The effect of rapid response teams on end-of-life care: A retrospective chart review

R apid response teams (RRTs) were designed to assess and treat deteriorating ward patients. The aim of RRTs is to decrease the number of cardiac arrests, intensive care unit (ICU) transfers and inhospital mortality. These goals have been met with variable success in the literature, with some prospective cohort studies reporting reductions in cardiac arrests (1-4). However, these results were not replicated in the large, multicentre, cluster randomized controlled Medical Early Response Intervention and Therapy (MERIT) trial (5). The MERIT trial suggested that there was an association with RRTs and an increase in do-not-resuscitate orders (6,7). Further studies have also documented RRT involvement in end-of-life (EOL) care (8-10). To support EOL care, our institution implemented a hospital-wide policy and associated preprinted order set known as the PhysicianOrdered Spectrum of Treatment (POST) form. The POST form acted as an extension of a 'do not resuscitate' status. The form engaged health care providers in conversations with patients and families regarding life-sustaining interventions such as cardiopulmonary resuscitation, intubation, defibrillation, ICU transfer, antibiotics, blood products or intravenous lines The premise of our study was that hospitalized patients are in fragile condition and, although restorative therapies are often the goal, there are patients who do not want or who would not benefit from aggressive resuscitative measures. As 'first responders' for critically ill ward patients, RRTs have the opportunity to recognize and treat patients who would benefit from EOL care. We sought to characterize the effect of RRT EOL discussions on EOL care. We also characterized the proportion of patients seen by RRTs with EOL care issues. Finally, we examined how the introduction of a hospital-wide EOL preprinted order set influenced EOL discussions and EOL care. Methods The present study was a single-centre, retrospective chart review conducted at the Hamilton Health Sciences Hamilton General Hospital BACkgRound: A subset of critically ill patients have end-of-life (EOL) goals that are unclear. Rapid response teams (RRTs) may aid in the identification of these patients and the delivery of their EOL care. oBJeCtives: To characterize the impact of RRT discussion on EOL care, and to examine how a preprinted order (PPO) set for EOL care influenced EOL discussions and outcomes. Methods: A single-centre retrospective chart review of all RRT calls (January 2009 to December 2010) was performed. The effect of RRT EOL discussions and the effect of a hospital-wide PPO set on EOL care was examined. Charts were from the Ontario Ministry of Health and LongTerm Care Critical Care Information Systemic database, and were interrogated by two reviewers. Results: In patients whose EOL status changed following RRT EOL discussion, there were fewer intensive care unit (ICU) transfers (8.4% versus 17%; P<0.001), decreased ICU length of stay (5.8 days versus 20 days; P=0.08), increased palliative care consultations (34% versus 5.3%; P<0.001) and an increased proportion who died within 24 h of consultation (25% versus 8.3%; P<0.001). More patients experienced a change in EOL status following the introduction of an EOL PPO, from 20% (before) to 31% (after) (P<0.05). ConClusions: A change in EOL status following RRT-led EOL discussion was associated with reduced ICU transfers and enhanced access to palliative care services. Further study is required to identify and deconstruct barriers impairing timely and appropriate EOL discussions. Effect of RRTs on EOL care Can Respir J Vol 21 No 5 September/October 2014 303 (Hamilton, Ontario), a 458-bed tertiary care centre and regional centre of excellence specializing in cardiac and vascular care, neuroscience, trauma and burn treatment, stroke and rehabilitation. The RRT at the authors' site has been a Ministry of Health and Long-Term Care of Ontario-funded team since 2006 and includes an ICU physician, critical care nurses and registered respiratory therapists. Critical care residents or fellows may support the team on some occasions. Any health care provider with concerns regarding patients' airway, breathing or circulation can activate the team. The nurses and respiratory therapists on the RRT also have several medical directives that allows them to initiate resuscitative therapy before a licensed physician arrives at the bedside. They have also received additional training in EOL discussions. The POST was implemented in January 2010 as a hospital-wide policy to improve EOL care. Institutional policy dictated that the POST form was to be completed for all hospitalized patients with a predicted life expectancy <1 year. Before its implementation, there was a one-month period of distributed education on using the POST form. The POST form was examined because it coincided with the study period and was a confounder that may have effected RRT EOL discussions. ethics The present study was approved by Hamilton Health Sciences Research Ethics Board (approval number was 11-463-C). The need for informed consent was waived. data collection The chart review was composed of all patients seen by the RRT team between January 1, 2009 and December 31, 2010. RRT-based EOL discussions were tracked. Data were gathered from the Ontario Ministry of Health and Long-Term Care Critical Care Information Systemic database. Charts were divided into code status discussion initiated, code status discussion revisited, code status previously established and code status discussion not appropriate at the time or for this patient. These distinctions were determined by the RRT's registered nurse or respiratory therapist, who completed the team call record at the time of RRT consultation. Charts coded as 'discussion initiated' and 'discussion revisited' were considered to be positive for EOL discussion. Two reviewers reviewed the charts independently. If the RRT had an EOL discussion, the patient's medical record was reviewed for patient demographics, admitting service, code status at time of consultation, completion of POST form, a change in EOL status following consultation, ICU transfer following consultation, total ICU length of stay (LOS) following transfer, if death occurred within 24 h following consultation and whether palliative care was involved in EOL care. data analysis The analysis focused on RRT EOL discussion with critically ill ward patients. To determine the effect of the RRT on EOL care, patients with and without a change in EOL status following RRT EOL discussion were compared. To determine the effect of the POST form on RRT EOL discussions, the outcomes before the introduction of the POST (January 1, 2009 to December 31 2009) and following the introduction of the POST (January 1, 2010 to Decemebr 31, 2010) were compared. Discrete variables were described as proportions and compared using χ 2 tests. Continuous variables were reported as mean ± SD and compared using unpaired t tests; P<0.05 was considered to be statistically significant. Results Patient population Between January 1, 2009 and December 31, 2010, the RRT saw 5320 patients. Of 5320 patients, 1254 (24%) were seen as a new RRT consultation while 3155 (59%) were seen in ICU discharge follow-up. The method in which RRT was involved was not documented for 911 patients (17%). Three hundred nineteen patients (6%) had their code status discussion initiated or revisited by the RRT; 3081 (58%) had a previously established code status. A code status discussion was deemed not appropriate for 1920 patients (36%) effect of RRt eol discussion on eol care Of the patients who RRT initiated or revisited code status, 276 (89%) were for full resuscitation at the time of consultation. The EOL status was changed in 83 (27%) patients, all of whom were for full resuscitation at the time of consultation. In patients with a change in EOL status, there were fewer ICU transfers (8% versus 16%; P<0.01), more palliative services arranged (34% versus 5%; P<0.01) and more patients who passed away within 24 h of RRT consultation (25% versus 8%; P<0.01). There was a trend toward decreased ICU LOS (six days versus 20 days; P=0.08) ( effect of Post form on eol care There were minimal differences when comparing outcomes before and following POST implementation. There were similar proportions of patients who were for full resuscitation at time of consultation (89% before versus 85% after; P=0.72). There was a significant increase in the proportion of patients who had a change in code status following implementation of the POST form (20% before versus 31% after; P<0.05). However, there was no difference in proportion transferred to the ICU (13% before versus 15% after; P=0.55), average ICU LOS (12 days before versus 14 days after; P=0.38), nor was there a difference in proportion with palliative care involved (14% before versus 12% after; P=0.55). There was a trend toward increased proportion of patients who died within 24 h of RRT consultation (8.6% before versus 16% after; P=0.08) ( disCussion We found that RRTs influenced EOL care through EOL discussions. In patients who experienced a change in EOL status following RRT EOL discussion, there were fewer ICU transfers, increased palliative services and more patients who died within 24 h. Furthermore, the POST form may be a tool that is associated with more EOL discussions, although it did not impact other EOL outcomes in our critical care setting. RRT involvement in EOL care is an evolving concept. Vasquez et al The extent of RRT involvement in EOL care is not yet clear. Downar et al (9,10) found that RRT involvement was not associated with improved access to palliative services, spiritual care and comfort medications. This outcome may be attributed to the study population. Downar et al (10) compared EOL care for patients who had died with versus without RRT consult. Patients referred to the RRT may have had a reversible condition amenable to restorative therapy as opposed to palliation. Conversely, patients who were not referred may have had irreversible conditions more suited to palliative care. This was suggested by the significantly increased proportion of patients with irreversible poor prognostic factors, palliative care consultations and shorter time to withdrawal of life support (10). In contrast, we studied patients who the RRT selected for an EOL discussion at the time of RRT consultation. As such, our study suggests that the RRT was able to identify and treat patients who would benefit from palliative care in the critical care setting. Although our study showed that RRTs could successfully initiate EOL care in critical care scenarios, this may not by the optimal time to discuss goals of care and resuscitation status. RRT involvement in EOL care suggests that there was room to enhance predeterioration EOL care. Previous studies have shown that clinical deterioration is not a sudden process and that the majority of cases present with antecedent clues such as hypotension or hypoxia (19). Responding to these clinical perturbations is only part of the care process. These fluctuations in clinical status should act as stop points for all health care providers to reassess the goals of care and resuscitation status with the patients and families. However, EOL care is not well addressed in hospital. Heyland (20) found that 76% of elderly patients have considered EOL care and only 12% preferred life-prolonging care. However, only 30% of medical documentation accurately reflected the patients' wishes. Reasons for not documenting an EOL status could be influenced by the patient and family, the clinician or the institution. Family/patient factors included unrealistic patients and families, inability of patients to participate in discussions and lack of advance directives (21,22). Clinician factors included insufficient training, competing time demands and insufficient remuneration (21-24). Institutional factors included suboptimal space for family meetings and lack of palliative care services Enhancing EOL quality will require multitiered interventions enacted through institutions, clinicians and patient/families. One intervention our institute implemented to support EOL discussions is the POST form. Previous literature suggested that similar forms may be used in a hospice or long-term care setting to effectively ensure adherence to patient wishes in an EOL setting (11-13). However, benefit of the POST form requires further study in critical care settings (15). Curtis et al Enhanced in-hospital EOL care is unlikely to arise from policy changes alone. There is room to improve clinician involvement in EOL care. O'Mahony et al (26) reported successful integration of a palliative care team into an ICU. They found that there was increased opioid use, formalized advanced directives and utilization of hospices, in addition to decreased investigations and nonbeneficial life-prolonging therapies. Furthermore, it is important to consider patient and family factors in a comprehensive plan for improving in-hospital EOL care. Heyland One systematic difference that may have influenced the results of our study was patient illness severity. The change in EOL status following RRT involvement may have been driven by illness severity as opposed to RRT EOL discussions. Due to data limitations, we were unable to determine whether there were any systematic differences in illness severity between patients who had a change in EOL status and those who did not. Even if this was the case, increased illness severity in patients with high unlikelihood of benefiting from resuscitative measures should drive EOL discussions and subsequent EOL care. The present study would then suggest that RRTs had the ability to identify deteriorating patients who benefited from palliation rather than resuscitation. More work is required to determine how accurately RRTs prognosticate patients. Furthermore, although we selected quantifiable and patientimportant outcomes to review, the scope of our analysis was limited by data restrictions inherent in a retrospective study. We found that 26% of patients who had an EOL discussion with the RRT had a subsequent change in EOL status; we do not know whether this number was appropriate. Seventy-four percent of patients who the RRT believed warranted an EOL discussion did not have a subsequent change in EOL status. EOL discussions could have resulted in more than a change in EOL status. Other outcomes that may have been affected include dyspnea management, avoiding unnecessary and invasive therapies, treatment of pain, ascertaining patient and family values, and providing support suMMARy We found that a change in EOL status following RRT-led EOL discussions was associated with reduced ICU transfers and enhanced access to palliative services. Our study suggested that there is a need to enhance predeterioration EOL planning. Moreover, there is a need to develop institutional support for EOL care, clinician training on EOL care and enhanced access to palliative care services. Future areas of study are to identify patients who will benefit from EOL discussion and to identify the barriers to engaging these patients in EOL discussion. ACknoWledgeMents: BT contributed to research design, dat

Effectiveness of Artemether/Lumefantrine for the Treatment of Uncomplicated Plasmodium vivax and P. falciparum Malaria in Young Children in Papua New Guinea

This study shows that artemether/lumefantrine provides a rapid clinical response against both Plasmodium falciparum and Plasmodium vivax clinical malaria, but is associated with a high rate of P. vivax recurrent clinical episodes due to relapsing infections from long-lasting hypnozoite

Rapid Diagnostic Test-Based Management of Malaria: An Effectiveness Study in Papua New Guinean Infants With Plasmodium falciparum and Plasmodium vivax Malaria

This study shows that treatment for malaria based exclusively on rapid diagnostic test results is safe and feasible even in infants living in areas with moderate to high endemicity for both Plasmodium falciparum and Plasmodium vivax infection

Blood-Stage Parasitaemia and Age Determine Plasmodium falciparum and P. vivax Gametocytaemia in Papua New Guinea

A better understanding of human-to-mosquito transmission is crucial to control malaria. In order to assess factors associated with gametocyte carriage, 2083 samples were collected in a cross-sectional survey in Papua New Guinea. Plasmodium species were detected by light microscopy and qPCR and gametocytes by detection of pfs25 and pvs25 mRNA transcripts by reverse-transcriptase PCR (qRT-PCR). The parasite prevalence by PCR was 18.5% for Plasmodium falciparum and 13.0% for P. vivax. 52.5% of all infections were submicroscopic. Gametocytes were detected in 60% of P. falciparum-positive and 51% of P. vivax-positive samples. Each 10-fold increase in parasite density led to a 1.8-fold and 3.3-fold increase in the odds of carrying P. falciparum and P. vivax gametocytes. Thus the proportion of gametocyte positive and gametocyte densities was highest in young children carrying high asexual parasite densities and in symptomatic individuals. Dilution series of gametocytes allowed absolute quantification of gametocyte densities by qRT-PCR and showed that pvs25 expression is 10-20 fold lower than pfs25 expression. Between 2006 and 2010 parasite prevalence in the study site has decreased by half. 90% of the remaining infections were asymptomatic and likely constitute an important reservoir of transmission. However, mean gametocyte densities were low (approx. 1-2 gametocyte/muL) and it remains to be determined to what extent low-density gametocyte positive individuals are infective to mosquitos

Decision-making factors for an autologous stem cell transplant for older adults with newly diagnosed multiple myeloma: A qualitative analysis

PurposeA utologous stem cell transplant (ASCT) remains a standard of care among older adults (aged ≥65) with multiple myeloma (MM). However, heterogeneity in the eligibility and utilization of ASCT remains. We identified decision-making factors that influence ASCT eligibility and utilization among older adults with MM.MethodsA qualitative study across two academic and two community centres in Ontario was conducted between July 2019-July 2020. Older adults with MM (newly diagnosed MM aged 65-75 in whom a decision had been made about ASCT in <12 months) and treating oncologists completed a baseline survey and a subsequent interview, which was analyzed using thematic analysis.ResultsEighteen patients completed the survey and 9 follow-up interviews were conducted. Patients were happy with their treatment decision with “trust in their oncologist” and “wanting the best treatment” as the most important to proceed with ASCT. “Afraid of side effects” was the most common reason for declining ASCT. Fifteen oncologists completed the survey and 10 follow-up interviews were conducted. Most relied on the ‘eye-ball’ test for ASCT eligibility over geriatric screening tools. The lack of both high-quality evidence and local guidelines impacted decision-making. Both oncologists and patients felt that chronological age alone should not affect ASCT eligibility.ConclusionWhile decision-making factors regarding ASCT can be variable, both oncologists and patients indicated that chronological age alone should not represent a barrier for ASCT among older adults. Future simplification and incorporation of ASCT eligibility geriatric assessment tools in studies as well as the inclusion of these tools in local guidelines may further improve ASCT decision-making

Assessment of ultra-sensitive malaria diagnosis versus standard molecular diagnostics for malaria elimination : an in-depth molecular community cross-sectional study

Submicroscopic malaria infections contribute to transmission in exposed populations but their extent is underestimated even by standard molecular diagnostics. Sophisticated sampling and ultra-sensitive molecular methods can maximise test sensitivity but are not feasible in routine surveillance. Here we investigate the gains achievable by using increasingly sensitive methods with the aim to understand what diagnostic sensitivity is necessary to guide malaria interventions.; Venous blood samples were collected from participants in a cross-sectional survey in two coastal medium-endemic villages in Madang province, Papua New Guinea. Using ultra-sensitive quantitative PCR (us-qPCR) on concentrated high-volume blood samples (2 mL) as reference, we quantified the proportion of Plasmodium falciparum and Plasmodium vivax infections and gametocyte carriers detectable in fingerprick blood volumes (200 μL) by standard 18S rRNA qPCR, us-qPCR, rapid diagnostic test (RDT), and ultra-sensitive P falciparum RDT. We further compared the epidemiological patterns observed with each diagnostic approach in the study population.; Venous blood samples were collected from 300 participants between Dec 5, 2016, and Feb 24, 2017 (ie, during peak rainy season). Standard qPCR identified 87 (54%) of 161 P falciparum infections and 73 (52%) of 141 P vivax infections detected by the reference method. us-qPCR identified an additional 11 (7%) P falciparum infections and 14 (10%) P vivax infections. 80 (86%) of 93 P falciparum gametocyte carriers and 75 (91%) of 82 P vivax gametocyte carriers were found among infections detectable by us-qPCR. Ultra-sensitive RDT missed half of P falciparum infections detected by standard qPCR, including high gametocytaemic infections. Epidemiological patterns corresponded well between standard qPCR and the reference method. As the prevalence of P vivax decreased with increasing age, the proportion of P vivax infections undetectable by standard qPCR increased.; Almost all potentially transmitting parasite carriers were identified with us-qPCR on fingerprick blood volumes. Analysing larger blood volumes revealed a large pool of ultra-low-density P falciparum and P vivax infections, which are unlikely to be transmitted. Therefore, current RDTs cannot replace molecular diagnostics for identifying potential P falciparum transmitters.; Swiss National Science Foundation

Investigating differences in village-level heterogeneity of malaria infection and household risk factors in Papua New Guinea

Malaria risk is highly heterogeneous. Understanding village and household-level spatial heterogeneity of malaria risk can support a transition to spatially targeted interventions for malaria elimination. This analysis uses data from cross-sectional prevalence surveys conducted in 2014 and 2016 in two villages (Megiar and Mirap) in Papua New Guinea. Generalised additive modelling was used to characterise spatial heterogeneity of malaria risk and investigate the contribution of individual, household and environmental-level risk factors. Following a period of declining malaria prevalence, the prevalence of P. falciparum increased from 11.4 to 19.1% in Megiar and 12.3 to 28.3% in Mirap between 2014 and 2016, with focal hotspots observed in these villages in 2014 and expanding in 2016. Prevalence of P. vivax was similar in both years (20.6% and 18.3% in Megiar, 22.1% and 23.4% in Mirap) and spatial risk heterogeneity was less apparent compared to P. falciparum. Within-village hotspots varied by Plasmodium species across time and between villages. In Megiar, the adjusted odds ratio (AOR) of infection could be partially explained by household factors that increase risk of vector exposure, such as collecting outdoor surface water as a main source of water. In Mirap, increased AOR overlapped with proximity to densely vegetated areas of the village. The identification of household and environmental factors associated with increased spatial risk may serve as useful indicators of transmission hotspots and inform the development of tailored approaches for malaria control

Artemether-lumefantrine versus artemisinin-naphthoquine in Papua New Guinean children with uncomplicated malaria: A six months post-treatment follow-up study

Background: In a recent trial of artemisinin-naphthoquine (artemisinin-NQ) and artemether-lumefantrine (AM-LM) therapy in young children from Papua New Guinea (PNG), there were no treatment failures in artemisinin-NQ-treated children with Plasmodium falciparum or Plasmodium vivax compared with 2.2% and 30.0%, respectively, in AM-LM-treated children during 42 days of follow-up. To determine whether, consistent with the long elimination half-life of NQ, this difference in efficacy would be more durable, clinical episodes of malaria were assessed in a subset of trial patients followed for six months post-treatment. Methods: For children completing trial procedures and who were assessable at six months, all within-trial and subsequent clinical malaria episodes were ascertained, the latter by clinic attendances and/or review of hand-held health records. Presentations with non-malarial illness were also recorded. Differences between allocated treatments for pre-specified endpoints were determined using Kaplan-Meier survival analysis. Results: Of 247 children who were followed to Day 42, 176 (71.3%) were included in the present sub-study, 87 allocated to AM-LM and 89 to artemisinin-NQ. Twenty children in the AM-LM group (32.8%) had a first episode of clinical malaria within six months compared with 10 (16.4%) in the artemisinin-NQ group (P=0.033, log rank test). The median (interquartile range) time to first episode of clinical malaria was 64 (50-146) vs 116 (77-130) days, respectively (P=0.20). There were no between-group differences in the incidence of first presentation with non-malarial illness (P=0.31). Conclusions: The greater effectiveness of artemisinin-NQ over conventional AM-LM extends to at least six months post-treatment for clinical malaria but not non-malarial illness. Trial registration: Australian New Zealand Clinical Trials Registry ACTRN12610000913077

Intermittent Preventive Treatment for Malaria in Papua New Guinean Infants Exposed to Plasmodium falciparum and P. vivax: A Randomized Controlled Trial

A three-arm randomized trial conducted among infants in Papua New Guinea estimates the preventive effect against malaria episodes of intermittent preventive treatment, in an area where children are exposed to both falciparum and vivax malaria

SARS-CoV-2 susceptibility and COVID-19 disease severity are associated with genetic variants affecting gene expression in a variety of tissues

Variability in SARS-CoV-2 susceptibility and COVID-19 disease severity between individuals is partly due to genetic factors. Here, we identify 4 genomic loci with suggestive associations for SARS-CoV-2 susceptibility and 19 for COVID-19 disease severity. Four of these 23 loci likely have an ethnicity-specific component. Genome-wide association study (GWAS) signals in 11 loci colocalize with expression quantitative trait loci (eQTLs) associated with the expression of 20 genes in 62 tissues/cell types (range: 1:43 tissues/gene), including lung, brain, heart, muscle, and skin as well as the digestive system and immune system. We perform genetic fine mapping to compute 99% credible SNP sets, which identify 10 GWAS loci that have eight or fewer SNPs in the credible set, including three loci with one single likely causal SNP. Our study suggests that the diverse symptoms and disease severity of COVID-19 observed between individuals is associated with variants across the genome, affecting gene expression levels in a wide variety of tissue types