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The primary goal of seamless care is improved patient outcomes and improved standards of care for patients with cancer. The pharmacy service of the Newfoundland Cancer Treatment and Research Foundation conducted a randomized control study that measured clinical and humanistic outcomes of a pharmacist-directed seamless care program in an ambulatory oncology clinic. This article focuses on the intervention group, particularly the identification of drug-related problems (DRPs) and utilization of health care services as well the satisfaction of 3 types of health professionals with the services provided by the pharmacist-directed seamless care program. Overall, the seamless care pharmacist (SCP) identified an average of 3.7 DRPs per intervention patient; the most common DRP reported was a patient not receiving or taking a drug therapy for which there is an indication. The SCP identified more DRPs in patients receiving adjuvant treatment compared to those receiving palliative treatment. On average, family physicians, oncology nurses, and hospital pharmacists were satisfied with the SCP intervention indicating that they agreed the information collected and distributed by the SCP was useful to them. Pharmacist-directed seamless care services in an ambulatory oncology clinic have a significant impact on clinical outcomes and processes of patient care. The presence of a SCP can help identify and resolve DRPs experienced by patients in an outpatient oncology clinic, ensuring that patients are receiving the highest standard of care.

Background: Human genomes harbor copy number variants (CNVs), which are regions of DNA gains or losses. Although pathogenic CNVs are associated with congenital heart disease (CHD), their effect on clinical outcomes is unknown. This study sought to determine whether pathogenic CNVs among infants with single ventricle physiology were associated with inferior neurocognitive and somatic growth outcomes., Methods and Results: Genomic DNAs from 223 subjects of 2 National Heart, Lung, and Blood Institute-sponsored randomized clinical trials in infants with single ventricle CHD and 270 controls from The Cancer Genome Atlas project were analyzed for rare CNVs>300 kb using array comparative genomic hybridization. Neurocognitive and growth outcomes at 14 months from the CHD trials were compared among subjects with and without pathogenic CNVs. Putatively pathogenic CNVs, comprising 25 duplications and 6 deletions, had a prevalence of 13.9%, significantly greater than the 4.4% rate of such CNVs among controls. CNVs associated with genomic disorders were found in 13 cases but not in controls. Several CNVs likely to be causative of single ventricle CHD were observed, including aberrations altering the dosage of GATA4, MYH11, and GJA5. Subjects with pathogenic CNVs had worse linear growth, and those with CNVs associated with known genomic disorders had the poorest neurocognitive and growth outcomes. A minority of children with pathogenic CNVs were noted to be dysmorphic on clinical genetics examination., Conclusions: Pathogenic CNVs seem to contribute to the cause of single ventricle forms of CHD in ≥10% of cases and are clinically subtle but adversely affect outcomes in children harboring them.

Sports concussions are an increasingly recognized common type of mild traumatic brain injury (TBI) that affect athletes of all ages. The need for an increased involvement of trained physicians in the diagnosis and treatment of concussion has become more obvious as the pathophysiology and long-term sequelae of sports concussion are better understood. To date, there has been great variability in the athletic community about the recognition of symptoms, diagnosis, management, and physician role in concussion care. An awareness assessment survey administered to 96 high school coaches in a large metropolitan city demonstrated that 37.5% of responders refer their concussed players to an emergency department after the incident, only 39.5% of responders have a physician available to evaluate their players after a concussion, 71.6% of those who had a physician available sent their players to a sports medicine physician, and none of the responders had their player's concussion evaluated by a neurologist. Interestingly, 71.8% of responders stated that their players returned to the team with "return to play" guidelines from their physician. This survey has highlighted two important areas where the medical community can better serve the athletic community. Because a concussion is a sport-inflicted injury to the nervous system, it is optimally evaluated and managed by a clinician with relevant training in both clinical neuroscience and sports medicine. Furthermore, all physicians who see patients suffering concussion should be educated in the current recommendations from the Consensus Statement on Concussion and provide return to play instructions that outline a graduated return to play, allowing the athlete to return to the field safely.

Rationale, Aims and Objectives: Value-based pricing has recently been discussed by international bodies as a means to estimate a drug price that is linked to the benefits it offers patients and society. The World Health Organization (WHO) has recommended using three times a country's per capita gross domestic product (GDP) as the threshold for economic value. Using the WHO criteria, pharmacoeconomic modelling was used to illustrate the application of value-based price towards bevacizumab, a relatively new drug that provides a 1.4-month survival benefit to patients with metastatic colorectal cancer (mCRC)., Methods: A decision model was developed to simulate outcomes in mCRC patients receiving chemotherapy ± bevacizumab. Clinical data were obtained from randomized trials and costs from Canadian cancer centres. Utility estimates were determined by interviewing 24 oncology nurses and pharmacists. A price per dose of bevacizumab was then estimated using a target threshold of $CAD117,000 per quality adjusted life year gained, which is three times the Canadian per capita GDP., Results: For a 1.4-month survival benefit, a price of $CAD830 per dose would be considered cost-effective from the Canadian public health care perspective. If the drug were able to improve patient quality of life or survival from 1.4 to 3 months, the drug price could increase to $CAD1560 and $CAD2180 and still be considered cost-effective., Discussion: The use of the WHO criteria for estimating a value-based price is feasible, but a balance between what patients/governments can afford to pay and the commercial viability of the product in the reference country would be required., (© 2010 Blackwell Publishing Ltd.)

Objective: To determine healthcare-associated infection (HAI) prevalence in 9 hospitals in Jacksonville, Florida; to evaluate the performance of proxy indicators for HAIs; and to refine methodology in preparation for a multistate survey., Design: Point prevalence survey., Patients: Acute care inpatients of any age., Methods: HAIs were defined using National Healthcare Safety Network criteria. In each facility a trained primary team (PT) of infection prevention (IP) staff performed the survey on 1 day, reviewing records and collecting data on a random sample of inpatients. PTs assessed patients with one or more proxy indicators (abnormal white blood cell count, abnormal temperature, or antimicrobial therapy) for the presence of HAIs. An external IP expert team collected data from a subset of patient records reviewed by PTs to assess proxy indicator performance and PT data collection., Results: Of 851 patients surveyed by PTs, 51 had one or more HAIs (6.0%; 95% confidence interval, 4.5%-7.7%). Surgical site infections ([Formula: see text]), urinary tract infections ([Formula: see text]), pneumonia ([Formula: see text]), and bloodstream infections ([Formula: see text]) accounted for 75.8% of 58 HAIs detected by PTs. Staphylococcus aureus was the most common pathogen, causing 9 HAIs (15.5%). Antimicrobial therapy was the most sensitive proxy indicator, identifying 95.5% of patients with HAIs., Conclusions: HAI prevalence in this pilot was similar to that reported in the 1970s by the Centers for Disease Control and Prevention's Study on the Efficacy of Nosocomial Infection Control. Antimicrobial therapy was a sensitive screening variable with which to identify those patients at higher risk for infection and reduce data collection burden. Additional work is needed on validation and feasibility to extend this methodology to a national scale.

Objective: To assess the impact and sustainability of a multifaceted intervention to prevent methicillin-resistant Staphylococcus aureus (MRSA) transmission implemented in 3 chronologically overlapping phases at 1 hospital., Design: Interrupted time-series analyses., Setting: A Veterans Affairs hospital in the northeastern United States., Patients and Participants: Individuals admitted to acute care units from October 1, 1999, through September 30, 2008. To calculate the monthly clinical incidence of MRSA colonization or infection, the number of MRSA-positive cultures obtained from a clinical site more than 48 hours after admission among patients with no MRSA-positive clinical cultures during the previous year was divided by patient-days at risk. Secondary outcomes included clinical incidence of methicillin-sensitive S. aureus colonization or infection and incidence of MRSA bloodstream infections., Interventions: The intervention--implemented in a surgical ward beginning October 2001, in a surgical intensive care unit beginning October 2003, and in all acute care units beginning July 2005--included systems and behavior change strategies to increase adherence to infection control precautions (eg, hand hygiene and active surveillance culturing for MRSA)., Results: Hospital-wide, the clinical incidence of MRSA colonization or infection decreased after initiation of the intervention in 2001, compared with the period before intervention (P = .002), and decreased by 61% (P < .001) in the 7-year postintervention period. In the postintervention period, the hospital-wide incidence of MRSA bloodstream infection decreased by 50% (P = .02), and the proportion of S. aureus isolates that were methicillin resistant decreased by 30% (P < .001)., Conclusions: Sustained decreases in hospital-wide clinical incidence of MRSA colonization or infection, incidence of MRSA bloodstream infection, and proportion of S. aureus isolates resistant to methicillin followed implementation of a multifaceted prevention program at one Veterans Affairs hospital. Findings suggest that interventions designed to prevent transmission can impact endemic antimicrobial resistance problems.

Clinical guidelines now recognize the importance of a multifactorial approach to managing cardiovascular (CV) risk. This idea was taken a step further with the concept of the Polypill™. There are, however, considerable patent, pharmacokinetic, pharmacodynamic, registration, and cost implications that will need to be overcome before the Polypill™ or other single-pill combinations of CV medications become widely available. However, a medication targeting blood pressure (BP) and lipids provides much of the proposed benefits of the Polypill™. A single-pill combination of the antihypertensive amlodipine besylate and the lipid-lowering medication atorvastatin calcium (SPAA) is currently available in many parts of the world. This review describes the rationale for this combination therapy and the clinical trials that have demonstrated that these two agents can be combined without the loss of efficacy for either agent or an increase in the incidence of adverse events. The recently completed Cluster Randomized Usual Care vs Caduet Investigation Assessing Long-term-risk (CRUCIAL trial) is discussed in detail. CRUCIAL was a 12-month, international, multicenter, prospective, open-label, parallel design, cluster-randomized trial, which demonstrated that a proactive intervention strategy based on SPAA in addition to usual care (UC) had substantial benefits on estimated CV risk, BP, and lipids over continued UC alone. Adherence with antihypertensive and lipid-lowering therapies outside of the controlled environment of clinical trials is very low (~30%-40% at 12 months). Observational studies have demonstrated that improving adherence to lipid-lowering and antihypertensive medications may reduce CV events. One means of improving adherence is the use of single-pill combinations. Real-world observational studies have demonstrated that patients are more adherent to SPAA than co-administered antihypertensive and lipid-lowering therapy, and this improved adherence translated to reduced CV events. Taken together, these findings suggest that SPAA can play an important role in helping physicians improve the management of CV risk in their patients.

Objectives: To examine the expression of B-cell-activating factor receptor (BAFF-R) on naive CD27- and memory CD27+ B cells in normal individuals and patients with rheumatoid arthritis (RA) undergoing B-cell depletion therapy with rituximab., Patients and Methods: BAFF-R expression on B-cell subsets was determined in normal controls (NC; n = 11), active patients with RA pre-rituximab (pre-RX; n = 15), relapsing patients either concordant for B-cell repopulation (C-R, n = 13) or discordant, with relapse more than 3 months after repopulation (D-R, n = 11) and patients in remission over 3 months postrepopulation (discordant non-relapsing (D-NR), n = 5). Serum BAFF was measured by ELISA and analysed using Mann-Whitney., Results: There was no significant difference between NC, pre-RX and D-NR patients in %BAFF-R-positive B cells or mean fluorescence intensity (MFI) in naive and memory B cells. Relapsing patients had significantly lower MFI and %BAFF-R-positive cells in both naive and memory compartments from NC and pre-RX (C-R and D-R; p < 0.01). BAFF levels in pre-RX patients were within the normal range and did not correlate with BAFF-R expression in any patient group. D-NR patients had relatively lower proportions of pre and postswitch CD27+ B cells than pre-RX patients (D-NR vs pre-RX; p < 0.05 for both) and also lower numbers of postswitch B cells than D-R patients (D-NR vs D-R, p < 0.05)., Conclusion: BAFF-R expression was significantly reduced on both naive and memory B cells in patients at relapse, regardless of the relationship with B-cell repopulation or serum BAFF levels. Re-establishment of active disease was also associated with an increase in class-switch recombination. Factors responsible for lower levels of BAFF-R may relate to altered thresholds for autoreactive B-cell generation at relapse in patients with RA.

Catatonia is a psychomotor and behavioral syndrome associated with mood disorders, psychotic disorders, neurological disease, and general medical conditions. Catatonia has also been described as a manifestation of partial onset seizures. We describe a case of catatonia following successful epilepsy surgery. A 38-year-old patient with congenital hydrocephalus and left hippocampal sclerosis underwent selective left amygdalohippocampectomy for medically refractory seizures. Three days after surgery, she became progressively less interactive. Verbal output was dramatically reduced. She exhibited waxy flexibility, stupor, mutism, posturing, rigidity, negativism, and grimacing. Video/EEG monitoring showed no evidence of ongoing seizure activity. She was treated with high-dose benzodiazepines for presumed catatonia, but the behavioral pattern did not resolve. Subsequently the patient underwent a full course of electroconvulsive therapy. Catatonia resolved over the ensuing 3 weeks. Following discharge from the hospital, the patient's global functioning returned to the premorbid level, and she has been seizure free for more than 4 years., (Copyright © 2010 Elsevier Inc. All rights reserved.)

Nonepileptic paroxysmal events in children are common, and may be more diverse in etiology than those seen in adults. We determined the types of nonepileptic events that are most prominent in the pediatric population, and stratified those events by age group. Ninety-four of 416 pediatric patients monitored during a 3-year period (23%) were found to have had nonepileptic events. Thirty-eight percent of these children were diagnosed with psychogenic nonepileptic seizures, and 72% of those were adolescents. In children younger than 5 years of age, behavioral events and parasomnias were the most common mimickers of epilepsy. Other events, including stereotyped movements and myoclonus, were also diagnosed. We suggest that children with refractory paroxysmal events should be considered for early inpatient monitoring., ((c) 2009 Elsevier Inc. All rights reserved.)

We examined interventions to optimize piperacillin-tazobactam use at 4 hospitals. Interventions for rotating house staff did not affect use. We could target empiric therapy in only 35% of cases. Because prescribing practices seemed to be institution specific, interventions should address attitudes of local prescribers. Interventions should target empiric therapy and ordering of appropriate cultures.

The localization of seizure onset relies on the concordance of clinical, electrographic, and imaging data, often supplemented by corroborating functional studies. On occasion, the presurgical evaluation may yield discordant information. Although the localization of seizure onset is sometimes in doubt, it is rare that the lateralization of the focus is in question. To date, there has been only a single publication on falsely lateralizing ictal EEG onsets in the setting of atrophic lesions. We describe two patients in whom the ictal EEG suggested seizure onset from the hemisphere opposite to the one with a sizeable atrophic lesion. The first patient was operated on without invasive EEG testing. In the second patient, we decided to place subdural electrodes before resection. In each case, resection of the lesion resulted in improvement of intractable seizures.

Background: The Advisory Committee on Immunization Practices and the Healthcare Infection Control Practices Advisory Committee recommended that hospitals establish on-site, daily assessments of health care workers vaccinated with smallpox vaccine. The Hospital Smallpox Vaccination Monitoring System (HSVMS) was 1 component of the smallpox vaccination plan to monitor adverse events on-site in hospitals. This report presents findings from February to August 2003., Methods: All US institutions participating in the smallpox vaccination program were eligible to enroll in and use HSVMS through the Internet-based Centers for Disease Control Secure Data Network., Results: Of the 730 enrolled vaccinees, 341 (47%) were nurses; 122 (17%) physicians; 75 (10%) laboratory, patient care, radiology, or other technicians; 39 (5%) administrators; 22 (3%) housekeepers; 21 (3%) physical or respiratory therapists; 20 (3%) infection control professionals; 19 (3%) safety or security staff; and 17 (2%) epidemiologists; and 54 (7%) were workers in other job categories. Most (86%) vaccinees had been previously vaccinated. Postvaccination signs and symptoms were frequent: itching (75.2%), pain at the vaccination site (31.6%), swollen or tender lymph nodes (26.4%), fatigue (26.2%), and headache (20.8%). Symptoms were highest during the first week after vaccination; symptoms were more frequently reported among vaccinees without previous vaccination. Adherence to recommended vaccination site care was reported in 2732 of 3091 (88.4%) follow-up visits among workers with patient contact. Of the 4379 days workers planned to work, during 31 (0.7 per 100) days, workers performed restricted activities, and, in 60 (1.4 per 100) days, workers were absent., Conclusions: Findings from HSVMS indicate that adherence to post-smallpox vaccination site care was high and that the number of days of work affected was low.

Creutzfeldt-Jakob disease (CJD) is a rare prion disease characterized by a spongiform encephalopathy in humans. Although the characteristic triad of myoclonus, dementia, and periodic EEG activity is easy to recognize, unusual manifestations of the disease may be challenging and create a diagnostic dilemma. We report a case of CJD that occurred in a 26-year-old patient who presented with a receptive (Wernicke's) aphasia secondary to nonconvulsive status epilepticus.

Purpose: To describe the effects of vagus nerve stimulation (VNS) on sleep-related breathing in a sample of 16 epilepsy patients., Methods: Sixteen adults with medically refractory epilepsy (nine men, seven women, ages 21-58 years) underwent baseline polysomnograms (PSGs). Three months after VNS therapy was initiated, PSGs were repeated. In addition, patient 7 had a study with esophageal pressure monitoring, and patient 1 had a continuous positive airway pressure (CPAP) trial., Results: Baseline PSGs: One of 16 patients had an apnea-hypopnea index (AHI) >5 (6.8). Treatment PSGs: Five of 16 patients had treatment AHIs >5. Respiratory events were more frequent during periods with VNS activation (on-time) than without VNS activation (off-time; p = 0.016). Follow-up studies: Esophageal pressure monitoring in patient 7 showed crescendos in esophageal pressure during VNS activation, supporting an obstructive pattern. The CPAP trial of patient 1 showed that all respiratory events were associated with VNS stimulation at low CPAP levels. They were resolved at higher CPAP levels., Conclusions: Treatment with VNS affects respiration during sleep and should be used with care, particularly in patients with preexisting obstructive sleep apnea. The AHI after VNS treatment remained <5 in the majority of patients and was only mildly elevated (<12) in five patients. In one patient, CPAP resolved VNS-related respiratory events.

Objective: To assess the impact of laparoscopy on surgical site infections (SSIs) following cholecystectomy in a large population of patients., Summary Background Data: Previous investigations have demonstrated that laparoscopic cholecystectomy is associated with a shorter postoperative stay and fewer overall complications. Less is known about the impact of laparoscopy on the risk for SSIs., Methods: Epidemiologic analysis was performed on data collected during a 7-year period (1992-1999) by participating hospitals in the National Nosocomial Infections Surveillance (NNIS) System in the United States., Results: For 54,504 inpatient cholecystectomy procedures reported, use of the laparoscopic technique increased from 59% in 1992 to 79% in 1999. The overall rate of SSI was significantly lower for laparoscopic cholecystectomy than for open cholecystectomy. Overall, infecting organisms were similar for both approaches. Even after controlling for other significant factors, the risk for SSI was lower in patients undergoing the laparoscopic technique than the open technique., Conclusions: Laparoscopic cholecystectomy is associated with a lower risk for SSI than open cholecystectomy, even after adjusting for other risk factors. For interhospital comparisons, SSI rates following cholecystectomy should be stratified by the type of technique.