Search

In 2017, The Ottawa Hospital initiated a unique‐in‐Canada quality improvement initiative by opening a novel, multi‐specialist limb‐preservation clinic. We sought to describe the structure, processes, and initial outcomes of the clinic and evaluate whether it is achieving its mandate of providing high‐quality wound clinical care, education, and research. We conducted a descriptive prospective cohort study alongside a nested study of 162 clinic patients requiring serial assessments. There have been 1623 visits, mostly (72.2%) from outpatients. During 17.8% of visits, patients were evaluated by >1 specialist. Therapies provided most often included negative‐pressure wound therapy (32.7%), biological wound dressings (21.6%), and total contact casting (18.5%). Furthermore, 1.2% underwent toe/ray amputations or skin grafting in clinic and 22.8% were initiated on antimicrobials. Mixed‐effects models suggested that mean wound volumes for those requiring serial assessments decreased by 1.6 (95% confidence interval = −0.86 to −2.27) cm3 between visits. The clinic provided seven rotations to vascular surgery, infectious diseases, dermatology, and palliative care physicians; three nursing preceptorships; and two educational workshops. It also initiated provincial and national vascular health and wound care research initiatives. This study may be used to guide development of other limb‐preservation clinics and programmes. Findings support that our programme is achieving its mandate.

Objective To raise awareness of the role of environmental biofilm in the emergence and spread of antibiotic resistance and its consideration in antimicrobial stewardship. Background Antibiotic resistance is a major threat to public health. Overuse of antibiotics, increased international travel, and genetic promiscuity amongst bacteria have contributed to antibiotic resistance, and global containment efforts have so far met with limited success. Antibiotic resistance is a natural mechanism by which bacteria have adapted to environmental threats over billions of years and is caused either by genetic mutations or by horizontal gene transfer. Another ancient survival strategy involves bacteria existing within a self-produced polymeric matrix, which today is termed biofilm. Biofilm similarly enables bacterial tolerance to environmental threats, and also encourages the transfer of antibiotic resistance genes between bacterial species. This natural and ubiquitous mode of bacterial life has not been considered amongst strategies to tackle antibiotic resistance in healthcare facilities, despite its ability to significantly enhance bacterial survival and persistence, and to encourage antibiotic resistance. Conclusion Biofilm must be considered synonymously with antibiotic resistance because of its proficiency in transferring resistance genes as well as its innate phenotypic tolerance to antibiotics. Although biofilm falls outside of the current definition of antimicrobial stewardship, greater awareness of the existence, ubiquity, and consequences of environmental biofilm amongst healthcare practitioners is crucial to improving hygiene practices and controlling the emergence and spread of antibiotic resistance in healthcare facilities.

BackgroundCurrently available treatments for Parkinson’s disease (PD) do not slow clinical progression nor target alpha-synuclein, the main pathology associated with the disease.ObjectiveThe study objective was to evaluate the efficacy and safety of prasinezumab, a humanized monoclonal antibody that binds aggregated alpha-synuclein, in individuals with early PD. The study rationale, design, and baseline characteristics of enrolled subjects are presented here.MethodsThe PASADENA study is a multicenter, randomized, double-blind, placebo-controlled treatment study. Individuals with early PD, recruited across the US and Europe, received monthly intravenous doses of prasinezumab (1500 mg or 4500 mg) or placebo for a 52-week period (Part 1), followed by a 52-week extension (Part 2) in which all participants received active treatment. Key inclusion criteria were: aged 40–80 years; Hoehn & Yahr (H&Y) Stage I or II; time from diagnosis ≤2 years; having bradykinesia plus one other cardinal sign of PD (e.g. resting tremor, rigidity); DAT-SPECT imaging consistent with PD; and either treatment naïve or on a stable monoamine oxidase B (MAO-B) inhibitor dose. Study design assumptions for sample size and study duration were built using a patient cohort from the Parkinson’s Progression Marker Initiative (PPMI). In this report, baseline characteristics are compared between the treatment-naïve and MAO-B inhibitor-treated PASADENA cohorts and between the PASADENA and PPMI populations.ResultsOf the 443 patients screened, 316 were enrolled into the PASADENA study between June 2017 and November 2018, with an average age of 59.9 years and 67.4% being male. The mean time from diagnosis at baseline was 10.11 months, with 75.3% in H&Y Stage II. Baseline motor and non-motor symptoms (assessed using Movement Disorder Society – Unified Parkinson’s Disease Rating Scale [MDS-UPDRS]) were similar in severity between the MAO-B inhibitor-treated and treatment-naïve PASADENA cohorts (MDS-UPDRS Total score [standard deviation (SD)]; 30.21 [11.96], 32.10 [13.20], respectively). The overall PASADENA population (63.6% treatment naïve and 36.4% on MAO-B inhibitor) also showed a similar severity in MDS-UPDRS scores (e.g. MDS-UPDRS Total score [SD]; 31.41 [12.78], 32.63 [13.04], respectively) to the PPMI cohort (all treatment naïve).ConclusionsThe PASADENA study population is suitable to investigate the potential of prasinezumab to slow disease progression in individuals with early PD.Trial RegistrationNCT03100149

Aims Myocardial infarction (MI) is the most common cause of heart failure (HF) worldwide. G protein-coupled receptor kinase 5 (GRK5) is upregulated in failing human myocardium and promotes maladaptive cardiac hypertrophy in animal models. However, the role of GRK5 in ischemic heart disease is still unknown. In this study, we evaluated whether myocardial GRK5 plays a critical role post-MI in mice and included the examination of specific cardiac immune and inflammatory responses. Methods and results Cardiomyocyte-specific GRK5 overexpressing transgenic mice (TgGRK5) and non-transgenic littermate control (NLC) mice as well as cardiomyocyte-specific GRK5 knockout mice (GRK5cKO) and wild type (WT) were subjected to MI and, functional as well as structural changes together with outcomes were studied. TgGRK5 post-MI mice showed decreased cardiac function, augmented left ventricular dimension and decreased survival rate compared to NLC post-MI mice. Cardiac hypertrophy and fibrosis as well as fetal gene expression were increased post-MI in TgGRK5 compared to NLC mice. In TgGRK5 mice, GRK5 elevation produced immuno-regulators that contributed to the elevated and long-lasting leukocyte recruitment into the injured heart and ultimately to chronic cardiac inflammation. We found an increased presence of pro-inflammatory neutrophils and macrophages as well as neutrophils, macrophages and T-lymphocytes at 4-days and 8-weeks respectively post-MI in TgGRK5 hearts. Conversely, GRK5cKO mice were protected from ischemic injury and showed reduced early immune cell recruitment (predominantly monocytes) to the heart, improved contractility and reduced mortality compared to WT post-MI mice. Interestingly, cardiomyocyte-specific GRK2 transgenic mice did not share the same phenotype of TgGRK5 mice and did not have increased cardiac leukocyte migration and cytokine or chemokine production post-MI. Conclusions Our study shows that myocyte GRK5 has a crucial and GRK-selective role on the regulation of leucocyte infiltration into the heart, cardiac function and survival in a murine model of post-ischemic HF, supporting GRK5 inhibition as a therapeutic target for HF., Graphical Abstract

Management of the axilla in the era of neoadjuvant chemotherapy for breast cancer is evolving. The aim of this study is to determine if conventional gadolinium-enhanced breast MRI can aid in evaluation of the response to neoadjuvant chemotherapy in the axilla. A retrospective review of a prospectively maintained database of patients undergoing neoadjuvant chemotherapy for breast cancer was performed. Pre and post-neoadjuvant chemotherapy MRI reports for node-positive patients were examined in conjunction with demographic data, treatment type, and final histopathology reports. One-hundred and fourteen patients with breast cancer undergoing neoadjuvant chemotherapy were included in the study. The sensitivity of magnetic resonance imaging in detecting nodal response post-neoadjuvant chemotherapy was 33.93% and the specificity was 82.76%. Magnetic resonance imaging had a positive predictive value of 65.52% and a negative predictive value of 56.47%. MRI was found to be most specific in the detection of triple-negative cancer response. Specificity was 100% in this group and sensitivity was 75%. Magnetic resonance imaging has a relatively high specificity in detecting nodal response post-neoadjuvant chemotherapy but has a low sensitivity. Alone it cannot be relied upon to identify active axillary malignancy post-neoadjuvant chemotherapy. However, given its increased specificity among certain subgroups, it may have a role in super-selecting patients suitable for sentinel lymph node biopsy post-neoadjuvant chemotherapy.

Introduction There has been limited study of patient-reported outcomes (PROs) in patients at risk of limb loss. Our primary objective was to estimate the prevalence of disability in this patient population using the World Health Organization Disability Assessment Schedule 2.0 (WHODAS 2.0). Materials and methods We recruited patients referred to a limb-preservation clinic. Patients self-reported their disability status using the 12-domain WHODAS 2.0. Severity of disability in each domain was scored from 1 = none to 5 = extreme and the total normalized to a 100-point scale (total score ≥25 = clinically significant disability). We also asked patients about wound-specific concerns and wound-related discomfort or distress. Results We included 162 patients. Reasons for clinic referral included arterial-insufficient (37.4%), postoperative (25.9%), and mixed etiology (10.8%) wounds. The mean WHODAS 2.0 disability score was 35.0 (standard deviation = 16.0). One-hundred-and-nineteen (73.5%) patients had clinically significant disability. Patients reported they had the greatest difficulty walking a long distance (mean score = 4.2), standing for long periods of time (mean score = 3.6), taking care of household responsibilities (mean score = 2.7), and dealing with the emotional impact of their health problems (mean score = 2.5). In the two-weeks prior to presentation, 87 (52.7%) patients expressed concern over their wound(s) and 90 (55.6%) suffered a moderate amount or great deal of wound-related discomfort or distress. In adjusted ordinary least squares regression models, although WHODAS 2.0 disability scores varied with changes in wound volume (p = 0.03) and total revised photographic wound assessment tool scores (p Discussion The majority of people at risk of limb loss report suffering a substantial burden of disability, pain, and wound-specific concerns. Research is needed to further evaluate the WHODAS 2.0 in a multicenter fashion among these patients and determine whether care and interventions may improve their PROs.

Dear Editor,In this retrospective IRB-approved case series, we describe two acetaminophen (APAP) toxic patients reported to a regional poison center who manifested arterial acidemia after fluid res...

Biofilm has been implicated as a barrier to wound healing and it is widely accepted that the majority of wounds not following a normal healing trajectory contain biofilm. Therefore, strategies that inform and engage clinicians to reduce biofilm and optimise the wound tissue environment to enable wound progression are of interest to wound care providers. In March 2019, an advisory board was convened where experts considered the barriers and opportunities to drive a broader adoption of a biofilm-based approach to wound care. Poor clarity and articulation of wound terminology were identified as likely barriers to clinical adoption of rigorous and proactive microbial decontamination that is supportive of wound healing advancement. A transition to an intuitive term such as ‘wound hygiene’ was proposed to communicate a comprehensive wound decontamination plan with an associated message of expected habitual routine. ‘Wound hygiene’, is a relatable concept that supports meticulous wound practice that addresses barriers to wound healing, such as biofilm, while aligning with antimicrobial stewardship programmes.

Thank you for the response to our letter. Our interest in fomepizole as an adjunct therapy for severe acetaminophen toxicity is grounded in preclinical investigations and initial human reports. Unf...

INTRODUCTION: Gadolinium-based contrast agents (GBCA) have been used to enhance magnetic resonance imaging (MRI) since 1985. Recently, the media and online groups have voiced concerns about gadolinium deposition in patients with normal renal function based on “elevated” urinary gadolinium levels. The determination of increased urinary gadolinium levels is based on reference ranges developed in individuals with normal renal function who were never exposed to GBCA. Studies suggest an elevated gadolinium urinary elimination greater than 72 h post GBCA scan. We evaluated urine gadolinium concentrations over a 30-day period in patients administered GBCA. METHODS: In this prospective, observational pilot study, we enrolled subjects between 18 and 65 years of age with normal renal function who received GBCA for the first time. Urinary gadolinium was measured at days zero (prior to GBCA exposure), 3, 10, and 30 after GBCA exposure. We compared urinary gadolinium levels after GBCA exposure to the current reference range and calculated an estimated duration of “elevated” gadolinium urine levels in the average patient. RESULTS: All 13 subjects had 24-h urinary gadolinium levels higher than 0.7 μg/24 h with means of 1944 (± 1432) μg/24 h on day 3, 301 (± 218) μg/24 h on day 10, and 34 (± 33) μg/24 h on day 30. Based on calculated urinary gadolinium elimination kinetics, we estimate urinary gadolinium levels will often remain above the current reference range for > 50 days. CONCLUSION: The current reference range of 0.7 μg/24 h for 24 h urinary gadolinium is not applicable to patients for at least 30 days following GBCA exposure.

The aim of this study was to compare changes in wound size and appearance and health complication rates in patients with vasculopathy and lower-extremity wounds treated with or without low-frequency contact ultrasound debridement (LFCUD) This study was a randomised controlled trial. The study was conducted in a vascular surgery service, including outpatient wound clinic and inpatient ward, in a tertiary care academic centre. In total, 70 patients with vasculopathy and lower-extremity wounds of mixed aetiology were enrolled in the trial; 68 completed the study. Patients were randomised to receive LFCUD plus usual care (n = 33) or usual care (n = 37) at 4 weekly visits, and were followed thereafter for up to 12 wk. The main outcome measures included closed wounds, change in wound surface area (WSA), and wound appearance by the revised Photographic Wound Assessment Tool (revPWAT). After 4 weekly LFCUD treatments, patients in the LFCUD group had significantly better wound appearance (total revPWAT score) compared with the control group treated only with usual care (P =

Aim: Nitromethane, found in fuels used for short distance racing, model cars, and model airplanes, produces a falsely elevated serum creatinine with standard creatinine analysis via the Jaffe method. Erroneous creatinine elevation often triggers extensive testing, leads to inaccurate diagnoses, and delayed or inappropriate medical interventions. Multiple reports in the literature identify “enzymatic assays“ as an alternative method to detect the true value of creatinine, but this ambiguity does not help providers translate what type of enzymatic assay testing can be done in real time to determine if there is indeed false elevation.Methods: We report seven cases of ingested nitromethane where creatinine was determined via Beckman Coulter® analyser using the Jaffe method, Vitros® analyser, or i-Stat® point-of-care testing. Nitromethane was detected and semi-quantified using a common clinical toxic alcohol analysis method, and quantified by headspace-gas chromatography-mass spectrometry.Results: When...

In this case, an 18-year-old male presents to the emergency department with status asthmaticus. He subsequently developed hyperlactemia during the first 8 h of his hospitalization. This chapter reviews causes of hyperlactemia, including specific discussions on propofol infusion syndrome, toxic alcohol-related hyperlactemia, clenbuterol exposure, and mitochondrial toxins.

Many exposures can cause liver injury. This case involves a 46-year-old patient with fever, nausea, vomiting, and signs of hepatic injury. In this chapter, we review pharmaceutical and supplement causes of hepatitis and hepatocellular necrosis.

In this case, a patient is envenomated by his friend’s exotic pet snake. The patient rapidly develops signs of neurotoxicity, including blurred vision, ptosis, and difficulty swallowing. He ultimately develops respiratory arrest and bradycardia. In this chapter, we review some of the toxins that can cause progressive neurologic symptoms including botulinum toxin, neurotoxic snakes in the US, and some of the exotic snakes that can cause neurologic effects.

A 21-year-old male presented to the emergency department in status epilepticus. He was hyperthermic, tachycardic, and hypertensive with hyperreflexia and clonus. Laboratory workup revealed a metabolic acidosis with associated hyperlactatemia. He was admitted to the intensive care unit where he was sedated, mechanically ventilated, and externally cooled. His hospital course was complicated by an aspiration pneumonia and rhabdomyolysis but he fully recovered.

This case involves a 2-year-old female who ingested some of her father’s prescribed medication. She presented early to the emergency department where she received activated charcoal. On a follow-up call from the local poison control center 3 days later, she had developed vomiting, agitation, and appeared to have increased work of breathing. We review possible causes for the patient’s symptoms including thyroid hormone toxicity, lithium toxicity, and management guidelines for her specific overdose.

In this chapter, we discuss the case of a toddler who acutely vomited following ingestion of a small container of liquid on his father’s nightstand. He subsequently developed ataxia and lethargy. This chapter explores possible causes of his symptoms, including GHB intoxication and nicotine exposure.

A 34-year-old female developed itching and jaundice after taking a “cultural medication” given to her by a friend. Laboratory studies from her initial emergency department evaluation suggest a cholestatic process. This chapter reviews herbal medications associated with hepatic injury and drugs that cause hepatic injury.

A 3-year-old male ingested several tablets of his mother’s diet supplement, which had been obtained from Mexico. While he did not develop clinical signs of toxicity, exposure to this product was concerning based on the active ingredient it reportedly contained. This chapter reviews some of the agents found in “diet pills,” how they cause toxicity, and clinical symptoms associated with toxicity.

This chapter delves into the case of an 8-year-old male who develops withdrawal symptoms after a chronic headache medication is discontinued. Multiple withdrawal syndromes are reviewed, as well as general management principles of withdrawal.

A 30-year-old male presented to the emergency department after undergoing ultra-rapid opioid detoxification. He was awake but nonverbal for the 8 h following the procedure. With this case, the process of and possible complications associated with ultra-rapid opioid detoxification are reviewed. Potential causes of the patient’s symptoms are reviewed, including carbon monoxide poisoning, ibogaine exposure, and spongiform leukencephalopathy.

Clinicians have limited experience with assessment and treatment of overdose from newer anticonvulsant medications. The aim of this investigation was to evaluate clinical effects of newer anticonvulsant overdose, determine if a relationship exists between dose and clinical effect, and if a particular agent appears more toxic in overdose. This was a retrospective study using electronic poison center data, evaluating clinical outcomes from newer anticonvulsant overdose. The Toxicall™ database from January 1, 2002 to December 31, 2011 was queried using key words: "gabapentin," "lamotrigine," "levetiracetam," "tiagabine," "topiramate," "zonisamide," "pregabalin," and "oxcarbazine." Polypharmacy overdose and children less than 15 years of age were excluded. Charts were reviewed by two abstractors for pharmaceutical, self-reported dose, clinical effect score, and clinical signs, symptoms, and vital signs recorded in the chart. Ordinal logistic regression was used to evaluate the relationship between drug type, dose, age, and sex to clinical effect score. Out of 501 cases identified, 347 met the final inclusion criteria. There were 116 gabapentin, 67 lamotrigine, 15 levetiracetam, 15 tiagabine, 56 topiramate, 23 pregabalin, and 55 oxcarbazepine cases. Overdose of newer anticonvulsants frequently results in altered mental status. Seizures may be more common with tiagabine, lamotrigine, and oxcarbazepine. There was one death reported from intentional overdose of topiramate. An information index was created to rank drug toxicity based on reported signs and symptoms for each overdose. There was no significant effect of dose on severity of outcome (β = 0.12, p = 0.23). However, the risk of a more severe outcome score was significantly increased with tiagabine relative to other drugs (β = 2.8, p = 0.001). Lamotrigine ranked highest in terms of toxicity (HT = 1.66) and number of interventions performed (HI = 1.17), and levetiracetam the lowest (HT = 0.98; HI = 0.88). We could not identify a dose-effect in these data which likely reflects the limitations of self-reported doses. Despite limitations of these data, the risk of more severe outcome scores appear to be higher with tiagabine overdose while lamotrigine overdose appears to result in more reported signs, symptoms, and interventions.

Animal studies and human case reports show promise in using lipid rescue to treat refractory calcium channel antagonist toxicity. However, the majority of research and clinical experience has focused on non-dihydropyridine agents. Thus, we sought to investigate the value of lipid emulsion (ILE) therapy for dihydropyridine-induced shock. This IACUC-approved study utilized seven swine that were sedated with alpha-chloralose, mechanically ventilated, and instrumented for drug delivery and hemodynamic measures. After stabilization and basal measures, nifedipine (0.01875 mg/kg/min) was infused until imminent cardiac arrest (seizure, end tidal CO2 < 10 mmHg, bradydysrhythmia, or pulseless electrical activity). Animals then received a 7 mL/kg bolus of 20% lipid emulsion via central catheter. Lipid circulation was visually confirmed by the presence of fat in peripheral arterial blood. Hemodynamics were continuously monitored until 10 min after lipid bolus. Surviving animals were euthanized. Pre- and post-lipid treatment parameters were analyzed using the Wilxocon signed rank test (p

Objective : The purpose of this study was to assess Inlow's 60-Second Diabetic Foot Screen Tool to ascertain consistency of risk recognition for development of ulceration independent of specific assessor and practice setting. Screening tools that assist clinicians in identifying risk require validation. The objectives were to determine the intrarater reliability, interrater reliability, and predictive validity of Inlow's 60-Second Diabetic Foot Screen Tool in 2 healthcare settings. Design : Following ethics board approval, a prospective observational study was completed. Setting and participants : A convenience sample of 69 persons with diabetes was recruited: n = 26 from an acute care setting (dialysis) and n = 43 from long-term-care (LTC) setting. Main outcome measures : The screening tool was administered by 2 assessors independently to determine interrater reliability and later the same day by one of the assessors to determine intrarater reliability. Occurrence of foot ulcers or amputation was noted 1 to 5 months later to determine predictive validity. Main results : Reliability is reported per setting using the intraclass correlation coefficient (2.1) and 95% confidence intervals. Intrarater reliability: LTC 0.96 (0.93-0.98) right foot, 0.97 (0.95-0.98) left foot; dialysis 1.00 right and 1.00 left foot. Interrater reliability: LTC 0.92 (0.86-0.96) right foot, 0.93 (0.87-0.96) left foot; dialysis 0.83 (0.65-0.92) right foot and left foot. Predictive validity: Two subjects had events-1 ulcer and 1 amputation-that were associated with high Inlow's screening tool scores. Conclusion : This study demonstrates excellent interrater and intrarater reliability and provides preliminary information about predictive validity.

Latrodectus mactans antivenin is a safe and effective therapy for severe black widow spider envenomations when given to most patients. We report a case of a 37-year-old male with a history of asthma that was given L. mactans antivenin for symptoms related to a black widow envenomation and developed a severe anaphylactic reaction resulting in cardiac arrest. When traditional therapies failed, the patient was given methylene blue for anaphylactic shock resulting in a 30-h period of hemodynamic stability. Despite initial resuscitation, the patient ultimately died 40 h after presentation. Under the right circumstances, L. mactans antivenin remains a safe and effective therapy for severe black widow envenomations. However, anaphylaxis is a risk for those receiving this therapy, even when the antivenin is diluted and given as an infusion. We report the first death related to diluted L. mactans antivenin given as an infusion.

We demonstrate the feasibility of generating thousands of transgenic Drosophila melanogaster lines in which the expression of an exogenous gene is reproducibly directed to distinct small subsets of cells in the adult brain. We expect the expression patterns produced by the collection of 5,000 lines that we are currently generating to encompass all neurons in the brain in a variety of intersecting patterns. Overlapping 3-kb DNA fragments from the flanking noncoding and intronic regions of genes thought to have patterned expression in the adult brain were inserted into a defined genomic location by site-specific recombination. These fragments were then assayed for their ability to function as transcriptional enhancers in conjunction with a synthetic core promoter designed to work with a wide variety of enhancer types. An analysis of 44 fragments from four genes found that >80% drive expression patterns in the brain; the observed patterns were, on average, comprised of D. melanogaster genome contains >50,000 enhancers and that multiple enhancers drive distinct subsets of expression of a gene in each tissue and developmental stage. We expect that these lines will be valuable tools for neuroanatomy as well as for the elucidation of neuronal circuits and information flow in the fly brain.

Cajal bodies (CBs) are nuclear organelles that are usually identified by the marker protein p80-coilin. Because no orthologue of coilin is known in Drosophila melanogaster, we identified D. melanogaster CBs using probes for other components that are relatively diagnostic for CBs in vertebrate cells. U85 small CB–specific RNA, U2 small nuclear RNA, the survival of motor neurons protein, and fibrillarin occur together in a nuclear body that is closely associated with the nucleolus. Based on its similarity to CBs in other organisms, we refer to this structure as the D. melanogaster CB. Surprisingly, the D. melanogaster U7 small nuclear RNP resides in a separate nuclear body, which we call the histone locus body (HLB). The HLB is invariably colocalized with the histone gene locus. Thus, canonical CB components are distributed into at least two nuclear bodies in D. melanogaster. The identification of these nuclear bodies now permits a broad range of questions to be asked about CB structure and function in a genetically tractable organism.

The germinal vesicle (GV) of Xenopus laevis is an enormous nucleus that contains 18 giant lampbrush chromosomes and thousands of inclusions. The inclusions are primarily of three types: approximately 1500 extrachromosomal nucleoli, 50-100 Cajal bodies, and several thousand B-snurposomes, which correspond to speckles or interchromatin granule clusters in other nuclei. The large size and abundance of the GV organelles, as well as the ease with which they can be studied both in vivo and in vitro, make the GV an ideal object for analysis of nuclear structure and function.

Cajal bodies (CBs) are evolutionarily conserved nuclear organelles that contain many factors involved in the transcription and processing of RNA. It has been suggested that macromolecular complexes preassemble or undergo maturation within CBs before they function elsewhere in the nucleus. Most such models of CB function predict a continuous flow of molecules between CBs and the nucleoplasm, but there are few data that directly support this view. We used fluorescence recovery after photobleaching (FRAP) on isolated Xenopus oocyte nuclei to measure the steady-state exchange rate between the nucleoplasm and CBs of three fluorescently tagged molecules: U7 small nuclear RNA, coilin, and TATA-binding protein (TBP). In the nucleoplasm, the apparent diffusion coefficients for the three molecules ranged from 0.26 to 0.40 μm2 s−1. However, in CBs, fluorescence recovery was markedly slower than in the nucleoplasm, and there were at least three kinetic components. The recovery rate within CBs was independent of bleach spot diameter and could not be attributed to high CB viscosity or density. We propose that binding to other molecules and possibly assembly into larger complexes are the rate-limiting steps for FRAP of U7, coilin, and TBP inside CBs.

As social media streams unfiltered personal information, the boundaries of privacy are being redefined. Modern technology permits near-instant access to news and information. Easy and open access to information places medical journals in a particularly vulnerable position when it comes to publishing case reports. Case reports provide practitioners with precedent in the treatment of a rare or unique illness, and in medical toxicology, often represent the only published guidance on rare exposures. Internet search engines quickly link published reports on unique poisoning cases with social media and news outlet reports, allowing for a potential, and often inadvertent, violation of patient privacy rights. Medical journals, as with other forms of publication, are subject to legal scrutiny regarding negligent publishing and personal privacy rights, but more poignantly, authors and editors have an ethical responsibility to protect patient health information. How then do we balance our duty to protect patient identity with our responsibility to the Journal of Medical Toxicology (JMT) mission of “advancing the science and practice of medical toxicology”? Recent Precedents

The ambulatory care subcommittee of the University HealthSystem Consortium (UHC) recently surveyed UHC members about medication therapy management (MTM) services. The purpose was to gather information regarding the Medicare prescription drug plans (PDPs) that contract with hospital pharmacies to

Objective To test the efficacy of the relationship‐focused behavioral coaching intervention Communicating and Relating Effectively (CARE) in increasing maternal/infant relational effectiveness between depressed mothers and their infants during the first 9 months postpartum. Design Randomized clinical trial (RCT) with three phases. Methods In this three‐phase study, women were screened for postpartum depression (PPD) in Phase I at 6 weeks postpartum. In Phase II, women were randomly assigned to treatment or control conditions and maternal/infant interaction was video recorded at four intervals postpartum: 6 weeks, 3 months, 6 months, and 9 months. Phase III involved focus group and individual interviews with study participants. Setting Phase I mothers were recruited from obstetric units of two major medical centers. Phase II involved the RCT, a series of nurse‐led home visits beginning at 6 weeks and ending at 9 months postpartum. Phase III focus groups were conducted at the university and personal interviews were conducted by telephone or in participants' homes. Participants Postpartum mother/infant dyads (134) representative of southeastern New England, United States participated in the RCT. One hundred and twenty‐five mother/infant dyads were fully retained in the 9‐month protocol. Results Treatment and control groups had significant increases in quality of mother/infant interaction and decreases in depression severity. Qualitative findings indicated presence of the nurse, empathic listening, focused attention and self‐reflection during data collection, directions for video‐recorded interaction, and assistance with referrals likely contributed to improvements for both groups. Conclusions Efficacy of the CARE intervention was only partially supported. Nurse attention given to the control group and the data collection process likely confounded results and constituted an unintentional treatment. Results suggest that nurse‐led home visits had a positive effect on outcomes for all participants.

The importance of establishing clinical pharmacy services in the community cannot be understated in light of current challenges to the traditional dispensing role as the primary service of the community pharmacist. Advancements in automated dispensing technology and declining prescription fee reimbursement are rapidly forcing pharmacists to seek alternative sources of revenue. Providing pharmaceutical care is a viable option to increase customer loyalty job satisfaction, and reimbursement. To support the development of clinical services, academic institutions are forming partnerships with individual community practitioners to overcome perceived educational and training barriers. The authors describe the design and development of two unique clinical skill development programs at the University of Illinois at Chicago. This paper also outlines the patient focused services that the participants have established upon completing the training. These programs successfully enhanced participants' therapeutic knowledge base and facilitated development of the clinical skills necessary for direct patient care.

19 The UltraHeal Randomized Controlled Trial: Investigating the Effects of Low Frequency Ultrasound Debridement in a Nurse-led Vascular Wound Clinic Christine Murphy, RN CETN(C) BSC(hons) MClScWH PhD(Cand), The Ottawa Hospital, Ottawa, Ontario Background: Patients with lower extremity wounds resulting from complications of vasculopathy are challenging to heal and are at high risk for amputation. Ultrasound is known to stimulate healing by improving fibroblast response and biofilm bacteria kill rates. This randomized controlled trial investigated if 22.5kHz ultrasonic debridement could accelerate wound healing, improve granulation appearance and would be feasible to implement in a nurse-led vascular wound clinic. Methods: After a 10 patient pilot feasibility study, 70 patients with lower extremity wounds were enrolled and randomized into ultrasound debridement plus usual care or usual care arm. Ultrasound debridement was applied for 4 weekly treatments until all necrotic debris was removed and light bleeding was attained. Wound surface area was measured by planimetry by a blinded assessor, and wound appearance was determined by revised Photographic Wound Assessment Tool (revPWAT).Usual care consisted of wound cleansing and light superficial mechanical debridement. Results: At the post-treatment visit, the median percentage reduction in wound surface area was greater in the ultrasound debridement group (39.09%) than the usual care group (26.77%) but this did not reach statistical significance (Mann Whitney Test p = 0.507). However there was a significant improvement in wound appearance in the ultrasound debridement group as median reduction in revPWAT score in the treatment group was 9.00 points and control group median declined by 2.00 points (p =

We established a collection of 7,000 transgenic lines of Drosophila melanogaster. Expression of GAL4 ineach line is controlled by a different, defined fragment of genomic DNA that serves as a transcriptional enhancer. We used confocal microscopy ofdissected nervous systems to determine the expression patterns driven by each fragment in the adult brain and ventral nerve cord. We present image data on 6,650 lines. Using both manual and machine-assisted annotation, we describe the expression patterns in the most useful lines. We illustrate the utility of these data for identifying novel neuronal cell types, revealing brain asymmetry, and describing the nature and extent of neuronal shape stereotypy. The GAL4 lines allow expression of exogenous genes in distinct, small subsets of the adult nervous system. The set of DNA fragments, each driving a documented expression pattern, will facilitate the generation of additional constructs for manipulating neuronal function.

Abuse of psychogenic substances sold as “bath salts” and “plant food” has escalated in recent years in the United States (USA). Previous reports suggest regional differences in the primary active β-keto phenylalkylamines found in these products and the corresponding signs and symptoms reported after exposure. Currently, there are only limited studies describing the clinical effects associated with reported “bath salts” exposure in the USA. This study describes the clinical effects associated with “bath salt” and “plant food” exposures as reported to the poison center serving the state of North Carolina (Carolinas Poison Center). We performed a retrospective review of the Carolinas Poison Center database for all cases of reported human exposure to “bath salt” and “plant food” products from 2010 to 2011 with specific attention to clinical effects and routes of exposure. Additionally, we reviewed therapies used, trended the volume of exposure cases reported over the study period, and evaluated the distribution of calls within state counties using descriptive statistics. Carolinas Poison Center received 485 total calls and 409 reported exposure calls regarding “bath salt” or “plant food” products between January of 2010 and December of 2011. The peak of reported exposures occurred in May of 2011. Clinical effects commonly reported in the exposure cases generated from these calls included tachycardia (53.3 %, n = 218), agitated/irritable (50.4 %, n = 206), hallucination/delusions (26.7 %, n = 109), and hypertension (25.2 %, n = 103). In addition to intravenous fluids, common therapies included benzodiazepines (46.0 %, n = 188), sedation (13.4 %, n = 55), alkalinization (3.90 %, n = 16), antihistamine (4.16 %, n = 17), and intubation (3.67 %, n = 15). Haloperidol was the antipsychotic agent used most often to treat agitation (n = 40). Serious complications associated with reported exposure to “bath salt” and “plant food” products included rhabdomyolysis, renal failure, excited delirium syndrome, and death. While treatments have not been empirically determined, sedation with benzodiazepines, aggressive cooling for hyperthermic patients, and use of small doses of antipsychotics for choreoathetoid movements not controlled with benzodiazepines are not likely to be harmful.

Review articles present an excellent overview of material pertaining to a specific topic or clinical question. There are different formats used to write review articles, and within academic medicine, a debate over the best format for review articles exists. The focus of a review may dictate the format; however, regardless of the format chosen, a structured approach is critical for crafting a comprehensive review with limited bias. There are two general categories or types of review articles: narrative and systematic. Narrative review articles provide an overview of a broad spectrum of material in an easily readable format. Systematic review articles traditionally have employed very detailed and extensive searches for literature pertaining to a given topic with a critical review of the literature selected [1, 2]. Many people consider the systematic review the gold standard of reviews because of the rigorous methods employed in evaluating existing literature. The thought behind this being that the more stringent the methods and critique are, the less author bias is introduced. Systematic reviews can be further broken down into qualitative and quantitative reviews (see Table 1 for examples). In both qualitative and quantitative systematic reviews, authors attempt to obtain all relevant primary research, search multiple databases, perform manual searches of relevant referenced material, contact authors of abstracts containing unpublished material, systematically review and rate the literature, and critically evaluate the studies included in the review [2]. The key difference is that quantitative reviews attempt to pool data between studies and statistically compare them (ex: meta-analysis). Table 1 Examples of systematic and narrative reviews Realistically, some topics are just better covered as a narrative review—historical reviews or reviews that are based heavily on historical information and studies do not fit well into systematic review formats. Additionally, within toxicology, research on a given topic may include multiple animal studies with varying animal models or clinical/in vivo evidence which may be limited to case series or case reports that do not fit well with the systematic review format. If the data are best presented in the narrative format, there are multiple ways to strengthen the review by incorporating elements of the systematic review to assist in limiting author bias (Table 1). First and foremost, provide full disclosure of the search methods used to allow for greater transparency and reproducibility. Use at minimum two databases for searching, as not all journals are indexed in MEDLINE and this will help to prevent accidental omission of key articles [2]. Finally, articles should convey a clear message. Review articles provide a great deal of information to readers. While editors prefer systematic over narrative reviews, both have strengths. Striking a balance between the two is necessary for topics that may lend themselves to more of a narrative style. Guidelines for preparation of review articles for JMT: Focused and comprehensive reviews are expected to be critical assessments of literature and data sources pertaining to clinical topics, emphasizing factors such as etiology, diagnosis, prognosis, therapy, or prevention. Systematic and narrative reviews are accepted, although a systematic approach should be used whenever possible. All articles or data sources should be searched for and selected systematically for inclusion and critically evaluated. The specific type of study or analysis, population, intervention, exposure, tests, or outcomes should be described for each article or data source. The title should indicate to the reader this is a review (ex: “Clearing the air: a review of the effects of particulate matter air pollution on human health” [9]) Review articles that address a specific clinical question should include a short case vignette or paragraph (no more than 100 words) describing the clinical question in the Introduction. The search and selection process of reviewed material must be described in the manuscript for all review types in the Methods section. At a minimum, this should include databases and years searched, and key words used, as well as inclusion and exclusion criteria. Presentation of this information in written or tabular form within this section is acceptable. Other sections should be included when appropriate and depending on the review topic (ex: Pathophysiology, Pharmacokinetics, Clinical Presentation, Diagnosis, Management, Prevention).

3,4-Methylenedioxypyrovalerone (MDPV) is a designer stimulant drug that has gained popularity in the USA. Although adverse effects of MDPV have been described, to our knowledge, this is the first reported death.We report the case of a 40-year-old male who injected and snorted "bath salts" containing MDPV and subsequently became agitated, aggressive, and experienced a cardiac arrest. He was resuscitated after his initial arrest; however, he developed hyperthermia, rhabdomyolysis, coagulopathy, acidosis, anoxic brain injury, and subsequently died.This is the first case in the medical literature to report death due to isolated confirmed MDPV intoxication. The manner of death is also consistent with excited delirium syndrome.

Objectives To conduct a community‐based, postpartum depression (PPD) screening initiative, and recommend PPD screening practices. Design Descriptive correlational. Settings Two academic medical centers, a university research office, and participants' homes. Participants Five thousand one hundred and sixty‐nine postpartum women age 14 to 49 years. Methods The Agency for Healthcare Research and Quality (AHRQ) framework was implemented by identifying a cohort of mothers and conducting PPD screening followed by diagnostic evaluation of those with positive screens. Mothers in the postpartum period were recruited from two academic medical centers and screened for PPD at 4 to 6 weeks postpartum by telephone or mail using the Edinburgh Postnatal Depression Scale (EPDS). Mothers with EPDS scores ≥10 were invited to participate in the Structured Clinical Interview for DSM IV (SCID) to confirm PPD. Results Six hundred and seventy‐four (13%) women had EPDS scores ≥10; 185 women with elevated EPDS scores agreed to have a SCID diagnostic interview, and 144 were diagnosed with minor or major depression. A significantly higher percentage of women who self‐administered and mailed in the EPDS than women who were screened via telephone had scores ≥10. Elevated PPD scores were not associated with age or parity. Race/ethnicity identification other than White and having less than high school education were associated with higher PPD scores. Conclusions The AHRQ framework was effective in guiding a large‐scale PPD screening initiative by identifying mothers at risk for PPD. Results support previous findings regarding prevalence, selected risk factors, and continued use of the EPDS with SCID confirmation.

An mAb library was produced against proteins from the germinal vesicle (GV) of the frog Xenopus laevis; mAb 104 was selected from this library on the basis of its immunofluorescent staining of lampbrush chromosome loops. Chromosomes from several species of frogs and salamanders stained equally well. The antibody also stained the surface of numerous small granules in the GV nucleoplasm. The interior of the same granules was stained by antibodies against small nuclear ribonucleoproteins (snRNPs). mAb 104 also stained somatic nuclei from many vertebrate and invertebrate species, usually in a finely punctate pattern similar to that described for anti-snRNP and other antinuclear antibodies. The staining of somatic nuclei was much stronger during the mitotic stages than during interphase. Immunoblot analysis showed that mAb 104 recognizes a phosphorylated epitope.

Cajal bodies are evolutionarily conserved nuclear organelles that are believed to play a central role in assembly of RNA transcription and processing complexes. Although knowledge of Cajal body composition and behavior has greatly expanded in recent years, little is known about the molecules and mechanisms that lead to the formation of these organelles in the nucleus. The Xenopus oocyte nucleus or germinal vesicle is an excellent model system for the study of Cajal bodies, because it is easy to manipulate and it contains 50-100 Cajal bodies with diameters up to 10 μm. In this study we show that numerous mini-Cajal bodies (less than 2 μm in diameter) form in the germinal vesicle after oocytes recover from heat shock. The mechanism for heat shock induction of mini-Cajal bodies is independent of U7 snRNA and does not require transcription or import of newly translated proteins from the cytoplasm. We suggest that Cajal bodies originate by self-organization of preformed components, preferentially on the surface of B-snurposomes.