitatory transmission under baseline conditions. Analysis of cumulative probability distributions revealed that acute nicotine challenge of P1-P2 preparations resulted in an increase in the frequency of nicotine-induced glutamatergic inputs to XIIMNs in both control and DNE. By contrast, P3-P5 DNE pups showed a decrease, rather than an increase in frequency. We suggest that this, together with previous studies showing that DNE is associated with a compensatory increase in inhibitory synaptic input to XIIMNs, leads to an excitatory-inhibitory imbalance. This imbalance may contribute to the blunting of airway protective reflexes observed in nicotine exposed animals and human infants.

Developmental nicotine exposure alters glycinergic neurotransmission to hypoglossal motoneurons in neonatal rats.

We tested the hypothesis that nicotine exposure in utero and after birth [developmental nicotine exposure (DNE)] disrupts development of glycinergic synaptic transmission to hypoglossal motoneurons (XIIMNs). Glycinergic spontaneous and miniature inhibitory postsynaptic currents (sIPSC/mIPSC) were recorded from XIIMNs in brain stem slices from 1- to 5-day-old rat pups of either sex, under baseline conditions and following stimulation of nicotinic acetylcholine (ACh) receptors with nicotine (i.e., an acute nicotine challenge). Under baseline conditions, there were no significant effects of DNE on the amplitude or frequency of either sIPSCs or mIPSCs. In addition, DNE did not alter the magnitude of the whole cell current evoked by bath application of glycine, consistent with an absence of change in postsynaptic glycine-mediated conductance. An acute nicotine challenge (bath application of 0.5 µM nicotine) increased sIPSC frequency in the DNE cells, but not control cells. In contrast, nicotine challenge did not change mIPSC frequency in either control or DNE cells. In addition, there were no significant changes in the amplitude of either sIPSCs or mIPSCs in response to nicotine challenge. The increased frequency of sIPSCs in response to an acute nicotine challenge in DNE cells reflects an enhancement of action potential-mediated input from glycinergic interneurons to hypoglossal motoneurons. This could lead to more intense inhibition of hypoglossal motoneurons in response to exogenous nicotine or endogenous ACh. The former would occur with smoking or e-cigarette use while the latter occurs with changes in sleep state and with hypercapnia. NEW & NOTEWORTHY Here we show that perinatal nicotine exposure does not impact baseline glycinergic neurotransmission to hypoglossal motoneurons but enhances glycinergic inputs to hypoglossal motoneurons in response to activation of nicotinic acetylcholine (ACh) receptors with acute nicotine. Given that ACh is the endogenous ligand for nicotinic ACh receptors, the latter reveals a potential mechanism whereby perinatal nicotine exposure alters motor function under conditions where ACh release increases, such as the transition from non-rapid-eye movement to rapid-eye movement sleep, and during hypercapnia.

Random forests of interaction trees for estimating individualized treatment effects in randomized trials.

Assessing heterogeneous treatment effects is a growing interest in advancing precision medicine. Individualized treatment effects (ITEs) play a critical role in such an endeavor. Concerning experimental data collected from randomized trials, we put forward a method, termed random forests of interaction trees (RFIT), for estimating ITE on the basis of interaction trees. To this end, we propose a smooth sigmoid surrogate method, as an alternative to greedy search, to speed up tree construction. The RFIT outperforms the "separate regression" approach in estimating ITE. Furthermore, standard errors for the estimated ITE via RFIT are obtained with the infinitesimal jackknife method. We assess and illustrate the use of RFIT via both simulation and the analysis of data from an acupuncture headache trial.

Developmental plasticity of GABAergic neurotransmission to brainstem motoneurons.

KEY POINTS: Critical homeostatic behaviours such as suckling, swallowing and breathing depend on the precise control of tongue muscle activity. Perinatal nicotine exposure has multiple effects on baseline inhibitory GABAergic neurotransmission to hypoglossal motoneurons (XIIMNs), consistent with homeostatic compensations directed at maintaining normal motoneuron output. Developmental nicotine exposure (DNE) alters how GABAergic neurotransmission is modulated by acute activation of nicotinic acetylcholine receptors, which may provide insight into mechanisms by which nicotine exposure alters motor function under conditions that result in increased release of GABA, such as hypoxia, or endogenous acetylcholine, as occurs in the transition from NREM to REM sleep, or in response to exogenous nicotine. ABSTRACT: Nicotinic acetylcholine receptor (nAChR) signalling regulates neuronal differentiation and synaptogenesis. Here we test the hypothesis that developmental nicotine exposure (DNE) disrupts the development of GABAergic synaptic transmission to hypoglossal motoneurons (XIIMNs). GABAergic spontaneous and miniature inhibitory postsynaptic currents (sIPSCs/mIPSCs) were recorded from XIIMNs in brainstem slices from control and DNE rat pups of either sex, 1-5 days old, at baseline and following acute stimulation of nAChRs with nicotine. At baseline, sIPSCs were less frequent and smaller in DNE cells (consistent with decreased action potential-mediated GABA release), and mIPSCs were more frequent (consistent with increased vesicular GABA release from presynaptic terminals). Acute nicotine challenge increased sIPSC frequency in both groups, though the increase was greater in DNE cells. Acute nicotine challenge did not change the frequency of mIPSCs in either group, though mIPSC amplitude increased significantly in DNE cells, but not control cells. Stimulation of postsynaptic GABAA receptors with muscimol caused a significantly greater chloride current in DNE cells than in control cells. The increased quantal release of GABA, coupled with the rise in the strength of postsynaptic inhibition may be homeostatic adjustments to the decreased action-potential-mediated input from GABAergic interneurons. However, this will exaggerate synaptic inhibition under conditions where the release of GABA (e.g. hypoxia) or ACh (sleep-wake transitions) is increased. These findings reveal a mechanism that may explain why DNE is associated with deficits in the ability to respond appropriately to chemosensory stimuli or to changes in neuromodulation secondary to changes in central nervous system state.

Developmental nicotine exposure alters potassium currents in hypoglossal motoneurons of neonatal rat.

We previously showed that nicotine exposure in utero and after birth via breast milk [developmental nicotine exposure (DNE)] is associated with many changes in the structure and function of hypoglossal motoneurons (XIIMNs), including a reduction in the size of the dendritic arbor and an increase in cell excitability. Interestingly, the elevated excitability was associated with a reduction in the expression of glutamate receptors on the cell body. Together, these observations are consistent with a homeostatic compensation aimed at restoring cell excitability. Compensation for increased cell excitability could also occur by changing potassium conductance, which plays a critical role in regulating resting potential, spike threshold, and repetitive spiking behavior. Here we test the hypothesis that the previously observed increase in the excitability of XIIMNs from DNE animals is associated with an increase in whole cell potassium currents. Potassium currents were measured in XIIMNs in brain stem slices derived from DNE and control rat pups ranging in age from 0 to 4 days by whole cell patch-clamp electrophysiology. All currents were measured after blockade of action potential-dependent synaptic transmission with tetrodotoxin. Compared with control cells, XIIMNs from DNE animals showed significantly larger transient and sustained potassium currents, but this was observed only under conditions of increased cell and network excitability, which we evoked by raising extracellular potassium from 3 to 9 mM. These observations suggest that the larger potassium currents in nicotine-exposed neurons are an important homeostatic compensation that prevents "runaway" excitability under stressful conditions, when neurons are receiving elevated excitatory synaptic input.NEW & NOTEWORTHY Developmental nicotine exposure is associated with increased cell excitability, which is often accompanied by compensatory changes aimed at normalizing excitability. Here we show that whole cell potassium currents are also increased in hypoglossal motoneurons from nicotine-exposed neonatal rats under conditions of increased cell and network excitability. This is consistent with a compensatory response aimed at preventing instability under conditions in which excitatory synaptic input is high and is compatible with the concept of homeostatic plasticity.

Influence of developmental nicotine exposure on glutamatergic neurotransmission in rhythmically active hypoglossal motoneurons.

Developmental nicotine exposure (DNE) is associated with increased risk of cardiorespiratory, intellectual, and behavioral abnormalities in neonates, and is a risk factor for apnea of prematurity, altered arousal responses and Sudden Infant Death Syndrome. Alterations in nicotinic acetylcholine receptor signaling (nAChRs) after DNE lead to changes in excitatory neurotransmission in neural networks that control breathing, including a heightened excitatory response to AMPA microinjection into the hypoglossal motor nucleus. Here, we report on experiments designed to probe possible postsynaptic and presynaptic mechanisms that may underlie this plasticity. Pregnant dams were exposed to nicotine or saline via an osmotic mini-pump implanted on the 5th day of gestation. We used whole-cell patch clamp electrophysiology to record from hypoglossal motoneurons (XIIMNs) in thick medullary slices from neonatal rat pups (N=26 control and 24 DNE cells). To enable the translation of our findings to breathing-related consequences of DNE, we only studied XIIMNs that were receiving rhythmic excitatory drive from the respiratory central pattern generator. Tetrodotoxin was used to isolate XIIMNs from presynaptic input, and their postsynaptic responses to bath application of l-glutamic acid (glutamate) and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) were studied under voltage clamp. DNE had no influence on inward current magnitude evoked by either glutamate or AMPA. However, in cells from DNE animals, bath application of AMPA was associated with a right shift in the amplitude distribution (P=0.0004), but no change in the inter-event interval distribution of miniature excitatory postsynaptic currents (mEPSCs). DNE had no influence on mEPSC amplitude or frequency evoked by glutamate application, or under (unstimulated) baseline conditions. Thus, in the presence of AMPA, DNE is associated with a small but significant increase in quantal size, but no change in the probability of glutamate release.

Developmental nicotine exposure disrupts dendritic arborization patterns of hypoglossal motoneurons in the neonatal rat.

Maternal smoking or use of other products containing nicotine during pregnancy can have significant adverse consequences for respiratory function in neonates. We have shown, in previous studies, that developmental nicotine exposure (DNE) in a model system compromises the normal function of respiratory circuits within the brainstem. The effects of DNE include alterations in the excitability and synaptic interactions of the hypoglossal motoneurons, which innervate muscles of the tongue. This study was undertaken to test the hypothesis that these functional consequences of DNE are accompanied by changes in the dendritic morphology of hypoglossal motoneurons. Hypoglossal motoneurons in brain stem slices were filled with neurobiotin during whole-cell patch clamp recordings and subjected to histological processing to reveal dendrites. Morphometric analysis, including the Sholl method, revealed significant effects of DNE on dendritic branching patterns. In particular, whereas within the first five postnatal days there was significant growth of the higher-order dendritic branches of motoneurons from control animals, the growth was compromised in motoneurons from neonates that were subjected to DNE. © 2016 Wiley Periodicals, Inc. Develop Neurobiol 76: 1125-1137, 2016.

Developmental nicotine exposure alters cholinergic control of respiratory frequency in neonatal rats.

Prenatal nicotine exposure with continued exposure through breast milk over the first week of life (developmental nicotine exposure, DNE) alters the development of brainstem circuits that control breathing. Here, we test the hypothesis that DNE alters the respiratory motor response to endogenous and exogenous acetylcholine (ACh) in neonatal rats. We used the brainstem-spinal cord preparation in the split-bath configuration, and applied drugs to the brainstem compartment while measuring the burst frequency and amplitude of the fourth cervical ventral nerve roots (C4VR), which contain the axons of phrenic motoneurons. We applied ACh alone; the nicotinic acetylcholine receptor (nAChR) antagonist curare, either alone or in the presence of ACh; and the muscarinic acetylcholine receptor (mAChR) antagonist atropine, either alone or in the presence of ACh. The main findings include: (1) atropine reduced frequency similarly in controls and DNE animals, while curare caused modest slowing in controls but no consistent change in DNE animals; (2) DNE greatly attenuated the increase in C4VR frequency mediated by exogenous ACh; (3) stimulation of nAChRs with ACh in the presence of atropine increased frequency markedly in controls, but not DNE animals; (4) stimulation of mAChRs with ACh in the presence of curare caused a modest increase in frequency, with no treatment group differences. DNE blunts the response of the respiratory central pattern generator to exogenous ACh, consistent with reduced availability of functionally competent nAChRs; DNE did not alter the muscarinic control of respiratory motor output. © 2016 Wiley Periodicals, Inc. Develop Neurobiol 76: 1138-1149, 2016.

Use of Adjuvant Cisplatin-Based Versus Carboplatin-Based Chemotherapy in Non-Small-Cell Lung Cancer: Findings From the Florida Initiative for Quality Cancer Care.

PURPOSE: For patients with resected non-small-cell lung cancer, national guidelines recommend cisplatin-based doublet chemotherapy as the preferred treatment. However, many patients receive a carboplatin-based regimen instead. We aimed to identify factors associated with use of a cisplatin-based regimen and explore its association with other quality-of-care measures. METHODS: This analysis was part of the Florida Initiative for Quality Cancer Care, an audit and feedback project among 11 medical oncology practices. Feedback-sharing sessions based on findings of year 2006 took place in 2008. Eligible patients were random samples of those with resected stage I to III non-small-cell lung cancer treated in 2006 and 2009. RESULTS: In both years combined, 81 patients received adjuvant platinum-based doublets: 33 patients (41%) received cisplatin, and 48 patients (59%) received carboplatin. Use of a cisplatin-based doublet significantly increased in 2009 compared with 2006, from 24% to 56% (P = .006). Multivariable analysis determined that academic practices used cisplatin more frequently than nonacademic practices (odds ratios, 3.26; 95% CI, 1.19 to 8.91; P = .02). Moreover, patients treated in 2009 were more likely to receive cisplatin than those treated in 2006 (odds ratio, 4.89; 95% CI, 1.75 to 13.67; P = .002). No significant association between use of cisplatin and other quality-of-care measures was found. CONCLUSION: In this study, academic practice status and treatment year predicted use of adjuvant cisplatin-based chemotherapy. The increase in use of cisplatin in 2009, as compared with 2006, suggests that audit and feedback may be effective ways to promote such use.

Influence of developmental nicotine exposure on spike-timing precision and reliability in hypoglossal motoneurons.

Smoothly graded muscle contractions depend in part on the precision and reliability of motoneuron action potential generation. Whether or not a motoneuron generates spikes precisely and reliably depends on both its intrinsic membrane properties and the nature of the synaptic input that it receives. Factors that perturb neuronal intrinsic properties and/or synaptic drive may compromise the temporal precision and the reliability of action potential generation. We have previously shown that developmental nicotine exposure (DNE) alters intrinsic properties and synaptic transmission in hypoglossal motoneurons (XIIMNs). Here we show that the effects of DNE also include alterations in spike-timing precision and reliability, and spike-frequency adaptation, in response to sinusoidal current injection. Current-clamp experiments in brainstem slices from neonatal rats show that DNE lowers the threshold for spike generation but increases the variability of spike-timing mechanisms. DNE is also associated with an increase in spike-frequency adaptation and reductions in both peak and steady-state firing rate in response to brief, square wave current injections. Taken together, our data indicate that DNE causes significant alterations in the input-output efficiency of XIIMNs. These alterations may play a role in the increased frequency of obstructive apneas and altered suckling strength and coordination observed in nicotine-exposed neonatal humans.

Florida Initiative for Quality Cancer Care: Changes in Psychosocial Quality of Care Indicators Over a 3-Year Interval.

PURPOSE: Identifying and addressing psychosocial concerns is increasingly recognized as an important aspect of cancer care that needs to be improved. As part of the Florida Initiative for Quality Cancer Care, medical record reviews were conducted to evaluate cancer care, including psychosocial care, at oncology practices in Florida in 2006. Results were subsequently disseminated to the practices, and performance was reassessed at the same practices in 2009. METHODS: Data were available for patients with colorectal, breast, and non-small-cell lung cancer first seen by a medical oncologist in 2006 (n = 1,609) and 2009 (n = 1,720) at the same 10 practice sites. Performance on each psychosocial indicator was evaluated for overall change over time and for variability in change based on practice site and cancer type. RESULTS: The percentage of patients identified as having a problem in emotional well-being increased significantly over time, from 24% to 31% among those assessed (P = .002) and from 13% to 16% overall (P = .026). In contrast, there no significant changes over time in assessment of emotional well-being (53% to 51%, P = .661) or in action taken to address problems (57% to 45%, P = .098). CONCLUSION: Findings suggest more intensive efforts than audit and feedback will be required to improve the quality of psychosocial care and that greater recognition of problems with emotional well-being may tax the ability of practices to link patients with appropriate services. Systematic research is needed to identify and disseminate effective strategies for implementing routine assessment of well-being and addressing the increased demands for care this will generate.

Florida Initiative for Quality Cancer Care: improvements in breast cancer quality indicators during a 3-year interval.

BACKGROUND: The Florida Initiative for Quality Cancer Care (FIQCC), composed of 11 practice sites across Florida, conducted its initial evaluation of adherence to breast cancer quality of care indicators (QCI) in 2006, with feedback provided to encourage quality improvement efforts at participating sites. In this study, our objective was to reassess changes over time resulting from these efforts. STUDY DESIGN: Quality care indicators were derived from the Quality Oncology Practice Initiative, the National Comprehensive Cancer Network, the American College of Surgeons, and expert panel consensus. Medical records were reviewed for breast cancer patients first seen by medical oncologists in 2009 at the FIQCC sites, using the same performance indicators as in 2006. Statistical comparisons of 2006 vs 2009 data across sites were made by Pearson chi-square exact test using Monte Carlo estimation. RESULTS: Charts of 602 patients in 2006 and 636 patients in 2009 were compared. Performance on medical oncology QCI improved over time for documentation of clinical trial participation discussion (p = 0.001), documentation of consent for chemotherapy (p = 0.047), definitive surgery done after neoadjuvant chemotherapy (p = 0.017), and planned dose of chemotherapy consistent with published regimens (p = 0.02). Improvements in surgical QCI were seen for documentation of specimen orientation (p < 0.001), inking of margins (p < 0.0001), and performance of sentinel lymph node biopsy (p = 0.035). CONCLUSIONS: The 2006 FIQCC study identified several medical and surgical oncology QCI improvement needs. Quality improvement efforts resulted in better performance for numerous metrics, therefore speaking to the benefits of reassessment of adherence to performance indicators to guide QCI efforts.

Electrophysiology of arcuate neurokinin B neurons in female Tac2-EGFP transgenic mice.

Neurons in the arcuate nucleus that coexpress kisspeptin, neurokinin B (NKB), and dynorphin (KNDy neurons) play an important role in the modulation of reproduction by estrogens. Here, we study the anatomical and electrophysiological properties of arcuate NKB neurons in heterozygous female transgenic mice with enhanced green fluorescent protein (EGFP) under the control of the Tac2 (NKB) promoter (Tac2-EGFP mice). The onset of puberty, estrous cyclicity, and serum LH were comparable between Tac2-EGFP and wild-type mice. The location of EGFP-immunoreactive neurons was consistent with previous descriptions of Tac2 mRNA-expressing neurons in the rodent. In the arcuate nucleus, nearly 80% of EGFP neurons expressed pro-NKB-immunoreactivity. Moreover, EGFP fluorescent intensity in arcuate neurons was increased by ovariectomy and reduced by 17ß-estradiol (E2) treatment. Electrophysiology of single cells in tissue slices was used to examine the effects of chronic E2 treatment on Tac2-EGFP neurons in the arcuate nucleus of ovariectomized mice. Whole-cell recordings revealed arcuate NKB neurons to be either spontaneously active or silent in both groups. E2 had no significant effect on the basic electrophysiological properties or spontaneous firing frequencies. Arcuate NKB neurons exhibited either tonic or phasic firing patterns in response to a series of square-pulse current injections. Notably, E2 reduced the number of action potentials evoked by depolarizing current injections. This study demonstrates the utility of the Tac2-EGFP mouse for electrophysiological and morphological studies of KNDy neurons in tissue slices. In parallel to E2 negative feedback on LH secretion, E2 decreased the intensity of the EGFP signal and reduced the excitability of NKB neurons in the arcuate nucleus of ovariectomized Tac2-EGFP mice.