Sheryl McDiarmid

Continuous Multi-Parameter Heart Rate Variability Analysis Heralds Onset of Sepsis in Adults

Background Early diagnosis of sepsis enables timely resuscitation and antibiotics and prevents subsequent morbidity and mortality. Clinical approaches relying on point-in-time analysis of vital signs or lab values are often insensitive, non-specific and late diagnostic markers of sepsis. Exploring otherwise hidden information within intervals-in-time, heart rate variability (HRV) has been documented to be both altered in the presence of sepsis, and correlated with its severity. We hypothesized that by continuously tracking individual patient HRV over time in patients as they develop sepsis, we would demonstrate reduced HRV in association with the onset of sepsis. Methodology/Principal Findings We monitored heart rate continuously in adult bone marrow transplant (BMT) patients (nu200a=u200a21) beginning a day before their BMT and continuing until recovery or withdrawal (12±4 days). We characterized HRV continuously over time with a panel of time, frequency, complexity, and scale-invariant domain techniques. We defined baseline HRV as mean variability for the first 24 h of monitoring and studied individual and population average percentage change (from baseline) over time in diverse HRV metrics, in comparison with the time of clinical diagnosis and treatment of sepsis (defined as systemic inflammatory response syndrome along with clinically suspected infection requiring treatment). Of the 21 patients enrolled, 4 patients withdrew, leaving 17 patients who completed the study. Fourteen patients developed sepsis requiring antibiotic therapy, whereas 3 did not. On average, for 12 out of 14 infected patients, a significant (25%) reduction prior to the clinical diagnosis and treatment of sepsis was observed in standard deviation, root mean square successive difference, sample and multiscale entropy, fast Fourier transform, detrended fluctuation analysis, and wavelet variability metrics. For infected patients (nu200a=u200a14), wavelet HRV demonstrated a 25% drop from baseline 35 h prior to sepsis on average. For 3 out of 3 non-infected patients, all measures, except root mean square successive difference and entropy, showed no significant reduction. Significant correlation was present amongst these HRV metrics for the entire population. Conclusions/Significance Continuous HRV monitoring is feasible in ambulatory patients, demonstrates significant HRV alteration in individual patients in association with, and prior to clinical diagnosis and treatment of sepsis, and merits further investigation as a means of providing early warning of sepsis.

Utility of Comorbidity Assessment in Predicting Transplantation-Related Toxicity Following Autologous Hematopoietic Stem Cell Transplantation for Multiple Myeloma

Patients with coexisting medical problems may suffer increased toxicity and reduced quality of life after autologous hematopoietic stem cell transplantation (HSCT). The benefit of high-dose therapy for some patients with multiple myeloma (MM) is debatable. Decision tools that aid in identifying those patients with MM most suited for autologous HSCT may avoid the risk of excess toxicity. An objective assessment of comorbidities was performed in 126 patients with MM undergoing autologous HSCT using the Charlson comorbidity index (CCI), the hematopoietic cell transplantation comorbidity index (HCT-CI), and a modified pretransplantation assessment of mortality (mPAM) to determine the strength of association with increased transplantation-related toxicity and increased length of hospital stay (LOS). Any comorbidity scored using the CCI or HCT-CI (score > 0) was associated with an increased number of organ systems with serious toxicity (at least grade 2 toxicity using the Seattle criteria), an increased total sum of toxicity grades for all organs, and prolonged LOS. An mPAM score > or = 24 was associated with increased LOS. When considering autologous HSCT for a patient with MM, assessment of comorbidities using the CCI or HCT-CI may assist in predicting the risk of transplantation-related toxicity as an adjunct to physician judgment and patient preference.

Outpatient autologous hematopoietic stem cell transplantation for patients with relapsed follicular lymphoma

Autologous stem cell transplantation (ASCT) has emerged as a viable option for the treatment of relapsed follicular non-Hodgkin’s lymphoma. We report on the outpatient experience of 60 patients who underwent ASCT for this condition. The median age was 51xa0years (30–65). Pre-transplantation conditioning regimens consisted of either etoposide/melphalan/TBI, CBV or BEAM. Patients participated in this transplant program for a median of 20.5xa0days (14–78), and 58.4% of the total program days were spent in the outpatient setting. Six patients were well enough to be treated solely as outpatients. Ninety percent of patients required at least one inpatient admission (median 7xa0days), and 70% of first inpatient transfers occurred within the first week following transplant and always before dayxa0+12. There were no predictors for prolonged inpatient stays. Febrile neutropenia and gastrointestinal toxicity were the main reasons for inpatient transfers. No outpatient required an urgent admission to the ICU or died in the outpatient setting. The treatment-related mortality at daysxa030 and 100 was 0 and 1.7%, respectively. The overall and progression-free survivals at 5xa0years were 65.7 and 56.1%, respectively. Outpatient ASCT with total body irradiation is feasible, safe, and effective for patients with relapsed follicular lymphoma.

Myasthenia Gravis Treated With Autologous Hematopoietic Stem Cell Transplantation

IMPORTANCEnSome patients with myasthenia gravis (MG) do not respond to conventional treatment and have severe or life-threatening symptoms. Alternate and emerging therapies have not yet proved consistently or durably effective. Autologous hematopoietic stem cell transplant (HSCT) has been effective in treating other severe autoimmune neurologic conditions and may have similar application in MG.nnnOBJECTIVEnTo report 7 cases of severe MG treated with autologous HSCT in which consistent, durable, symptom-free, and treatment-free remission was achieved.nnnDESIGN, SETTING, AND PARTICIPANTSnThis retrospective cohort study reports outcomes at The Ottawa Hospital, a large, Canadian, tertiary care referral center with expertise in neurology and HSCT, from January 1, 2001, through December 31, 2014, with a median follow-up of 40 months (range, 29-149 months). Data collection and analysis were performed from February 1 through August 31, 2015. All patients with MG treated with autologous HSCT at The Ottawa Hospital were included. All had persistent severe or life-threatening MG-related symptoms despite continued use of intensive immunosuppressive therapies.nnnINTERVENTIONSnAutologous hematopoietic stem cell grafts were mobilized with cyclophosphamide and granulocyte colony-stimulating factor, collected by peripheral blood leukapheresis, and purified away from contaminating lymphocytes using CD34 immunomagnetic selection. Patients were treated with intensive conditioning chemotherapy regimens to destroy the autoreactive immune system followed by graft reinfusion for blood and immune reconstitution.nnnMAIN OUTCOMES AND MEASURESnThe primary outcome was MG disease activity after autologous HSCT measured by frequency of emergency department visits and hospitalizations and Myasthenia Gravis Foundation of America (MGFA) clinical classification, MGFA therapy status, and MGFA postintervention status. Safety outcomes included all severe autologous HSCT-related complications.nnnRESULTSnSeven patients underwent autologous HSCT, 6 for MG and 1 for follicular lymphoma with coincident active MG. Mean (SD) ages at MG diagnosis and at autologous HSCT were 37 (11) and 44 (10) years, respectively. Five patients (71%) had concurrent autoimmune or lymphoproliferative illnesses related to immune dysregulation. All patients had distinct clinical and electromyographic evidence of MG (MGFA clinical classification IIIb-V). All patients achieved durable MGFA complete stable remission with no residual MG symptoms and freedom from any ongoing MG therapy (MGFA postintervention status of complete stable remission). Three patients (43%) experienced transient viral reactivations, and 1 (14%) developed a secondary autoimmune disease after autologous HSCT, all of which resolved or stabilized with treatment. There were no treatment- or MG-related deaths.nnnCONCLUSIONS AND RELEVANCEnAutologous HSCT results in long-term symptom- and treatment-free remission in patients with severe MG. The application of autologous HSCT for this and other autoimmune neurologic conditions warrants prospective study.

Selection of appropriate venous access for the collection of peripheral blood progenitor cells by experienced apheresis nurses.

Peripheral blood progenitor cells (PBPC) have been extensively used to restore hematopoiesis after myeloablative chemotherapy. While collection regimens designed for optimal mobilization of PBPC are becoming standardized, the ideal venous access option for collection remains unresolved. The purpose of this study was to determine if the venous access of patients could be accurately assessed and appropriate intervention, if necessary, electively undertaken prior to PBPC collection. In this prospective study, 95 consecutive patients about to undergo PBPC collection were evaluated at time of referral to determine the type of venous access necessary for adequate PBPC collection. There were three possible interventions: 1. No access device for patients determined to have an adequate antecubital vein for apheresis access. 2. Insertion of a double lumen Quinton PermCath for those patients with poor antecubital veins. 3. Insertion of a double lumen Hickman catheter for patients with adequate antecubital veins for apheresis but poor peripheral veins for chemotherapy administration. The blood and marrow transplant nurse coordinator evaluated the patients veins. Of the 95 patients having 192 PBPC collections, 65 were collected using antecubital veins, 21 were collected from PermCaths, and 9 from Hickman catheters. All patients predicted to collect peripherally did so and achieved flow rates equivalent to the PermCath. No patient required urgent line placement at time of PBPC collection. There was no difference in the number of cells collected between the three groups. The result of this study strongly supports a policy of appropriate venous access based on patient vein assessment by experienced nurses. J. Clin. Apheresis 14:51–56, 1999.

Leading change: Retrospective evaluation of a nurse-led initiative in vascular access options for autologous stem cell transplant recipients ranging from Hickman catheters to peripherally inserted central catheters.

Central venous access is essential for patients undergoing autologous hematopoietic stem cell transplantation (ASCT). Traditionally, tunneled silastic catheters have been inserted in these patients. However, changes in resource allocation, resulting in reduced surgery and surgeon time and decreasing toxicity associated with ASCT, have caused changes in venous access needs and options. This led the advanced practice nurse in the transplant program to evaluate other central access devices, which resulted in the introduction of peripherally inserted central catheters (PICCs) for this patient population. This study reports the results of a retrospective analysis comparing efficacy and complication profiles between 50 patients with the traditional Hickman catheter and 70 patients with PICCs.

Outcomes in a nurse-led peripherally inserted central catheter program: a retrospective cohort study

BACKGROUNDnPeripherally inserted central catheters (PICCs) provide enormous benefit to patients. However, recent publications have highlighted relatively high PICC-associated complication rates. We report on patient and device outcomes from a nurse-led program.nnnMETHODSnWe performed a retrospective analysis of a prospective cohort of consecutive patients undergoing PICC insertion at The Ottawa Hospital between Jan. 1, 2013 and Dec. 31, 2014. Of the 8314 BioFlo PASV PICCs inserted, we randomly selected a sample of 700 and obtained a complete data set for 656. We measured the cumulative incidence of major complications (catheter-related bloodstream infections and deep vein thrombosis) and use of a thrombolytic to alleviate occlusions.nnnRESULTSnThe total number of catheter days was 58u202f486, and the median dwell time 45 days. We observed 4 cases of catheter-related bloodstream infection (0.6% [95% CI 0.17%-1.55%]) (0.07/1000 catheter days). Ten patients (1.5% [95% CI 0.83%-2.78%]) (0.17/1000 catheter days) had catheter-related deep venous thrombosis. At least 1 dose of thrombolytic was required in 75 catheters (11.4% [95% CI 8.61%-13.39]), 31 (7.1%) of the 436 single-lumen catheters and 113 (25.7%) of the 440 lumina of dual-lumen catheters (p < 0.001).nnnINTERPRETATIONnWe attribute our low rates of major complications to a nurse-led expert insertion team, standardized care and maintenance protocols, high insertion volumes, novel catheter material and continuous quality-improvement initiatives that are implemented and evaluated regularly. We conclude that the considerable benefits PICCs provide to patients are attained with a low risk of major complications.

Self-administration of intravenous C1 esterase inhibitor (Berinertâ) in patients with Hereditary Angioedema decreases number of days spent in an emergency room

Background Hereditary Angioedema (HAE) is a rare, inherited, autosomal dominant disease caused by a deficiency in C1-esterase inhibitor. It affects one in every 50,000 to 100,000 individuals. There were no approved treatments for HAE in North America until 2009, when C1-esterase inhibitor (Berinertâ) was released. It is an intravenous medication that requires patients to present to an emergency room (ER) for treatment. We present two cases of patients with HAE who self-administered the medications, decreasing their number of emergency room visits substantially.