Rheumatic heart disease in pregnancy and neonatal outcomes: A systematic review and meta-analysis.

PURPOSE: Associations between rheumatic heart disease (RHD) in pregnancy and fetal outcomes are relatively unknown. This study aimed to review rates and predictors of major adverse fetal outcomes of RHD in pregnancy. METHODS: Medline (Ovid), Pubmed, EMcare, Scopus, CINAHL, Informit, and WHOICTRP databases were searched for studies that reported rates of adverse perinatal events in women with RHD during pregnancy. Outcomes included preterm birth, intra-uterine growth restriction (IUGR), low-birth weight (LBW), perinatal death and percutaneous balloon mitral valvuloplasty intervention. Meta-analysis of fetal events by the New-York Heart Association (NYHA) heart failure classification, and the Mitral-valve Area (MVA) severity score was performed with unadjusted random effects models and heterogeneity of risk ratios (RR) was assessed with the I2 statistic. Quality of evidence was evaluated using the GRADE approach. The study was registered in PROSPERO (CRD42020161529). FINDINGS: The search identified 5949 non-duplicate records of which 136 full-text articles were assessed for eligibility and 22 studies included, 11 studies were eligible for meta-analyses. In 3928 pregnancies, high rates of preterm birth (9.35%-42.97%), LBW (12.98%-39.70%), IUGR (6.76%-22.40%) and perinatal death (0.00%-9.41%) were reported. NYHA III/IV pre-pregnancy was associated with higher rates of preterm birth (5 studies, RR 2.86, 95%CI 1.54-5.33), and perinatal death (6 studies, RR 3.23, 1.92-5.44). Moderate /severe mitral stenosis (MS) was associated with higher rates of preterm birth (3 studies, RR 2.05, 95%CI 1.02-4.11) and IUGR (3 studies, RR 2.46, 95%CI 1.02-5.95). INTERPRETATION: RHD during pregnancy is associated with adverse fetal outcomes. Maternal NYHA III/IV and moderate/severe MS in particular may predict poor prognosis.

Lessons to be learned: Using National Immunisation strategies to improve adherence to acute rheumatic fever secondary prophylaxis.

Rheumatic heart disease, as a result of a single or recurrent episode of acute rheumatic fever (ARF), remains a significant cause of morbidity and mortality in northern and remote Australia; ARF has a peak incidence among 5-14-year-old Aboriginal and Torres Strait Islander children. Long-term regular benzathine penicillin G injections are the only currently successful secondary prevention strategy; however, rates of adherence remain critically low. In contrast, rates of adherence to immunisations on the National Immunisation Program (NIP) Schedule are high, even among this target population. This article compares strategies used to implement and improve ARF secondary prophylaxis with those used in the NIP. Some successful NIP strategies, such as Service Incentive Payment for health providers, home-visiting delivery models and integration into the National Immunisation Register, if applied to ARF secondary prophylaxis have the potential to improve benzathine penicillin G adherence.

Paediatric thoracic empyema in the tropical North Queensland region of Australia: Epidemiological trends over a decade.

AIM: The Townsville Hospital and Health Service is the regional referral centre for children in the north of Queensland. Aboriginal and Torres Strait Islander (ATSI) people make up 7-10% of the population. Increasing numbers of children with paediatric thoracic empyema (pTE) are being referred to Townsville Hospital and Health Service for management. This study aims to describe the incidence rates, epidemiology, microbiology and trends of this disease in North Queensland over a 10-year period. METHODS: A retrospective chart review of all children (1 month to 16 years), admitted in the years 2007-2016, with community-acquired pTE was conducted. International Classification of Diseases codes were used to identify the patients. Epidemiological and microbiological data were extracted from records. RESULTS: Of the 123 cases identified, incidence rates per 100 000 were 8.5 (95% confidence interval (CI) 8.4-8.6) in all children and much higher at 19.8 (95% CI: 19.5-21.9) in ATSI children. The under 5 years age group had the highest rate (24.5; 95% CI: 24.4-24.6). There was a progressive rise in incidence during the 10-year period, with the highest incidence of 15.2 (95% CI: 15.1-15.2) occurring in 2016. A pathogen was isolated in 76% of cases. Non-multi-resistant methicillin-resistant Staphylococcus aureus was the most common pathogen isolated in 22 of 64 ATSI children (34%), while Streptococcus pneumoniae was the most common pathogen isolated in 27 of 59 non-ATSI children (46%). CONCLUSIONS: A high and increasing incidence of pTE in North Queensland is being observed. ATSI children have higher incidence rates and are more likely to have non-multi-resistant methicillin-resistant Staphylococcus aureus as a causative agent.

The influence of birthweight, past poststreptococcal glomerulonephritis and current body mass index on levels of albuminuria in young adults: the multideterminant model of renal disease in a remote Australian Aboriginal population with high rates of renal disease and renal failure.

BACKGROUND: Australian Aborigines in remote areas have very high rates of kidney disease, which is marked by albuminuria. We describe a 'multihit' model of albuminuria in young adults in one remote Aboriginal community. METHODS: Urinary albumin/creatinine ratios (ACRs) were measured in 655 subjects aged 15-39 years and evaluated in the context of birthweights, a history of 'remote' poststreptococcal glomerulonephritis (PSGN; ≥5 years earlier) and current body mass index (BMI). Birthweight had been <2.5 kg (low birthweight, LBW) in 25.4% of subjects and 22.8% had a remote history of PSGN. RESULTS: ACR levels rose with age. It exceeded the microalbuminuria threshold in 33.6% of subjects overall (25% of males and 45% of females). In multivariate models, birthweight (inversely), remote PSGN and current BMI were all independent predictors of ACR levels. The effects of birthweight and PSGN and their combination were expressed through amplification of ACR levels in relation to age and around the group median BMI of 20.8 kg/m(2). In people with BMI <20.8 (57.8% of all males and 40.3% of the females), LBW and PSGN alone had minimal effects on ACR, but in combination they strikingly amplified ACR in relation to age. Those with BMI ≥20.8 (which included 42.2% of the males and 59.7% of the females) had higher ACR levels, and both LBW and a PSGN history, separately and in combination, were associated with striking further amplification of ACR in the context of age. CONCLUSION: Much of the great excess of disease in this population is explained by high rates of the early life risk factors, LBW and PSGN. Their effects are expressed through amplification of ACR in the context of increasing age and are further moderated by levels of current body size. Both early life risk factors are potentially modifiable.

Three-weekly doses of azithromycin for indigenous infants hospitalized with bronchiolitis: a multicentre, randomized, placebo-controlled trial.

BACKGROUND: Bronchiolitis is a major health burden in infants globally, particularly among Indigenous populations. It is unknown if 3 weeks of azithromycin improve clinical outcomes beyond the hospitalization period. In an international, double-blind randomized controlled trial, we determined if 3 weeks of azithromycin improved clinical outcomes in Indigenous infants hospitalized with bronchiolitis. METHODS: Infants aged ≤24 months were enrolled from three centers and randomized to receive three once-weekly doses of either azithromycin (30 mg/kg) or placebo. Nasopharyngeal swabs were collected at baseline and 48 h later. Primary endpoints were hospital length of stay (LOS) and duration of oxygen supplementation monitored every 12 h until judged ready for discharge. Secondary outcomes were: day-21 symptom/signs, respiratory rehospitalizations within 6 months post-discharge and impact upon nasopharyngeal bacteria and virus shedding at 48 h. RESULTS: Two hundred nineteen infants were randomized (n = 106 azithromycin, n = 113 placebo). No significant between-group differences were found for LOS (median 54 h for each group, difference = 0 h, 95% CI: -6, 8; p = 0.8), time receiving oxygen (azithromycin = 40 h, placebo = 35 h, group difference = 5 h, 95% CI: -8, 11; p = 0.7), day-21 symptom/signs, or rehospitalization within 6 months (azithromycin n = 31, placebo n = 25 infants, p = 0.2). Azithromycin reduced nasopharyngeal bacterial carriage (between-group difference 0.4 bacteria/child, 95% CI: 0.2, 0.6; p < 0.001), but had no significant effect upon virus detection rates. CONCLUSION: Despite reducing nasopharyngeal bacterial carriage, three large once-weekly doses of azithromycin did not confer any benefit over placebo during the bronchiolitis illness or 6 months post hospitalization. Azithromycin should not be used routinely to treat infants hospitalized with bronchiolitis. CLINICAL TRIAL REGISTRATION: The trial was registered with the Australian and New Zealand Clinical Trials Register: Clinical trials number: ACTRN1261000036099.

The multideterminant model of renal disease in a remote Australian Aboriginal population in the context of early life risk factors: lower birth weight, childhood post-streptococcal glomerulonephritis, and current body mass index influence levels of albuminuria in young Aboriginal adults.

BACKGROUND: Australian Aborigines in remote areas have very high rates of kidney disease, which is marked by albuminuria. We describe a "multihit" model of albuminuria in young adults in one remote Aboriginal community. METHODS: Urinary albumin/creatinine ratios (ACR) were measured in all subjects who volunteered to participate in a community-wide health screen. Subjects for this study were young adults who had birth weights recorded and whose medical records were inspected for a history of post-streptococcal glomerulonephritis (PSGN). Urine ACR levels were evaluated in the context of birth weights, PSGN history and current BMI. RESULTS: 580 subjects (335 males and 245 females) who were aged 18 - 39 years at time of screening and qualified for inclusion. 26% of subjects had birth weights of < 2.5 kg, and the median birth weight was 2.8 kg. 23% of subjects had a remote history of PSGN, all 3 or more years earlier. Median BMI for the group was 21 kg/m2. Urine ACR levels exceeded the microalbuminuria threshold of 3.4 g/mol in 35.5% of subjects. Birth weight (inversely), remote PSGN, and current BMI were all independent predictors of ACR levels. Median levels of ACR were lowest in those with birth weights ≥ 2.5 kg, and no history of PSGN, intermediate in those with either birth weights < 2.5 kg or a history of PSGN, and highest in those with both low birth weights and a PSGN history. ACR levels were higher in those with BMIs above the median values, most notably in those with lower birth weights or a PSGN history or both. INTERPRETATION: Much of the great excess of disease in this population is explained by high rates of the early life risk factors, low birth weight and PSGN. Their effects are expressed through amplification of ACR in the context of increasing age, and are further moderated by levels of current body size. Both early life risk factors are potentially modifiable.

Mobile phones support adherence and retention of indigenous participants in a randomised controlled trial: strategies and lessons learnt.

BACKGROUND: Ensuring adherence to treatment and retention is important in clinical trials, particularly in remote areas and minority groups. We describe a novel approach to improve adherence, retention and clinical review rates of Indigenous children. METHODS: This descriptive study was nested within a placebo-controlled, randomised trial (RCT) on weekly azithromycin (or placebo) for 3-weeks. Indigenous children aged ≤24-months hospitalised with acute bronchiolitis were recruited from two tertiary hospitals in northern Australia (Darwin and Townsville). Using mobile phones embedded within a culturally-sensitive approach and framework, we report our strategies used and results obtained. Our main outcome measure was rates of adherence to medications, retention in the RCT and self-presentation (with child) to clinic for a clinical review on day-21. RESULTS: Of 301 eligible children, 76 (21%) families declined participation and 39 (13%) did not have access to a mobile phone. 186 Indigenous children were randomised and received dose one under supervision in hospital. Subsequently, 182 (99%) children received dose two (day-7), 169 (93%) dose three (day-14) and 180 (97%) attended their clinical review (day-21). A median of 2 calls (IQR 1-3) were needed to verify adherence. Importantly, over 97% of children remained in the RCT until their clinical endpoint at day-21. CONCLUSIONS: In our setting, the use of mobile phones within an Indigenous-appropriate framework has been an effective strategy to support a clinical trial involving Australian Indigenous children in urban and remote Australia. Further research is required to explore other applications of this approach, including the impact on clinical outcomes. TRIAL REGISTRATION: ACTRN12608000150347 (RCT component).

A single dose of azithromycin does not improve clinical outcomes of children hospitalised with bronchiolitis: a randomised, placebo-controlled trial.

OBJECTIVE: Bronchiolitis, one of the most common reasons for hospitalisation in young children, is particularly problematic in Indigenous children. Macrolides may be beneficial in settings where children have high rates of nasopharyngeal bacterial carriage and frequent prolonged illness. The aim of our double-blind placebo-controlled randomised trial was to determine if a large single dose of azithromycin (compared to placebo) reduced length of stay (LOS), duration of oxygen (O2) and respiratory readmissions within 6 months of children hospitalised with bronchiolitis. We also determined the effect of azithromycin on nasopharyngeal microbiology. METHODS: Children aged ≤18 months were randomised to receive a single large dose (30 mg/kg) of either azithromycin or placebo within 24 hrs of hospitalisation. Nasopharyngeal swabs were collected at baseline and 48 hrs later. Primary endpoints (LOS, O2) were monitored every 12 hrs. Hospitalised respiratory readmissions 6-months post discharge was collected. RESULTS: 97 children were randomised (n = 50 azithromycin, n = 47 placebo). Median LOS was similar in both groups; azithromycin = 54 hours, placebo = 58 hours (difference between groups of 4 hours 95%CI -8, 13, p = 0.6). O2 requirement was not significantly different between groups; Azithromycin = 35 hrs; placebo = 42 hrs (difference 7 hours, 95%CI -9, 13, p = 0.7). Number of children re-hospitalised was similar 10 per group (OR = 0.9, 95%CI 0.3, 2, p = 0.8). At least one virus was detected in 74% of children. The azithromycin group had reduced nasopharyngeal bacterial carriage (p = 0.01) but no difference in viral detection at 48 hours. CONCLUSION: Although a single dose of azithromycin reduces carriage of bacteria, it is unlikely to be beneficial in reducing LOS, duration of O2 requirement or readmissions in children hospitalised with bronchiolitis. It remains uncertain if an earlier and/or longer duration of azithromycin improves clinical and microbiological outcomes for children. The trial was registered with the Australian and New Zealand Clinical Trials Register. Clinical trials number: ACTRN12608000150347. http://www.anzctr.org.au/TrialSearch.aspx.

Post-streptococcal glomerulonephritis is a strong risk factor for chronic kidney disease in later life.

Although unusual in western countries and in Australia in general, post-streptococcal glomerulonephritis (PSGN) is still common in Australian Aboriginal children living in remote communities. Here, we evaluated whether episodes of acute PSGN increased the risk for chronic kidney disease in later life in 1519 residents of a remote Aboriginal community (85% of those age eligible), with high rates of renal and cardiovascular disease, who participated in a health screen over a 3-year period. Of these, 200 had had at least one episode of PSGN, with 27 having had multiple episodes, usually in childhood. High levels of albuminuria (albumin/creatinine ratio) with increasing age were confirmed. All PSGN episodes were associated with group A streptococcal skin infections, often related to scabies. In both genders, aged 10-39 years at screening, about one in five had such a history. Among them, PSGN (5 years or more earlier) was significantly associated with higher levels of albuminuria than those without. In women, aged 30-39 years, a history of PSGN was associated with a significantly higher frequency of estimated glomerular filtration rates <60 ml/min. The adjusted odds ratios for an albumin/creatinine ratio over 34 g/mol (overt albuminuria) in males and females with a history of PSGN were 4.6 and 3.1, respectively, compared with those without a history. Thus, PSGN contributes to the very serious burden of chronic kidney disease in this community. Rigorous strategies to prevent scabies and Group A streptococcal infections will reduce this burden.

Randomized placebo-controlled trial on azithromycin to reduce the morbidity of bronchiolitis in Indigenous Australian infants: rationale and protocol.

BACKGROUND: Acute lower respiratory infections are the commonest cause of morbidity and potentially preventable mortality in Indigenous infants. Infancy is also a critical time for post-natal lung growth and development. Severe or repeated lower airway injury in very young children likely increases the likelihood of chronic pulmonary disorders later in life. Globally, bronchiolitis is the most common form of acute lower respiratory infections during infancy. Compared with non-Indigenous Australian infants, Indigenous infants have greater bacterial density in their upper airways and more severe bronchiolitis episodes. Our study tests the hypothesis that the anti-microbial and anti-inflammatory properties of azithromycin, improve the clinical outcomes of Indigenous Australian infants hospitalised with bronchiolitis. METHODS: We are conducting a dual centre, randomised, double-blind, placebo-controlled, parallel group trial in northern Australia. Indigenous infants (aged ≤ 24-months, expected number = 200) admitted to one of two regional hospitals (Darwin, Northern Territory and Townsville, Queensland) with a clinical diagnosis of bronchiolitis and fulfilling inclusion criteria are randomised (allocation concealed) to either azithromycin (30 mg/kg/dose) or placebo administered once weekly for three doses. Clinical data are recorded twice daily and nasopharyngeal swab are collected at enrollment and at the time of discharge from hospital. Primary outcomes are 'length of oxygen requirement' and 'duration of stay,' the latter based upon being judged as 'ready for respiratory discharge'. The main secondary outcome is readmission for a respiratory illness within 6-months of leaving hospital. Descriptive virological and bacteriological (including development of antibiotic resistance) data from nasopharyngeal samples will also be reported. DISCUSSION: Two published studies, both involving different patient populations and settings, as well as different macrolide antibiotics and treatment duration, have produced conflicting results. Our randomised, placebo-controlled trial of azithromycin in Indigenous infants hospitalised with bronchiolitis is designed to determine whether it can reduce short-term (and potentially long-term) morbidity from respiratory illness in Australian Indigenous infants who are at high risk of developing chronic respiratory illness. If azithromycin is efficacious in reducing the morbidly of Indigenous infants hospitalised with bronchiolitis, the intervention would lead to improved short term (and possibly long term) health benefits.

Zinc and vitamin A supplementation in Indigenous Australian children hospitalised with lower respiratory tract infection: a randomised controlled trial.

OBJECTIVE: To evaluate the efficacy of supplementation with zinc and vitamin A in Indigenous children hospitalised with acute lower respiratory infection (ALRI). DESIGN: Randomised controlled, 2-by-2 factorial trial of supplementation with zinc and vitamin A. SETTING AND PARTICIPANTS: 187 Indigenous children aged < 11 years hospitalised with 215 ALRI episodes at Alice Springs Hospital (April 2001 to July 2002). INTERVENTIONS: Vitamin A was administered on Days 1 and 5 of admission at a dose of 50 000 IU (infants under 12 months), or 100 000 IU; and zinc sulfate was administered daily for 5 days at a daily dose of 20 mg (infants under 12 months) or 40 mg. MAIN OUTCOME MEASURE: Time to clinical recovery from fever and tachypnoea, duration of hospitalisation, and readmission for ALRI within 120 days. RESULTS: There was no clinical benefit of supplementation with vitamin A, zinc or the two combined, with no significant difference between zinc and no-zinc, vitamin A and no-vitamin A or zinc + vitamin A and placebo groups in time to resolution of fever or tachypnoea, or duration of hospitalisation. Instead, we found increased morbidity; children given zinc had increased risk of readmission for ALRI within 120 days (relative risk, 2.4; 95% CI, 1.003-6.1). CONCLUSION: This study does not support the use of vitamin A or zinc supplementation in the management of ALRI requiring hospitalisation in Indigenous children living in remote areas. Even in populations with high rates of ALRI and poor living conditions, vitamin A and zinc therapy may not be useful. The effect of supplementation may depend on the prevalence of deficiency of these micronutrients in the population.

Renal ultrasound findings in an Australian Aboriginal population with high rates of renal disease.

BACKGROUND: Rates of albuminuria and haematuria are extremely high with haematuria prevalence as high as 30-50% in adults of some Aboriginal groups. Dipstick testing of urine is routinely carried out in Aboriginal communities and as part of school screening programmes. Evaluation of the many affected individuals has traditionally included renal ultrasound examination, which involves considerable expense and logistic problems in remote communities. The present study was conducted to evaluate the usefulness of ultrasound in this setting. METHODS: A population survey was conducted in a remote community. Urine dipstick analysis and the albumin:creatinine ratio (ACR; g/mol) were measured in 1440 people over 5 years of age (89% of the eligible population), and a detailed renal ultrasound examination was performed in a random subset of 647 people (41.1% of the whole group), 276 aged 5-19 years and 371 over 20 years of age. RESULTS: Urine dipstick proteinuria (>1+) was present in 8.5% (23/271) of those aged 5-19 years and 37.9% (132/348) in those aged over 20 years; pathological albuminuria (ACR>3.4) was present in 7.6% (21/276) and 54.7% (203/371), respectively, and isolated haematuria was present in 7.7% (21/273) and 11.5% (40/347), respectively. Eight ultrasound abnormalities were found. Ultrasound findings did not change the management of any individual. CONCLUSION: Renal ultrasound added little to the evaluation of people with asymptomatic proteinuria or haematuria in this setting. In this scenario, ultrasound examination could be reserved for the cases with an unusual presentation where findings are likely to influence the prognosis or treatment, or in preparation for a renal biopsy.

Zinc and vitamin A supplementation in Australian Indigenous children with acute diarrhoea: a randomised controlled trial.

OBJECTIVE: To evaluate the role of zinc and vitamin A supplementation in the recovery of Indigenous children hospitalised for acute diarrhoea. DESIGN: A randomised controlled 2 by 2 factorial trial of supplementation with zinc and vitamin A. SETTING AND PARTICIPANTS: Aboriginal children (aged < 11 years) hospitalised for acute diarrhoea at Alice Springs Hospital, Northern Territory, April 2001-July 2002. MAIN OUTCOME MEASURES: Duration of diarrhoeal illness; re-admission for diarrhoeal illness within 120 days. RESULTS: Our study involved 392 Aboriginal children with 436 episodes of diarrhoea. Supplementation with zinc, vitamin A, or combined zinc and vitamin A had no significant effect on duration of diarrhoea or rate of re-admission compared with placebo. Median diarrhoea duration after starting supplementation was 3.0 days for the vitamin A and zinc supplemented and placebo groups (P values 0.25 and 0.69, respectively). The number of re-admissions did not differ significantly between those receiving vitamin A or zinc and the relevant placebo groups (relative risk [95% CI], 1.2 [0.7-2.1] and 1.3 [0.8-2.1], respectively). CONCLUSION: Vitamin A and zinc supplementation may not be indicated for in-hospital management of acute diarrhoeal disease in Aboriginal children living in remote areas. This finding may not apply to children with malnutrition, for whom other studies suggest a benefit. Larger trials incorporating more comprehensive data on the vitamin A and zinc status as well as nutritional status of study populations might help to explain the different results in different populations.

Evaluation of hospitalisation for indigenous children with malnutrition living in central Australia.

OBJECTIVE: To evaluate the effectiveness of hospital admissions for indigenous children with malnutrition in a rural/remote Australian centre. DESIGN: Retrospective review of the medical records. SETTING: Rural secondary hospital. SUBJECTS: Remote and rural indigenous children aged less than four years managed for malnutrition in Alice Springs Hospital (ASH). MAIN OUTCOME MEASURE: The primary outcome measure was weight gain during hospitalisation and posthospitalisation. Secondary outcome measures were yield of investigations, diagnoses made, treatments given, social interventions, readmission rate and nosocomial infection. RESULTS: Median age of the 55 children was 15.1 months. Median weight change was 1.5 g day(-1)prior to hospitalisation, 36.7 g day(-1)during and 9 g day(-1)two months following hospitalisation (P < 0.05). Investigations performed had high yields (80% of children had a treatable organic contributor to malnutrition). Nosocomial infection occurred in 21 (38%) children. Readmission occurred at an average of 1.9 times per child (range 0-5), 34 (37%) occurred within three months and 48 (52%) within six months. CONCLUSION: In rural Indigenous children with malnutrition, hospitalisation was effective in re-establishing growth and defining organic contributors to malnutrition. However, the high readmission rate and nosocomial infection mandates that alternative models to nutritional rehabilitation, in addition to a broad psychosocial and public health approach to prevention and management of malnutrition, is required.