Reducing Unnecessary Transfusions of RBCs in Inpatients Admitted Across Niagara Health Community Hospitals.

BACKGROUND AND OBJECTIVES: Blood products are scarce resources. Audits on the use of red blood cells (RBCs) in tertiary centers have repeatedly highlighted inappropriate use. Earlier retrospective audit at our local community hospitals has demonstrated that only 85% and 54% of all requests met Choosing Wisely Canada guidelines for pre-transfusion hemoglobin (Hb) of 80 g/L or less and single unit, respectively.We sought to improve RBC utilization by 15% over a period of 12 months (meeting Choosing Wisely Canada criteria of pre-transfusion Hb ≤80g/L by >80% and single-unit transfusion by >65%). METHODS: Following repeated PDSA (Plan-Do-Study-Act) cycles, we implemented educational strategies, prospective transfusion medicine (TM) technologist-led screening of orders, and an RBC order set. RESULTS: The 3-month median percentages of appropriate RBC use for pre-transfusion Hb and single unit (September-November 2021) across all 3 hospitals were 90% and 71%, respectively. Overall, the rate of appropriate RBCs based on pre-transfusion Hb remained above target (>80%), with minimal improvement across all hospitals (median percentage at pre- and post-technologist screening periods of 87% and 90%, respectively). The median percentage of appropriate RBCs based on single-unit transfusion orders has improved across all Niagara Health hospitals with sustained targets (3-month median percentage at pre- and post-technologist screening and most recent time periods of 54%, 56%, and 71%, respectively). CONCLUSIONS: We have taken a collaborative, multifaceted approach to optimizing utilization of RBCs across the Niagara Health hospitals. The rates of appropriate RBC use were comparable with the provincial and national accreditation benchmark standards. In particular, the TM technologist-led screening was effective in producing sustained improvement with respect to single-unit transfusion. One of the balancing outcomes was increasing workload on technologists. Local and provincial efforts are needed to facilitate recruitment and retention of laboratory technologists, especially in community hospitals.

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

Purpose: A 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. Methods: A 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. Results: Eighteen 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. Conclusion: While 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.

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.

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

BACKGROUND: 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. METHODS: 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. FINDINGS: 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. INTERPRETATION: 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. FUNDING: Swiss National Science Foundation.

Direct Oral Anticoagulants in the Real World: Insights Into Appropriate Prescribing and Medication Use.

Background Direct oral anticoagulants are convenient because of their fixed dosing and without laboratory monitoring. There are instructions on avoidance of moisture, no crushing of capsules, and administration with food for some direct oral anticoagulants. Whether patients adhere to this and are prescribed appropriate doses are unknown. Aims To assess direct oral anticoagulant dosing and medication use. Methods Patients ≥18 years old, receiving a direct oral anticoagulant for any diagnosis, were prospectively included. Nurses at our perioperative anticoagulation clinic helped patients complete a 12-item questionnaire. Results Ninety-three consecutive patients were recruited. Forty-nine were on dabigatran, 18 on apixaban, and 26 were on rivaroxaban. Sixty-two patients (67%) received appropriate direct oral anticoagulant dosing and administered the medication correctly. Eighteen patients (19%) administered the direct oral anticoagulant properly but at an inappropriate dose. Thirteen patients (14%) received an appropriate dose but administered the direct oral anticoagulant inappropriately: 10 (11%) removed dabigatran from its packaging before administration (exposing it to moisture); 2 (2%) did not take rivaroxaban with food; and 1 (1%) crushed the dabigatran capsule. Conclusion Our study demonstrates a large variability in how direct oral anticoagulants are dosed, and how patients take them. Improved medication literacy around direct oral anticoagulants is needed. Our study highlights opportunities that nurses have to improve patients' medication literacy.

Risk factors for Plasmodium falciparum and Plasmodium vivax gametocyte carriage in Papua New Guinean children with uncomplicated malaria.

There are limited data on gametocytaemia risk factors before/after treatment with artemisinin combination therapy in children from areas with transmission of multiple Plasmodium species. We utilised data from a randomised trial comparing artemether-lumefantrine (AL) and artemisinin-naphthoquine (AN) in 230 Papua New Guinean children aged 0.5-5 years with uncomplicated malaria in whom determinants of gametocytaemia by light microscopy were assessed at baseline using logistic regression and during follow-up using multilevel mixed effects modelling. Seventy-four (32%) and 18 (8%) children presented with P. falciparum and P. vivax gametocytaemia, respectively. Baseline P. falciparum gametocytaemia was associated with Hackett spleen grade 1 (odds ratio (95% CI) 4.01 (1.60-10.05) vs grade 0; P<0.001) and haemoglobin (0.95 (0.92-0.97) per 1g/L increase; P<0.001), and P. falciparum asexual parasitaemia in slide-positive cases (0.36 (0.19-0.68) for a 10-fold increase; P=0.002). Baseline P. vivax gametocytaemia was associated with Hackett grade 2 (12.66 (1.31-122.56); P=0.028), mixed P. falciparum/vivax infection (0.16 (0.03-1.00); P=0.050), P. vivax asexual parasitaemia (5.68 (0.98-33.04); P=0.053) and haemoglobin (0.94 (0.88-1.00); P=0.056). For post-treatment P. falciparum gametocytaemia, independent predictors were AN vs AL treatment (4.09 (1.43-11.65)), haemoglobin (0.95 (0.93-0.97)), presence/absence of P. falciparum asexual forms (3.40 (1.66-0.68)) and day post-treatment (0.086 (0.82-0.90)) (P<0.001). Post-treatment P. vivax gametocytaemia was predicted by presence of P. vivax asexual forms (596 (12-28,433); P<0.001). Consistent with slow P. falciparum gametocyte maturation, low haemoglobin, low asexual parasite density and higher spleen grading, markers of increased prior infection exposure/immunity, were strong associates of pre-treatment gametocyte positivity. The persistent inverse association between P. falciparum gametocytaemia and haemoglobin during follow-up suggests an important role for bone marrow modulation of gametocytogenesis. In P. vivax infections, baseline and post-treatment gametocyte carriage was positively related to the acute parasite burden, reflecting the close association between the development of asexual and sexual forms.

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/µL) and it remains to be determined to what extent low-density gametocyte positive individuals are infective to mosquitos.

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 .

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

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 Long-Term 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.

Continuous venovenous hemofiltration versus continuous venovenous hemodiafiltration in critically ill patients: a retrospective cohort study from a Canadian tertiary centre.

BACKGROUND: Studies comparing continuous renal replacement therapy modalities are lacking. Theoretically, continuous venovenous hemofiltration (CVVH) could be more effective than continuous venovenous hemodiafiltration (CVVHDF), and may be associated with fewer complications; however, there are no published data to support this hypothesis. OBJECTIVE: To examine the effect of CVVH on mortality and other clinically important outcomes compared with CVVHDF in the intensive care unit (ICU) setting. METHODS: Using a log of all continuous renal replacement therapy performed at a Canadian tertiary centre between 2007 and 2010, the records of patients meeting the inclusion criteria of being admitted to the ICU, and receiving either CVVH or CVVHDF for management of acute renal failure, were reviewed. The information retrieved included demographic data, death events, and hospital and ICU length of stay. RESULTS: Data from 153 patients were included in the present study. Hospital and 30-day mortality were similar in the CVVH and CVVHDF groups (OR 0.85 [95% CI 0.38 to 1.89]; P=0.69 and OR 1.35 [95% CI 0.62 to 2.95]; P=0.45, respectively). There was no difference in hospital length of stay (mean difference -34.14 [95% CI -72.92 to 4.65]; P=0.08). CONCLUSION: The present retrospective review suggests that the use of CVVH does not reduce mortality or hospital length of stay when compared with CVVHDF. Future randomized trials should control for different patient populations and continue to evaluate the removal of small molecules such as hormones.

Use of antibiotics within the IMCI guidelines in outpatient settings in Papua New Guinean children: an observational and effectiveness study.

INTRODUCTION: There is a need to investigate the effectiveness and appropriateness of antibiotics prescription within the Integrated Management of Childhood Illness (IMCI) strategy in the context of routine outpatient clinics. METHODS: Making use of a passive case detection system established for a malaria prevention trial in outpatient clinics in Papua New Guinea, the appropriateness and effectiveness of the use of antibiotics within the IMCI was assessed in 1605 young children. Main outcomes were prescription of antibiotics and re-attendances within 14 days for mild pneumonia, mild diarrhoea and uncomplicated malaria whether they were managed with or without antibiotics (proxy of effectiveness). Appropriateness was assessed for both mild and severe cases, while effectiveness was assessed only for mild diseases. RESULTS: A total of 6975 illness episodes out of 8944 fulfilled inclusion criteria (no previous attendance <14 days+full medical records). Clinical incidence rates (episodes/child/year; 95% CI) were 0.85 (0.81-0.90) for pneumonia, 0.62 (0.58-0.66) for malaria and 0.72 (0.65-0.93) for diarrhoea. Fifty three percent of 6975 sick children were treated with antibiotics, 11% were not treated with antibiotics when they should have been and in 29% antibiotics were prescribed when they should not have been. Re-attendance rates within 14 days following clinical diagnosis of mild pneumonia were 9% (126/1401) when managed with antibiotics compared to 8% (56/701) when managed without (adjusted Hazard Ratio (aHR) = 1.00 (0.57-1.76), p = 0.98). Rates for mild diarrhoea were 8% (73/874) and 9% (79/866) respectively (aHR = 0.8 (0.42-1.57), p = 0.53). CONCLUSION: Non-adherence to IMCI recommendations for prescription of antibiotics is common in routine settings in Papua New Guinea. Although recommended, the use of antibiotics in young children with mild pneumonia as defined by IMCI criteria did not impact on their outcome. Better tools and new strategies for the identification of bacterial infections that require antibiotics are urgently needed.

Effectiveness of artemether/lumefantrine for the treatment of uncomplicated Plasmodium vivax and P. falciparum malaria in young children in Papua New Guinea.

BACKGROUND: Artemisinin combination therapy is recommended as treatment for uncomplicated Plasmodium falciparum (Pf) malaria, whereas chloroquine is still widely used for non-Pf infections. A common treatment for both vivax and falciparum malaria would be welcome. METHODS: A longitudinal prospective effectiveness study of 1682 children aged 3-27 months in outpatient clinics in Papua New Guinea. The main outcome was clinical treatment failure rate following treatment with artemether/lumefantrine (AL). RESULTS: Among 5670 febrile episodes, 1682 (28%) had positive rapid diagnostic test (RDT) results and were treated with AL. A total of 1261 (22%) had an infection confirmed by blood slide examination. Of these, 594 Pv and 332 Pf clinical malaria cases were included in the primary effectiveness analysis. Clinical treatment failure rates at 7, 28, and 42 days were 0.2%, 2.2%, and 12.0%, respectively, for Pv and 0.3%, 1.2%, and 3.6%, respectively, for Pf. A single malaria-unrelated death occurred within 42 days following treatment with AL, in a child who was aparasitemic by blood slide at reattendance. CONCLUSIONS: AL provides a rapid clinical response against both Pf and Pv malaria, but is associated with a high rate of Pv recurrent clinical episodes between days 28 and 42. In order to prevent relapsing infections from long-lasting hypnozoites, AL should ideally be complemented with a course of primaquine. In the absence of better treatment and diagnostic options, the use of AL in young children in routine practice is an acceptable, interim option in coendemic areas where Pv is resistant to chloroquine and specific treatment for Pv hypnozoites not feasible.

Intermittent preventive treatment for malaria in Papua New Guinean infants exposed to Plasmodium falciparum and P. vivax: a randomized controlled trial.

BACKGROUND: Intermittent preventive treatment in infants (IPTi) has been shown in randomized trials to reduce malaria-related morbidity in African infants living in areas of high Plasmodium falciparum (Pf) transmission. It remains unclear whether IPTi is an appropriate prevention strategy in non-African settings or those co-endemic for P. vivax (Pv). METHODS AND FINDINGS: In this study, 1,121 Papua New Guinean infants were enrolled into a three-arm placebo-controlled randomized trial and assigned to sulfadoxine-pyrimethamine (SP) (25 mg/kg and 1.25 mg/kg) plus amodiaquine (AQ) (10 mg/kg, 3 d, n = 374), SP plus artesunate (AS) (4 mg/kg, 3 d, n = 374), or placebo (n = 373), given at 3, 6, 9 and 12 mo. Both participants and study teams were blinded to treatment allocation. The primary end point was protective efficacy (PE) against all episodes of clinical malaria from 3 to 15 mo of age. Analysis was by modified intention to treat. The PE (compared to placebo) against clinical malaria episodes (caused by all species) was 29% (95% CI, 10-43, p ≤ 0.001) in children receiving SP-AQ and 12% (95% CI, -11 to 30, p = 0.12) in those receiving SP-AS. Efficacy was higher against Pf than Pv. In the SP-AQ group, Pf incidence was 35% (95% CI, 9-54, p = 0.012) and Pv incidence was 23% (95% CI, 0-41, p = 0.048) lower than in the placebo group. IPTi with SP-AS protected only against Pf episodes (PE = 31%, 95% CI, 4-51, p = 0.027), not against Pv episodes (PE = 6%, 95% CI, -24 to 26, p = 0.759). Number of observed adverse events/serious adverse events did not differ between treatment arms (p > 0.55). None of the serious adverse events were thought to be treatment-related, and the vomiting rate was low in both treatment groups (1.4%-2.0%). No rebound in malaria morbidity was observed for 6 mo following the intervention. CONCLUSIONS: IPTi using a long half-life drug combination is efficacious for the prevention of malaria and anemia in infants living in a region highly endemic for both Pf and Pv.

Rapid diagnostic test-based management of malaria: an effectiveness study in Papua New Guinean infants with Plasmodium falciparum and Plasmodium vivax malaria.

BACKGROUND: In malaria-endemic areas it is recommended that febrile children be tested for malaria by rapid diagnostic test (RDT) or blood slide (BS) and receive effective malaria treatment only if results are positive. However, RDTs are known to perform less well for Plasmodium vivax. We evaluated the safety of withholding antimalarial drugs from young Papua New Guinean children with negative RDT results in areas with high levels of both Plasmodium falciparum and P. vivax infections. METHODS: Longitudinal prospective study of children aged 3-27 months visiting outpatient clinics for fever. RDT was administered at first visit. RDT and microscopy were performed if children returned because of persistent symptoms. Outcomes were rates of reattendance and occurrence of severe illnesses. RESULTS: Of 5670 febrile episodes, 3942 (70%) involved a negative RDT result. In 133 cases (3.4%), the children reattended the clinic within 7 days for fever, of whom 29 (0.7%) were parasitemic by RDT or microscopy. Of children who reattended, 24 (0.7%) presented with a severe illness: 2 had lower respiratory tract infections (LRTIs) with low-density P. vivax on BS; 2 received a diagnosis of P. vivax malaria on the basis of RDT but BSs were negative; 16 had LRTIs; 3 had alternative diagnoses. Of these 24, 22 were cured at day 28. Two children died of illnesses other than malaria and were RDT and BS negative at the initial and subsequent visits. CONCLUSION: Treatment for malaria based on RDT results is safe and feasible even in infants living in areas with moderate to high endemicity for both P. falciparum and P. vivax infections.