Fatal Respiratory Diphtheria Caused by ß-Lactam-Resistant Corynebacterium diphtheriae.

BACKGROUND: Diphtheria is a potentially fatal respiratory disease caused by toxigenic Corynebacterium diphtheriae. Although resistance to erythromycin has been recognized, ß-lactam resistance in toxigenic diphtheria has not been described. Here, we report a case of fatal respiratory diphtheria caused by toxigenic C. diphtheriae resistant to penicillin and all other ß-lactam antibiotics, and describe a novel mechanism of inducible carbapenem resistance associated with the acquisition of a mobile resistance element. METHODS: Long-read whole-genome sequencing was performed using Pacific Biosciences Single Molecule Real-Time sequencing to determine the genome sequence of C. diphtheriae BQ11 and the mechanism of ß-lactam resistance. To investigate the phenotypic inducibility of meropenem resistance, short-read sequencing was performed using an Illumina NextSeq500 sequencer on the strain both with and without exposure to meropenem. RESULTS: BQ11 demonstrated high-level resistance to penicillin (benzylpenicillin minimum inhibitory concentration [MIC] ≥ 256 µg/ml), ß-lactam/ß-lactamase inhibitors and cephalosporins (amoxicillin/clavulanic acid MIC ≥ 256 µg/mL; ceftriaxone MIC ≥ 8 µg/L). Genomic analysis of BQ11 identified acquisition of a novel transposon carrying the penicillin-binding protein (PBP) Pbp2c, responsible for resistance to penicillin and cephalosporins. When strain BQ11 was exposed to meropenem, selective pressure drove amplification of the transposon in a tandem array and led to a corresponding change from a low-level to a high-level meropenem-resistant phenotype. CONCLUSIONS: We have identified a novel mechanism of inducible antibiotic resistance whereby isolates that appear to be carbapenem susceptible on initial testing can develop in vivo resistance to carbapenems with repeated exposure. This phenomenon could have significant implications for the treatment of C. diphtheriae infection, and may lead to clinical failure.

The effects of culture independent diagnostic testing on the diagnosis and reporting of enteric bacterial pathogens in Queensland, 2010 to 2014.

Changes in diagnostic laboratory testing procedures can impact on the number of cases notified and the public health surveillance of enteric pathogens. Culture independent diagnostic testing using a multiplex polymerase chain reaction (PCR) test was introduced for the rapid detection of bacterial enteric pathogens in pathology laboratories in Queensland, Australia, from late 2013 onwards. We conducted a retrospective descriptive study using laboratory data to assess the impact of the introduction of PCR testing on four common enteric pathogens, Salmonella, Campylobacter, Shigella and Yersinia, in Queensland between 2010 and 2014. The number of stool specimens tested and the proportion positive for each of the four pathogens increased in 2014 after the introduction of culture independent diagnostic testing. Among the specimens tested by both PCR and culture, 12% of Salmonella positive stools, 36% of Campylobacter positive stools, 74% of Shigella / enteroinvasive Escherichia coli positive stools and 65% of Yersinia positive stools were PCR positive only. Including those where culture was not performed, 19% of Salmonella positive stools, 44% of Campylobacter positive stools, 83% of Shigella positive stools and 79% of Yersinia positive stools had no cultured isolate available for further characterisation. The detection and tracking of foodborne and non-foodborne gastrointestinal outbreaks will become more difficult as culture independent diagnostic testing becomes more widespread. Until new techniques for characterisation of pathogens directly from clinical specimens have been developed, we recommend laboratories continue to culture specimens concurrently or reflexively with culture independent diagnostic tests.

Enhanced surveillance for gonorrhoea in two diverse settings in Queensland in the 2000s: comparative epidemiology and selected management outcomes.

Gonorrhoea is an important sexually transmitted notifiable condition. This paper describes findings from two gonorrhoea enhanced surveillance programs operating during the 2000s in Queensland: one in the remote Torres and Northern Peninsula Area (T&NPA); the other in an urban region. The overall response rate in the T&NPA (2006-2011) was 82% (723 of 879), and in Brisbane Southside and West Moreton (BSWM) (2003-2011), it was 62% (1,494 of 2,401 notifications). In the T&NPA, cases were young (80% <25 years), Indigenous (97%) and 44% were male. In the BSWM, cases were predominantly male (76%), non-Indigenous (92%) and 42% were aged less than 25 years. Co-infection with chlamydia was found in 54% of males and 60% of females in the Torres, and in 18% of males and 35% of females in the BSWM. In the BSWM 35% of the men without a syphilis test recorded had reported sexual contact with men; similarly 34% of the men without an HIV test recorded had reported sexual contact with men. Compliance with recommended treatment (ceftriaxone) was greater than 90% in all years except 2008 (84%) in the T&NPA. Treatment compliance increased significantly, from 40% in 2003 to 84.4% in 2011 (P<0.0001) in the BSWM cohort. The proportion of contacts with a documented treatment date increased significantly in the T&NPA from 56% in 2009 to 76% in 2011 (P=0.019), after a system for follow-up with the clinician became routine. Gonorrhoea epidemiology and management challenges vary across Queensland populations. Enhanced surveillance allows public health authorities to monitor epidemiology and reminds clinicians to prioritise effective sexually transmitted infection treatment for their clients.

Epidemiology of mumps outbreaks and the impact of an additional dose of MMR vaccine for outbreak control in regional Queensland, Australia, 2017-2018.

BACKGROUND: In recent years, there have been ongoing outbreaks of mumps reported in Northern and North-Western Queensland, Western Australia and the Northern Territory, Australia. We aimed to define the epidemiology of mumps outbreaks in Central Queensland, Australia between October 2017 and October 2018 and evaluate the effectiveness of an additional dose of measles, mumps, rubella (MMR) vaccine. METHODS: A retrospective case control study was conducted, including outbreak investigations with laboratory-confirmed cases of mumps and subsequent comparison with matched controls. We analysed mandatory notifications from the Queensland Health Notifiable Conditions System database and immunisation information from the Queensland Health Vaccination Information and Admin System (VIVAS) and the Australian Immunisation Register. RESULTS: Between October 2017 and October 2018, there were 93 cases of mumps reported in Central Queensland with three distinct outbreaks: a discrete Indigenous community; a correctional facility; and a boarding school. Among all cases, 74 (79.6%) were fully vaccinated and 14 (15.1%) were partially vaccinated with MMR vaccine. Eighty-six cases (92.5%) were reported among Aboriginal and Torres Strait Islander people. In all outbreaks, an additional dose of MMR vaccine was offered with 35.4%, 73.6% and 35.8% of the target population being immunised in the discrete Indigenous community, the correctional facility and the boarding school, respectively. Prior to this additional dose of MMR, the mumps attack rate was 31.0 (95% confidence interval [95% CI]: 24.2-39.0) per 1000 population, compared to the post-additional dose MMR attack rate of 10.6 (95% CI: 6.7-15.9) per 1000 population. CONCLUSION: An additional or booster dose of MMR should be included as an effective public health intervention strategy, particularly in communal or high-density living conditions to control mumps outbreaks in highly vaccinated populations.

Re-emergence of dengue virus in regional Queensland: 2019 dengue virus outbreak in Rockhampton, Central Queensland, Australia.

OBJECTIVE(S): To describe an autochthonous dengue virus type 2 (DENV-2) outbreak in Central Queensland from May 2019 and subsequent public health actions. DESIGN AND SETTING: Public health outbreak investigation of locally acquired DENV-2 cases in Rockhampton, Central Queensland. This included laboratory investigations, associated mosquito vector surveillance, and control measures implemented in response to the outbreak. RESULTS: Twenty-one locally-acquired DENV-2 cases were identified during the Rockhampton outbreak (from 23 May to 7 October 2019): 13 laboratory-confirmed and eight probable cases. Clinical symptoms included lethargy (100%); fever (95%); headache (95%); and aches and pains (90%). Inspections of premises demonstrated that Aedes aegypti was present in 9.5% of those investigated which was more than half of the premises identified as containing mosquitoes. Nucleotide sequencing of a DENV-2 isolate recovered from the first confirmed case and DENV-2 RNA from an additional 5 patients indicated a single DENV-2 strain was responsible for the outbreak which was most closely related to DENV-2 strains from Southeast Asia. CONCLUSIONS: The 2019 DENV-2 outbreak in Rockhampton, Central Queensland, Australia, likely resulted from the importation of a strain, most closely related to DENV-2 strains from Southeast Asia and is the first reported outbreak in the region specifically implicating DENV-2. Given the presence of Aedes aegypti in Rockhampton, appropriate medical and mosquito avoidance advice; ongoing surveillance; and deployment of mosquito control strategies for the prevention of dengue and other mosquito-borne diseases should be priorities for this region.

Estimating the attributable fraction for melanoma: a meta-analysis of pigmentary characteristics and freckling.

Epidemiologic research has demonstrated convincingly that certain pigmentary characteristics are associated with increased relative risks of melanoma; however there has been no comprehensive review to rank these characteristics in order of their importance on a population level. We conducted a systematic review of the literature and meta-analysis to quantify the contribution of pigmentary characteristics to melanoma, estimated by the population-attributable fraction (PAF). Eligible studies were those that permitted quantitative assessment of the association between histologically confirmed melanoma and hair colour, eye colour, skin phototype and presence of freckling; we identified 66 such studies using citation databases, followed by manual review of retrieved references. We calculated summary relative risks using weighted averages of the log RR, taking into account random effects, and used these to estimate the PAF. The pooled RRs for pigmentary characteristics were: 2.64 for red/red-blond, 2.0 for blond and 1.46 for light brown hair colour (vs. dark); 1.57 for blue/blue-grey and 1.51 for green/grey/hazel eye colour (vs. dark); 2.27, 1.99 and 1.35 for skin phototypes I, II and III respectively (vs. IV); and 1.99 for presence of freckling. The highest PAFs were observed for skin phototypes 1/II (0.27), presence of freckling (0.23), and blond hair colour (0.23). For eye colour, the PAF for blue/blue-grey eye colour was higher than for green/grey/hazel eye colour (0.18 vs. 0.13). The PAF of melanoma associated with red hair colour was 0.10. These estimates of melanoma burden attributable to pigmentary characteristics provide a basis for designing prevention strategies for melanoma.

Exclusion of electrical and mechanical function of the left atrial appendage in patients with persistent atrial fibrillation: differences in efficacy and safety between endocardial ablation vs epicardial LARIAT ligation (the EXCLUDE LAA study).

BACKGROUND: Electrical isolation of the left atrial appendage (LAA) may provide incremental benefits for arrhythmia management in patients undergoing radiofrequency ablation (RFA) for persistent atrial fibrillation (AF). OBJECTIVE: The aim of this study was to compare efficacy and safety of endocardial ablation and LAA exclusion with LARIAT device for electrical and mechanical exclusion of LAA. METHODS: We compared patients who underwent endocardial LAA isolation during index RFA for persistent AF and underwent a repeat RFA to patients who underwent LAA exclusion with LARIAT device followed by RFA for AF in this multicenter registry. Efficacy of electrical and mechanical isolation of LAA was assessed. RESULTS: We included 182 patients of which 91 patients underwent endocardial LAA isolation during RFA for AF, and 91 patients underwent LAA exclusion with LARIAT device followed by RFA for AF. Baseline characteristics were similar except for higher CHA2DS2-VASc score, coronary artery disease, and prior stroke rate in LARIAT arm. Persistence of electrical isolation (measured at beginning of second procedure) after LARIAT procedure was higher than one-time AF-RFA (96.7% vs 52.8%, p < 0.01). Acute pulmonary vein isolation rates were similar in both arms. AF recurrence rate after second isolation attempts at 1 year was similar in both arms. No difference in major complications was noted between both arms. CONCLUSIONS: LAA exclusion with LARIAT device appears to be more efficacious as compared to one-time endocardial ablation, but not compared to repeat isolation, in achieving complete electrical isolation of LAA for persistent AF.

Safety, tolerability, pharmacokinetics, and immunogenicity of a human monoclonal antibody targeting the G glycoprotein of henipaviruses in healthy adults: a first-in-human, randomised, controlled, phase 1 study.

BACKGROUND: The monoclonal antibody m102.4 is a potent, fully human antibody that neutralises Hendra and Nipah viruses in vitro and in vivo. We aimed to investigate the safety, tolerability, pharmacokinetics, and immunogenicity of m102.4 in healthy adults. METHODS: In this double-blind, placebo-controlled, single-centre, dose-escalation, phase 1 trial of m102.4, we randomly assigned healthy adults aged 18-50 years with a body-mass index of 18·0-35·0 kg/m2 to one of five cohorts. A sentinel pair for each cohort was randomly assigned to either m102.4 or placebo. The remaining participants in each cohort were randomly assigned (5:1) to receive m102.4 or placebo. Cohorts 1-4 received a single intravenous infusion of m102.4 at doses of 1 mg/kg (cohort 1), 3 mg/kg (cohort 2), 10 mg/kg (cohort 3), and 20 mg/kg (cohort 4), and were monitored for 113 days. Cohort 5 received two infusions of 20 mg/kg 72 h apart and were monitored for 123 days. The primary outcomes were safety and tolerability. Secondary outcomes were pharmacokinetics and immunogenicity. Analyses were completed according to protocol. The study was registered on the Australian New Zealand Clinical Trials Registry, ACTRN12615000395538. FINDINGS: Between March 27, 2015, and June 16, 2016, 40 (52%) of 77 healthy screened adults were enrolled in the study. Eight participants were assigned to each cohort (six received m102.4 and two received placebo). 86 treatment-emergent adverse events were reported, with similar rates between placebo and treatment groups. The most common treatment-related event was headache (12 [40%] of 30 participants in the combined m102.4 group, and three [30%] of ten participants in the pooled placebo group). No deaths or severe adverse events leading to study discontinuation occurred. Pharmacokinetics based on those receiving m102.4 (n=30) were linear, with a median half-life of 663·3 h (range 474·3-735·1) for cohort 1, 466·3 h (382·8-522·3) for cohort 2, 397·0 h (333·9-491·8) for cohort 3, and 466·7 h (351·0-889·6) for cohort 4. The elimination kinetics of those receiving repeated dosing (cohort 5) were similar to those of single-dose recipients (median elimination half-time 472·0 [385·6-592·0]). Anti-m102.4 antibodies were not detected at any time-point during the study. INTERPRETATION: Single and repeated dosing of m102.4 were well tolerated and safe, displayed linear pharmacokinetics, and showed no evidence of an immunogenic response. This study will inform future dosing regimens for m102.4 to achieve prolonged exposure for systemic efficacy to prevent and treat henipavirus infections. FUNDING: Queensland Department of Health, the National Health and Medical Research Council, and the National Hendra Virus Research Program.

Safety of rapid switching from amiodarone to dofetilide in atrial fibrillation patients with an implantable cardioverter-defibrillator.

BACKGROUND: Dofetilide is a class III antiarrhythmic drug commonly used for treatment of atrial fibrillation. Drug guidelines mandate a 3-month waiting period before initiating dofetilide after amiodarone use. Whether patients with an implantable cardioverter-defibrillator (ICD) can be rapidly switched from amiodarone to dofetilide is not known. OBJECTIVE: The purpose of this study was to evaluate whether rapid switching from amiodarone to dofetilide is safe in atrial fibrillation patients with an ICD. METHODS: In this retrospective observational study, we assessed the feasibility and the short- and long-term safety of rapid switching from amiodarone to dofetilide in hospitalized atrial fibrillation with an ICD. RESULTS: The study included a total of 179 patients who were followed for 12.6 ± 2.2 months. All patients had drug initiation during hospitalization. Dofetilide resulted in successful cardioversion in 66% (118/179). Twenty percent of patients (36/179) required dofetilide dose adjustments in the initiation phase because of QT prolongation and decreased creatinine clearance. A total of 6.1% of patients (11/179) required drug discontinuation. The incidence of torsades de pointes was 1.1% (2/179) during initiation. One patient (0.5%) had self-terminating ventricular tachycardia at follow-up. No other significant adverse events were noted during follow-up. CONCLUSION: Atrial fibrillation patients with an ICD can be rapidly switched to dofetilide after 7 days of discontinuation of amiodarone without significant arrhythmia-related complications. Prospective studies with large sample sizes, especially of women, should be performed to further validate these findings.

Myocarditis Causing Premature Ventricular Contractions: Insights From the MAVERIC Registry.

BACKGROUND: Premature ventricular contractions are a common clinical presentation that drives further diagnostic workup. We hypothesize the presence of underlying inflammation is often unrecognized in these patients with a potential for continued disease progression if not diagnosed and treated early in the disease course. METHODS: This is a single-center, prospective study including 107 patients with frequent symptomatic premature ventricular contractions (>5000/24 h) and no known ischemic heart disease. Patients underwent a combination of laboratory testing, 18F-fluorodeoxyglucose positron emission tomography scan, cardiac magnetic resonance imaging, and biopsy. Patients were diagnosed with myocarditis based on a multidisciplinary approach and treated with immunosuppressive therapy. RESULTS: The mean age of the cohort was 57±15 years, 41% were males, and left ventricular ejection fraction was 47±11.8%. Positive positron emission tomography scan was seen in 51% (55/107), of which 51% (28/55) had preserved left ventricle function. Based on clinical profile, 18F-fluorodeoxyglucose-positron emission tomography imaging, cardiac magnetic resonance, and histological data 58% patients (32/55) received immunosuppressive therapy alone and 25.4% (14/55) received immunosuppressive therapy and catheter ablation. Optimal response was seen in 67% (31/46) over a mean follow-up of 6±3 months. In patients with left ventricle systolic dysfunction, 37% (10/27) showed an improvement in mean left ventricular ejection fraction of 13±6%. CONCLUSIONS: Approximately 51% of patients presenting with frequent premature ventricular contractions have underlying myocardial inflammation in this cohort. 18F-fluorodeoxyglucose-positron emission tomography scan can be a useful modality for early diagnosis and treatment with immunosuppressive therapy in selected patients can improve clinical outcomes.

Equine Caregiver Information-Seeking Preferences: Surveys in the Midwest.

Two surveys of equine owners/managers and professionals using convenience sampling via multimodal distribution were conducted on perceptions of equid health and well-being (n = 142) and equine nutrition and feeding practices (n = 151). Surveys were distributed in 2014-2015 (health and well-being) and 2016 (nutrition and feeding) to similar email lists and social media sites; both included questions regarding information-seeking preferences. Respondents were mostly female (62% health and well-being, 84% nutrition and feeding) and had over 20 years of equine ownership/management experience (47% and 61%, respectively). Participants in the Nutrition and Feeding survey reported seeking information from veterinarians (77%), books/magazines (42%), horse enthusiasts (38%), friends/family (35%), Internet/social media (28%), feed company representative (28%), farrier (25%), scientific publications (25%), trainer/instructor (21%), equine nutritionist (19%), equine dentist (7%), extension specialist (7%), and radio (1%). The Health and Well-Being survey requested information regarding participants' likeliness (5-point Likert scale) of trusting various sources for animal well-being information. Respondents from the Health and Well-Being survey indicated veterinarians/nutritionists (average = 4.5) and extension specialists/university personnel (average = 4.0) as their top two trusted sources of information, and local (average = 2.9) and national humane societies/rescues (average = 2.8) their least-trusted sources of information. These results elucidated the information-seeking preferences of horse owners from the Upper Midwest regarding two equine topics. Veterinarians are sought as a source of equine information in the Upper Midwest.

Perceptions of Equid Well Being Well-Being in South Dakota.

In South Dakota, the status of equid well being is relatively unknown. This study sought to (a) gain understanding about the current perceptions of nonhuman animal well being in South Dakota, with an emphasis on horses and other equids; (b) determine the level of care equids are reportedly receiving and the perceived challenges to equine well being in South Dakota, and (c) determine if people from diverse geographical locations (east or west of the Missouri River) have similar views on the well being of equids in South Dakota. Respondents indicated the current level of equid well being in South Dakota is sufficient, but there is room for improvement. Current challenges for the equid population of South Dakota were the high annual cost of horse care, poor horsemanship, dental problems, and whether caregivers understand basic equine care. Several significant associations arose between where a respondent lives (Western or Eastern South Dakota) and their level of agreement with various statements. The results provide a benchmark to gauge well being and help give direction for future educational needs that can continue to improve equid care.

Dairy Tool Box Talks: A Comprehensive Worker Training in Dairy Farming.

Today's dairies are growing rapidly, with increasing dependence on Latino immigrant workers. This requires new educational strategies for improving milk quality and introduction to state-of-the-art dairy farming practices. It also creates knowledge gaps pertaining to the health of animals and workers, mainly due to the lack of time and language barriers. Owners, managers, and herdsmen assign training duties to more experienced employees, which may not promote "best practices" and may perpetuate bad habits. A comprehensive and periodic training program administered by qualified personnel is currently needed and will enhance the sustainability of the dairy industry. Strategic management and employee satisfaction will be achieved through proper training in the employee's language, typically Spanish. The training needs to address not only current industry standards but also social and cultural differences. An innovative training course was developed following the same structure used by the engineering and construction industries, giving farm workers basic understanding of animal care and handling, cow comfort, and personal safety. The "Dairy Tool Box Talks" program was conducted over a 10-week period with nine sessions according to farm's various employee work shifts. Bulk milk bacterial counts and somatic cell counts were used to evaluate milk quality on the three dairy farms participating in the program. "Dairy Tool Box Talks" resulted in a general sense of employee satisfaction, significant learning outcomes, and enthusiasm about the topics covered. We conclude this article by highlighting the importance of educational programs aimed at improving overall cross-cultural training.

Informing the public health management of typhoid and paratyphoid: the Australian context.

OBJECTIVE: To examine outcomes of public health management of notified enteric fever cases in South-East Queensland over the past five years. METHODS: Notification records of typhoid and paratyphoid infection in South-East Queensland 2008-2012 (inclusive) were reviewed to determine likelihood of cases and contacts adhering to present or previous recommendations for faecal clearance/screening, duration of infectiousness of cases and extent of local transmission to contacts. RESULTS: Sixty-nine of 85 cases and 218 of 265 contacts submitted at least one faecal specimen. Cases were 2.7 (95%CI 1.2-6.0) and contacts were 4.4 (95%CI 3.0-6.4) times more likely to complete recommended faecal clearance/screening under previous compared to present guidelines (requiring more specimens). In ten cases with positive post-treatment specimens, last recorded infectiousness was 19 days to six months after notification. The documented rate of local transmission of infection was 18/1,000 contacts submitting at least one faecal specimen (95%CI 6-48/1,000). CONCLUSIONS: Local transmission risk of enteric fever in South-East Queensland is low, although small numbers of cases may have prolonged bacilli excretion post-treatment. More complex clearance/screening regimens are associated with decreased compliance. IMPLICATIONS: Pursuing extensive faecal clearance/screening regimens is unlikely to be effective in terms of public health management of enteric fever in South-East Queensland. We suggest a unified national approach focussing on cases/contacts at high risk of disease transmission.

Familial melanoma: a meta-analysis and estimates of attributable fraction.

Melanoma commonly clusters in families, and the recent identification of numerous genotypes predicting higher risks of melanoma has led to the widespread perception that this cancer is predominantly a genetic disease. We conducted a systematic review of the literature and meta-analysis to quantify the contribution of familial factors to melanoma, estimated by the population attributable fraction (PAF). Eligible studies were those that permitted quantitative assessment of the association between histologically confirmed melanoma and family history of the disease; we identified 22 such studies using citation databases, followed by manual review of retrieved references. We calculated summary RRs using weighted averages of the log RR, taking into account random effects, and used these to estimate the PAF. Overall, family history was associated with a significant 2-fold increased risk of melanoma (odds ratio, 2.06; 95% confidence interval, 1.72-2.45); however, there was significant heterogeneity (P = 0.01). The pooled estimate for population-based studies (n = 11) was 2.03 (1.70-2.43), and 2.51 (1.55-4.07) for clinic/hospital-based studies (n = 11), both with significant heterogeneity (P = 0.049 and P = 0.013, respectively). Two studies used record linkage to verify family history in relatives; the pooled risk estimate from these two studies was 2.52 (2.11-3.00) with no evidence of heterogeneity (P = 0.258). Estimates of PAF associated with a positive family history ranged from 0.007 for Northern Europe to 0.064 for Australia (0.040 for all regions combined). Our findings suggest that only a small percentage of melanoma cases (always <7%) are attributable to familial risk; the majority of melanomas are presumably attributable to other factors.

Estimating the attributable fraction for cancer: A meta-analysis of nevi and melanoma.

Epidemiologic research has shown convincingly that certain phenotypic attributes are associated with increased relative risks of melanoma. Although such findings have intrinsic utility, there have been few attempts to translate such knowledge into estimates of disease burden suitable for framing public health policy. We aimed to estimate the population attributable fraction (PAF) for melanoma associated with melanocytic nevi using relative risk estimates derived from a systematic review and meta-analysis. We identified eligible studies using citation databases, followed by manual review of retrieved references. Of 49 studies identified, 25 and 23, respectively, were included in meta-analyses of atypical and common nevi. For people with > or =1 atypical nevi, the summary relative risk was 3.63 (95% confidence interval, 2.85-4.62), with a PAF of 0.25. The relative risk increased by 1.017 (95% confidence interval, 1.014-1.020) for each common nevus; however, significant heterogeneity in risk estimates was observed. We estimated that 42% of melanomas were attributable to having > or =25 common nevi (PAF 25-49 nevi = 0.15; PAF > or =50 nevi = 0.27), whereas PAFs for low nevus counts were modest (PAF 0-10 nevi = 0.04; PAF 11-24 nevi = 0.07). We modeled PAF under scenarios of varying nevus prevalence; the highest melanoma burden was always among those with high nevus counts (PAF range of 0.31-0.62 for > or =25 common nevi). Patients with > or =25 common nevi and/or > or =1 atypical nevi are a high-risk group, which might be targeted for identification, screening, and education. This work is the necessary first step in designing targeted preventive strategies for melanoma, which must now be overlaid with information about cost and utility.

Antenatal care implications of population-based trends in Down syndrome birth rates by rurality and antenatal care provider, Queensland, 1990-2004.

OBJECTIVE: To assess whether the rates of Down syndrome births in Queensland vary according to rurality (ie, whether the mother lives in a rural or urban area) and type of antenatal care provider, and to consider any implications for antenatal care. DESIGN AND SETTING: Population-based study of Down syndrome births in Queensland between 1990 and 2004, stratified by rurality and type of antenatal care provider (private obstetrician, public hospital or shared care). RESULTS: Since 2000, there has been a large fall in maternal-age-adjusted rates of Down syndrome births among mothers living in urban areas (-14.3% per year; 95% CI, -22.7%, -5.0%) and among mothers receiving their antenatal care from private obstetricians (-27.5% per year; 95% CI, -37.6%, -15.8%). Similar decreases have not occurred among mothers living in rural areas (0.0%; 95% CI, -11.7%, 13.1%) or among mothers receiving antenatal care from public hospitals (+2.9%, 95% CI, -10.3%, 17.9%). CONCLUSION: Possible reasons for the observed trends include unequal access to antenatal screening; confusion about screening guidelines and protocols; late presentation for antenatal care; and differences in attitudes to screening and termination of pregnancy among expectant parents, such that they may choose not to have screening or not to act on a positive screening test result.