Citations

The ability to aggregate clinical data across multiple diverse organizations and to use it for performance measurement, quality improvement, evaluation, and research is rapidly becoming a national necessity, but there are few examples of how to do that. This article uses lessons from a national effort to implement the collaborative care management model for patients with both depression and diabetes or heart disease across 8 partner organizations, 18 medical groups, and more than 170 clinics in 8 states to identify the challenges and provide experience-based recommendations for those tasks. The challenges are divided into those needed for (1) collecting similar data, (2) aggregating those data across care systems, and (3) using the data to both improve and evaluate care. Start with agreement on goals, methods, transparency, and a data system integrated into the electronic medical record while promptly addressing all the legal, regulatory, and human subject requirements.

Objective: To update the 2002 version of “Clinical practice guidelines for sustained neuromuscular blockade in the adult critically ill patient.” Design: A Task Force comprising 17 members of the Society of Critical Medicine with particular expertise in the use of neuromuscular-blocking agents; a Grading of Recommendations Assessment, Development, and Evaluation expert; and a medical writer met via teleconference and three face-to-face meetings and communicated via e-mail to examine the evidence and develop these practice guidelines. Annually, all members completed conflict of interest statements; no conflicts were identified. This activity was funded by the Society for Critical Care Medicine, and no industry support was provided. Methods: Using the Grading of Recommendations Assessment, Development, and Evaluation system, the Grading of Recommendations Assessment, Development, and Evaluation expert on the Task Force created profiles for the evidence related to six of the 21 questions and assigned quality-of-evidence scores to these and the additional 15 questions for which insufficient evidence was available to create a profile. Task Force members reviewed this material and all available evidence and provided recommendations, suggestions, or good practice statements for these 21 questions. Results: The Task Force developed a single strong recommendation: we recommend scheduled eye care that includes lubricating drops or gel and eyelid closure for patients receiving continuous infusions of neuromuscular-blocking agents. The Task Force developed 10 weak recommendations. 1) We suggest that a neuromuscular-blocking agent be administered by continuous intravenous infusion early in the course of acute respiratory distress syndrome for patients with a Pa o 2 /F io 2 less than 150. 2) We suggest against the routine administration of an neuromuscular-blocking agents to mechanically ventilated patients with status asthmaticus. 3) We suggest a trial of a neuromuscular-blocking agents in life-threatening situations associated with profound hypoxemia, respiratory acidosis, or hemodynamic compromise. 4) We suggest that neuromuscular-blocking agents may be used to manage overt shivering in therapeutic hypothermia. 5) We suggest that peripheral nerve stimulation with train-of-four monitoring may be a useful tool for monitoring the depth of neuromuscular blockade but only if it is incorporated into a more inclusive assessment of the patient that includes clinical assessment. 6) We suggest against the use of peripheral nerve stimulation with train of four alone for monitoring the depth of neuromuscular blockade in patients receiving continuous infusion of neuromuscular-blocking agents. 7) We suggest that patients receiving a continuous infusion of neuromuscular-blocking agent receive a structured physiotherapy regimen. 8) We suggest that clinicians target a blood glucose level of less than 180 mg/dL in patients receiving neuromuscular-blocking agents. 9) We suggest that clinicians not use actual body weight and instead use a consistent weight (ideal body weight or adjusted body weight) when calculating neuromuscular-blocking agents doses for obese patients. 10) We suggest that neuromuscular-blocking agents be discontinued at the end of life or when life support is withdrawn. In situations in which evidence was lacking or insufficient and the study results were equivocal or optimal clinical practice varies, the Task Force made no recommendations for nine of the topics. 1) We make no recommendation as to whether neuromuscular blockade is beneficial or harmful when used in patients with acute brain injury and raised intracranial pressure. 2) We make no recommendation on the routine use of neuromuscular-blocking agents for patients undergoing therapeutic hypothermia following cardiac arrest. 3) We make no recommendation on the use of peripheral nerve stimulation to monitor degree of block in patients undergoing therapeutic hypothermia. 4) We make no recommendation on the use of neuromuscular blockade to improve the accuracy of intravascular-volume assessment in mechanically ventilated patients. 5) We make no recommendation concerning the use of electroencephalogram-derived parameters as a measure of sedation during continuous administration of neuromuscular-blocking agents. 6) We make no recommendation regarding nutritional requirements specific to patients receiving infusions of neuromuscular-blocking agents. 7) We make no recommendation concerning the use of one measure of consistent weight over another when calculating neuromuscular-blocking agent doses in obese patients. 8) We make no recommendation on the use of neuromuscular-blocking agents in pregnant patients. 9) We make no recommendation on which muscle group should be monitored in patients with myasthenia gravis receiving neuromuscular-blocking agents. Finally, in situations in which evidence was lacking or insufficient but expert consensus was unanimous, the Task Force developed six good practice statements. 1) If peripheral nerve stimulation is used, optimal clinical practice suggests that it should be done in conjunction with assessment of other clinical findings (e.g., triggering of the ventilator and degree of shivering) to assess the degree of neuromuscular blockade in patients undergoing therapeutic hypothermia. 2) Optimal clinical practice suggests that a protocol should include guidance on neuromuscular-blocking agent administration in patients undergoing therapeutic hypothermia. 3) Optimal clinical practice suggests that analgesic and sedative drugs should be used prior to and during neuromuscular blockade, with the goal of achieving deep sedation. 4) Optimal clinical practice suggests that clinicians at the bedside implement measure to attenuate the risk of unintended extubation in patients receiving neuromuscular-blocking agents. 5) Optimal clinical practice suggests that a reduced dose of an neuromuscular-blocking agent be used for patients with myasthenia gravis and that the dose should be based on peripheral nerve stimulation with train-of-four monitoring. 6) Optimal clinical practice suggests that neuromuscular-blocking agents be discontinued prior to the clinical determination of brain death.

AbstractObjectivesto compare healthcare utilization including coronary angiography, percutaneous coronary intervention (PCI), rehospitalization, and rate of subsequent acute myocardial infarction (AMI) within 30 days, among patients presenting to the emergency department (ED) with chest pain admitted as short‐term inpatient (≤2 days) versus observation (in‐ED observation units combined with in‐hospital observation).MethodsWe identified adults diagnosed with acute chest pain in the ED from 2010 to 2014 using administrative claims from privately insured and Medicare Advantage. Patients having AMI during the index visit were excluded. One‐to‐one propensity‐score matching and logistic regression were used. Odds ratios (ORs) with 95% confidence intervals (CIs) were reported.ResultsA total of 774,017 chest pain visits were included. After matching, healthcare utilization was lower among observation versus short inpatient, with 10.9% versus 24.4% (OR = 0.38, 95% CI = 0.36 to 0.39) undergoing cardiac catheterization and 1.8% versus 7.6% (OR = 0.23, 95% CI = 0.21 to 0.24) having PCI. The incidence of subsequent AMI within the following 30 days was similar in patients admitted as observation versus short inpatient (0.23% vs. 0.21%; OR = 1.09, 95% CI = 0.84 to 1.42).ConclusionsThere were higher rates of cardiac catheterization and PCI among those admitted as a short inpatient compared to observation, while the incidence of subsequent AMI within 30 days was similar.

Objective Oesophageal adenocarcinoma (OA) incidence has risen sharply in Western countries over recent decades. Local and systemic inflammation is considered an important contributor to OA pathogenesis. Established risk factors for OA and its precursor, Barrett's oesophagus (BE), include symptomatic reflux, obesity and smoking. The role of inherited genetic susceptibility remains an area of active investigation. Here, we explore whether germline variation related to inflammatory processes influences susceptibility to BE/OA. Design We used data from a genomewide association study of 2515 OA cases, 3295 BE cases and 3207 controls. Our analysis included 7863 single-nucleotide polymorphisms (SNPs) in 449 genes assigned to five pathways: cyclooxygenase (COX), cytokine signalling, oxidative stress, human leucocyte antigen and nuclear factor-κB. A principal components-based analytic framework was employed to evaluate pathway-level and gene-level associations with disease risk. Results We identified a significant signal for the COX pathway in relation to BE risk (p=0.0059, false discovery rate q=0.03), and in gene-level analyses found an association with microsomal glutathione-S-transferase 1 (MGST1); (p=0.0005, q=0.005). Assessment of 36 MGST1 SNPs identified 14 variants associated with elevated BE risk (q<0.05). Four of these were subsequently confirmed (p<5.5×10−5) in a meta-analysis encompassing an independent set of 1851 BE cases and 3496 controls, and are known strong expression quantitative trait loci for MGST1. Three such variants were associated with similar elevations in OA risk. Conclusions This study provides the most comprehensive evaluation of inflammation-related germline variation in relation to risk of BE/OA and suggests that variants in MGST1 influence disease susceptibility.

Abstract Several papers have implicated mutations in the AT-rich interactive domain containing protein 1B (ARID1B) in carcinoma formation in multiple tissue types, including the lung. The ARID1B protein functions as part of SWI/SNF, a multi-subunit chromatin remodeling complex that repositions nucleosomes and may act as a tumor suppressor in cancer. ARID1B is located in a region in 6q that was previously shown to have strong evidence of linkage with lung cancer risk. As it is one of the more promising candidates within the target region, this study presents the viability of ARID1B as a candidate gene for familial lung cancer. Here, we chose individuals from families in our previous linkage study that showed the strongest linkage signal on 6q. 75 individuals from 9 families were sequenced for 37Mb of chromosome 6 from 130Mb to 167Mb using Illumina technology and a custom Agilent kit. Genotypes were imported into GoldenHelix SVS 7 for quality control and dropped if read depth &lt; 10, quality score &lt; 10 or a quality score to read depth ratio &lt; 0.5. Variants with more than 1 Mendelian error were dropped. Variants with a single Mendelian inconsistency were dropped only for that family. Two-point parametric linkage analysis at theta = 0 was performed using R and an implementation of the Elston-Stewart algorithm in the paramlink package using a penetrance model of 0.01/0.1/0.1 (dd/Dd/DD) and a disease allele (D) frequency of 0.01. Family 102 showed strong evidence for linkage near ARID1B. The highest LOD score (1.34) out of all sequenced variants was located near this gene in a known conserved intergenic region between ARID1B and NOX3. Four other LOD scores &gt; 0.7 were found in the intergenic region between these two genes. Two are transcription factor binding sites; two are conserved genomic elements. We also observed two linked intronic variants of ARID1B in this family; an enhancer (LOD = 0.89) and a transcribed region (LOD = 0.73). Two other families (47 and 59) displayed evidence of linkage in ARID1B. Here, the interest is not the value of the LOD scores (top scores were 0.64 and 0.54), but the centering of the linked haplotype around the gene. Family 47 has 60 variants with LODs between 0.64 and 0.61; 45 located within ARID1B or known regulatory regions. Family 59 has 61 variants with LODs between 0.54 and 0.51; 29 located within ARID1B or known regulatory regions The variants appear to be spread evenly throughout ARID1B, suggesting the presence of linked haplotypes. Analyses are currently underway to reconstruct possible haplotypes in these families. The results of this study show that variants in the ARID1B gene at least partially account for the linkage signal on 6q in three of the nine most strongly linked families in our cohort and thus we believe that ARID1B is a plausible candidate gene for further studies involving familial lung cancer. Replication studies using 27 new extended families are currently underway to confirm this initial result. Citation Format: Anthony M. Musolf, Claire L. Simpson, Mariza de Andrade, Diptasri Mandal, Colette Gaba, Ping Yang, Ming You, Elena Y. Kupert, Marshall W. Anderson, Ann G. Schwartz, Susan M. Pinney, Christopher I. Amos, Joan E. Bailey-Wilson. Chromatin remodeling gene ARID1B is linked to familial lung cancer. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 2542.

Background Antiepileptic drugs (AED) are often considered first line for monotherapy in treatment of patients with migraines, and also those with comorbid migraine and epilepsy. Topiramate, a newer generation AED, has broad mechanism of action and evidence of benefit in patients with either episodic or chronic migraine along with epilepsy, both generalized and focal. Methods Our goal is to review the relevant mechanisms of action along with any supportive evidence published to date on the use of topiramate (TPM) in patients with both migraine headache and epilepsy. Conclusions There has been very little published to date on the use of TPM in patients diagnosed with both disorders. Despite this, TPM has been adopted as first line therapy in this patient population. Future studies investigating the effectiveness of this treatment strategy are warranted in order to determine the most effective use of this medication in patients diagnosed with migraine headaches and epilepsy.

BACKGROUNDPatients with myeloproliferative neoplasms (MPNs) including polycythemia vera, essential thrombocythemia, and myelofibrosis, are faced with oppressive symptom profiles that compromise daily functioning and quality of life. Among these symptoms, sexuality‐related symptoms have emerged as particularly prominent and largely unaddressed. In the current study, the authors evaluated how sexuality symptoms from MPN relate to other patient characteristics, disease features, treatments, and symptoms.METHODSA total of 1971 patients with MPN (827 with essential thrombocythemia, 682 with polycythemia vera, 456 with myelofibrosis, and 6 classified as other) were prospectively evaluated and patient responses to the Myeloproliferative Neoplasm Symptom Assessment Form (MPN‐SAF) and the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC‐QLQ C30) were collected, along with information regarding individual disease characteristics and laboratory data. Sexuality scores were compared with an age‐matched, healthy control population.RESULTSOverall, patients with MPN were found to have greater sexual dysfunction compared with the healthy population (MPN‐SAF score of 3.6 vs 2.0; P<.001), with 64% of patients with MPN describing some degree of sexual dysfunction and 43% experiencing severe symptoms. The presence of sexual symptoms correlated closely with all domains of patient functionality (physical, social, cognitive, emotional, and role functioning) and were associated with a reduced quality of life. Sexual problems also were found to be associated with other MPN symptoms, particularly depression and nocturnal and microvascular‐related symptoms. Sexual dysfunction was more severe in patients aged >65 years and in those with cytopenias and transfusion requirements, and those receiving certain therapies such as immunomodulators or steroids.ConclusionsThe results of the current study identify the topic of sexuality as a prominent issue for the MPN population, and this area would appear to benefit from additional investigation and management. Cancer 2016;122:1888–96. © 2016 American Cancer Society.

A healthy 27‐year‐old man with a lump in the lateral midneck was examined. Results of a recent biopsy performed elsewhere indicated amelanotic melanoma. A careful search for a primary integumentary or upper respiratory site of origin, including appropriate roentgenograms and a thyroid scan, was negative.At right radical neck dissection, the pathologic diagnosis was expanded to include anaplastic carcinoma. Subsequent examinations of the head and neck were negative. The neck and upper aerodigestive system were subjected to a full course of radiotherapy.Pathologic study of this tumor was continued. Electron microscopy indicated the tumor was epithelial, possibly of glandular epithelial origin.A tumor nodule reappeared in the right tracheoesophageal groove. Surgery was performed and the nodule was removed. The right thyroid lobe was removed also and submitted for histopathologic study. A solitary microscopic tumor focus, presumably anaplastic thyroid carcinoma, was found within the thyroid. Further pathologic studies were undertaken. Eventually, amyloid deposits were discovered, and a final diagnosis of cellular medullary thyroid carcinoma was established. Further studies of this patient and his family for multiple endocrine adenoma have been negative.