Sputum mast cell/basophil gene expression relates to inflammatory and clinical features of severe asthma.

BACKGROUND: Mast cells (MCs) and basophils are important in asthma pathophysiology, however direct measurement is difficult, and clinical and inflammatory associations in severe asthma are poorly understood. Transcriptomic hallmarks of MCs/basophils may allow their measurement in sputum using gene expression. OBJECTIVES: This study sought to develop and validate a sputum MC/basophil gene signature and investigate its relationship to inflammatory and clinical characteristics of severe asthma. METHODS: A total of 134 candidate MC/basophil genes (identified by the Immunological Genome Project Consortium) were screened in sputum microarray for differential expression among control subjects (n = 18), patients with eosinophilic (n = 29), and patients with noneosinophilic asthma (n = 30). Candidate genes were validated by confirming correlation of gene expression with flow cytometry-quantified sputum MCs and basophils in a separate asthma cohort (n = 20). The validated gene signature was measured in a severe asthma cohort (n = 81), and inflammatory and clinical associations were tested. RESULTS: Through microarray screening and subsequent validation, we found quantitative PCR gene expression of 8 targets correlated with sputum MCs/basophils: TPSAB1/TPSB2, CPA3, ENO2, GATA2, KIT, GPR56, HDC, SOCS2. In severe asthma, MC/basophil genes were associated with eosinophilic airway inflammation (GATA2, TPSB2, CPA3, GPR56, HDC, SOCS2), blood eosinophils (TPSB2, CPA3, GATA2, SOCS2, FCER1A, HDC), fractional exhaled NO (GATA2, SOCS2), decreased lung function (KIT, ENO2), and moderate exacerbation history (GATA2, SOCS2). CONCLUSIONS: Quantitative PCR-based measures reflect varying sputum MC/basophil abundance, demonstrating associations of MCs/basophils with eosinophilic inflammation, spirometry and exacerbation history in severe asthma.

Impact of Perinatal Depression and Anxiety on Birth Outcomes: A Retrospective Data Analysis.

OBJECTIVES: During the perinatal period, 10-20% of women experience anxiety and/or depression. Untreated perinatal depression has the potential for adverse effects on the family and infant resulting in long-term deleterious consequences. This study measured the association between self-reported depression using the Edinburgh Postnatal Depression Scale scores, self-reported anxiety and neonatal birth outcomes. METHODS: A retrospective design was used with ObstetriX™ data retrieved from 16 metropolitan and rural hospitals in NSW, Australia during 2009-2014. Data were available for 53,646 singleton births. The Edinburgh Postnatal Depression Scale was used to identify self-reported depression while women self-reported pregnancy related anxiety. Regression modelling measured the effects of self-reported depression and self-reported pregnancy related anxiety on neonatal birth outcomes. Linear regression and logistic regression were used to model the effect on birth weight, gestational age, admission to NICU or the SCN, outcome (stillborn vs livebirth), and Apgar scores. Cox proportional hazards regression was used to estimate the effect on neonatal length of stay. RESULTS: Babies born to women self-reporting anxiety were more likely to have birth complications, be admitted to the nursery, had lower Apgar scores and longer hospital stays. Babies born to women self-identifying as experiencing a level of depression were more likely to have a lower birth weight, shorter gestational age, and, lower Apgar score. These babies were more likely to be admitted to the nursery with an increased length of stay. CONCLUSIONS: Perinatal anxiety and depression contribute to poor birth outcomes. Early detection of maternal perinatal anxiety and depression is an important step towards treatment interventions. More research is needed to identify models of care that are effective in identifying and managing perinatal depression and anxiety to improve birth outcomes for women and their babies.

Medical oncology outpatients' preferences and experiences with advanced care planning: a cross-sectional study.

BACKGROUND: Medical oncology outpatients are a group for whom advance care planning (ACP) activities are particularly relevant. Patient views can help prioritise areas for improving end of life communication. The study aimed to determine in a sample of medical oncology outpatients: (1) the perceived importance of participating in ACP activities; (2) the proportion of patients who have ever participated in ACP activities; and (3) the proportion of patients who had not yet participated in ACP activities who were willing to do so in next month. METHODS: Adult medical oncology outpatients in two Australian cancer treatment centres were consecutively approached to complete a pen-and-paper survey. Items explored perceived importance, previous participation, and willingness to participate across key ACP activities including: discussing wishes with their family or doctor; recording wishes in a written document; appointing a substitute decision maker (SDM); and discussing life-expectancy. RESULTS: 185 participants completed the survey (51% consent rate). Most patients agreed it was important to: discuss end of life wishes with family (85%) and doctors (70%) and formally record wishes (73%). Few had discussed end of life wishes with a doctor (11%), recorded their wishes (15%); chosen a SDM (28%); discussed life expectancy (30%); or discussed end of life wishes with family (30%). Among those who had not participated in ACP, most were willing to discuss life expectancy (66%); discuss end of life wishes with family (57%) and a doctor (55%); and formally record wishes (56%) in the next month. Fewer wanted to appoint a SDM (40%). CONCLUSION: Although medical oncology outpatients perceive ACP activities are important, rates of uptake are relatively low. The willingness of many patients to engage in ACP activities suggests a gap in current ACP practice. Efforts should focus on ensuring patients and families have clarity about the legal and other ramifications of ACP activities, and better education and training of health care providers in initiating conversations about end of life issues.

A case for not adjusting birthweight customized standards for ethnicity: observations from a unique Australian cohort.

BACKGROUND: Low birthweight is more common in infants of indigenous (Aboriginal and/or Torres Strait Islander) than of White Australian mothers. Controversy exists on whether fetal growth is normally different in different populations. OBJECTIVE: We sought to determine the relationships of birthweight, birthweight percentiles, and smoking with perinatal outcomes in indigenous vs nonindigenous infants to determine whether the White infant growth charts could be applied to indigenous infants. STUDY DESIGN: Data were analyzed for indigenous status, maternal age and smoking, and perinatal outcomes in 45,754 singleton liveborn infants of at least 20 weeks gestation or 400 g birthweight delivered in New South Wales, Australia, between June 2010 and July 2015. RESULTS: Indigenous infants (n=6372; 14%) had a mean birthweight 67 g lower than nonindigenous infants (P<.0001; with adjustment for infant sex and maternal body mass index). Indigenous mean birthweight percentile was 4.2 units lower (P<.0001). Adjustment for maternal age, smoking, body mass index, and infant sex reduced the difference in birthweight/percentiles to nonsignificance (12 g; P=.07). CONCLUSION: Disparities exist between indigenous and non-indigenous Australian infants for birthweight, birthweight percentile, and adverse outcome rates. Adjustment for smoking and maternal age removed any significant difference in birthweights and birthweight percentiles for indigenous infants. Our data indicate that birthweight percentiles should not be adjusted for indigenous ethnicity because this normalizes disadvantage; because White and indigenous Australians have diverged for approximately 50,000 years, it is likely that the same conclusions apply to other ethnic groups. The disparities in birthweight percentiles that are associated with smoking will likely perpetuate indigenous disadvantage into the future because low birthweight is linked to the development of chronic noncommunicable disease and poorer educational attainment; similar problems may affect other indigenous populations.

Development and Validation of the MiPrep Survey: An Instrument Assessing Patients' Perceived Preparation for Medical Interventions Including Medical Imaging, Radiotherapy, and Surgery.

BACKGROUND: Adequately preparing patients for medical interventions is an important component of quality healthcare. Nevertheless, few instruments for assessing patients' preparation exist. OBJECTIVES: To develop a psychometrically rigorous instrument to assess patients' perceptions of the quality of preparation. METHODS: An instrument to measure patients' preparation for medical interventions (MiPrep) was developed and tested with patients undergoing medical imaging, radiotherapy, or surgery. Patients were recruited and asked to complete 2 surveys. Survey A assessed patient and intervention characteristics. Survey B (postintervention) contained MiPrep to assess validity (face, content, and construct) and reliability (internal consistency and test-retest). RESULTS: A total of 869 (85%) patients consented to participate and 551 (63%) returned the postintervention survey. Face and content validity were demonstrated. Exploratory factor analysis identified 2 survey modules: receipt and adequacy of information (2 domains) and overall appraisal of patient-centered care (1 domain). Reliability was evidenced by adequate internal consistency (Cronbach α 0.81-0.89) and item-total correlations higher than 0.20. Nevertheless, individual item test-retest reliability requires further confirmation. The final instrument contained 27 items. CONCLUSIONS: The MiPrep instrument has evidence of being a valid and reliable instrument of preparation for medical interventions. Healthcare providers can use the instrument as a quality assurance tool to identify areas for improvement and areas of excellence in patients' preparation. Future studies should verify these findings in other populations and examine the divergent and predictive validity of the instrument.

Evaluating recruitment strategies for AUSPICE, a large Australian community-based randomised controlled trial.

OBJECTIVES: To examine the effectiveness of different strategies for recruiting participants for a large Australian randomised controlled trial (RCT), the Australian Study for the Prevention through Immunisation of Cardiovascular Events (AUSPICE). DESIGN, SETTING, PARTICIPANTS: Men and women aged 55-60 years with at least two cardiovascular risk factors (hypertension, hypercholesterolaemia, overweight/obesity) were recruited for a multicentre placebo-controlled RCT assessing the effectiveness of 23-valent pneumococcal polysaccharide vaccine (23vPPV) for preventing cardiovascular events. METHODS: Invitations were mailed by the Australian Department of Human Services to people in the Medicare database aged 55-60 years; reminders were sent 2 weeks later. Invitees could respond in hard copy or electronically. Direct recruitment was supplemented by asking invitees to extend the invitation to friends and family (snowball sampling) and by Facebook advertising. MAIN OUTCOME: Proportions of invitees completing screening questionnaire and recruited for participation in the RCT. RESULTS: 21 526 of 154 992 invited people (14%) responded by completing the screening questionnaire, of whom 4725 people were eligible and recruited for the study. Despite the minimal study burden (one questionnaire, one clinic visit), the overall participation rate was 3%, or an estimated 10% of eligible persons. Only 16% of eventual participants had responded within 2 weeks of the initial invitation letter (early responders); early and late responders did not differ in their demographic or medical characteristics. Socio-economic disadvantage did not markedly influence response rates. Facebook advertising and snowball sampling did not increase recruitment. CONCLUSIONS: Trial participation rates are low, and multiple concurrent methods are needed to maximise recruitment. Social media strategies may not be successful in older age groups. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry, ACTRN12615000536561.

Can models of self-management support be adapted across cancer types? A comparison of unmet self-management needs for patients with breast or colorectal cancer.

PURPOSE: There is an increased focus on supporting patients with cancer to actively participate in their healthcare, an approach commonly termed 'self-management'. Comparing unmet self-management needs across cancer types may reveal opportunities to adapt effective self-management support strategies from one cancer type to another. Given that breast and colorectal cancers are prevalent, and have high survival rates, we compared these patients' recent need for help with self-management. METHOD: Data on multiple aspects of self-management were collected from 717 patients with breast cancer and 336 patients with colorectal cancer attending one of 13 Australian medical oncology treatment centres. RESULTS: There was no significant difference between the proportion of patients with breast or colorectal cancer who reported a need for help with at least one aspect of self-management. Patients with breast cancer were significantly more likely to report needing help with exercising more, while patients with colorectal cancer were more likely to report needing help with reducing alcohol consumption. When controlling for treatment centre, patients who were younger, experiencing distress or had not received chemotherapy were more likely to report needing help with at least one aspect of self-management. CONCLUSIONS: A substantial minority of patients reported an unmet need for self-management support. This indicates that high-quality intervention research is needed to identify effective self-management support strategies, as well as implementation trials to identify approaches to translating these strategies into practice. Future research should continue to explore whether self-management support strategies could be adapted across cancer types.

What is a 'timely' diagnosis? Exploring the preferences of Australian health service consumers regarding when a diagnosis of dementia should be disclosed.

BACKGROUND: Recently the dementia field has shifted focus away from the early diagnosis debate in favour of 'timely' diagnosis. 'Timely' diagnosis disclosure takes into consideration the preferences and unique circumstances of the individual. Determining when diagnosis disclosure is 'timely' may be particularly complex if there are differing views between the individual, their family, and their health care providers regarding disclosure. This study explores the preferences of consumers regarding when a diagnosis of dementia should be communicated. METHODS: A cross-sectional survey was conducted with English-speaking adults attending outpatient clinics at an Australian hospital. Participants were recruited by a research assistant in the clinic waiting room and invited to complete the survey on a web-connected iPad. The survey included questions examining socio-demographics and experience with dementia. Two scenarios were used to explore preferences for timing of diagnosis disclosure. RESULTS: Of 446 participants, 92% preferred a diagnosis of dementia to be disclosed as soon as possible. Preferences were not associated with socio-demographics or previous dementia experience. Most participants also preferred disclosure to occur as soon as possible if their spouse or partner was diagnosed with dementia (88%). There was strong correlation between preferences for self and preferences for spouse (0.91). CONCLUSIONS: These findings provide guidance to health care providers about preferences for disclosure of a dementia diagnosis, and may help to overcome potential barriers to timely diagnosis. As the prevalence of dementia increases, consumers' preference for diagnosis to occur as soon as possible has important implications for the health system.

Mortality and Readmission Following Hospitalisation for Heart Failure in Australia: A Systematic Review and Meta-Analysis.

BACKGROUND: Heart failure (HF) is a common, costly condition with an increasing burden on Australian health care system resources. Knowledge of the burden of HF on patients and on the health system is important for resource allocation. This study is the first systematic review to estimate the mortality and readmission rates after hospitalisation for HF in the Australian population. METHODS: We searched for studies of HF hospitalisation in Australia published between January 1990 and May 2016, using a systematic search of PubMed, Medline, Scopus, Web of Science, EMBASE and Cochrane Library databases. Studies reporting 30-day and/or 1-year outcomes for mortality or readmission following hospitalisation were eligible and included in this study. RESULTS: Out of 2889 articles matching the initial search criteria, a total of 13 studies representing 67,255 patients were included in the final analysis. The pooled mean age of heart failure patients was 76.3 years and 51% were male (n=34,271). The pooled estimated 30-day and 1-year all-cause mortality were 8% and 25% respectively. The pooled estimated 30-day and 1-year all-cause readmission rates were 20% and 56% respectively. There is a high prevalence of comorbidities in heart failure patients. There were limited data on readmission and mortality in rural patients and Indigenous people. CONCLUSIONS: Heart failure hospitalisations in Australia are followed by substantial readmission and mortality rates.

Expanding the genetic basis of copy number variation in familial breast cancer.

INTRODUCTION: Familial breast cancer (fBC) is generally associated with an early age of diagnosis and a higher frequency of disease among family members. Over the past two decades a number of genes have been identified that are unequivocally associated with breast cancer (BC) risk but there remain a significant proportion of families that cannot be accounted for by these genes. Copy number variants (CNVs) are a form of genetic variation yet to be fully explored for their contribution to fBC. CNVs exert their effects by either being associated with whole or partial gene deletions or duplications and by interrupting epigenetic patterning thereby contributing to disease development. CNV analysis can also be used to identify new genes and loci which may be associated with disease risk. METHODS: The Affymetrix Cytogenetic Whole Genome 2.7 M (Cyto2.7 M) arrays were used to detect regions of genomic re-arrangement in a cohort of 129 fBC BRCA1/BRCA2 mutation negative patients with a young age of diagnosis (<50 years) compared to 40 unaffected healthy controls (>55 years of age). RESULTS: CNV analysis revealed the presence of 275 unique rearrangements that were not present in the control population suggestive of their involvement in BC risk. Several CNVs were found that have been previously reported as BC susceptibility genes. This included CNVs in RPA3, NBN (NBS1), MRE11A and CYP19A1 in five unrelated fBC patients suggesting that these genes are involved in BC initiation and/or progression. Of special interest was the identification of WWOX and FHIT rearrangements in three unrelated fBC patients. CONCLUSIONS: This study has identified a number of CNVs that potentially contribute to BC initiation and/or progression. The identification of CNVs that are associated with known tumour suppressor genes is of special interest that warrants further larger studies to understand their precise role in fBC.

Combined analysis of three Lynch syndrome cohorts confirms the modifying effects of 8q23.3 and 11q23.1 in MLH1 mutation carriers.

Two colorectal cancer (CRC) susceptibility loci have been found to be significantly associated with an increased risk of CRC in Dutch Lynch syndrome (LS) patients. Recently, in a combined study of Australian and Polish LS patients, only MLH1 mutation carriers were found to be at increased risk of disease. A combined analysis of the three data-sets was performed to better define this association. This cohort-study includes three sample populations combined totaling 1,352 individuals from 424 families with a molecular diagnosis of LS. Seven SNPs, from six different CRC susceptibility loci, were genotyped by both research groups and the data analyzed collectively. We identified associations at two of the six CRC susceptibility loci in MLH1 mutation carriers from the combined LS cohort: 11q23.1 (rs3802842, HR = 2.68, p ≤ 0.0001) increasing risk of CRC, and rs3802842 in a pair-wise combination with 8q23.3 (rs16892766) affecting age of diagnosis of CRC (log-rank test; p ≤ 0.0001). A significant difference in the age of diagnosis of CRC of 28 years was observed in individuals carrying three risk alleles compared to those with 0 risk alleles for the pair-wise SNP combination. A trend (due to significance threshold of p ≤ 0.0010) was observed in MLH1 mutation carriers towards an increased risk of CRC for the pair-wise combination (p = 0.002). This study confirms the role of modifier loci in LS. We consider that LS patients with MLH1 mutations would greatly benefit from additional genotyping of SNPs rs3802842 and rs16892766 for personalized risk assessment and a tailored surveillance program.

Colorectal cancer susceptibility loci on chromosome 8q23.3 and 11q23.1 as modifiers for disease expression in Lynch syndrome.

OBJECTIVE: Recently, six colorectal cancer (CRC) susceptibility loci have been identified, and two single-nucleotide polymorphisms (SNPs)--rs16892766 (8q23.3) and rs3802842 (11q23.1)--from two of these regions have been found to be significantly associated with an increased CRC risk in patients with Lynch syndrome. The objective of this study was to genotype nine SNPs within these six loci to confirm previous findings and investigate whether they act as modifiers of disease risk in patients with Lynch syndrome. DESIGN: The patient cohort consisted of 684 mutation-positive patients with Lynch syndrome from 298 Australian and Polish families. Nine SNPs were genotyped: rs16892766 (8q23.3), rs7014346 and rs6983267 (8q24.21), rs10795668 (10p14), rs3802842 (11q23.1), rs10318 and rs4779584 (15q13.3), and rs4939827 and rs4464148 (18q21.1). The data were analysed to investigate possible associations between the presence of variant alleles and the risk of developing disease. RESULTS: An association between SNP rs3802842 on chromosome 11q23.1 and rs16892766 on chromosome 8q23.3 and the risk of developing CRC and age of diagnosis was found in MLH1 mutation carriers. Female MLH1 mutation carriers harbouring the homozygous variant genotype for SNP rs3802842 have the highest risk of developing CRC. When the number of risk alleles for the two SNPs combined was analysed, a difference of 24 years was detected between individuals carrying three risk alleles and those carrying no risk alleles. CONCLUSION: The authors were able to replicate the association between the CRC susceptibility loci on chromosomes 8q23.3 and 11q23 and the risk of developing CRC in patients with Lynch syndrome, but the association could only be detected in MLH1 mutation carriers in this study.

Prevalence and Correlates of Water, Sanitation, and Hygiene (WASH) and Spatial Distribution of Unimproved WASH in Nepal.

This study aims to estimate the prevalence and correlation of household levels of water, sanitation, and hygiene (WASH), including the identification of areas where WASH facilities are unimproved in Nepal. The study population was 11,040 household heads, using the data collected in the Nepal Demographic and Health Survey 2016. Logistic regression analysis was performed and crude odds ratios (OR) with 95% confidence intervals (CI) using a 0.05 significance level are presented. Getis-Ord Gi* statistics were used to identify the hot and cold spot areas of unimproved WASH. GPS locations of WASH points were used for spatial analysis. Approximately 95% of households had an improved water source, 84% had improved sanitation facilities, 81% had a fixed place for handwashing, and 47% had soap and water. Education, wealth, and ecology were significantly associated with WASH. The people from the hills were less likely to have an improved water source (OR = 0.32; 95% CI: 0.16-0.64) than those from the plain. Households with a poor wealth index had 78% lower odds of having an improved water source compared to households with a rich wealth index. Respondents from Madhes Province had lower odds (OR = 0.15; 95% CI: 0.08-0.28) and Gandaki Pradesh had the highest odds (OR = 2.92; 95% CI: 1.52-5.61) of having improved sanitation facilities compared to Province 1. Respondents aged 35-44 years had higher odds (OR = 1.16; 95% CI: 1.04-1.29) of having soap and water available compared to those aged 45 years and older. Education and geographical disparities were the factors associated with having reduced access to WASH. These findings suggest the need to focus on advocacy, services, and policy approaches.

Generation of cardio-protective antibodies after pneumococcal polysaccharide vaccine: Early results from a randomised controlled trial.

BACKGROUND AND AIMS: Observational studies have demonstrated that the pneumococcal polysaccharide vaccine (PPV) is associated with reduced risk of cardiovascular events. This may be mediated through IgM antibodies to OxLDL, which have previously been associated with cardioprotective effects. The Australian Study for the Prevention through Immunisation of Cardiovascular Events (AUSPICE) is a double-blind, randomised controlled trial (RCT) of PPV in preventing ischaemic events. Participants received PPV or placebo once at baseline and are being followed-up for incident fatal and non-fatal myocardial infarction or stroke over 6 years. METHODS: A subgroup of participants at one centre (Canberra; n = 1,001) were evaluated at 1 month and 2 years post immunisation for changes in surrogate markers of atherosclerosis, as pre-specified secondary outcomes: high-sensitive C-reactive protein (CRP), pulse wave velocity (PWV), and carotid intima-media thickness (CIMT). In addition, 100 participants were randomly selected in each of the intervention and control groups for measurement of anti-pneumococcal antibodies (IgG, IgG2, IgM) as well as anti-OxLDL antibodies (IgG and IgM to CuOxLDL, MDA-LDL, and PC-KLH). RESULTS: Concentrations of anti-pneumococcal IgG and IgG2 increased and remained high at 2 years in the PPV group compared to the placebo group, while IgM increased and then declined, but remained detectable, at 2 years. There were statistically significant increases in all anti-OxLDL IgM antibodies at 1 month, which were no longer detectable at 2 years; there was no increase in anti-OxLDL IgG antibodies. There were no significant changes in CRP, PWV or CIMT between the treatment groups at the 2-year follow-up. CONCLUSIONS: PPV engenders a long-lasting increase in anti-pneumococcal IgG, and to a lesser extent, IgM titres, as well as a transient increase in anti-OxLDL IgM antibodies. However, there were no detectable changes in surrogate markers of atherosclerosis at the 2-year follow-up. Long-term, prospective follow-up of clinical outcomes is continuing to assess if PPV reduces CVD events.

Perceived problems with involvement in decision making about breast cancer treatment and care: A cross-sectional study.

OBJECTIVE: To examine perceived problems with involvement in medical decision making among people with breast cancer from various phases of the cancer care trajectory. METHODS: Breast cancer outpatients (n = 663) from 13 treatment centres completed a survey of perceived involvement in treatment and care decisions in the last month, psychological distress, demographic and clinical factors. A subsample (n = 98) from three centres completed a follow-up survey on preferred and perceived treatment decision making roles. RESULTS: Overall, 112 (17 %) of 663 respondents from 13 oncology centres had experienced problems with involvement in decision making about their treatment and care in the last month, and of these, 36 (32 %) reported an unmet need for help with this problem. Elevated psychological distress was associated with 5.7 times the odds of reporting this problem and 6.6 times the odds of reporting this unmet need in the last month. Among the follow-up subsample (n = 98), 39% (n = 38) reported discordance between preferred and perceived role in a major treatment decision. Psychological distress was not associated with this outcome. CONCLUSION: Psychological distress was significantly associated with recently experiencing problems with involvement in treatment and care decisions, but not with misalignment of preferred and perceived roles in prior major treatment decisions. PRACTICE IMPLICATIONS: There is a need to maintain support for patient involvement in healthcare decisions across the cancer care continuum.

A genetic variant in telomerase reverse transcriptase (TERT) modifies cancer risk in Lynch syndrome patients harbouring pathogenic MSH2 variants.

Individuals with Lynch syndrome (LS), have an increased risk of developing cancer. Common genetic variants of telomerase reverse transcriptase (TERT) have been associated with a wide range of cancers, including colorectal cancer (CRC) in LS. We combined genotype data from 1881 LS patients, carrying pathogenic variants in MLH1, MSH2 or MSH6, for rs2075786 (G>A, intronic variant), 1207 LS patients for rs2736108 (C>T, upstream variant) and 1201 LS patients for rs7705526 (C>A, intronic variant). The risk of cancer was estimated by heterozygous/homozygous odds ratio (OR) with mixed-effects logistic regression to adjust for gene/gender/country of sample origin considering family identity. The AA genotype of SNP rs2075786 is associated with 85% higher odds at developing cancer compared to GG genotype in MSH2 pathogenic variant carriers (p = 0.0160). Kaplan-Meier analysis also shows an association for rs2075786; the AA allele for MSH2 variant carriers confers risk for earlier diagnosis of LS cancer (log-rank p = 0.0011). We report a polymorphism in TERT to be a possible modifier of disease risk in MSH2 pathogenic variant carriers. The rs2075786 SNP in TERT is associated with a differential risk of developing cancer for MSH2 pathogenic variant carriers. Use of this information has the potential to personalise screening protocols for LS patients.

Prevalence and characteristics associated with concurrent smoking and alcohol misuse within Australian general practice patients.

Objectives This study sought to determine, among a large sample of Australian general practice patients: (1) the prevalence of smoking among different levels of alcohol misuse; and (2) whether the associations between demographic characteristics and alcohol use differ according to smoking status. Methods A cross-sectional survey was administered from 2010 to 2011 to 3559 patients from 12 Australian urban general practices. Patients reported their demographic details, smoking status and their alcohol intake. Results The overall prevalence of reported concurrent smoking and alcohol misuse was 7.8%. Smokers were 3.81-fold more likely to have a higher level of alcohol consumption than non-smokers (95% confidence interval 3.13-4.63; P<0.0001). There was evidence that smoking was an effect modifier of the relationship between alcohol misuse and chronic illness. Conclusions There was an increasing prevalence of smoking with increasing level of alcohol consumption. In addition, those with chronic conditions who smoked had greater odds of higher levels of alcohol consumption. Preventative interventions for these substances are needed to reduce the burden associated with concurrent smoking and alcohol misuse. What is known about the topic? Tobacco and alcohol are the most commonly used substances and contribute to over 10million deaths annually. The risk of disease is high when using either of these substances, however, concurrent use is associated with a greatly compounded risk. Australian data is limited regarding the prevalence of concurrent tobacco and alcohol misuse, however, international studies suggest variation in prevalence rates between different clinical settings. What does this paper add? This study examined the prevalence of concurrent smoking and alcohol misuse among different levels of alcohol misuse severity within an Australian general practice setting. Additionally it explored whether the associations between demographic characteristics and alcohol use differ according to smoking status. What are the implications for practitioners? This study has important implications for disease prevention and the delivery of preventive health services by general practitioners. Considering one in 100 clinical treatments provided in general practice relate to preventative smoking or alcohol counselling, it is critical that efforts are made to ascertain risk factors such as smoking and alcohol misuse to increase treatment rates. General practitioners should consider screening for smoking and alcohol misuse opportunistically during routine clinical encounters, as well as screening for smoking or alcohol misuse if one or the other is present.

Exploring the evidence-practice gap in the use of plain radiography for acute abdominal pain and intestinal obstruction: a systematic review and meta-analysis.

AIM: Previous studies, some dating back several decades, have recommended that the use of plain abdominal radiography should be curbed, particularly with the growth of more accurate imaging modalities. However, evidence from referral data suggests that plain abdominal radiography continues to be a commonly requested examination. The aim of this review was to explore the gap between evidence and practice by re-examining the evidence using a robust methodology, investigating the diagnostic accuracy of plain abdominal radiography. METHODS: Studies were identified from electronic databases and reference lists. Eligible studies provided data as to the sensitivity and specificity of plain abdominal radiography for either acute abdominal pain (Group A) or suspected intestinal obstruction (Group B). Version 2 of the Quality Assessment of Diagnostic Accuracy Studies was used to assess the quality of studies and hierarchical summary receiver operator characteristic curves and coupled forest plots were generated. RESULTS: Four studies evaluated plain abdominal radiography for acute abdominal pain (Group A) and 10 for suspected intestinal obstruction (Group B). Two studies investigated both presentations and were included in both groups. Methodological quality of studies was moderately high, though incorporation bias was a common limitation. Sensitivity for Group A studies ranged from 30 to 46%, with specificity from 75 to 88%. For Group B, the range of sensitivity was 48 to 96% and specificity from 50 to 100%. CONCLUSION: The results suggest that use of plain abdominal radiography could be substantially reduced, particularly for patients with undifferentiated acute abdominal pain. While some guidelines exist, there is sound argument for clinical decision rules for abdominal imaging to inform evidence-based clinical decision-making and radiology referrals.

Cognition in the First Year After a Minor Stroke, Transient Ischemic Attack, or Mimic Event and the Role of Vascular Risk Factors.

Background: Cognitive impairment following a minor stroke or transient ischemic attack (TIA) is common; however, due to diagnostic difficulties, the prevalence and underlying cause of impairment remain poorly defined. We compared cognition in patients after a minor stroke, TIA, or mimic event at three time points in the first year following the event. We examine whether cognitive impairment occurs following these events and whether this impairment differs based on the event type. Further, we measure whether these findings persist after controlling for age, education, and the presence of vascular risk factors and whether the presence of vascular risk factors, independent of event etiology, is associated with cognitive impairment. Lastly, we investigate whether increased stroke risk, as assessed by the ABCD2, is associated with reduced cognition. Methods: Medical information, a cognitive screening test, and a measure of executive functioning were collected from 613 patients (123 minor stroke, 175 TIA, and 315 mimics) using phone interviews at three time points in the first year following the event. Linear mixed models were used to determine the effect of event type, vascular risk factors, and predicted stroke risk on cognitive performance while controlling for confounders. Results: There was no relationship between event type and performance on either cognitive measure. When all confounders are controlled for, performance on the cognitive screening test was uniquely accounted for by the presence of heart failure, myocardial infarction, angina, and hypertension (all p < 0.047), whereas the measure of executive functioning was uniquely accounted for by the presence of hypertension and angina (all p < 0.032). Increased stroke risk also predicted performance on the cognitive screening test and the measure of executive functioning (all p < 0.002). Conclusions: Our findings indicate that cognitive impairment following a minor stroke or TIA may be attributed to the high prevalence of chronic vascular risk factors in these patients. This highlights the importance of long-term management of vascular risk factors beyond event recovery to reduce the risk of cognitive impairment. Increased stroke risk (i.e., ABCD2 score) was also associated with reduced cognition, suggesting that it may be helpful in signaling the need for further cognitive evaluation and intervention post-event.