Kirsten Wentlandt

Referral practices of oncologists to specialized palliative care.

PURPOSE To describe current referral practices of oncologists to specialized palliative care (SPC) and define demographic characteristics, practice situations, and opinions associated with referral. METHODS Physician members of the Canadian Association of Medical Oncologists, Canadian Association of Radiation Oncologists, and Canadian Society of Surgical Oncology were invited to participate in an anonymous survey assessing SPC referral practices. Participants received two e-mailed and two mailed invitations. RESULTS The response rate was 72% (603 of 839 physicians); 37% were medical oncologists/hematologists, 50% were radiation oncologists, and 12% were surgical oncologists. Ninety-four percent reported that SPC was available to them, but only 37% reported that these services accepted patients on chemotherapy. Eighty-four percent referred terminally ill patients usually/always, but generally for uncontrolled symptoms or discharge planning late in the disease course. One third would refer to SPC earlier if it was renamed supportive care. Predictors of higher referral frequency included comprehensiveness of available SPC services (P = .004), satisfaction with SPC availability (P < .001), SPC acceptance of patients receiving chemotherapy (P < .001), and oncologist ease with referring patients to a palliative care service before they were close to death (P < .001). Controlling for specialty, predictors of referral at diagnosis or during chemotherapy, rather than later, included satisfaction with SPC service availability (P < .001) and SPC service acceptance of patients on chemotherapy (P < .001). CONCLUSION Oncologists referred patients frequently to SPC, but generally late in the disease course for patients with uncontrolled symptoms. Availability of comprehensive SPC, especially for patients receiving chemotherapy, and persisting definitional issues seem to be the main barriers preventing timely referral.

Epileptiform activity in hippocampal slice cultures exposed chronically to bicuculline: increased gap junctional function and expression

Chronic (18 h) exposure of cultured hippocampal slices to the type‐A GABA receptor blocker, bicuculline methiodide (BMI) 10 μm increased the levels of connexin 43 (Cx43) and connexin 32 (Cx32) mRNAs, but not connexin 26 and connexin 36, as demonstrated by RNase protection assays. The levels of Cx43 and Cx32 proteins in membrane fractions detected by western blotting were also significantly increased. Immunoblotting indicated that BMI also promoted a significant expression of the transcription protein c‐fos. The rate of fluorescence recovery after photobleaching, an index of gap junctional coupling, was also significantly increased, whereas it was blocked by the gap junctional blocker, carbenoxolone (100 μm). Extracellular recordings in CA1 stratum pyramidale, performed in BMI‐free solution, demonstrated that BMI‐exposed cultures possessed synaptic responses characteristic of epileptiform discharges: (i) significantly greater frequency of spontaneous epileptiform discharges, (ii) post‐synaptic potentials with multiple population spikes, and (iii) significantly longer duration of primary afterdischarges. Carbenoxolone (100 μm), but not its inactive analog, oleanolic acid (100 μm), reversibly inhibited spontaneous and evoked epileptiform discharges. The findings of BMI‐induced parallel increases in levels of gap junction expression and function, and the increase in epileptiform discharges, which were sensitive to gap junctional blockers, are consistent with the hypothesis that increased gap junctional communication plays an intrinsic role in the epileptogenic process.

Connexin 43 mimetic peptides inhibit spontaneous epileptiform activity in organotypic hippocampal slice cultures.

Gap junctions are cytoplasmic channels connecting adjacent cells and mediating their electrical and metabolic coupling. Different cell types in the CNS express various gap junction forming proteins, the connexins, in a cell-specific manner. Using the general gap junctional blocker, carbenoxolone, and two synthetic connexin mimetic peptides, corresponding to amino acid sequences of segments within the second extracellular loop of connexin 43, we studied the role of gap junctions in the generation of epileptiform activity in rat organotypic hippocampal slice cultures. While carbenoxolone inhibited both spontaneous and evoked seizure-like events, connexin mimetic peptides selectively attenuated spontaneous recurrent epileptiform activity, and only after prolonged (>10 h) treatment. The effects were mediated through reduced gap junctional coupling as indicated by suppressed fluorescent dye transfer between the cells. Assuming a selective inhibition of a connexin 43-dependent process by the mimetic peptides and preferential localization of this connexin isoform in astrocytes, the data suggest that, in developing hippocampal networks, the generation and/or initiation of spontaneous recurrent seizure-like activity may depend in large part upon the opening of glial gap junctions. Furthermore, this study shows that the use of a synthetic peptide that mimics a short sequence of a specific connexin isoform and, hence, blocks gap junctional communication in targeted cell types in the CNS, is a viable strategy for the modulation of cerebral activity.

The Toronto General Hospital Transitional Pain Service: development and implementation of a multidisciplinary program to prevent chronic postsurgical pain.

Chronic postsurgical pain (CPSP), an often unanticipated result of necessary and even life-saving procedures, develops in 5–10% of patients one-year after major surgery. Substantial advances have been made in identifying patients at elevated risk of developing CPSP based on perioperative pain, opioid use, and negative affect, including depression, anxiety, pain catastrophizing, and posttraumatic stress disorder-like symptoms. The Transitional Pain Service (TPS) at Toronto General Hospital (TGH) is the first to comprehensively address the problem of CPSP at three stages: 1) preoperatively, 2) postoperatively in hospital, and 3) postoperatively in an outpatient setting for up to 6 months after surgery. Patients at high risk for CPSP are identified early and offered coordinated and comprehensive care by the multidisciplinary team consisting of pain physicians, advanced practice nurses, psychologists, and physiotherapists. Access to expert intervention through the Transitional Pain Service bypasses typically long wait times for surgical patients to be referred and seen in chronic pain clinics. This affords the opportunity to impact patients’ pain trajectories, preventing the transition from acute to chronic pain, and reducing suffering, disability, and health care costs. In this report, we describe the workings of the Transitional Pain Service at Toronto General Hospital, including the clinical algorithm used to identify patients, and clinical services offered to patients as they transition through the stages of surgical recovery. We describe the role of the psychological treatment, which draws on innovations in Acceptance and Commitment Therapy that allow for brief and effective behavioral interventions to be applied transdiagnostically and preventatively. Finally, we describe our vision for future growth.

General anesthetics inhibit gap junction communication in cultured organotypic hippocampal slices.

Gap junctions are protein channels that directly connect the cytosol of neighboring cells, thus forming electrical synapses and promoting synchronous neuronal activities. Such activities lead to the initiation and propagation of electroencephalogram oscillations implicated in cognition and consciousness. In this study, we investigated the effects of propofol, thiopental, and halothane on gap junction communication in cultured organotypic hippocampal slices by recovery of fluorescence after photo bleaching (FRAP) technique and electrophysiological recordings. Propofol 15 &mgr;M and thiopental 10 &mgr;M attenuated gap junction communication in slice cultures by 46.7% ± 4.5% and 48.8% ± 5.5%, respectively, as measured by FRAP. Smaller concentrations of propofol 5 &mgr;M and thiopental 2 &mgr;M did not change gap junction coupling. Accompanying the decreased gap junction communication, hippocampus slice cultures exposed to propofol 15 &mgr;M and thiopental 10 &mgr;M were found to have reduced electrophysiologic spontaneous discharges and primary after discharges evoked by a tetanic train of 50 Hz for 2 s. On the other hand, halothane 0.64 mM, a concentration slightly larger than twice its minimum alveolar concentration had no effect on gap junction coupling while halothane 2.8 mM blocked FRAP by 70%. The current study illustrates that anesthetic concentrations of propofol and thiopental, but not halothane, attenuate gap junction communication in cultured hippocampal slices. Suppression of gap junction function could compound the mechanisms of anesthetic actions.

Preventive analgesia and novel strategies for the prevention of chronic post-surgical pain

Chronic post-surgical pain (CPSP) is a serious complication of major surgery that can impair a patient’s quality of life. The development of CPSP is a complex process which involves biologic, psychosocial, and environmental mechanisms that have yet to be fully understood. Currently perioperative pharmacologic interventions aim to suppress and prevent sensitization with the aim of reducing pain and analgesic requirement in acute as well as long-term pain . Despite the detrimental effects of CPSP on patients, the body of literature focused on treatment strategies to reduce CPSP remains limited and continues to be understudied. This article reviews the main pharmacologic candidates for the treatment of CPSP, discusses the future of preventive analgesia, and considers novel strategies to help treat acute post-operative pain and lessen the risk that it becomes chronic. In addition, this article highlights important areas of focus for clinical practice including: multimodal management of CPSP patients, psychological modifiers of the pain experience, and the development of a Transitional Pain Service specifically designed to manage patients at high risk of developing chronic post-surgical pain.

General anesthetics attenuate gap junction coupling in P19 cell line

Gap junction communication is widespread throughout the mammalian nervous system among neurons as well as glia. We addressed the hypothesis that general anesthetics attenuate gap junction mediated coupling in P19 cell line that can differentiate into neuronal‐like cells and astrocytes and oligodendrocytes. We characterized the extent of dye coupling over time in the P19 cell line using colocalization of chlormethylbenzamido‐1,1 dioctadecyl‐3,3,3′,3′‐tetramethylindocarbocyamine (CM‐DiI) and calcein‐AM in donor and recipient cells in cocultures. After seeding, the gap junction permeant dye calcein spreads from donor to recipient cells. CM‐DiI and calcein fluorescence identified donor and recipient cells, respectively. The extent of intercellular connections was evaluated using cell counting and flow cytometry up to 2 hr after treatment. Clinically relevant concentrations of the intravenous anesthetics propofol (15 μM) and thiopental (10 μM) attenuated gap junction permeability in P19 cell cultures. In contrast, halothane, a volatile anesthetic in a concentration (0.64 mM) relevant to its free aqueous EC50 had no effect on gap junction coupling; however, very high halothane concentrations (2.8 mM) blocked dye transfer by ∼90%. The results indicate that halothane concentrations pertinent to clinical anesthesia were unable to attenuate gap junction communication in a cell line that can express neuronal and glial gap junction proteins; however, clinically relevant concentrations of propofol and thiopental depressed gap junction coupling.

Quality of Care and Satisfaction With Care on Palliative Care Units

CONTEXT There is little research on quality of care specific to palliative care units (PCUs). OBJECTIVES To delineate important aspects of satisfaction with care and quality of care on a PCU, as described by inpatients, family caregivers, and health care professionals. METHODS Qualitative interviews and focus groups were conducted across four Toronto PCUs, with a total of 46 patient/caregiver interviews and eight staff focus groups. Interviews and focus groups were semistructured to elicit comments about satisfaction with care and quality of care for inpatients and families on a PCU. Data were analyzed using a grounded theory method, with an inductive, constant comparison approach to identify themes, and were coded to saturation. RESULTS Key elements of quality care and patient satisfaction on a PCU were grouped into six domains: 1) interprofessional team: a team of experts comprising multiple disciplines functioning as a unit; 2) communication: developing rapport, addressing expectations, providing information, listening actively, and facilitating end-of-life discussions; 3) attentive, personalized care: anticipatory and responsive compassionate care with tailored management of physical and nonphysical symptoms; 4) family-centered: support of patients and caregivers within a family; 5) accessible and consistent: appropriate resources and adequate staff to provide consistent care; and 6) supportive setting: a bright noninstitutionalized setting allowing both privacy and socialization. CONCLUSION The elements identified support the delivery of quality care. They may act as a guide for those planning to develop PCUs and form the basis for measures of satisfaction with care.

Impact of a transplant palliative care clinic on symptoms for patients awaiting lung transplantation.

Impact of a transplant palliative care clinic on symptoms for patients awaiting lung transplantation Nicole Freeman, MD, Lisa W. Le, MSc, Lianne G. Singer, MD, Rebecca Colman, MD, Camilla Zimmermann, MD, PhD, and Kirsten Wentlandt, PhD, MHSci, MD From the Department of Family Medicine Windsor Program, Schulich School of Medicine and Dentistry, Western University, London; Department of Biostatistics, Princess Margaret Cancer Centre, University Health Network, Toronto; Division of Respirology, Department of Medicine, University Health Network, University of Toronto; Department of Supportive Care, University Health Network; Division of Medical Oncology, Department of Medicine, University of Toronto; Campbell Family Cancer Research Institute, Ontario Cancer Institute; and the Department of Family and Community Medicine, University of Toronto, Toronto, Ontario, Canada

Measuring quality of life in advanced heart failure.

Purpose of review Patients with Stage D heart failure can benefit from palliative care consultation to help them manage unpleasant symptoms and improve quality of life. Although guidelines describe how to manage symptoms, very little direction is provided on how to evaluate the effectiveness of those interventions. Recent findings Numerous studies have used the measurement of symptoms, emotional distress, functional capacity and quality of life to evaluate the effectiveness of interventions in heart failure. There is limited evidence on the use of these instruments in heart failure palliative care. Four studies were identified that evaluate the effectiveness of palliative care consultation for patients with advanced heart failure. All four studies measured symptom severity, emotional distress, and quality of life. The application of appropriate instruments is discussed. Suggestions for scores that should trigger palliative care consultation are identified. Summary The routine administration of standardized instruments to measure symptom severity and quality of life may improve the assessment and management of patients with Stage D heart failure. Ongoing discussion and research is needed to determine if these instruments are the best tools to use with heart failure palliative care patients.