Examining the Characteristics of Patients With Non-Malignant Lung Disease at the Time of Referral to An Inter-Professional Supportive Care Clinic.

CONTEXT: Patients with non-malignant, advanced lung diseases (NMALD), such as chronic obstructive pulmonary disease (COPD) and interstitial lung disease (ILD), experience a high symptom burden over a prolonged period. Involvement of palliative care has been shown to improve symptom management, reduce hospital visits and enhance psychosocial support; however, optimal timing of referral is unknown. OBJECTIVE: The aim of this study was to identify the stage in the illness trajectory that patients with NMALD are referred to an ambulatory palliative care clinic. METHODS: A retrospective chart review was conducted on all patients with NMALD who attended a Supportive Care Clinic (SCC) between March 1, 2017 and March 31, 2019. RESULTS: Thirty patients attended the SCC during the study period. The most common diagnoses included COPD (36.7%), ILD (36.7%), and bronchiectasis (3.3%). At the time of initial consultation, the majority (89.4%) had Medical Research Council (MRC) class 4-5 dyspnea, however, only 1 patient had been prescribed opioids for management of breathlessness. Twenty-six patients had advance care planning discussions in the SCC. Phone appointments were a highly utilized feature of the program as patients had difficulty attending in-person appointments due to frailty and dyspnea. One-half of patients had at least 1 disease-related hospital admission in the previous year. Six patients were referred directly to home palliative care at their initial consultation. CONCLUSIONS: Referral to palliative care often occurs at late stages in non-malignant lung disease. Further, opioids for the management of dyspnea are significantly underutilized by non-palliative providers.

A Retrospective Study Reviewing Interprofessional Advance Care Planning Group Discussions in Pulmonary Rehabilitation: A Proof-of-Concept and Feasibility Study.

BACKGROUND: Advance care planning (ACP) is a process of reflection and discussion wherein a patient, in consultation with a health-care provider, family, and/or loved ones, clarifies values and treatment preferences and establishes goals, including a plan for end-of-life (EOL) care. Advance care planning encompasses appreciating and understanding illness and treatment options, elucidating patient values and beliefs, and identifying a substitute decision maker (SDM) or designating a power of attorney (POA) for personal care. These discussions have proven to be effective in improving patient-family satisfaction, reducing anxiety regarding EOL care in patients and family members, and improving patient-centered care by empowering patients to direct their care at EOL. However, ACP conversations are often difficult to have due to the sensitive nature of such discussions. OBJECTIVE: The aim of this study was to determine whether group facilitation for teaching and discussing ACP enhances participants' understanding of ACP and allows them to feel comfortable and supported when discussing these sensitive issues. METHODS: Patients who were registered in North York General Hospital's (NYGH) pulmonary rehabilitation program from June 2016 until August 2017 were given the opportunity to attend two 1-hour sessions related to ACP. The first session was dedicated to educating patients on ACP, explaining the hierarchy of the SDM and the role of the POA for personal care. The second session, provided a short time later, was devoted to discussions of values, wishes, fears, and trade-offs for future medical and EOL care. These discussions led by the supportive care nurse practitioner and a physician who are members of the NYGH Freeman Palliative Care Team were held in a group-facilitated format. Anonymous feedback forms, including both qualitative and quantitative feedback, were completed by the participants and analyzed. PARTICIPANTS: Analysis of a sample of 30 participants who attended 1 or 2 of the ACP sessions revealed that 21 identified as female and 9 identified as male. The average age of the participants was 76 years. FINDINGS: Participants felt the content was relevant to their needs and were comfortable asking questions with all feedback averages ranging from good to very good. Participants appreciated the opportunity to share their thoughts in an open and interactive format. CONCLUSION: Discussing issues relevant to ACP, including providing information about ACP, sharing fears, wishes, and tradeoffs, were well-received in a group-support environment. Future studies should assess the impact of ACP group discussion on the individual, such as identifying a POA, having discussions regarding wishes and values with the SDM/POA, and examining the clinical impact of such sessions.

Pain in patients with newly diagnosed or relapsed acute leukemia.

PURPOSE: Acute leukemia (AL) is associated with substantial morbidity and mortality. We assessed the prevalence and correlates of pain in patients with newly diagnosed or relapsed AL. METHODS: Patients with newly diagnosed or relapsed AL admitted to a comprehensive cancer center completed the Memorial Symptom Assessment Scale (MSAS), which assesses prevalence, severity, and distress associated with pain and other symptoms. Factors associated with severe pain were assessed using logistic regression. Two raters completed chart reviews in duplicate for patients with severe pain (MSAS severity ≥ 3/4) to determine the site of pain. RESULTS: Three hundred eighteen patients were recruited from January 2008 to October 2013: 245 (77.0%) had acute myeloid or acute promyelocytic leukemia (AML/APL) and 73 (23.0%) had acute lymphoblastic leukemia (ALL); 289 (90.9%) were newly diagnosed and 29 (9.1%) had relapsed disease. Pain was reported in 156/318 (49.2%), of whom 55/156 (35.3%) reported severe pain (≥ 3/4). Pain was associated with all psychological symptoms (all p < 0.005) and some physical symptoms. Severe pain was associated with younger age (p = 0.02), worse performance status (p = 0.04), ALL diagnosis (p = 0.04), and time from onset of chemotherapy (p = 0.03), with pain peaking at 4 weeks after chemotherapy initiation. The most common sites of severe pain were oropharynx (22; 40%), head (12; 21.8%), and abdomen (11; 20%). Only 3 patients (0.9%) were referred to the symptom control/palliative care team during the month prior to or following assessment. CONCLUSIONS: Pain is frequent, distressing, and predictable in patients undergoing induction chemotherapy for AL. Further research is needed to assess the efficacy of early supportive care in this population.

Use of Standardized Assessment Tools to Improve the Effectiveness of Palliative Care Rounds: A Quality Improvement Initiative.

BACKGROUND: Optimal care for patients in the palliative care setting requires effective clinical teamwork. Communication may be challenging for health-care workers from different disciplines. Daily rounds are one way for clinical teams to share information and develop care plans for patients. OBJECTIVE: The objective of this initiative was to improve the structure and process of daily palliative care rounds by incorporating the use of standardized tools and improved documentation into the meeting. We chose a quality improvement (QI) approach to address this initiative. Our aims were to increase the use of assessment tools when discussing patient care in rounds and to improve the documentation and accessibility of important information in the health record, including goals of care. METHODS: This QI initiative used a preintervention and postintervention comparison of the outcome measures of interest. The initiative was tested in a palliative care unit (PCU) over a 22-month period from April 2014 to January 2016. Participants were clinical staff in the PCU. RESULTS: Data collected after the completion of several plan-do-study-act cycles showed increased use and incorporation of the Edmonton Symptom Assessment System and Palliative Performance Scale into patient care discussions as well as improvement in inclusion of goals of care into the patient plan of care. CONCLUSION: Our findings demonstrate that the effectiveness of daily palliative care rounds can be improved by incorporating the use of standard assessment tools and changes into the meeting structure to better focus and direct patient care discussions.

Simple prognostic model for patients with advanced cancer based on performance status.

PURPOSE: Providing survival estimates is important for decision making in oncology care. The purpose of this study was to provide survival estimates for outpatients with advanced cancer, using the Eastern Cooperative Oncology Group (ECOG), Palliative Performance Scale (PPS), and Karnofsky Performance Status (KPS) scales, and to compare their ability to predict survival. METHODS: ECOG, PPS, and KPS were completed by physicians for each new patient attending the Princess Margaret Cancer Centre outpatient Oncology Palliative Care Clinic (OPCC) from April 2007 to February 2010. Survival analysis was performed using the Kaplan-Meier method. The log-rank test for trend was employed to test for differences in survival curves for each level of performance status (PS), and the concordance index (C-statistic) was used to test the predictive discriminatory ability of each PS measure. RESULTS: Measures were completed for 1,655 patients. PS delineated survival well for all three scales according to the log-rank test for trend (P < .001). Survival was approximately halved for each worsening performance level. Median survival times, in days, for each ECOG level were: EGOG 0, 293; ECOG 1, 197; ECOG 2, 104; ECOG 3, 55; and ECOG 4, 25.5. Median survival times, in days, for PPS (and KPS) were: PPS/KPS 80-100, 221 (215); PPS/KPS 60 to 70, 115 (119); PPS/KPS 40 to 50, 51 (49); PPS/KPS 10 to 30, 22 (29). The C-statistic was similar for all three scales and ranged from 0.63 to 0.64. CONCLUSION: We present a simple tool that uses PS alone to prognosticate in advanced cancer, and has similar discriminatory ability to more complex models.

Costs of recalled and recommended diets for pregnant women with type 1, type 2 and gestational diabetes.

OBJECTIVE: The costs associated with nutritious foods may be a barrier to healthy dietary choices and of particular concern to pregnancies complicated by diabetes. Therefore, a survey was conducted in a tertiary care diabetes and pregnancy clinic to compare the associated costs of actual food choices versus the cost of a constructed recommended diet. METHODS: Women with types 1, 2 and gestational diabetes mellitus (GDM) completed 24-hour dietary recalls under the supervision of the research coordinator (Actual Diet). A Recommended Diet for this population was constructed independent of participant responses. Actual and Recommended Diets were standardized per 2000 kcal, priced and compared for content and cost. RESULTS: Seventy-five women participated: 27 with GDM, 29 with type 1 diabetes and 19 with type 2 diabetes. There were no significant cost differences between Recommended and Actual Diets food choices expressed per 2000 kcal: Recommended Diet $10.14±3.72; Actual Diet GDM: $11.30±3.88; Actual Diet type 1 diabetes: $9.00±3.16; Actual Diet type 2 diabetes: $10.24±3.92. Percentage of fibre intake was lower for Actual Diets than Recommended Diet for all groups, while percentage of protein intake was lower in Actual than Recommended Diet for women with type 1 diabetes. CONCLUSION: Clinical recommendations for healthy food choices may not be more expensive than actual choices made by pregnant women with diabetes.

Efficacy of Routine Notification and Request on reducing corneal transplantation wait times in Canada.

OBJECTIVE: To determine whether the implementation of Routine Notification and Request (RNR) has been effective in increasing the amount of donor corneal tissue available and reducing wait times for corneal transplant (CT) surgeries. DESIGN: Survey of the CT surgeons and eye banks in Canada. PARTICIPANTS: CT surgeons and representatives of the 10 eye banks in Canada. METHODS: Voluntary, anonymous questionnaires were distributed between May 1 and September 30, 2006. RESULTS: Following the implementation of RNR, 3 eye banks had an increase in the amount of corneal tissue available: Manitoba, 81% (from 42 tissues in 2004 to 76 tissues in 2006); Ontario, 25% (from 1304 tissues in 2005 to 1626 tissues in 2006); New Brunswick, 129% (from 86 tissues in 2005 to 197 tissues in 2006). British Columbia, where RNR was implemented in 1999, had a 6% increase (from 766 in 2005 to 812 in 2006). There has been a significant decrease in wait times from the time of diagnosis by CT surgeons to the time of surgery in British Columbia (from 48+/-18 weeks in 2004 to 39+/-20 weeks in 2006), Manitoba (from 82+/-56 weeks in 2004 to 32+/-23 weeks in 2006), Ontario (from 82+/-56 weeks in 2004 to 31+/-34 weeks in 2006), and Nova Scotia (from 44+/-12 weeks in 2004 to 32+/-28 weeks in 2006). CONCLUSIONS: RNR has been effective in increasing corneal tissue availability and decreasing wait times in provinces where it has been implemented. We recommend similar legislative changes to be considered in those provinces where corneal tissue shortage is delaying the availability of CT surgery.

Insulin increases the potency of glycine at ionotropic glycine receptors.

The mechanisms by which insulin modulates neuronal plasticity and pain processes remain poorly understood. Here we report that insulin rapidly increases the function of glycine receptors in murine spinal neurons and recombinant human glycine receptors expressed in human embryonic kidney cells. Whole-cell patch-clamp recordings showed that insulin reversibly enhanced current evoked by exogenous glycine and increased the amplitude of spontaneous glycinergic miniature inhibitory postsynaptic currents recorded in cultured spinal neurons. Insulin (1 microM) also shifted the glycine concentration-response plot to the left and reduced the glycine EC(50) value from 52 to 31 microM. Currents evoked by a submaximal concentration of glycine were increased to approximately 140% of control. The glycine receptor alpha subunit was sufficient for the enhancement by insulin because currents from recombinant homomeric alpha(1) receptors and heteromeric alpha(1)beta receptors were both increased. Insulin acted at the insulin receptor via pathways dependent on tyrosine kinase and phosphatidylinositol 3 kinase because the insulin effect was eliminated by the insulin receptor antagonist, hydroxy-2-naphthalenylmethylphosphonic acid trisacetoxymethyl ester, the tyrosine kinase inhibitor lavendustin A, and the phosphatidylinositol 3 kinase antagonist wortmannin. Together, these results show that insulin has a novel regulatory action on the potency of glycine for ionotropic glycine receptors.

Selective enhancement of tonic GABAergic inhibition in murine hippocampal neurons by low concentrations of the volatile anesthetic isoflurane.

Volatile (inhaled) anesthetics cause amnesia at concentrations well below those that cause loss of consciousness and immobility; however, the underlying neuronal mechanisms are unknown. Although many anesthetics increase inhibitory GABAergic synaptic transmission, this effect occurs only at high concentrations (>100 microm). Molecular targets for low concentrations of inhaled anesthetics have not been identified. Here, we report that a tonic inhibitory conductance in hippocampal pyramidal neurons generated by alpha5 subunit-containing GABA(A) receptors is highly sensitive to low concentrations of the volatile anesthetic isoflurane (ISO) (25 and 83.3 microm). The alpha5 subunit is necessary for enhancement of the tonic current by these low concentrations of isoflurane because potentiation is absent in neurons from alpha5-/- mice. Furthermore, ISO (25 microm) potentiated recombinant human alpha5beta3gamma2L GABA(A) receptors, whereas this effect was not seen with alpha1beta3gamma2L GABA(A) receptors. These studies suggest that an increased tonic inhibition in the hippocampus may contribute to amnestic properties of volatile anesthetics.

Insulin decreases isoflurane minimum alveolar anesthetic concentration in rats independently of an effect on the spinal cord.

UNLABELLED: The observation that insulin supplies an element of analgesia suggests that insulin administration might decrease the concentration of inhaled anesthetic required to produce MAC (the minimum alveolar anesthetic concentration required to eliminate movement in response to noxious stimulation in 50% of subjects). We hypothesized that insulin decreases MAC by directly affecting the nervous system, by decreasing blood glucose, or both. To test these hypotheses, we infused increasing doses of insulin either intrathecally or IV in rats anesthetized with isoflurane and determined the resulting MAC change (assessing forelimb and hindlimb movement separately). Infusion of insulin produced a dose-related decrease in MAC that did not differ among groups. That is, the IV and intrathecal infusions caused similar decreases in MAC at a given infusion rate. Blood glucose concentrations were larger in the rats given insulin with 5% dextrose. However, the percentage change in MAC determined from forelimb versus hindlimb movement did not differ. For a given insulin infusion rate, MAC changes and glucose levels did not correlate with each other, except, possibly, for the most rapid infusion rate, for which smaller glucose concentrations were associated with a marginally larger decrease in MAC. Intrathecal infusions of insulin did not produce spinal cord injury. In summary, we found that insulin decreases isoflurane MAC in a dose-related manner independently of its effects on the blood concentration of glucose. The sites at which insulin acts to decrease MAC appear to be supraspinal rather than spinal. The effect may be due to a capacity of insulin to produce analgesia through an action on one or more neurotransmitter receptors. IMPLICATIONS: Intrathecal and IV insulin administration equally decrease isoflurane MAC in rats, regardless of the concentration of blood sugar. These findings indicate that although insulin decreases MAC, the decrease is not mediated by actions on the spinal cord.

Tonic inhibition in mouse hippocampal CA1 pyramidal neurons is mediated by alpha5 subunit-containing gamma-aminobutyric acid type A receptors.

The principal inhibitory neurotransmitter in the mammalian brain, gamma-aminobutyric acid (GABA), is thought to regulate memory processes by activating transient inhibitory postsynaptic currents. Here we describe a nonsynaptic, tonic form of inhibition in mouse CA1 pyramidal neurons that is generated by a distinct subpopulation of GABA type A receptors (GABA(A)Rs). This tonic inhibitory conductance is predominantly mediated by alpha5 subunit-containing GABA(A)Rs (alpha5GABA(A)Rs) that have different pharmacological and kinetic properties compared to postsynaptic receptors. GABA(A)Rs that mediate the tonic conductance are well suited to detect low, persistent, ambient concentrations of GABA in the extracellular space because they are highly sensitive to GABA and desensitize slowly. Moreover, the tonic current is highly sensitive to enhancement by amnestic drugs. Given the restricted expression of alpha5GABA(A)Rs to the hippocampus and the association between reduced alpha5GABA(A)R function and improved memory performance in behavioral studies, our results suggest that tonic inhibition mediated by alpha5GABA(A)Rs in hippocampal pyramidal neurons plays a key role in cognitive processes.

Tyrosine kinases enhance the function of glycine receptors in rat hippocampal neurons and human alpha(1)beta glycine receptors.

Glycine receptors (GlyRs) are transmitter-gated channels that mediate fast inhibitory neurotransmission in the spinal cord and brain. The GlyR beta subunit contains a putative tyrosine phosphorylation site whose functional role has not been determined. To examine if protein tyrosine kinases (PTKs) regulate the function of GlyRs, we analysed whole-cell currents activated by applications of glycine to CA1 hippocampal neurons and spinal neurons. The role of a putative site for tyrosine phosphorylation at position 413 of the beta subunit was examined using site-directed mutagenesis and expression of recombinant (alpha(1)beta(Y413F)) receptors in human embryonic kidney (HEK 293) cells. Lavendustin A, an inhibitor of PTKs, depressed glycine-evoked currents (I(Gly)) in CA1 neurons and spinal neurons by 31 % and 40 %, respectively. In contrast, the intracellular application of the exogenous tyrosine kinase, cSrc, enhanced I(Gly) in CA1 neurons by 56 %. cSrc also accelerated GlyR desensitization and increased the potency of glycine 2-fold (control EC(50) = 143 microM; cSrc EC(50) = 74 microM). Exogenous cSrc, applied intracellularly, upregulated heteromeric alpha(1)beta receptors but not homomeric alpha(1) receptors. Substitution mutation of the tyrosine to phenylalanine at position beta-413 prevented this enhancement. Furthermore, a selective inhibitor of the Src family kinases, PP2, down-regulated wild-type alpha(1)beta but not alpha(1)beta(Y413F) receptors. Together, these findings indicate that GlyR function is upregulated by PTKs and this modulation is dependent on the tyrosine-413 residue of the beta subunit.