Timeline to dysphagia resolution after endoscopic intervention of an interarytenoid defect based on Video Fluoroscopic Swallow Study dysphagia severity.

INTRODUCTION: We previously reported that endoscopic repair of a Type 1 Laryngeal Cleft (LC1) or Deep Interarytenoid Groove (DIG) improves swallowing function postoperatively. However, caregivers often ask about the timeline to resolution of the need for thickening. This study re-examines this cohort to answer this important caregiver-centered question. METHODS: We reassessed a 3-year retrospective, single-center dataset of children with dysphagia found to have a LC-1 or DIG on endoscopic exam. The primary outcome was rate of complete resolution of dysphagia at 2, 6, and 12 months after endoscopic intervention. A sub-group analysis was made based on severity of dysphagia prior to intervention and by type of endoscopic repair. RESULTS: Thirty-nine patients with mean age 1.35 years that had a LC-1 or DIG met criteria for inclusion. Rate of complete dysphagia resolution increased over time. Those with mild dysphagia (flow-reducing nipple and/or IDDSI consistency 1 or 2) had brisker resolution than those with moderate dysphagia (IDDSI consistency 3 or 4) at 2 months (67% vs 5%, p < 0.01) and at 6 months (80% vs 18%, p < 0.01) after endoscopic repair. There was no difference in dysphagia resolution between patients grouped by type of endoscopic repair. CONCLUSION: Addressing an interarytenoid defect in patients will not result in immediate, complete dysphagia resolution in most patients. However, patients that only require a flow-reducing nipple and/or thickening to an IDDSI consistency 1 or 2 have brisker resolution of the need for thickening than those that require an IDSSI consistency 3 or 4 prior to intervention. These results inform pre-operative discussions of the timeline to resolution based upon severity of dysphagia and help manage caregiver expectations.

Reinforcer Pathology: The Behavioral Economics of Abuse Liability Testing.

Understanding the abuse liability of novel drugs is critical to understanding the risk these new compounds pose to society. Behavioral economics, the integration of psychology and economics, can be used to predict abuse liability of novel substances. Here, we describe the behavioral economic concept of reinforcer pathology and how it may predict the use of novel drugs in existing drug-users and initiation of use in the drug-naive.

Medically inoperable peripheral lung cancer treated with stereotactic body radiation therapy.

BACKGROUND: Lung cancer is the most frequent cause of cancer-related death in North America. There is wide variation between patients who are medically inoperable and those managed surgically. The use of stereotactic body radiotherapy (SBRT) has narrowed the gap in survival rates between operative and non-operative management for those with early stage disease. This retrospective study reports outcomes for the treatment of peripheral non-small cell lung carcinoma (NSCLC) with SBRT from a single community practice. METHODS: Sixty-seven consecutive patients (pts) with inoperable, untreated peripheral lung tumors were treated from 2010 through 2012 and included in this study. Stereotactic targeting was facilitated by either spine or lung-based image guidance, either with or without fiducial marker tracking with a frameless robotic radiosurgery system. Peripheral tumors received a median biological effective dose (BED) of 105.6 Gy10 or in terms of a median physical dose, 48 Gy delivered over 4 daily fractions. Survival was measured using the Kaplan-Meier method to determine rates of local control, progression of disease and overall survival. The Cox proportional hazards regression model was used to study the effects of tumor size, stage, histology, patient age, tumor location (lobe), tracking method, and BED on the survival distributions. RESULTS: The median follow-up for this cohort was 24.5 months (range: 2.4-50.3) with an overall (OS) 3-year survival of 62.4 % (95 % CI: 74.3-47.3). The median progression-free survival was 28.5 months (95 % CI: 15.8 months to not reached). Local control (LC), defined as a lack of FDG uptake on PET/CT or the absence of tumor growth was achieved in 60 patients (90.9 %) at the time of first follow-up (median 3 months, range: 1-6). Local control at one year for the entire cohort was 81.8 % (95 % CI, 67.3-90.3). The one-year OS probability among those who achieved local control at first follow-up was 86.2 % (95 % CI, 74.3-92.9) but no patients who did not achieve LC at first follow-up survived one year. Of the 60 pts that achieved initial LC, 16 have died. The rates of local control, progression-free survival and overall survival were not statistically different for patients treated using a fiducial target tracking system versus non-invasive guidance. (p = 0.44, p = 0.97 and p = 0.66, respectively). No National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE-4) grade 3 or greater toxicity was observed. CONCLUSION: SBRT is an effective treatment for medically inoperable NSCLC patients with peripherally located tumors. This therapy appears to be well tolerated with low toxicity, and patient outcomes when using non-invasive tumor tracking systems are not inferior to traditional fiducial-based techniques.

The role of the subthalamic nucleus in response inhibition: evidence from deep brain stimulation for Parkinson's disease.

We measured reaction times during a stop-signal task while patients with Parkinson's disease were on and off unilateral deep brain stimulation (DBS) of the subthalamic nucleus (STN). While reaction times to a "go" stimulus improved, there was no change in reaction times to the "stop" stimulus (SSRTs). However, changes in SSRTs induced by DBS were highly dependent on baseline SSRTs (measured off stimulation), with the greatest improvements being achieved by those with particularly slow reaction times. We therefore selected only those patients whose baseline SSRTs were within the limits of a control sample (N=10). In this group, SSRTs became slower when DBS was on. This finding suggests a role for the STN in response inhibition, which can be interrupted by DBS, observable only when more general improvements in Parkinson's function are minimised. We also compared the effects of unilateral left and right sided stimulation. We found a greater increase in SSRTs after DBS of the left STN.

Expression of basic helix-loop-helix transcription factors in explant hematopoietic progenitors.

The basic helix-loop-helix (bHLH) transcription factors form heterodimers and control steps in cellular differentiation. We have studied four bHLH transcription factors, SCL, lyl-1, E12/E47, and ld-1, in individual lineage-defined progenitors and hematopoietic growth factor-dependent cell lines, evaluating mRNA expression and the effects of growth factors and cell cycle phase on this expression. Single lineage-defined progenitors selected from early murine colony starts and grown under permissive conditions were analyzed by RT-PCR. SCL and E12/E47 were expressed in the vast majority of tri-, bi-, and unilineage progenitors of erythroid, macrophage, megakaryocyte, and neutrophil lineages. Expression for E12/E47 was not seen in unilineage megakaryocyte and erythroid or bilineage neutrophil/mast cell progenitors. Lyl-1 showed a more restricted pattern of expression, although expression was seen in some bi- and unilineage progenitors. No expression was detected in erythroid, erythroid-megakaryocyte-macrophage, macrophage-neutrophil, macrophage, or megakaryocytic progenitors. Id-1, an inhibitory bHLH transcription factor, was also widely expressed in all bi- and unilineage progenitors; only the trilineage erythroid-megakaryocyte-macrophage progenitors failed to show expression. Expression of these factors within a progenitor class was generally heterogeneous, with some progenitors showing expression and some not. This was seen even when two sister cells from the same colony start were analyzed. Id-1, but not E12/E47, mRNA was increased in FDC-P1 and MO7E hematopoietic cell lines after exposure to IL-3 or GM-CSF. Id-1, E12, and lyl-1 showed marked variation at different points in cell cycle in isoleucine-synchronized FDC-P1 cells. These results suggest that SCL, lyl-1, E12/E47, and Id-1 are important in hematopoietic progenitor cell regulation, and that their expression in hematopoietic cells varies in response to cytokines and/or during transit through cell cycle.

Medicare reimbursement for preventive care. Changes in performance of services, quality of life, and health care costs.

A randomized, controlled trial was conducted to assess the effects of a financial and office systems intervention to increase preventive care in physicians' offices for patients aged 65 years or older. A total of 1,914 patients from 10 primary-care medical practices in central North Carolina were randomized within practices to an intervention and a usual-care control group. The intervention consisted of full Medicare reimbursement to physicians for preventive care and health promotion packages (thus making these services free for patients), regular prompting of physicians to routinely schedule preventive care visits, a new office system in which nurses carried out many preventive procedures, and a form for charting preventive care. The performance of screening tests dramatically increased in the intervention group relative to control (P < 0.001), but there was evidence of lack of follow-up of abnormal findings by physicians. At the 2-year follow-up, there were minimal differences between intervention and control groups in health-related quality-of-life indicators. Relative to the $294 per patient 3-year cost to Medicare for waivered services, the intervention was reimbursed-cost neutral or slightly cost reducing ($190 over 3 years) for Medicare. It is concluded that adding reimbursement for preventive services to Medicare--even with the office systems changes made in this study--will not by itself lead to effective implementation of preventive services in community medical practices. To enhance patient benefit from preventive services, greater attention needs to be focused on an organized approach to patient follow-up.

Gunshot wounds to the upper extremity. Evaluation and management of vascular injuries.

Gunshot wounds to the upper extremity are uncommonly life threatening but are associated with a high incidence of significant long-term disability. The identification of vascular injuries is dependent on careful clinical examination and the liberal use of arteriography. Standard techniques of vascular repair should be followed for arterial reconstruction. The rate of successful vascular repair is in excess of 90%, but long-term function is limited by a high incidence of associated nerve injury.

Axillary-contralateral brachial artery bypass for radiation-induced occlusion of the subclavian artery.

Symptomatic occlusion of the subclavian artery is a rare complication of radiation therapy for carcinoma of the breast. The first case of revascularization of this entity using saphenous vein was described in 1974. A total of only 24 patients have been reported in the English literature, of whom 14 have undergone successful arterial reconstruction. Three additional cases of occlusion of the subclavian artery 27, 18 and 7 years after radical mastectomy and postoperative radiotherapy are reported. These patients presented with pain, coldness, paresthesia and absence of pulses in the affected arm, and angiographic evidence of complete occlusion of the subclavian artery. All patients underwent axillary-contralateral brachial artery reconstruction using a 6-mm polytetrafluoroethylene graft tunneled subcutaneously through the previously irradiated area. In each case, the patient noted complete resolution of symptoms with the return of palpable distal pulses. One patient had a thrombosed graft 5 weeks after initial surgery and underwent successful thrombectomy. There were no complications associated with the subcutaneous tunnel or the production of a subclavian steal syndrome. Although there are other possibilities for the origin of the bypass, this technique avoids extensive dissection in previously irradiated areas and does not require complicated dissection of the subclavian artery or clamping of the carotid artery.

The effect of electromagnetic stimulation of the posterior parietal cortex on eye movements.

The posterior parietal cortex probably plays a central role in the sensorimotor transformations needed to make an accurate saccadic eye movement to a visual target. In an attempt to disrupt the normal programming of saccades, we magnetically stimulated the posterior parietal cortex in human volunteers, 80 ms after a small target moved 5 degrees horizontally from the centre of a VDU screen. Saccadic eye movements were recorded and experimental trials were compared with control, unstimulated trials. Magnetic stimulation was triggered in 70% of the trials selected randomly. The main effects of stimulation were: increased divergence of the eyes before each saccade, greater latency of saccade onset, and a tendency to undershoot the target. These results support the hypothesis that the posterior parietal cortex is involved in the programming of accurate saccades to visual targets.

The effects of a hyperosmolar intravenous contrast medium on blood viscosity.

The effects of the hyperosmolar contrast medium, diatrizoate meglumine (Renografin-76) on blood viscosity and other metabolic parameters were measured in 20 immature piglets. Intravenous contrast medium caused a significant (P less than .5) increase in serum osmolality, cardiac output, and urine output, and a decrease in hematocrit. There was a fall in blood viscosity that was not statistically significant. These changes, which are attributed to an acute shift of fluid into the hyperosmolar vascular compartment, were greatest at 3 minutes following injection and subsequently returned towards baseline levels. We conclude that blood viscosity is not increased following intravenous injection of hyperosmolar radiocontrast media.

The treatment of patients with asthma by specialists and generalists.

The authors investigated possible differences between specialists and generalists in the intensity with which they treat patients with asthma by studying the care of 283 patients between the ages of six and 40 provided by 13 allergists and 40 randomly selected physicians in two primary care specialties: pediatrics and family practice. After excluding patients with more than one physician, allergists' patients were nearly identical to primary care physicians' patients in the frequency and duration of symptoms, and they had a similar number of asthma-related emergency room visits in the previous year and asthma-related hospitalizations in the preceding 3 years. The allergists treated their patients significantly more intensively than did the primary care physicians. Sixty-two percent of allergists' patients had received oral corticosteroids in the preceding year compared with 30% of primary care patients (P less than 0.001). More of the allergists' patients had received oral corticosteroids throughout the year (9% vs. 0%, respectively, P less than 0.01). They were also more likely to have used corticosteroid inhalers (46% vs. 19%) and a greater number of asthma medications (mean = 2.8 vs. 1.3). In a separate survey of the same physicians, using clinical vignettes, the allergists were more likely to prescribe corticosteroid tablets and inhalers. These findings suggest that specialists and generalists differ in the intensity with which they treat patients with asthma and cannot be explained by patient selection or severity differences.

Comparison of the structural organization and expression of germinal and somatic rat histone H4 genes.

A rat somatic histone H4 gene was isolated by screening a rat genomic library using a cloned cell-cycle-regulated human histone H4 gene as a probe. The somatic histone H4 gene was subcloned and the nucleotide sequence was determined. The structural organization and expression of the somatic histone H4 gene and the rat germinal histone H4t gene were compared. Although the predicted amino-acid sequences of the two histones were identical, 49 out of 102 codons differed. The leader sequence of the germinal histone H4t mRNA was 17 bases compared to 40 bases for the somatic histone H4 mRNA, and the 3' terminal sequence of the germinal histone H4t mRNA was 52 bases compared to 75 bases for the somatic histone H4 mRNA. The germinal histone H4 gene also lacked a consensus purine-rich motif which was present in the 5' noncoding region of the somatic histone H4 gene. Northern blot analyses and S1-nuclease protection analyses revealed that the germinal histone H4t and H1t genes were expressed during spermatogenesis in rat pachytene spermatocytes, and the somatic histone H4 gene was expressed only in nongerminal rat cells and tissues. The histone H4t gene was also expressed in some other rat cell types. The differences in expression of the histone H4t and H1t genes may reflect differences in transcription, differences in turnover rates of the mRNAs, or a combination of these factors.

Hemodynamic effects of verapamil in the beta-blocked dog.

The use of the calcium channel-blocking agent, verapamil, in beta-blocked patients has been the subject of intense investigation, particularly because both verapamil and the beta-blockers can produce negative inotropic effects. We studied the hemodynamic effects of verapamil in beta-blocked dogs to establish specific measurements that could be used clinically for early identification of combined negative inotropism. Seven anesthetized, mongrel dogs were beta-blocked with propranolol, and then given 2.5-, 5.0-, and 10.0-mg iv boluses of verapamil. The 2.5- and 5.0-mg boluses represent clinical doses, whereas the 10.0-mg bolus is a large pharmacologic dose. Hemodynamic measurements showed that verapamil was well tolerated at clinical doses; increases in stroke volume compensated for decreases in mean arterial pressure. At high doses of verapamil this response was not observed and left ventricular stroke work decreased. Cardiac and stroke indices were not useful indicators of combined drug toxicity in this dog model.

An evaluation of subsidized rural primary care programs: I. A typology of practice organizations.

The design of a comprehensive evaluation of subsidized rural primary care programs on a large national scale is described, Its major purpose is to derive data whose analysis will answer major policy questions about the factors influencing the outcome of the major types of such programs in different communities. This first paper also delineates a typology which was developed of five principal organizational forms of these programs. This classification appears to provide suitable operational definitions of forms of rural practice as a basis for evaluating the differential impact of alternative types of primary care programs.

The program implications of administrative relationships between local health departments and state and local government.

A typology of organizational arrangements between state and local public health agencies was used as a framework within which the organizational environment of the local health department was studied for its effects on program development and implementation by local public health departments. Data collected in a national sample of local health officers were used in measuring the effect of four different patterns of administrative relationships on the selected characteristics of local health department programs. Important differences were observed among the four organizational types with regard to constraints on programs and program priorities, and health officers' perceptions of the primary functions of local health departments and sources of local health department funding. These findings were then used as a baseline from which to consider the possible impact of recent federal health budgetary proposals (specifically, block grants) both on existing patterns of intergovernmental relations and on the funding and operation of local health department programs. It was determined that the most likely general development arising from these proposed changes in federal budgetary policy is that the administrative control of state health agencies over those at the local level is likely to be enhanced. Other likely developments include changes in the programs and priorities of local health departments related to reductions in overall funding levels for human services and forced competition for fewer dollars by an enlarged constituency.