Contamination of the central medical air supply with water leading to mass ventilator failure.

Here, we present a case of mass ventilator failure due to contaminated medical air. Multiple ventilators failed routine tests, including almost all of the ventilators in our intensive care unit. A faulty air compressor had led to water contamination of our centre's supply of medical air. Water entered the pipeline supply of air and, hence the ventilators and anaesthetic machines. The disruption of the machines' proportional mixer valve resulted in unreliable delivery of fresh gas flow. This malfunction was discovered during routine pre-use checks, and backup ventilators were available to replace the faulty ventilators. A shortage of equipment was averted due to a serendipitous availability of ventilator stockpiles prepared for the COVID-19 pandemic. Ventilator shortages are commonly described in mass casualty and pandemic scenarios. While there are multiple strategies described in literature to augment and maximise equipment available for mechanical ventilation, stockpiling equipment remains an expensive but necessary component of disaster contingency planning.

Efficacy of erector spinae plane block for analgesia in breast surgery: a systematic review and meta-analysis.

The erector spinae plane block is a new regional anaesthesia technique that provides truncal anaesthesia for breast surgery. This systematic review and meta-analysis was undertaken to determine if the erector spinae plane block is effective at reducing pain scores and opioid consumption after breast surgery. This study also evaluated the outcomes of erector spinae plane blocks compared with other regional blocks. PubMed, Embase, Scopus, the Cochrane Central Register of Controlled Trials and ClinicalTrials.gov were searched. We included randomised controlled trials reporting the use of the erector spinae plane block in adult breast surgery. Risk of bias was assessed with the revised Cochrane risk-of-bias tool. The Grading of Recommendations, Assessment, Development and Evaluation (GRADE) framework was used to assess trial quality. Thirteen randomised controlled trials (861 patients; 418 erector spinae plane block, 215 no blocks, 228 other blocks) were included. Erector spinae plane block reduced postoperative pain compared with no block: at 0-2 hours (mean difference (95% CI) -1.63 (-2.97 to -0.29), 6 studies, 329 patients, high-quality evidence, I2  = 98%, p = 0.02); at 6 hours (mean difference (95% CI) -0.90 (-1.49 to -0.30), 5 studies, 250 patients, high-quality evidence, I2  = 91%, p = 0.003); at 12 hours (mean difference (95% CI) -0.46 (-0.67 to -0.25), 5 studies, 250 patients, high-quality evidence, I2  = 58%, p < 0.0001); and at 24 hours (mean difference (95% CI) -0.50 (-0.70 to -0.30), 6 studies, 329 patients, high-quality evidence, I2  = 76%, p < 0.00001). Compared with no block, erector spinae plane block also showed significantly lower postoperative oral morphine equivalent requirements (mean difference (95% CI) -21.55mg (-32.57 to -10.52), 7 studies, 429 patients, high-quality evidence, I2  = 99%, p = 0.0001). Separate analysis of studies comparing erector spinae plane block with pectoralis nerve block and paravertebral block showed that its analgesic efficacy was inferior to pectoralis nerve block and similar to paravertebral block. The incidence of pneumothorax was 2.6% in the paravertebral block group; there were no reports of complications of the other blocks. This review has shown that the erector spinae plane block is more effective at reducing postoperative opioid consumption and pain scores up to 24 hours compared with general anaesthesia alone. However, it was inferior to the pectoralis nerve block and its efficacy was similar to paravertebral block. Further evidence, preferably from properly blinded trials, is required to confirm these findings.

Poor sleep is associated with higher blood pressure and uterine artery pulsatility index in pregnancy: a prospective cohort study.

OBJECTIVE: To elucidate the association between sleep disturbances and blood pressure as well as uterine artery Doppler during pregnancy in women with no pre-existing hypertension. DESIGN: Prospective cohort study. SETTING: Outpatient specialist clinics at KK Women's and Children's Hospital, Singapore. POPULATION: Women with viable singleton pregnancies confirmed by ultrasonography at less than 14 weeks of amenorrhoea at first visit. METHODS: In all, 926 subjects were recruited for this study in the outpatient specialist clinics at KK Women's and Children's Hospital, Singapore, between 1 September 2010 and 31 August 2014. They were followed up throughout pregnancy with sleep quality, blood pressure and uterine artery Doppler assessed at each visit. MAIN OUTCOME MEASURES: Sleep quality, blood pressure and uterine artery Doppler. RESULTS: Sleep progressively worsened as pregnancy advanced. Shorter sleep duration and poorer sleep efficiency were associated with higher blood pressure, especially in the first trimester. Mixed model analysis demonstrated an overall positive association between sleep quality represented by Pittsburgh Sleep Quality Index (PSQI) score and diastolic blood pressure (DBP) (P < 0.001) and mean arterial pressure (MAP) (P = 0.005) during pregnancy after considering all trimesters. Sleep duration was found to be negatively associated with both systolic blood pressure (SBP) (P = 0.029) and DBP (P = 0.002), whereas sleep efficiency was negatively correlated with DBP (P = 0.002) only. Overall poor sleep during pregnancy was also found to be associated with a higher uterine artery pulsatility index. CONCLUSION: Our prospective study demonstrated that poor sleep quality is significantly associated with higher blood pressure and uterine artery pulsatility index during pregnancy. TWEETABLE ABSTRACT: Poor sleep quality is significantly associated with higher blood pressure and higher uterine artery pulsatility index during pregnancy.

Caries Risk Prediction Models in a Medical Health Care Setting.

Despite development of new technologies for caries control, tooth decay in primary teeth remains a major global health problem. Caries risk assessment (CRA) models for toddlers and preschoolers are rare. Among them, almost all models use dental factors (e.g., past caries experience) to predict future caries risk, with limited clinical/community applicability owing to relatively uncommon dental visits compared to frequent medical visits during the first year of life. The objective of this study was to construct and evaluate risk prediction models using information easily accessible to medical practitioners to forecast caries at 2 and 3 y of age. Data were obtained from the Growing Up in Singapore Towards Healthy Outcomes (GUSTO) mother-offspring cohort. Caries was diagnosed using modified International Caries Detection and Assessment System criteria. Risk prediction models were constructed using multivariable logistic regression coupled with receiver operating characteristic analyses. Imputation was performed using multiple imputation by chained equations to assess effect of missing data. Caries rates at ages 2 y (n = 535) and 3 y (n = 721) were 17.8% and 42.9%, respectively. Risk prediction models predicting overall caries risk at 2 and 3 y demonstrated area under the curve (AUC) (95% confidence interval) of 0.81 (0.75-0.87) and 0.79 (0.74-0.84), respectively, while those predicting moderate to extensive lesions showed 0.91 (0.85-0.97) and 0.79 (0.73-0.85), respectively. Postimputation results showed reduced AUC of 0.75 (0.74-0.81) and 0.71 (0.67-0.75) at years 2 and 3, respectively, for overall caries risk, while AUC was 0.84 (0.76-0.92) and 0.75 (0.70-0.80), respectively, for moderate to extensive caries. Addition of anterior caries significantly increased AUC in all year 3 models with or without imputation (all P < 0.05). Significant predictors/protectors were identified, including ethnicity, prenatal tobacco smoke exposure, history of allergies before 12 mo, history of chronic maternal illness, maternal brushing frequency, childbearing age, and so on. Integrating oral-general health care using medical CRA models may be promising in screening caries-susceptible infants/toddlers, especially when medical professionals are trained to "lift the lip" to identify anterior caries lesions.

Recaptures of feral Bactrocera dorsalis and B. umbrosa (Diptera: Tephritidae) males after feeding on methyl eugenol.

Two major fruit fly pest species, Bactrocera dorsalis and B. umbrosa, are strongly attracted to methyl eugenol (ME) found in >450 plant species. They are, however, exclusive pollinators of certain daciniphilous (attracting Dacini fruit flies) Bulbophyllum orchids. A comparison between the recaptures of feral males after feeding ad libitum on 0.6 mg ME (simulating an average floral quantity of an orchid flower - Trial 1) and 480 mg in Trial 2 was investigated using the non-invasive capture-mark-release-recapture (CMRR) technique. Based on daily CMRR over a 16-day period, using a different colour enamel paint each day, percentages of B. dorsalis males recaptured in Trial 1 were significantly higher than those in Trial 2. However, for B. umbrosa, percentages of recaptures for different day-specific colours were highly variable due to low fly numbers captured/day. In Trial 1, of 756 B. dorsalis males released, 36.4% were recaptured once, 7.7 twice, 2.4 three times and 0.4 four times. While in Trial 2 of 1157 released males, 6% were recaptured once and 0.3% twice. Of 67 B. umbrosa males released, 28.4% were recaptured once and none more than once in Trial 1. Nevertheless, of 119 flies released in Trial 2, 25.2% were recaptured once and 3.3% twice. Overall, many marked males did return to a single ME-source to 'refuel' ME (a sex pheromone precursor). The results also show that a relatively high number of flies paid multi-visitations to a single 0.6 mg ME-source and indicate that the presence of natural ME-sources may impact area-wide IPM programmes.

Female adiposity and time-to-pregnancy: a multiethnic prospective cohort.

STUDY QUESTION: Are higher overall and central adiposity associated with reduced fecundability, measured by time-to-pregnancy (TTP), in Asian women? SUMMARY ANSWER: Higher overall adiposity, but not central adiposity, was associated with longer TTP in Asian women. WHAT IS KNOWN ALREADY: High body mass index (BMI) has been associated with a longer TTP, although the associations of body composition and distribution with TTP are less clear. There are no previous studies of TTP in Asian women, who have a relatively higher percentage of body fat and abdominal fat at relatively lower BMI. STUDY DESIGN, SIZE, DURATION: Prospective preconception cohort using data from 477 Asian (Chinese, Malay and Indian) women who were planning to conceive and enrolled in the Singapore PREconception Study of long-Term maternal and child Outcomes (S-PRESTO) study, 2015-2017. PARTICIPANTS/MATERIALS, SETTING, METHODS: Women's mean age was 30.7 years. Overall adiposity was assessed by BMI, sum of 4-site skinfold thicknesses (SFT) and total body fat percentage (TBF%, measured using air displacement plethysmography); central adiposity was assessed by waist circumference (WC), waist-to-hip ratio (WHR), waist-to-height ratio (WHtR) and A body Shape Index (ABSI). Pregnancy occurring within one year from recruitment was ascertained by ultrasonography. Those who did not conceive within one year of recruitment, were lost to follow-up, or initiated fertility treatment were censored. TTP was measured in cycles. Discrete-time proportional hazards models were used to estimate the fecundability ratio (FR) and 95% confidence interval (CI) for each anthropometric measure in association with fecundability, adjusting for confounders. MAIN RESULTS AND THE ROLE OF CHANCE: Compared to women with a normal BMI of 18.5-22.9 kg/m2, women with higher BMI of 23-27.4 and ≥27.5 kg/m2 showed lower FR of 0.66 (95% CI 0.45, 0.97) and 0.53 (0.31, 0.89), respectively. Compared to women in the lowest quartile of SFT (25-52.9 mm), those in the highest quartile of ≥90.1 mm showed lower FR of 0.58 (95% CI 0.36, 0.95). Compared to women in the lowest quartile of TBF% (13.6-27.2%), those in the upper two quartiles of 33.0-39.7% and ≥39.8% showed lower FR of 0.56 (95% CI 0.32, 0.98) and 0.43 (0.24, 0.80), respectively. Association of high BMI with reduced fecundability was particularly evident among nulliparous women. Measures of central adiposity (WC, WHR, WHtR, ABSI) were not associated with fecundability. LIMITATIONS REASONS FOR CAUTION: Small sample size could restrict power of analysis.The analysis was confined to planned pregnancies, which could limit generalizability of findings to non-planned pregnancies, estimated at around 44% in Singapore. Information on the date of last menstrual period for each month was not available, hence the accuracy of self-reported menstrual cycle length could not be validated, potentially introducing error into TTP estimation. Measures of exposures and covariates such as cycle length were not performed repeatedly over time; cycle length might have changed during the period before getting pregnant. WIDER IMPLICATIONS OF THE FINDINGS: Other than using BMI as the surrogate measure of body fat, we provide additional evidence showing that higher amounts of subcutaneous fat that based on the measure of SFT at the sites of biceps, triceps, suprailiac and subscapular, and TBF% are associated with longer TTP. Achieving optimal weight and reducing total percentage body fat may be a potential intervention target to improve female fertility. The null results observed between central adiposity and TTP requires confirmation in further studies. STUDY FUNDING/COMPETING INTEREST(S): This research is supported by Singapore National Research Foundation under its Translational and Clinical Research Flagship Programme and administered by the Singapore Ministry of Health's National Medical Research Council, (NMRC/TCR/004-NUS/2008; NMRC/TCR/012-NUHS/2014). Additional funding is provided by the Singapore Institute for Clinical Sciences, Agency for Science Technology and Research (A*STAR), Singapore. Y.S.C., K.M.G., F.Y. and Y.S.L. have received reimbursement to speak at conferences sponsored by companies selling nutritional products. Y.S.C., K.M.G. and S.Y.C. are part of an academic consortium that has received research funding from Abbott, Nutrition, Nestle and Danone. Other authors declared no conflicts of interest. TRIAL REGISTRATION NUMBER: N/A.

Child, Maternal and Demographic Factors Influencing Caregiver-Reported Autistic Trait Symptomatology in Toddlers.

Current research on children's autistic traits in the general population relies predominantly on caregiver-report, yet the extent to which individual, caregiver or demographic characteristics are associated with informants' ratings has not been sufficiently explored. In this study, caregivers of 396 Singaporean two-year-olds from a birth cohort study completed the Quantitative Checklist for Autism in Toddlers. Children's gender, cognitive functioning and birth order, maternal age, and ethnic group membership were not significant predictors of caregiver-reported autistic traits. Poorer child language development and higher maternal depressive symptoms significantly predicted more social-communicative autistic traits, while lower maternal education predicted more behavioural autistic traits. Children's language and informants' educational level and depressive symptomatology may need to be considered in caregiver-reports of autistic traits.

Which anthropometric measures best reflect neonatal adiposity?

BACKGROUND: Studying the determinants and the long-term consequences of fetal adipose accretion requires accurate assessment of neonatal body composition. In large epidemiological studies, in-depth body composition measurement methods are usually not feasible for cost and logistical reasons, and there is a need to identify anthropometric measures that adequately reflect neonatal adiposity. METHODS: In a multiethnic Asian mother-offspring cohort in Singapore, anthropometric measures (weight, length, abdominal circumference, skinfold thicknesses) were measured using standardized protocols in newborn infants, and anthropometric indices (weight/length, weight/length2 (body mass index, BMI), weight/length3 (ponderal index, PI)) derived. Neonatal total adiposity was measured using air displacement plethysmography (ADP) and abdominal adiposity using magnetic resonance imaging (MRI). Correlations of the anthropometric measures with ADP- and MRI-based adiposity were assessed using Pearson's correlation coefficients (rp), including in subsamples stratified by sex and ethnicity. RESULTS: Study neonates (n=251) had a mean (s.d.) age of 10.2 (2.5) days. Correlations between ADP-based fat mass (ADPFM) and anthropometric measures were moderate (rp range: 0.44-0.67), with the strongest being with weight/length, weight, BMI and sum of skinfolds (rp=0.67, 0.66, 0.62, 0.62, respectively, all P<0.01). All anthropometric measures except skinfold thicknesses correlated more strongly with ADP-based fat-free mass than ADPFM, indicating that skinfold measures may have more discriminative power in terms of neonatal total body adiposity. For MRI-based measures, weight and weight/length consistently showed strong positive correlations (rp⩾0.7) with abdominal adipose tissue compartments. These correlations were consistent in boys and girls, across different ethnic groups, and when conventional determinants of neonatal adiposity were adjusted for potential confounding. Abdominal circumference was not strongly associated with ADPFM or abdominal fat mass. CONCLUSIONS: Simple anthropometric measures (weight and weight/length) correlated strongly with neonatal adiposity, with some evidence for greater discriminative power for skinfold measures. These simple measures could be of value in large epidemiological studies.

Body composition measurement in young children using quantitative magnetic resonance: a comparison with air displacement plethysmography.

BACKGROUND: Quantitative magnetic resonance (QMR) has been increasingly used to measure human body composition, but its use and validation in children is limited. OBJECTIVE: We compared body composition measurement by QMR and air displacement plethysmography (ADP) in preschool children from Singapore's multi-ethnic Asian population (n = 152; mean ± SD age: 5.0 ± 0.1 years). METHODS: Agreements between QMR-based and ADP-based fat mass and fat mass index (FMI) were assessed using intraclass correlation coefficient (ICC), reduced major axis regression and Bland-Altman plot analyses. Analyses were stratified for the child's sex. RESULTS: Substantial agreement was observed between QMR-based and ADP-based fat mass (ICC: 0.85) and FMI (ICC: 0.82). Reduced major axis regression analysis suggested that QMR measurements were generally lower than ADP measurements. Bland-Altman analysis similarly revealed that QMR-based fat mass were (mean difference [95% limits of agreement]) -0.5 (-2.1 to +1.1) kg lower than ADP-based fat mass and QMR-based FMI were -0.4 (-1.8 to +0.9) kg/m2 lower than ADP-based FMI. Stratification by offspring sex revealed better agreement of QMR and ADP measurements in girls than in boys. CONCLUSIONS: QMR-based fat mass and FMI showed substantial agreement with, but was generally lower than, ADP-based measures in young Asian children.

Hyperbaric vs. isobaric bupivacaine for spinal anaesthesia for elective caesarean section: a Cochrane systematic review.

Both isobaric and hyperbaric bupivacaine have been used for spinal anaesthesia for elective caesarean section, but it is not clear if one is better than the other. The primary objective of this systematic review was to determine the effectiveness and safety of hyperbaric bupivacaine compared with isobaric bupivacaine administered during spinal anaesthesia for elective caesarean section. We included 10 studies with 614 subjects in the analysis. There was no evidence of differences either in the risk of conversion to general anaesthesia, with a relative risk (95%CI) of 0.33 (0.09-1.17) (very low quality of evidence), or in the need for supplemental analgesia, the relative risk (95%CI) being 0.61 (0.26-1.41) (very low quality of evidence). There was also no evidence of a difference in the use of ephedrine, the amount of ephedrine used, nausea and vomiting, or headache. Hyperbaric bupivacaine took less time to reach a sensory block height of T4, with a mean difference (95%CI) of -1.06 min (-1.80 to -0.31). Due to the rarity of some outcomes, dose variability, use of adjuvant drugs and spinal technique used, future clinical trials should look into using adequate sample size to investigate the primary outcome of the need for supplemental analgesia.

Maternal hyperglycemia in singleton pregnancies conceived by IVF may be modified by first-trimester BMI.

STUDY QUESTION: Does IVF independently increase the risk of gestational diabetes mellitus (GDM) and is this increase in risk modified by maternal body mass index? SUMMARY ANSWER: IVF appears to be an independent risk factor for GDM and elevated blood glucose levels in overweight women (BMI > 25 kg/m2). WHAT IS KNOWN ALREADY: IVF has been associated with increased risk of GDM, but most previous studies did not adequately assess confounding or effect modification by other risk factors. STUDY DESIGN, SIZE, DURATION: Cross-sectional study using data from 1089 women with singleton pregnancies who participated in a Singaporean birth cohort study (GUSTO) and received a 75 g oral glucose tolerance test (OGTT) at 26-28 weeks gestation. PARTICIPANTS/MATERIALS, SETTING, METHODS: A total of 1089 women (n = 1013 conceived spontaneously, n = 76 conceived through IVF) with singleton pregnancies received a 75 g OGTT at 26-28 weeks gestation. Fasting and 2 h postprandial blood glucose levels were assayed. World Health Organization criteria (1999) standard criteria were used to classify GDM: ≥7.0 mmol/L for fasting and/or ≥7.8 mmol/L for 2-h postprandial plasma glucose levels, which was the clinical guideline in use during the study. MAIN RESULTS AND THE ROLE OF CHANCE: IVF pregnancies had nearly double the odds of GDM (OR = 1.83, 95% CI: 1.03-3.26) and elevated fasting (mean difference = 0.12 mmol/L, 95% CI: 0.00-0.24) and OGTT 2-h blood glucose levels (mean difference = 0.64 mmol/L, 95% CI: 0.27-1.01), after adjusting for commonly recognized risk factors for GDM. After stratification by first-trimester BMI, these increased risks of GDM (OR = 3.54, 95% CI: 1.44-8.72) and elevated fasting (mean difference = 0.39 mmol/L, 95% CI: 0.13-0.65) and 2-h blood (mean difference = 1.24 mmol/L, 95% CI: 0.56-1.91) glucose levels were significant only in the IVF group who is also overweight or obese (BMI > 25 kg/m2). LIMITATIONS REASONS FOR CAUTION: One limitation of our study is the absence of a 1 h post-OGTT plasma glucose sample, as we were using the 1999 WHO diagnostic criteria (the clinical guideline in Singapore) at the time of our study, instead of the revised 2013 WHO diagnostic criteria. Our cohort may not be representative of the general Singapore obstetric population, although participants were recruited from the two largest maternity hospitals in the country and include both private and subsidized patients. WIDER IMPLICATIONS OF THE FINDINGS: IVF appears to be an independent risk factor for GDM and elevated blood glucose levels in overweight women. Our findings reinforce the need to advise overweight or obese women contemplating IVF to lose weight before the procedure to reduce their risk of GDM and hyperglycemia-related adverse outcomes arising therefrom. In settings where universal GDM screening is not routine, overweight or obese women who conceive by IVF should be screened. STUDY FUNDING/COMPETING INTEREST(S): This research was supported by the Singapore National Research Foundation under its Translational and Clinical Research (TCR) Flagship Program and administered by the Singapore Ministry of Health's National Medical Research Council (NMRC), Singapore (NMRC/TCR/004-NUS/2008; NMRC/TCR/012-NUHS/2014). Additional funding was provided by the Singapore Institute for Clinical Sciences, Agency for Science, Technology and Research (A*STAR). K.M.G. and Y.S.C. have received lecture fees from Nestle Nutrition Institute and Danone, respectively. K.M.G., Y.S.C. and S.Y.C. are part of an academic consortium that has received research funding from Abbott Nutrition, Nestec and Danone. The other authors have nothing to disclose. The other authors have nothing to disclose. TRIAL REGISTRATION NUMBER: N/A.

Sterilization of rotary NiTi instruments within endodontic sponges.

AIM: To determine whether the following can be sterilized by autoclaving - endodontic sponges, rotary nickel-titanium (NiTi) instruments within endodontic sponges, and rotary NiTi instruments with rubber stoppers. METHODOLOGY: Sixty-four samples of eight different endodontic sponges (n = 512) were placed into brain heart infusion broth (BHI) for 72 h. An aliquot of this was then spread onto horse blood agar and cultured aerobically and anaerobically to test sterility at purchase. Bacterial suspensions of Enterococcus faecalis, Porphyromonas gingivalis and Geobacillus stearothermophilus in BHI were used to contaminate sterile sponges and rotary NiTi instruments (with and without rubber stoppers) inserted into sponges. The various samples were autoclaved and then cultured aerobically and anaerobically. Success of sterilization was measured qualitatively as no growth. The experiment was repeated with clinically used rotary NiTi instruments (n = 512). All experiments were conducted in quadruplicate. RESULTS: No sponges on purchase had microbial growth when anaerobically cultured but some did when aerobically cultured. All autoclaved sponges and instruments (within or without sponges, and with or without rubber stoppers) were associated with no microbial growth. All nonautoclaved positive control samples showed microbial growth. CONCLUSIONS: Autoclaving was effective in the sterilization of sponges and endodontic instruments. Endodontic sponges should be autoclaved before clinical use. For clinical efficiency and cost-effectiveness, rotary NiTi instruments can be sterilized in endodontic sponges without removal of rubber stoppers.

Heart failure with preserved ejection fraction in women: the Dutch Queen of Hearts program.

Heart failure (HF) poses a heavy burden on patients, their families and society. The syndrome of HF comes in two types: with reduced ejection fraction (HFrEF) and preserved ejection fraction (HFpEF). The latter is on the increase and predominantly present in women, especially the older ones. There is an urgent need for mortality-reducing drugs in HFpEF, a disease affecting around 5 % of those aged 65 years and over. HFpEF develops in patients with risk factors and comorbidities such as obesity, hypertension, diabetes, COPD, but also preeclampsia. These conditions are likely to drive microvascular disease with involvement of the coronary microvasculature, which may eventually evolve into HFpEF. Currently, the diagnosis of HFPEF relies mainly on echocardiography. There are no biomarkers that can help diagnose female microvascular disease or facilitate the diagnosis of (early stages of) HFpEF. Recently a Dutch consortium was initiated, Queen of Hearts, with support from the Netherlands Heart Foundation, with the aim to discover and validate biomarkers for diastolic dysfunction and HFpEF in women. These biomarkers come from innovative blood-derived sources such as extracellular vesicles and circulating cells. Within the Queen of Hearts consortium, we will pursue female biomarkers that have the potential for further evolution in assays with point of care capabilities. As a spin-off, the consortium will gain knowledge on gender-specific pathology of HFpEF, possibly opening up novel treatment options.

Quantifying the natural history of breast cancer.

BACKGROUND: Natural history models of breast cancer progression provide an opportunity to evaluate and identify optimal screening scenarios. This paper describes a detailed Markov model characterising breast cancer tumour progression. METHODS: Breast cancer is modelled by a 13-state continuous-time Markov model. The model differentiates between indolent and aggressive ductal carcinomas in situ tumours, and aggressive tumours of different sizes. We compared such aggressive cancers, that is, which are non-indolent, to those which are non-growing and regressing. Model input parameters and structure were informed by the 1978-1984 Ostergotland county breast screening randomised controlled trial. Overlaid on the natural history model is the effect of screening on diagnosis. Parameters were estimated using Bayesian methods. Markov chain Monte Carlo integration was used to sample the resulting posterior distribution. RESULTS: The breast cancer incidence rate in the Ostergotland population was 21 (95% CI: 17-25) per 10 000 woman-years. Accounting for length-biased sampling, an estimated 91% (95% CI: 85-97%) of breast cancers were aggressive. Larger tumours, 21-50 mm, had an average sojourn of 6 years (95% CI: 3-16 years), whereas aggressive ductal carcinomas in situ took around half a month (95% CI: 0-1 month) to progress to the invasive ≤10 mm state. CONCLUSION: These tumour progression rate estimates may facilitate future work analysing cost-effectiveness and quality-adjusted life years for various screening strategies.

Virulence factors of the oral spirochete Treponema denticola.

There is compelling evidence that treponemes are involved in the etiology of several chronic diseases, including chronic periodontitis as well as other forms of periodontal disease. There are interesting parallels with other chronic diseases caused by treponemes that may indicate similar virulence characteristics. Chronic periodontitis is a polymicrobial disease, and recent animal studies indicate that co-infection of Treponema denticola with other periodontal pathogens can enhance alveolar bone resorption. The bacterium has a suite of molecular determinants that could enable it to cause tissue damage and subvert the host immune response. In addition to this, it has several non-classic virulence determinants that enable it to interact with other pathogenic bacteria and the host in ways that are likely to promote disease progression. Recent advances, especially in molecular-based methodologies, have greatly improved our knowledge of this bacterium and its role in disease.

Markedly-elevated serum CA125 in a woman with pulmonary tuberculosis.

A 26-year-old Chinese woman first presented to the Singapore Anti-Tuberculosis Association with fever and cough, and was diagnosed with pulmonary tuberculosis. She was then referred to KK Women's & Children's Hospital to exclude a gynaecological pathology when she was found to have abnormally high levels of cancer antigen CA125 in a health screening done concomitantly. Pelvic examination and pelvic ultrasonography were normal. Other tumour markers (CA19-9, CEA, AFP and BHCG) were normal. The level of CA125 was monitored and returned to normal levels with anti-tuberculosis treatment. A non-gynaecological diagnosis like pulmonary tuberculosis must always be considered as one of a differential diagnosis in a woman presenting with a markedly-raised CA125.