Extending the post-thaw shelf-life of cryoprecipitate when stored at refrigerated temperatures.

BACKGROUND AND OBJECTIVES: The post-thaw shelf-life of cryoprecipitate is 6 h, leading to high wastage. Storage of thawed cryoprecipitate at refrigerated temperatures may be feasible to extend the shelf-life. This study aimed to evaluate the quality of thawed cryoprecipitate stored at 1-6°C for up to 14 days. MATERIALS AND METHODS: Cryoprecipitate (mini- and full-size packs derived from both apheresis and whole blood [WB] collections) was thawed, immediately sampled and then stored at 1-6°C for up to 14 days. Mini-packs were sampled at 6, 24, 48 and 72 h, day 7 and 14; full-size cryoprecipitate was sampled on day 3, 5 or 7. Coagulation factors (F) II, V, VIII, IX, X and XIII, von Willebrand factor (VWF) and fibrinogen were measured using a coagulation analyser. Thrombin generation was measured by calibrated automated thrombogram. RESULTS: FVIII decreased during post-thaw storage; this was significant after 24 h for WB (p = 0.0002) and apheresis (p < 0.0001). All apheresis and eight of 20 WB cryoprecipitate met the FVIII specification (≥ 70 IU/unit) on day 14 post-thaw. Fibrinogen remained stable for 48 h, and components met the specification on day 14 post-thaw. There were no significant differences in VWF (WB p = 0.1292; apheresis p = 0.1507) throughout storage. There were small but significant decreases in thrombin generation lag time, endogenous thrombin potential and time to peak for both WB and apheresis cryoprecipitate. CONCLUSION: Whilst coagulation factors in cryoprecipitate decreased after post-thaw storage, the thawed cryoprecipitate met the Council of Europe specifications when stored at refrigerated temperatures for 7 days.

Fifteen-minute consultation: Group A streptococcal pharyngitis, diagnosis and treatment in children.

Group A streptococcus (GAS) is the most common bacterial cause of pharyngitis in children. GAS causes significant suppurative and non-suppurative complications including invasive GAS disease and acute rheumatic fever. This article describes the current epidemiology and clinical presentation of GAS pharyngitis and explores how diagnostic and treatment decisions differ globally. Several key decision support tools are discussed including international guidelines, clinical decision scores and laboratory tests along with the evidence for treatment choice and duration. With recent international reports describing an increase in GAS infections, clinicians should be familiar with their local GAS pharyngitis guidelines and the rationale for diagnosis and treatment of this common childhood illness.

Pediatric Invasive Meningococcal Disease, Auckland, New Zealand (Aotearoa), 2004-2020.

New Zealand (Aotearoa) experienced a Neisseria meningitidis serogroup B epidemic during 1991-2006, and incidence remains twice that of other high-income countries. We reviewed clinical, laboratory, and immunization data for children <15 years of age with laboratory-confirmed invasive meningococcal disease in Auckland, New Zealand, during January 1, 2004-December 31, 2020. Of 319 cases in 318 children, 4.1% died, and 23.6% with follow-up data experienced sequelae. Children of Maori and Pacific ethnicity and those living in the most deprived areas were overrepresented. Eighty-one percent were positive for N. meningitidis serogroup B, 8.6% for serogroup W, 6.3% for serogroup C, and 3.7% for serogroup Y. Seventy-nine percent had bacteremia, and 63.9% had meningitis. In New Zealand, Maori and Pacific children are disproportionately affected by this preventable disease. N. meningitidis serogroup B vaccine should be included in the New Zealand National Immunization Schedule to address this persistent health inequity.

Group A Streptococcus Primary Peritonitis in Children, New Zealand.

Group A Streptococcus (GAS) primary peritonitis is a rare cause of pediatric acute abdomen (sudden onset of severe abdominal pain); only 26 pediatric cases have been reported in the English language literature since 1980. We discuss 20 additional cases of pediatric primary peritonitis caused by GAS among patients at Starship Children's Hospital, Auckland, New Zealand, during 2010-2022. We compare identified cases of GAS primary peritonitis to cases described in the existing pediatric literature. As rates of rates of invasive GAS increase globally, clinicians should be aware of this cause of unexplained pediatric acute abdomen.

Increasing the time-to-freezing for clinical apheresis plasma meets quality specifications.

BACKGROUND AND OBJECTIVES: In Australia, the vast distances between blood collection centres and processing facilities make it challenging to align supply with demand. Increasing the time to freezing for clinical plasma beyond 6 h would alleviate supply issues. This study aimed to determine the quality of clinical apheresis plasma frozen within 12 h of collection. MATERIALS AND METHODS: Apheresis plasma (n = 20) collected at donor centres was immediately transported to a blood processing facility, stored at 26°C and sampled aseptically at 6, 8 and 12 h post collection. Frozen samples were thawed, and coagulation factors (F) II, V, VII, VIII and XIII, von Willebrand factor (vWF) and fibrinogen were measured using a coagulation analyser. RESULTS: FVIII concentrations declined in plasma frozen at 6, 8 and 12 h post collection (1.22 ± 0.27, 1.21 ± 0.25 and 1.16 ± 0.24 IU/mL, respectively) but not significantly (p = 0.3338). Importantly, all components met the FVIII specification (>0.7 IU/mL) for clinical plasma. Fibrinogen concentrations were stable from 6 to 12 h (p = 0.3100), as were vWF concentrations (p = 0.1281). Coagulation factors II, V, VII and XIII were not significantly different (p > 0.05 for all factors). CONCLUSION: Clinical apheresis plasma can be frozen within 12 h of collection, allowing collections from donor centres further from processing centres and increasing supply.

Outcomes of adults with invasive meningococcal disease with reduced penicillin susceptibility in Auckland 2004-2017.

PURPOSE: The purpose of this study was to assess the clinical outcomes of adults with invasive meningococcal disease (IMD) and to compare the outcomes of patients with IMD caused by a penicillin susceptible isolate (minimum inhibitory concentration (MIC) ≤ 0.06 mg/L) with patients with IMD caused by an isolate with reduced penicillin susceptibility (MIC > 0.06 mg/L). We also assessed the outcomes of patients with IMD caused by an isolate with reduced penicillin susceptibility who were treated exclusively with intravenous (IV) benzylpenicillin. METHODS: Retrospective study of all culture positive IMD in adult patients (age ≥ 15 years) in the Auckland region from 2004 to 2017. RESULTS: One hundred and thirty-nine patients were included; 94 had penicillin susceptible isolates (88 cured, 6 died), and 45 had an isolate with reduced penicillin susceptibility (41 cured, 1 possible relapse, 3 died). The median benzylpenicillin/ceftriaxone treatment duration was 3 days for both groups. There was no difference in the patient outcomes of both groups. Eighteen patients with IMD caused by an isolate with reduced penicillin susceptibility received benzylpenicillin alone and were cured. CONCLUSIONS: This study provides further support to existing data that has shown that short duration IV beta-lactam treatment is effective for IMD in adults. Only a small number of patients with meningitis caused by an isolate with reduced penicillin susceptibility received benzylpenicillin alone, limiting its evaluation. For Neisseria meningitidis meningitis, we recommend ceftriaxone as empiric treatment and as definitive treatment when this is caused by an isolate with reduced penicillin susceptibility.

Internal consistency reliability of mental health questionnaires in college student athletes.

OBJECTIVES: To examine the internal consistency reliability and measurement invariance of a questionnaire battery designed to identify college student athletes at risk for mental health symptoms and disorders. METHODS: College student athletes (N=993) completed questionnaires assessing 13 mental health domains: strain, anxiety, depression, suicide and self-harm ideation, sleep, alcohol use, drug use, eating disorders, attention deficit hyperactivity disorder (ADHD), bipolar disorder, post-traumatic stress disorder (PTSD), gambling and psychosis. Internal consistency reliability of each measure was assessed and compared between sexes as well as to previous results in elite athletes. Discriminative ability analyses were used to examine how well the cut-off score on the strain measure (Athlete Psychological Strain Questionnaire) predicted cut-offs on other screening questionnaires. RESULTS: Strain, anxiety, depression, suicide and self-harm ideation, ADHD, PTSD and bipolar questionnaires all had acceptable or better internal consistency reliability. Sleep, gambling and psychosis questionnaires had questionable internal consistency reliability, although approaching acceptable for certain sex by measure values. The athlete disordered eating measure (Brief Eating Disorder in Athletes Questionnaire) had poor internal consistency reliability in males and questionable internal consistency reliability in females. CONCLUSIONS: The recommended mental health questionnaires were generally reliable for use with college student athletes. To truly determine the validity of the cut-off scores on these self-report questionnaires, future studies need to compare the questionnaires to a structured clinical interview to determine the discriminative abilities.

Pediatric Staphylococcus aureus Bacteremia: Clinical Spectrum and Predictors of Poor Outcome.

BACKGROUND: Staphylococcus aureus is a common cause of bacteremia, yet the epidemiology and predictors of poor outcome remain inadequately defined in childhood. METHODS: ISAIAH (Invasive Staphylococcus aureus Infections and Hospitalizations in children) is a prospective, cross-sectional study of S. aureus bacteremia (SAB) in children hospitalized in Australia and New Zealand over 24 months (2017-2018). RESULTS: Overall, 552 SABs were identified (incidence 4.4/100 000/year). Indigenous children, those from lower socioeconomic areas and neonates were overrepresented. Although 90-day mortality was infrequent, one-third experienced the composite of: length of stay >30 days (26%), intensive care unit admission (20%), relapse (4%), or death (3%). Predictors of mortality included prematurity (adjusted odds ratio [aOR],16.8; 95% confidence interval [CI], 1.6-296.9), multifocal infection (aOR, 22.6; CI, 1.4-498.5), necrotizing pneumonia (aOR, 38.9; CI, 1.7-1754.6), multiorgan dysfunction (aOR, 26.5; CI, 4.1-268.8), and empiric vancomycin (aOR, 15.7; CI, 1.6-434.4); while infectious diseases (ID) consultation (aOR, 0.07; CI .004-.9) was protective. Neither MRSA nor vancomycin trough targets impacted survival; however, empiric vancomycin was associated with nephrotoxicity (OR, 3.1; 95% CI 1.3-8.1). CONCLUSIONS: High SAB incidence was demonstrated and for the first time in a pediatric setting, necrotizing pneumonia and multifocal infection were predictors of mortality, while ID consultation was protective. The need to reevaluate pediatric vancomycin trough targets and limit unnecessary empiric vancomycin exposure to reduce poor outcomes and nephrotoxicity is highlighted. One in 3 children experienced considerable SAB morbidity; therefore, pediatric inclusion in future SAB comparator trials is paramount to improve outcomes.

Red cells manufactured from lipaemic whole blood donations: Do they have higher haemolysis?

BACKGROUND AND OBJECTIVES: Lipaemia in blood donations is thought to influence haemolysis in stored red blood cell (RBC) components. Higher lipid concentrations are believed to increase red cell fragility, exacerbating haemolysis during collection and subsequent red cell storage. This study aimed to investigate associations between lipoproteins in plasma and haemolysis of red cells stored in saline-adenine-glucose-mannitol (SAGM). MATERIALS AND METHODS: Fifty-four plasma and matched RBCs were obtained from lipaemic whole blood donations. Plasma was tested for coagulation factors, triglycerides and cholesterol. Haemolysis, glucose, lactate, extracellular potassium, lactate dehydrogenase and adenosine triphosphate (ATP) were measured in RBC on Days 7, 21 and 42 of storage. Additionally, 20 plasma and matched RBCs from non-lipaemic donations were tested as controls. RESULTS: Lipaemic plasma had significantly higher triglyceride concentrations compared with non-lipaemic plasma. However, there was no significant difference in plasma cholesterol between the two groups. There were no significant differences in glucose, extracellular potassium or ATP concentrations in RBC from either group. There was no significant difference in haemolysis at expiry in lipaemic-derived and control RBC, with a weak correlation between haemolysis and either triglycerides or cholesterol. CONCLUSION: There was no significant difference in haemolysis in RBC manufactured from lipaemic and non-lipaemic whole blood donations when stored in SAGM; however, the proportion of RBC from lipaemic donations with higher haemolysis was greater than in the controls. There was a weak correlation between red cell haemolysis and plasma triglycerides. Therefore, RBCs derived from lipaemic donations are suitable for blood bank inventories.

Microbiology of septic arthritis in young Auckland children.

BACKGROUND: Kingella kingae is an important cause of septic arthritis in young children, with modern laboratory methods leading to increased detection. Prevalence of this pathogen in New Zealand, where there are high rates of childhood infections due to Staphylococcus aureus and Streptococcus pyogenes, is not known. METHODS: We conducted a retrospective review of children <5 years with septic arthritis (without osteomyelitis) at a tertiary children's hospital in Auckland, over 10 years (2005-2014). Data were collected on demographics, microbiology, clinical presentation, investigations and management. RESULTS: Of the 68 cases of septic arthritis, 57 (83.8%) occurred in children aged <24 months. Among those <3 months, Streptococcus agalactiae (Group B streptococcus) was predominant (45.5% of 11 cases), followed by S. aureus (36.4%). The most common pathogen in those 3 to <12 months was Streptococcus pneumoniae (38.5% of 13 cases). In children aged 12 to <24 months, K. kingae was most common (30.3% of 33 cases). Of the 12 cases of K. kingae, 91.7% were identified from synovial fluid culture. All K. kingae isolates were susceptible to amoxicillin. CONCLUSIONS: K. kingae is the leading pathogen in septic arthritis in New Zealand children aged 12 to <24 months. Routine inoculation of synovial fluid into blood culture bottles at time of sample collection, in addition to use of polymerase chain reaction methods, should be encouraged to improve detection rates. For infants and preschool children presenting with single joint septic arthritis, empiric antibiotics should include cover for S. aureus and K. kingae.

Medical Treatment for Rheumatic Heart Disease: A Narrative Review.

BACKGROUND: Acute rheumatic fever (ARF) and rheumatic heart disease (RHD) are rare in high-income countries; however, in Aotearoa New Zealand ARF and RHD disproportionately affect Indigenous Maori and Pacific Peoples. This narrative review explores the evidence regarding non-surgical management of patients with clinically significant valve disease or heart failure due to RHD. METHODS: Medline, EMBASE and Scopus databases were searched, and additional publications were identified through cross-referencing. Included were 28 publications from 1980 onwards. RESULTS: Of the available interventions, improved anticoagulation management and a national RHD register could improve RHD outcomes in New Zealand. Where community pharmacy anticoagulant management services (CPAMS) are available good anticoagulation control can be achieved with a time in the therapeutic range (TTR) of more than 70%, which is above the internationally recommended level of 60%. The use of pharmacists in anticoagulation control is cost-effective, acceptable to patients, pharmacists, and primary care practitioners. There is a lack of local data available to fully assess other interventions; including optimal therapy for heart failure, equitable access to specialist RHD care, prevention, and management of endocarditis. CONCLUSION: As RHD continues to disproportionately affect Indigenous and minority groups, pro-equity tertiary prevention interventions should be fully evaluated to ensure they are reducing disease burden and improving outcomes in patients with RHD.

COVID-19 and Infant Hospitalizations for Seasonal Respiratory Virus Infections, New Zealand, 2020.

In March 2020, a national elimination strategy for coronavirus disease was introduced in New Zealand. Since then, hospitalizations for lower respiratory tract infection among infants <2 years of age and cases of respiratory syncytial or influenza virus infection have dramatically decreased. These findings indicate additional benefits of coronavirus disease control strategies.

Rising Ethnic Inequalities in Acute Rheumatic Fever and Rheumatic Heart Disease, New Zealand, 2000-2018.

We describe trends in acute rheumatic fever (ARF), rheumatic heart disease (RHD), and RHD deaths among population groups in New Zealand. We analyzed initial primary ARF and RHD hospitalizations during 2000-2018 and RHD mortality rates during 2000-2016. We found elevated rates of initial ARF hospitalizations for persons of Maori (adjusted rate ratio [aRR] 11.8, 95% CI 10.0-14.0) and Pacific Islander (aRR 23.6, 95% CI 19.9-27.9) ethnicity compared with persons of European/other ethnicity. We also noted higher rates of initial RHD hospitalization for Maori (aRR 3.2, 95% CI 2.9-3.5) and Pacific Islander (aRR 4.6, 95% CI 4.2-5.1) groups and RHD deaths among these groups (Maori aRR 12.3, 95% CI 10.3-14.6, and Pacific Islanders aRR 11.2, 95% CI 9.1-13.8). Rates also were higher in socioeconomically disadvantaged neighborhoods. To curb high rates of ARF and RHD, New Zealand must address increasing social and ethnic inequalities.

The Utility of Rapid Group A Streptococcus Molecular Testing Compared with Throat Culture for the Diagnosis of Group A Streptococcal Pharyngitis in a High-Incidence Rheumatic Fever Population.

Group A streptococcus (GAS) causes significant morbidity and mortality in New Zealand and is responsible for invasive disease and immune sequelae, including acute rheumatic fever (ARF). Early treatment of GAS pharyngitis reduces the risk of ARF. In settings with a high burden of GAS disease, a rapid GAS pharyngitis diagnostic test with a strong negative predictive value is needed to enable prompt and accurate treatment. This prospective study compares the Xpert Xpress Strep A molecular test (Cepheid) to throat culture and a second molecular method, the BioGX group A streptococcus-open system reagent (OSR) for BD Max for the diagnosis of GAS pharyngitis. Throat swabs were collected from the emergency department and wards of Middlemore Hospital, New Zealand. The BioGX group A streptococcus OSR for BD Max contributes to the composite gold standard of throat culture or both molecular methods positive. Basic demographic, clinical, and laboratory data were collected. Two hundred five out of two hundred fourteen swabs were suitable for analysis. Of those, 28/205 (13.7%) were GAS culture positive, 45/205 (22%) Xpert Xpress Strep A positive, and 38/205 (18.5%) BioGX positive. Compared to culture, the sensitivity, specificity, and positive and negative predictive values of the Xpert Xpress Strep A molecular test were 100%, 90.4%, 62.2%, and 100%, respectively. Compared to the composite gold standard, the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were 100%, 95.8%, 84.4%, and 100%, respectively. Seventeen samples were Xpert Xpress positive but culture negative; 6 of these 17 swabs represent true positives with evidence of recent GAS infection. Ten samples were culture negative but both Xpert Xpress and BioGX positive. The Xpert Xpress Strep A molecular test is highly sensitive with a strong negative predictive value and rapid turnaround time. It can be safely introduced as a first-line test for throat swabs in a high-incidence ARF population.

X- and gamma-irradiation have similar effects on the in vitro quality of stored red cell components.

BACKGROUND: Blood components are irradiated to inactivate lymphocytes to prevent transfusion-associated graft versus host disease. As there are little data regarding the effects of X-irradiation on red blood cell components (RBCs), the in vitro quality of stored red cells (standard, pediatric, washed, and intra-uterine transfusion [IUT]) following X- or gamma-irradiation was compared. STUDY DESIGN AND METHODS: RBCs were pooled, split, and processed to produce standard (<14 days and < 5 days post-collection), pediatric (<5 days post-collection), washed (<14 days post-collection), or IUT RBCs (<5 days post-collection). Standard RBCs were either X- or gamma-irradiated (n = 10 pairs). A further 10 replicates were prepared by pooling and splitting three matched RBCs (X-, gamma-, and non-irradiated). All other RBCs were either X- or gamma-irradiated (n = 20 pairs). Red cell indices, hemolysis, potassium release, metabolism, microparticles, ATP, and 2,3-DPG were measured pre-irradiation and 6 h, 1, 2, 3, 7, 10, and 14 days post-irradiation, depending on the component type. Data were analyzed using two-way repeated measures ANOVA. RESULTS: There were no significant differences in any in vitro quality measurements, with the exception of marginally higher potassium release in washed, IUT, and RBCs <5 days old (p < .0001) following X-irradiation. Both irradiation types increased generation of microvesicles, particularly in components that were older at the time of irradiation or stored for longer post-irradiation. CONCLUSION: X- and gamma-irradiation have similar effects on the in vitro quality of RBCs, indicating that either technology is suitable for blood component irradiation.

Early diagnosis of acute rheumatic fever and rheumatic heart disease as part of a secondary prevention strategy: Narrative review.

Acute rheumatic fever (ARF) and its sequela rheumatic heart disease (RHD) remain significant causes of morbidity and mortality. In New Zealand, ARF almost exclusively affects Indigenous Maori and Pacific children. This narrative review aims to present secondary interventions to improve early and accurate diagnosis of ARF and RHD, in order to minimise disease progression in New Zealand. Medline, EMBASE and Scopus databases were searched as well as other electronic publications. Included were 56 publications from 1980 onwards. Diagnosing ARF and RHD as early as possible is central to reducing disease progression. Recent identification of specific ARF biomarkers offer the opportunity to aid initial diagnosis and portable echocardiography has the potential to detect undiagnosed RHD in high-risk areas. However, further research into the benefits and risks to children with subclinical RHD is necessary, as well as an economic evaluation.

Structured review of primary interventions to reduce group A streptococcal infections, acute rheumatic fever and rheumatic heart disease.

Rheumatic heart disease (RHD) is a large, preventable, global public health burden. In New Zealand (NZ), acute rheumatic fever (ARF) and RHD rates are highest for Maori and Pacific children. This structured review explores the evidence for primary prevention interventions to diagnose and effectively treat group A Streptococcus (GAS) pharyngitis and skin infections to reduce rates of ARF and RHD. Medline, EMBASE and Scopus databases were searched as well as other electronic publications. Included were 50 publications from 1980 onwards. This review has identified that there is little available evidence for effective primary prevention strategies to reduce ARF rates in NZ. However, two primary intervention strategies that should be considered by communities at high-risk of ARF are: the use of school-based clinics to identify and treat GAS pharyngitis and GAS skin infections; and intramuscular benzathine penicillin G with lignocaine analgesia in children who present with a GAS positive throat.

Serum growth factor stability in different eye drop packaging systems during storage.

Serum eye drops (SED) have shown beneficial effects in patients suffering from dry eye syndrome and are manufactured for an increasing number of patients in Australia every year. Previous studies have examined the stability of serum growth factors during storage in either experimental vessels not used as the final packaging system or in eye drop bottles. To ensure the quality and safety of SED product manufactured in Australia, the stability of growth factors in serum packaged into two different systems during storage at different temperatures was examined. Healthy blood donors provided a whole blood donation, from which serum was prepared, diluted to 20% and dispensed into either a tube or a vial packaging system. The stability of growth factors, fibronectin and total protein in tube segments was comparable to matched vials samples during storage at -30 °C, 4 °C, 22 °C and 37 °C, with the exception of EGF and fibronectin in 20% SED stored in tube segments, which were more sensitive to storage conditions at 4 °C and 22 °C when compared to vials. Additionally, the growth factor, fibronectin and total protein concentration in both tube segments and vials was stable during storage at -30 °C for at least 9 months. This study highlights the impact of different manufacturing procedures on serum growth factor stability during storage.