Trajectories of otitis media and association with health determinants among Indigenous children in Australia: the Longitudinal Study of Indigenous Children.

OBJECTIVES: Indigenous children in Australia experience high burden of persistent otitis media (OM) from very early age. The aim was to identify distinct trajectories of OM in children up to age 10-12 years and examine the association with socio-economic determinants. STUDY DESIGN: A multistage clustered national panel survey. METHODS: The study analysed the birth cohort of the Longitudinal Study of Indigenous Children from 2008 to 2018, comprising 11 study waves. Group-based trajectory modelling was used to identify different trajectories of OM outcome. Multinomial logistic regression was applied to examine the relationship between trajectories and individual, household and community-level socio-economic determinants. RESULTS: This analysis included 894 children with at least three responses on OM over the 11 waves, and the baseline mean age was 15.8 months. Three different trajectories of OM were identified: non-severe OM prone, early/persistent severe OM and late-onset severe OM. Overall, 11.4% of the children had early/persistent severe OM from birth to 7.5 to nine years, while late-onset severe OM consisted of 9.8% of the children who had first OM from age 3.5 to five years. Children in communities with middle and the highest socio-economic outcomes have lower relative risk of early/persistent severe OM (adjusted relative risk ratio = 0.39, 95% confidence interval = 0.22-0.70 and adjusted relative risk ratio = 0.22, 95% confidence interval = 0.09-0.52, respectively) compared to children in communities with lowest socio-economic outcomes. CONCLUSION: Efforts to close the gap in the quality of life of Indigenous children must prioritise strategies that prevent severe ear disease (runny ears and perforation), including improved healthcare access, reduced household crowding, and better education, and more employment opportunities.

Nasopharyngeal carriage and macrolide resistance in Indigenous children with bronchiectasis randomized to long-term azithromycin or placebo.

Although long-term azithromycin decreases exacerbation frequency in bronchiectasis, increased macrolide resistance is concerning. We investigated macrolide resistance determinants in a secondary analysis of a multicenter randomized controlled trial. Indigenous Australian children living in remote regions and urban New Zealand Maori and Pacific Islander children with bronchiectasis were randomized to weekly azithromycin (30 mg/kg) or placebo for up to 24 months and followed post-intervention for up to 12 months. Nurses administered and recorded medications given and collected nasopharyngeal swabs 3-6 monthly for culture and antimicrobial susceptibility testing. Nasopharyngeal carriage of Haemophilus influenzae and Moraxella catarrhalis was significantly lower in azithromycin compared to placebo groups, while macrolide-resistant Streptococcus pneumoniae and Staphylococcus aureus carriage was significantly higher. Australian children, compared to New Zealand children, had higher carriage overall, significantly higher carriage of macrolide-resistant bacteria at baseline (16/38 versus 2/40 children) and during the intervention (69/152 versus 22/239 swabs), and lower mean adherence to study medication (63 % versus 92 %). Adherence ≥70 % (versus <70 %) in the Australian azithromycin group was associated with lower carriage of any pathogen [odds ratio (OR) 0.19, 95 % confidence interval (CI) 0.07-0.53] and fewer macrolide-resistant pathogens (OR 0.34, 95 % CI 0.14-0.81). Post-intervention (median 6 months), macrolide resistance in S. pneumoniae declined significantly in the azithromycin group, from 79 % (11/14) to 7 % (1/14) of positive swabs, but S. aureus strains remained 100 % macrolide resistant. Azithromycin treatment, the Australian remote setting, and adherence <70 % were significant independent determinants of macrolide resistance in children with bronchiectasis. Adherence to treatment may limit macrolide resistance by suppressing carriage.

Diversity of nontypeable Haemophilus influenzae strains colonizing Australian Aboriginal and non-Aboriginal children.

Nontypeable Haemophilus influenzae (NTHI) strains are responsible for respiratory-related infections which cause a significant burden of disease in Australian children. We previously identified a disparity in NTHI culture-defined carriage rates between Aboriginal and non-Aboriginal children (42% versus 11%). The aim of this study was to use molecular techniques to accurately determine the true NTHI carriage rates (excluding other culture-identical Haemophilus spp.) and assess whether the NTHI strain diversity correlates with the disparity in NTHI carriage rates. NTHI isolates were cultured from 595 nasopharyngeal aspirates collected longitudinally from asymptomatic Aboriginal (n=81) and non-Aboriginal (n=76) children aged 0 to 2 years living in the Kalgoorlie-Boulder region, Western Australia. NTHI-specific 16S rRNA gene PCR and PCR ribotyping were conducted on these isolates. Confirmation of NTHI by 16S rRNA gene PCR corrected the NTHI carriage rates from 42% to 36% in Aboriginal children and from 11% to 9% in non-Aboriginal children. A total of 75 different NTHI ribotypes were identified, with 51% unique to Aboriginal children and 13% unique to non-Aboriginal children (P<0.0001). The strain richness (proportion of different NTHI ribotypes) was similar for Aboriginal (19%, 65/346) and non-Aboriginal children (19%, 37/192) (P=0.909). Persistent carriage of the same ribotype was rare in the two groups, but colonization with multiple NTHI strains was more common in Aboriginal children than in non-Aboriginal children. True NTHI carriage was less than that estimated by culture. The Aboriginal children were more likely to carry unique and multiple NTHI strains, which may contribute to the chronicity of NTHI colonization and subsequent disease.

Otitis media at 6-monthly assessments of Australian First Nations children between ages 12-36 months: Findings from two randomised controlled trials of combined pneumococcal conjugate vaccines.

OBJECTIVES: In remote communities of northern Australia, First Nations children with hearing loss are disproportionately at risk of poor school readiness and performance compared to their peers with no hearing loss. The aim of this trial is to prevent early childhood persisting otitis media (OM), associated hearing loss and developmental delay. To achieve this, we designed a mixed pneumococcal conjugate vaccine (PCV) schedule that could maximise immunogenicity and thereby prevent bacterial otitis media (OM) and a trajectory of educational and social disadvantage. METHODS: In two sequential parallel, open-label, randomised controlled trials, eligible infants were first allocated 1:1:1 to standard or mixed PCV primary schedules at age 28-38 days, then at age 12 months to a booster dose (1:1) of 13-valent PCV, PCV13 (Prevenar13®, +P), or 10-valent pneumococcal non-typeable Haemophilus influenzae protein D conjugated vaccine, PHiD-CV10 (Synflorix®, +S). Here we report findings of standardised ear assessments conducted six-monthly from age 12-36 months, by booster dose. RESULTS: From March 2013 to September 2018, 261 children were allocated to booster + P (n = 131) or + S (n = 130). There were no significant differences in prevalence of any OM diagnosis by booster dose or when stratified by primary schedule. We found high, almost identical prevalence of OM in both boost groups at each age (for example 88% of 129 and 91% of 128 children seen, respectively, at primary endpoint age 18 months, difference -3% [95% Confidence Interval -11, 5]). At each age prevalence of bilateral OM was 52%-78%, and tympanic membrane perforation was 10%-18%. CONCLUSION: Despite optimal pneumococcal immunisation, the high prevalence of OM persists throughout early childhood. Novel approaches to OM prevention are needed, along with improved early identification strategies and evaluation of expanded valency PCVs.

Culture and PCR detection of Haemophilus influenzae and Haemophilus haemolyticus in Australian Indigenous children with bronchiectasis.

A PCR for protein D (hpd#3) was used to differentiate nontypeable Haemophilus influenzae (NTHI) from Haemophilus haemolyticus. While 90% of nasopharyngeal specimens and 100% of lower-airway specimens from 84 Indigenous Australian children with bronchiectasis had phenotypic NTHI isolates confirmed as H. influenzae, only 39% of oropharyngeal specimens with phenotypic NTHI had H. influenzae. The nasopharynx is therefore the preferred site for NTHI colonization studies, and NTHI is confirmed as an important lower-airway pathogen.

Nasopharyngeal carriage of otitis media pathogens in infants receiving 10-valent non-typeable Haemophilus influenzae protein D conjugate vaccine (PHiD-CV10), 13-valent pneumococcal conjugate vaccine (PCV13) or a mixed primary schedule of both vaccines: A randomised controlled trial.

BACKGROUND: Aboriginal children in Northern Australia have a high burden of otitis media, driven by early and persistent nasopharyngeal carriage of otopathogens, including non-typeable Haemophilus influenzae (NTHi) and Streptococcus pneumoniae (Spn). In this context, does a combined mixed primary series of Synflorix and Prevenar13 provide better protection against nasopharyngeal carriage of NTHi and Spn serotypes 3, 6A and 19A than either vaccine alone? METHODS: Aboriginal infants (n = 425) were randomised to receive Synflorix™ (S, PHiD-CV10) or Prevenar13™ (P, PCV13) at 2, 4 and 6 months (_SSS or _PPP, respectively), or a 4-dose early mixed primary series of PHiD-CV10 at 1, 2 and 4 months and PCV13 at 6 months of age (SSSP). Nasopharyngeal swabs were collected at 1, 2, 4, 6 and 7 months of age. Swabs of ear discharge were collected from tympanic membrane perforations. FINDINGS: At the primary endpoint at 7 months of age, the proportion of nasopharyngeal (Np) swabs positive for PCV13-only serotypes 3, 6A, or 19A was 0%, 0.8%, and 1.5% in the _PPP, _SSS, and SSSP groups respectively, and NTHi 55%, 52%, and 52% respectively, and no statistically significant vaccine group differences in other otopathogens at any age. The most common serotypes (in order) were 16F, 11A, 10A, 7B, 15A, 6C, 35B, 23B, 13, and 15B, accounting for 65% of carriage. Ear discharge swabs (n = 108) were culture positive for NTHi (52%), S. aureus (32%), and pneumococcus (20%). CONCLUSIONS: Aboriginal infants experience nasopharyngeal colonisation and tympanic membrane perforations associated with NTHi, non-PCV13 pneumococcal serotypes and S. aureus in the first months of life. Nasopharyngeal carriage of pneumococcus or NTHi was not significantly reduced in the early 4-dose combined SSSP group compared to standard _PPP or _SSS schedules at any time point. Current pneumococcal conjugate vaccine formulations do not offer protection from early onset NTHi and pneumococcal colonisation in this high-risk population.

The nonserotypeable pneumococcus: phenotypic dynamics in the era of anticapsular vaccines.

Nonserotypeable pneumococci (NSP) are commonly carried by Australian Indigenous children in remote communities. The purpose of this study was to characterize carriage isolates of NSP from Indigenous children vaccinated with the seven-valent pneumococcal conjugate vaccine (PCV7) and to use these data to guide decisions on reporting of NSP. A total of 182 NSP were characterized by BOX typing, antibiogram analysis, and multilocus sequence typing (MLST) of common BOX types. NSP positive for the wzg capsule gene were analyzed by a multiplex PCR-based reverse line blot hybridization assay (mPCR/RLB-H) targeting capsule genes to determine the serotype. Among 182 NSP, 49 BOX types were identified. MLST of 10 representative isolates found 7 STs, including ST448 (which accounted for 11% of NSP). Non-penicillin susceptibility was evident in 51% of the isolates. Pneumococcal wzg sequences were detected in only 23 (13%) NSP, including 10 that contained an approximately 1.2-kb insert in the region. mPCR/RLB-H identified serotype 14 wzy sequences in all 10 NSP, and 1 also contained a serotype 3-specific wze sequence. Among the remaining 13 wzg-positive NSP, few belonged to the serotypes represented in PCV7. It appears that most NSP identified in Australian Indigenous children are from a true nonencapsulated lineage. Few NSP represented serotypes in PCV7 that suppress capsular expression. High rates of carriage and penicillin resistance and the occasional presence of capsule genes suggest a role for NSP in the maintenance and survival of capsulated pneumococci. To avoid the inflation of pneumococcal carriage and antibiotic resistance rates, in clinical trials, we recommend separate reporting of rates of capsular strains and NSP and the exclusion of data for NSP from primary analyses.

A comprehensive approach to health promotion for the reduction of dental caries in remote Indigenous Australian children: a clustered randomised controlled trial.

AIM: To evaluate the effect of a community-oriented primary health care (CPHC) intervention on oral health behaviours of Indigenous preschool children living in remote communities of Australia's Northern Territory. METHODS: The study was a community-clustered randomised controlled trial over two years, set in 30 remote Indigenous communities in the Northern Territory of Australia. Children aged 18-47 months at baseline were enrolled in the study. The intervention included fluoride varnish applications, training of primary care workers, and health promotion for oral health at an individual, family and community level. Intervention communities received six-monthly visits over two years and control communities were visited at baseline and two years later with no contact in the intervening period. The outcome measures reported in this paper are the impact of the intervention on two secondary endpoints: oral health promotion activities in the community and personal oral health practice of children. RESULTS: The intervention did not produce any significant change in oral health behaviours, clinical measures of oral hygiene, or community programmes promoting oral health. Dental caries can be reduced but will continue to be a problem among young remote Indigenous children while they experience major social disadvantage.

Preventative and medical treatment of ear disease in remote or resource-constrained environments.

BACKGROUND: Important ear problems can affect the outer ear, the middle ear and the inner ear. Globally, the greatest burden of disease is due to ear conditions that are associated with otorrhoea and hearing loss. METHODS: This study reviewed the literature on the prevention and treatment of common ear conditions that are most relevant to settings with high rates of ear disease and limited resources. The grading of recommendations assessment, development and evaluation ('GRADE') approach was utilised to assess interventions. RESULTS: Accurate diagnosis of ear disease is challenging. Much of the preventable burden of ear disease is associated with otitis media. Nine otitis media interventions for which there is moderate to high certainty of effect were identified. While most interventions only provide modest benefit, the impact of treatment is more substantial in children with acute otitis media with perforation and chronic suppurative otitis media. CONCLUSION: Disease prevention through good hygiene practices, breastfeeding, reducing smoke exposure, immunisation and limiting noise exposure is recommended. Children with acute otitis media with perforation, chronic suppurative otitis media, complications of otitis media, and significant hearing loss should be prioritised for medical treatment.

Microbiology of otitis media in Indigenous Australian children: review.

OBJECTIVES: To review research addressing the polymicrobial aetiology of otitis media in Indigenous Australian children in order to identify research gaps and inform best practice in effective prevention strategies and therapeutic interventions. METHODS: Literature review. RESULTS: Studies of aspirated middle-ear fluid represented a minor component of the literature reviewed. Most studies relied upon specimens from middle-ear discharge or the nasopharynx. Culture-based middle-ear discharge studies have found that non-typeable Haemophilus influenzae and Streptococcus pneumoniae predominate, with Moraxella catarrhalis, Staphylococcus aureus and Streptococcus pyogenes isolated in a lower proportion of samples. Alloiococcus otitidis was detected in a number of studies; however, its role in otitis media pathogenesis remains controversial. Nasopharyngeal colonisation is a risk factor for otitis media in Indigenous infants, and bacterial load of otopathogens in the nasopharynx can predict the ear state of Indigenous children. CONCLUSION: Most studies have used culture-based methods and specimens from middle-ear discharge or the nasopharynx. Findings from these studies are consistent with international literature, but reliance on culture may incorrectly characterise the microbiology of this condition. Advances in genomic technologies are now providing microbiologists with the ability to analyse the entire mixed bacterial communities ('microbiomes') of samples obtained from Indigenous children with otitis media.

Antibiotics for the prevention of acute and chronic suppurative otitis media in children.

BACKGROUND: Acute otitis media (AOM) is a common childhood illness. These middle ear infections may be frequent and painful. AOM may be associated with perforation of the tympanic membrane and can progress to chronic suppurative otitis media (CSOM). OBJECTIVES: To determine the effectiveness of long-term antibiotics (for longer than six weeks) in preventing any AOM, AOM with perforation and CSOM. SEARCH STRATEGY: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library Issue 1, 2006), MEDLINE (January 1966 to March Week 3 2006), OLD MEDLINE (1950 to 1965), EMBASE (1990 to December 2005) and the references of relevant studies. SELECTION CRITERIA: All randomised controlled trials of long-term (longer than six weeks) antibiotics versus placebo or no treatment for the prevention of AOM, AOM with perforation, or CSOM were eligible. DATA COLLECTION AND ANALYSIS: Two authors independently extracted the data for: any AOM; episodes of AOM; any recurrent AOM; episodes of illness; any side effects; any antibiotic resistance, as well as outcomes at end of intervention (any AOM); and following cessation of intervention (any AOM). For dichotomous outcomes, the summary risk ratio (fixed and random-effects models) was calculated. For rate outcomes, the summary incidence rate ratio was calculated. MAIN RESULTS: Sixteen studies involving 1483 children met our inclusion criteria. All studies enrolled children at increased risk of AOM, and in seven studies the children were prone to otitis media. The majority of studies were high quality and most (15 studies) reported data for our primary outcomes. None reported AOM with perforation or CSOM. Long-term antibiotics reduced any episode of AOM (13 studies, 1358 children, risk ratio (RR) 0.62, 95% CI 0.52 to 0.75; random-effects model) and number of episodes of AOM (12 studies, 1112 children, incidence rate ratio (IRR) 0.48, 95% CI 0.37 to 0.62; random-effects model). Approximately five children would need to be treated long term to prevent one child experiencing AOM whilst on treatment. Antibiotics prevented 1.5 episodes of AOM for every 12 months of treatment per child. Statistical heterogeneity was explored. Long-term antibiotics were not associated with a significant increase in adverse events (11 studies, 714 children, RR 1.99, 95% CI 0.25 to 15.89; random-effects model). AUTHORS' CONCLUSIONS: For children at risk, antibiotics given once or twice daily will reduce the probability of AOM while the child is on treatment. Antibiotics will reduce the number of episodes of AOM per year from around three to around 1.5. We believe that larger absolute benefits are likely in high-risk children. These conclusions were not affected by sensitivity analyses.

Exercise echocardiography after coronary artery bypass surgery: correlation with coronary angiography.

OBJECTIVES: Our aim was to assess, in patients after coronary artery bypass surgery, how well exercise echocardiography predicts the presence of vascular compromise on angiography. BACKGROUND: Because late graft failure frequently occurs after bypass surgery, a reliable noninvasive technique is needed to identify those patients who would benefit from angiographic study. METHODS: In 182 patients, a total of 213 symptom-limited treadmill exercise electrocardiograms (ECGs) and exercise echocardiograms were performed in association with coronary and bypass angiography 2 weeks to 21 years after bypass surgery. RESULTS: There were more inconclusive exercise ECGs (28%) than exercise echocardiograms (9%). The positive predictive value was 85% for the exercise echocardiogram versus 62% for the exercise ECG; the corresponding negative predictive values were 81% versus 52%. The accuracy of the exercise echocardiogram was linked to the degree of underlying vascular compromise. After excluding cases with nondiagnostic results, due to either submaximal stress or poor image quality, the exercise echocardiogram detected 46 of the 60 cases with vascular compromise in one region (sensitivity 77%) and 47 of the 49 cases with compromise in two or three regions (sensitivity 96%). Similarly, an abnormal exercise echocardiogram had a positive predictive value of 71% for vascular compromise in one region and 98% for compromise in two or three regions. Most false negative exercise echocardiographic results were associated with posterolateral single-region vascular compromise on angiography. CONCLUSIONS: This study confirms a high positive and negative predictive value of exercise echocardiography in the detection of vascular compromise in patients after bypass surgery. It is clearly superior to exercise electrocardiography in predicting which patients will have angiographically significant graft or arterial lesions, and it can be used to obtain a better selection of patients for angiographic study.

Coronary bypass graft fate: long-term angiographic study.

In 222 patients, 741 venous coronary bypass grafts were studied angiographically early, at 1 year and at a late examination at greater than 6.5 years (mean 9.6) after operation; 565 of these grafts were also examined 5 years postoperatively. Grafts were graded for patency and disease considered to be atherosclerotic and for both extent and profile of lesions. Graft occlusion rates increased steadily from 8% early to 20% at 5, 41% at 10 and 45% at greater than 11.5 years after operation. All grafts were considered free of atherosclerosis early, but disease appeared in 8% at 1 year, increasing to 38% at 5 and 75% at 10 years postoperatively. Increasing involvement of vessel wall area was associated with greater protrusion of lesions into the graft lumen. Diseased grafts became more so at subsequent examinations, with occlusion occurring in many. However, absence of disease had little prognostic significance because diseased and abruptly occluded grafts were generated in those with healthy appearance at earlier examinations. For instance, 82% of very diseased grafts at the 5 year study originated from normal grafts at 1 year and 73% of occluded grafts at 1 year had appeared normal early postoperatively. Of 590 patent grafts free of disease at 1 year, 30% were occluded at the late examination, 76% of those patent were diseased, 55% of these were diffusely diseased and 35% were greater than 50% narrowed. Only 17% of the original 590 patent grafts were healthy at this time. Bypass graft atherosclerosis severely limits the long-term utility of these grafts. It is suggested that the solution may lie in some powerful drug regimen.

Coronary artery disease and coronary bypass grafting in young men: experience with 138 subjects 39 years of age and younger.

One hundred thirty-eight men aged less than or equal to 39 years had coronary bypass grafting during a 13 year period. Angina was the presenting symptom in 77% and of these patients, one-third had unstable angina. More than half of the patients had experienced at least one myocardial infarct. There was a high incidence of coronary risk factors, especially smoking. Nineteen patients (13.8%) had left main coronary artery stenosis (it was isolated in two); 13.8, 24.6 and 60.2% had single, double and triple vessel disease, respectively. Left ventriculograms showed serious functional impairment in 42%. A total of 461 coronary bypass grafts, 3.34 per patient, were placed; almost all were vein grafts. There were no operative deaths. Transmural myocardial infarction occurred in 4.3% of patients. All bypass grafts were opacified angiographically early after operation, 95% at 1 year, 56% at 5 years and 26% at 10 years after operation. Some patients also had coronary angiograms, dictated by clinical events, between 1 and 5 and between 5 and 10 years postoperatively. Patency rates for bypass grafts were comparable with those previously reported and were acceptable, although they decreased with time. However, increasing evidence of atherosclerosis of bypass grafts was seen beyond 1 year, particularly beyond 5 years. Of 23 subjects with a coronary bypass reoperation, 2 died and 44% had perioperative transmural myocardial infarction. During follow-up, 13.8% of the patients died, survival being 95, 84 and 76% at 5, 10 and 12 years, respectively. It is considered that the patients were advantageously treated with coronary bypass grafting especially in the short-term. However, bypass graft patency steadily decreased with the passage of time and graft atherosclerosis became an increasingly important problem.

Coronary bypass graft fate and patient outcome: angiographic follow-up of 5,065 grafts related to survival and reoperation in 1,388 patients during 25 years.

OBJECTIVES: We sought to examine, angiographically, the longterm fate of a large number of mainly venous coronary bypass grafts and to correlate graft patency and disease with patient survival and reoperation. BACKGROUND: Much is known about bypass graft patency and disease, but the precise relation between graft fate and patient outcome has not been substantiated and documented. METHODS: A total of 1,388 patients underwent a first coronary artery bypass graft procedure at a mean age of 48.9 years, 234 had a second bypass procedure at a mean age of 53.3 years, and 15 had a third bypass procedure at a mean age of 58.2 years during the 25-year period from 1969 to 1994. Most were male military personnel or veterans; 12% were < or = 39 years old. Of 5,284 grafts placed, 91% were venous and 9% arterial. Angiograms were performed on 5,065 (98% of surviving) grafts early, on 3,993 grafts at 1 year and on 1,978 grafts at 5 years after operation; other examinations were also performed up to 22.5 years after operation, and 353 grafts were examined after > or = 15 years. Grafts were graded for patency and disease. The status of all patients was known at the study's end. RESULTS: The perioperative mortality rate was 1.4% for an isolated first coronary bypass procedure, 6.6% for reoperation. Vein graft patency was 88% early, 81% at 1 year, 75% at 5 years and 50% at > or = 15 years; when suboptimal grafts, graded B, were excluded from calculation, the proportion of excellent grafts, graded A, decreased to 40% after > or = 12.5 years. After the early study, the vein graft occlusion rate was 2.1%/year. Internal mammary artery graft patency was significantly better but decreased with time. Vein graft disease appeared by 1 year and the rate accelerated by > or = 2.5 years, involving 48% of grafts at 5 years and 81% at > or = 15 years; 44% of the latter grafts were narrowed > 50%. Survival of all patients was 93.6% at 5 years. 81.1% at 10 years, 62.1% at 15 years, 46.7% (150 patients) at 20 years and 38.4% (25 patients) at 23 years after operation. Survival decreased as age increased, but curves approximated "normal" life expectancy for older patients. Survival curves at all ages showed a steeper decline after 7 years. The rate of reoperation increased between 5 years and 10 to 14 years, then decreased to stable levels. Coronary atheroembolism from vein grafts was the major cause of morbidity and mortality associated with reoperation. Vein graft patency and disease were temporally and closely related to reoperation and survival. CONCLUSIONS: Coronary bypass graft disease and occlusion are common after coronary artery bypass grafting and increase with time. They are major determinants of clinical prognosis, specifically measured by reoperation rate and survival. Intraoperative graft atheroembolism was a major reoperation hazard. Reoperation is definitely worthwhile but entails identifiable risks that must be dealt with.

Haemophilus influenzae isolates survive for up to 20 years at -70 °C in skim milk tryptone glucose glycerol broth (STGGB) if thawing is avoided during re-culture.

Haemophilus influenzae remains a major cause of disease worldwide requiring continued study. Recently, isolates of Streptococcus pneumoniae and Moraxella catarrhalis, but not H. influenzae, were reported to survive long-term ultra-freeze storage in STGGB. We show that nontypeable H. influenzae isolates survive for up to 20 years when thawing is avoided.

Cardiac depression by intravenous disopyramide in patients with left ventricular dysfunction.

The hemodynamic effects of disopyramide phosphate were studied in nine patients with left ventricular dysfunction. After control measurements, administration of a 2 mg/kg bolus of disopyramide phosphate over 5 or 15 minutes was followed by a 20 minute 0.4 mg/kg/hour infusion and a 15 minute recovery period. Response to the 5 and 15 minute bolus injection was similar. Maximum hemodynamic effects occurred immediately after the bolus was given; there were decrements in systolic pressure (142 to 124 mm Hg)(p less than 0.005), cardiac index (2.5 to 1.8 liters/min/m2)(p less than 0.001) and stroke index (29.4 to 20.6 ml/beat/m2)(p less than 0.001), and increases in right atrial pressure (9 to 12 mm Hg)(p less than 0.005) and total peripheral resistance (21.2 to 25.7 U)(p less than 0.005). Two studies had to be terminated after the bolus was given due to profound hemodynamic deterioration. In the remainder, the systolic pressure returned to control by the end of the infusion, whereas the mean arterial pressure increasd significantly (92 to 96 mm Hg)(p less than 0.01). Little further change in mean arterial pressure, cardiac and stroke index, and total peripheral resistance occurred during the recovery period. These data indicated that intravenous disopyramide phosphate is a potent cardiac depressant when given over 5 to 15 minutes to patients with left ventricular dysfunction. It is concluded that disopyramide should not be administered to such patients unless conventional therapy fails. In such circumstances it should be used with extreme caution and careful monitoring.

Coronary bypass graft fate. Angiographic study of 1,179 vein grafts early, one year, and five years after operation.

A total of 1,179 vein grafts were studied angiographically in 353 (45%) unselected survivors (male, mean age 45.5 years) of 786 coronary bypass operations. Studies were conducted early (0.96 months), 1 year (12.8 months), and 5 years (59.7 months) postoperatively. A previously described technique was used to grade the patency of the grafts, and a new technique was used to assess intimal irregularity, presumably caused by atherosclerosis; this new technique indicated both intimal surface distribution of disease and profile (relief or elevation). Ten percent, 17%, and 26% of grafts were occluded early, at 1 year, and at 5 years, respectively. Distal anastomotic defects were the commonest cause for low grades in the patency classification. Irregularities in patent grafts increased from 9% at 1 year to 42% at 5 years, with 11% of all the 1 year lesions and 20% of all the 5 year lesions having a high profile (more than 50% graft stenosis); of the lesions categorized as showing the widest surface spread, 17% were in high relief at 1 year and 34% at 5 years. Thus, the lesions we believed to be atherosclerotic proliferated in both surface spread and elevation. All severely diseased grafts at the 1 year study had been normal in outline early; 79% at the 5 year study had been disease free at 1 year. All newly occluded grafts at the 1 year study had been normal in outline and 82% had had good patency early; 78% of newly occluded grafts at the 5 year study had been disease free at 1 year and 77% had had good patency. Normal appearance of the intima in grafts studied at 1 year had no prognostic value for 5 year findings. However, 62% of all grafts with the appearance of intimal disease at 1 year showed deterioration by 5 years, and 28% were occluded. The differences between these outcomes are highly significant (p less than 0.0005). In conclusion, the appearance of intimal irregularity compatible with atherosclerosis in a coronary bypass graft 1 year after operation carried a poor prognosis for adverse angiographic change at 5 years. On the other hand, normally appearing intima at 1 year had no predictive valve for the 5 year study despite a generally better prognosis for nondiseased grafts.

Perioperative myocardial infarction complicating coronary bypass. Clinical and angiographic correlations and prognosis.

To investigate the importance and the causes of myocardial infarction complicating the coronary bypass operation, we have reviewed clinical and preoperative angiographic data on 717 patients operated on over an 81/2 year period and postoperative angiography on all but one survivor. The hospital mortality was 0.6%. Of the 56 (7.8%) patients who sustained perioperative myocardial infarction, two died. Left ventricular angiography supported the diagnosis in 40 patients and aided in quantification of myocardial infarction. Age, preoperative symptomatic status, incidence of prior myocardial infarction, and perfusion and axoxia timed did not correlate with myocardial infarction, but extent of coronary disease, number of grafts, and associated endarterectomy did. There have been no late deaths in the 54 survivors of perioperative infarction, which appears usually to be a benign event. Graft occlusion was nearly three times commoner in patients with myocardial infarction, and in 42 of 54 survivors the myocardial infarction could be explained by new impairment of perfusion, usually owing to compromise of the grafted artery. The relationship of perioperative infarction to iatrogenic diminution of perfusion, of the infarcted segment suggests that technical factors, especially meticulous attention to the quality of the graft-coronary artery anastomosis might further reduce the perioperative infarction rate.

Bacterial colonization of the nasopharynx predicts very early onset and persistence of otitis media in Australian aboriginal infants.

Otitis media (OM) develops in the first months of life and persists throughout childhood in many rural Aboriginal children. We have followed Aboriginal and non-Aboriginal infants from birth to determine the relationship of the early onset of OM to nasopharyngeal colonization with respiratory pathogens. Aboriginal infants were colonized with multiple species of respiratory bacteria (Moraxella catarrhalis, Haemophilus influenzae, Streptococcus pneumoniae) at a rate of 5% per day and the timing of colonization predicted the onset of persistent OM in individual Aboriginal infants. Non-Aboriginal infants became colonized by M. catarrhalis alone at the slower rate of 1% per day and experienced transient episodes of OM in the absence of colonization. We attribute early bacterial colonization in most Aboriginal infants to high rates of cross-infection due to overcrowding, poor hygiene and high rates of bacterial carriage. Early age of infection and the multiplicity of bacterial types may contribute to prolonged carriage and to eustachian tube damage leading to persistent OM. Thus Aboriginal infants are "otitis-prone" and might qualify for prophylactic antibiotics.