Making it out of hospital alive: the art of open abdomen management – a pilot study

Purpose: In the management of patients with an open abdomen (OA), failure of fascial closure, decreased GCS, and presence of acute renal failure have been identified as having a significant effect on in-hospital mortality. The aim of this study is to develop a probability nomogram in order to predict the likelihood of in-hospital mortality amongst patients being managed with an OA. Methodology: All patients admitted to the Cairns Hospital from 1999 to 2015 that were managed with an OA were identified. Statistical analysis was performed using multivariate logistic regression methods using 54 prognostic factors in regards to in-hospital mortality. Results: A total of 133 patients were managed with an OA. 31 (23%) patients died in-hospital. Four prognostic factors were found to significantly contribute to in-hospital mortality. These included APACHE III score (odds ratio (OR) 1.29), presence of one or more cardiac risk factors (OR 5.00), normal pulse rate (50-80 beats per minute; OR 0.19) and the use of enteral feeding (OR 0.25). Probability nomograms were developed in order to demonstrate a patient's likelihood of in-hospital mortality, as well as identify specific aspects that may improve their overall outcome. Internal validation using receiver operator curve analysis showed an area under the curve of 0.825. Conclusion: Four prognostic factors were identified in regards to in-hospital mortality in patients being managed with an OA. The use of these probability nomograms will not only aid in predicting the likelihood of in-hospital mortality, but also show aspects which can be targeted in order to improve their overall outcome

Making it out of hospital alive: the art of open abdomen management – a pilot study

Purpose: In the management of patients with an open abdomen (OA), failure of fascial closure, decreased GCS, and presence of acute renal failure have been identified as having a significant effect on in-hospital mortality. The aim of this study is to develop a probability nomogram in order to predict the likelihood of in-hospital mortality amongst patients being managed with an OA. Methodology: All patients admitted to the Cairns Hospital from 1999 to 2015 that were managed with an OA were identified. Statistical analysis was performed using multivariate logistic regression methods using 54 prognostic factors in regards to in-hospital mortality. Results: A total of 133 patients were managed with an OA. 31 (23%) patients died in-hospital. Four prognostic factors were found to significantly contribute to in-hospital mortality. These included APACHE III score (odds ratio (OR) 1.29), presence of one or more cardiac risk factors (OR 5.00), normal pulse rate (50-80 beats per minute; OR 0.19) and the use of enteral feeding (OR 0.25). Probability nomograms were developed in order to demonstrate a patient's likelihood of in-hospital mortality, as well as identify specific aspects that may improve their overall outcome. Internal validation using receiver operator curve analysis showed an area under the curve of 0.825. Conclusion: Four prognostic factors were identified in regards to in-hospital mortality in patients being managed with an OA. The use of these probability nomograms will not only aid in predicting the likelihood of in-hospital mortality, but also show aspects which can be targeted in order to improve their overall outcome

Treatments and other prognostic factors in the management of the open abdomen: a systematic review

Purpose: The open abdomen (OA) is an important approach for managing intra-abdominal catastrophes and continues to be the standard of care. Despite this, challenges remain and the technique is still associated with a high incidence of complications and poor outcomes. A systematic review was performed to identify prognostic factors associated with OA management in relation to definitive fascial closure (DFC), mortality and intra-abdominal complications. Methodology: An electronic database search was conducted involving Medline, Excerpta Medica, Central Register of Controlled Trials, Cumulative Index to Nursing and Allied Health Literature and Clinicaltrials.gov databases. Results: There were 31 studies included in the final synthesis. Prognostic factors associated with delaying DFC included the presence of deep surgical site infection, fascial necrosis or an intestinal fistula. Failed clearance of the abdomen, failure of fascial closure, unconsciousness and acute renal failure were associated with in-hospital mortality. Failed DFC, large bowel resection and administration of > 5-10 litres or > 10 litres of intravenous fluids in < 48 hours were associated with the development of entero-atmospheric fistula and/or intra-abdominal abscess. The source of infection (small bowel in relation to colon) was associated with the development of a ventral hernia. Fascial closure on or after day 5 or the presence of a bowel anastomosis were associated with the development of an anastomotic leak. Conclusion: The OA has earned a huge amount of popularity in recent decades. Careful selection and management of patients with an OA will aid in avoiding prolonged treatment and facilitate early DFC, decrease mortality and reduce intra-abdominal complications

External validation of the Cairns Prediction Model (CPM) to predict conversion from laparoscopic to open cholecystectomy

Background: Valid and user-friendly prediction models for conversion to open cholecystectomy allow for proper planning prior to surgery. The Cairns Prediction Model (CPM) has been in use clinically in the original study site for the past three years, but has not been tested at other sites. Methods: A retrospective, single-centred study collected ultrasonic measurements and clinical variables alongside with conversion status from consecutive patients who underwent laparoscopic cholecystectomy from 2013 to 2016 in The Townsville Hospital, North Queensland, Australia. An area under the curve (AUC) was calculated to externally validate of the CPM. Results: Conversion was necessary in 43 (4.2%) out of 1035 patients. External validation showed an area under the curve of 0.87 (95% CI 0.82 – 0.93, p = 1.1 x 10-14). Conclusions: In comparison with most previously published models, which have an AUC of approximately 0.80 or less, the CPM has the highest AUC of all published prediction models both for internal and external validation

Achieving High Breast Cancer Survival for Women in Rural and Remote Areas

Background: Significant improvements in breast cancer survival have been made in the past few decades in many developed countries including Australia with a five-year relative survival of 90%. The aim of the present study is to obtain a brief estimate of the relative importance of demographic factors such as rurality, socio-economic standard and ethnicity versus traditional risk factors for women diagnosed with breast cancer in Far North Queensland, Australia. Methods: This was a retrospective longitudinal study of all women diagnosed with their first episode of breast cancer in 1999-2013 in Far North Queensland, Australia. Cox proportional hazards regression analysis was used to identify factors independently associated with mortality for women with any type of breast cancer (in situ or invasive) and for women with invasive cancer. Life tables were used to assess five and ten-year absolute survival. Standard linear regression and binary logistic regression were used to identify any association between demographic factors and late presentation. Results: Five and ten-year absolute survival was 0.90 and 0.86 respectively. Aboriginal and Torres Strait Islander status, remoteness of area of residence, and socioeconomic status were not associated with more advanced disease at presentation or increased risk of breast cancer death. Only traditional risk factors such as increased tumour size, absence of progesterone receptor, high tumour grade and presence of metastasis in axillary lymph nodes were associated with increased risk of breast cancer death. Conclusion: The effect of the classical risk factors on breast cancer mortality outweighs the effects of demographic factors. The fact that ethnicity, remoteness and socioeconomic status is not associated with late presentation or breast cancer death suggests that given appropriate resources it may be possible to close the gap of inequalities in breast cancer

Urine culture doubtful in determining etiology of diffuse symptoms among elderly individuals: a cross-sectional study of 32 nursing homes

Background: The high prevalence of bacteriuria in elderly individuals makes it difficult to know if a new symptom is related to bacteria in the urine. There are different views concerning this relationship and bacteriuria often leads to antibiotic treatments. The aim of this study was to investigate the relationship between bacteria in the urine and new or increased restlessness, fatigue, confusion, aggressiveness, not being herself/himself, dysuria, urgency and fever in individuals at nursing homes for elderly when statistically considering the high prevalence of asymptomatic bacteriuria in this population.\ud \ud Methods: In this cross-sectional study symptoms were registered and voided urine specimens were collected for urinary cultures from 651 elderly individuals. Logistic regressions were performed to evaluate the statistical correlation between bacteriuria and presence of a symptom at group level. To estimate the clinical relevance of statistical correlations at group level positive and negative etiological predictive values (EPV) were calculated.\ud \ud Results: Logistic regression indicated some correlations at group level. Aside from Escherichia coli in the urine and not being herself/himself existing at least one month, but less than three months, EPV indicated no clinically useful correlation between any symptoms in this study and findings of bacteriuria.\ud \ud Conclusions: Urinary cultures provide little or no useful information when evaluating diffuse symptoms among elderly residents of nursing homes. Either common urinary tract pathogens are irrelevant, or urine culture is an inappropriate test

Evaluation of dipstick analysis among elderly residents to detect bacteriuria: a cross-sectional study in 32 nursing homes

Background: Up to half the residents of nursing homes for the elderly have asymptomatic bacteriuria (ABU), which should not be treated with antibiotics. Thus, it is difficult to know if new symptoms in residents with bacteriuria are caused by urinary tract infection (UTI), or if bacteriuria only represents an ABU. This is especially difficult in the presence of non-urinary tract specific symptoms. The diagnostic uncertainty is likely to generate significant overtreatment with UTI antibiotics. Aim: The general aim was to clarify the association between symptoms, bacteriuria, dipstick urinalysis and urine Interleukin-6 (IL-6) among nursing home residents to improve the diagnostic procedure of a suspected lower UTI. Methods: In 2003 a study protocol including newly onset symptoms was completed, and single voided urine specimens collected for dipstick urinalysis and cultures from 651 residents of 32 participating Swedish nursing homes for the elderly. This data was used for a study of dipstick urinalysis (Paper I) and for a study of nonspecific symptoms and bacteriuria (Paper II). In 2012, similar data was collected for 421 elderly residents of 22 nursing homes, which also included an analysis of IL-6 in urine and urine specimens from another 59 residents with urinary catheters. The association between bacteriuria, IL-6 in urine, dipstick urinalysis and newly onset symptoms was analysed (Paper III). Antimicrobial resistance rates were described among residents of nursing homes in 2012 and compared with those from 2003 (Paper IV). Results: Paper I: The negative predictive value for predicting absence of bacteriuria was 88 (84-92)% when dipstick urinalysis for nitrite and leukocyte esterase were simultaneously negative. A positive dipstick or any combination thereof could not sufficiently predict bacteriuria. Papers II-III: New or increased nonspecific symptoms were common among elderly residents of nursing homes. Residents without nonspecific symptoms had positive urine cultures as often as those with nonspecific symptoms with a duration of up to one month. Paper III: Residents with positive urine cultures had higher concentrations of IL-6 in the urine. However, among residents with positive urine cultures there were no differences in IL-6 concentrations or dipstick findings between those with or without nonspecific symptoms. Paper IV: The average rates of antimicrobial resistance were low and did not increase between 2003 and 2012 in Escherichia coli (E. coli) urinary isolates among Swedish nursing home residents. Any antibiotic treatment during the last month and hospitalization during the last six months predicted higher resistance rates among E. coli. Conclusions: Nonspecific symptoms among elderly residents of nursing homes are unlikely to be caused by bacteria in the urine. Therefore, dipstick urinalysis, IL-6 in the urine and urine cultures are of little or no value in clarifying the aetiology of nonspecific symptoms. If there is a reason for testing for bacteriuria, dipstick urinalysis for nitrite and leukocyte esterase can rule out but cannot reliably rule in bacteriuria. Antimicrobial resistance in urinary pathogens among Swedish nursing home residents remained low. It is important to use antibiotics rationally to preserve the effectiveness of antibiotics

Polygenic prediction of educational attainment within and between families from genome-wide association analyses in 3 million individuals

We conduct a genome-wide association study (GWAS) of educational attainment (EA) in a sample of ~3 million individuals and identify 3,952 approximately uncorrelated genome-wide-significant single-nucleotide polymorphisms (SNPs). A genome-wide polygenic predictor, or polygenic index (PGI), explains 12-16% of EA variance and contributes to risk prediction for ten diseases. Direct effects (i.e., controlling for parental PGIs) explain roughly half the PGI's magnitude of association with EA and other phenotypes. The correlation between mate-pair PGIs is far too large to be consistent with phenotypic assortment alone, implying additional assortment on PGI-associated factors. In an additional GWAS of dominance deviations from the additive model, we identify no genome-wide-significant SNPs, and a separate X-chromosome additive GWAS identifies 57

Genome-wide association study identifies 74 loci associated with educational attainment

Educational attainment is strongly influenced by social and other environmental factors, but genetic factors are estimated to account for at least 20% of the variation across individuals1. Here we report the results of a genome-wide association study (GWAS) for educational attainment that extends our earlier discovery sample1,2 of 101,069 individuals to 293,723 individuals, and a replication study in an independent sample of 111,349 individuals from the UK Biobank. We identify 74 genome-wide significant loci associated with the number of years of schooling completed. Single-nucleotide polymorphisms associated with educational attainment are disproportionately found in genomic regions regulating gene expression in the fetal brain. Candidate genes are preferentially expressed in neural tissue, especially during the prenatal period, and enriched for biological pathways involved in neural development. Our findings demonstrate that, even for a behavioural phenotype that is mostly environmentally determined, a well-powered GWAS identifies replicable associated genetic variants that suggest biologically relevant pathways. Because educational attainment is measured in large numbers of individuals, it will continue to be useful as a proxy phenotype in efforts to characterize the genetic influences of related phenotypes, including cognition and neuropsychiatric diseases

Microbiologic diagnostic tests when asymptomatic carriers are present. Aspects of the use of conventional throat and nasopharyngeal culture as examples

Carriers of potentially pathogenic bacteria simultaneously ill from a viral infection complicatethe diagnostic procedure in respiratory tract infections. The present statistical methodsavailable to evaluate common diagnostic tests either ignore the phenomenon of carriers orprovide test characteristics that are difficult to apply in clinical decision making. In thisdissertation, the influence of carriers on the diagnostic process has been elucidated.· The etiologic predictive value (EPV) is a new statistical method developed to predictdisease caused by the bacteriological findings, taking carriers into consideration. Tocalculate EPV, it is necessary to have the proportion of positive tests among patients, theproportion of positive tests among a healthy control population and the sensitivity of thetest. This enables calculating the positive and negative EPV with a 95% confidenceinterval.· A throat culture was found to be a reliable indicator for illness caused by group A beta-haemolyticstreptococci (GABHS) in adult patients with a sore throat. Positive EPV(PEPV) was 99% (95% confidence interval is 94-100%). A seasonal variation, however,was found in pre-school children (0-6 years of age). A throat culture with growth ofGABHS was found to be reliable only in the winter season, with a PEPV of 94% (75-100%) as opposed to only 61% (0-91%) in the summer. However, our data did not permitus to conclude that this seasonal variation will be found every year.· Findings of Haemophilus influenzae in a nasopharyngeal culture, taken from patients witha sore throat, may indicate the true etiology of the disease. The prediction in regard todisease caused by H. influenzae (PEPV) was 93% (73-99%) for adults ³16 years of ageand 86% (28-99%) for pre-school children 0-6 years of age.· In adults with a long-standing cough combined with other symptoms of a respiratory tractinfection, it was found that growth of H. influenzae in a nasopharyngeal culture wouldindicate the etiology for infection with PEPV 90% (30-99%). Growth of Moraxellacatarrhalis in a nasopharyngeal sample, taken from a pre-school child with a long-standingcough 0-6 years of age, will indicate the etiology for infection with a PEPV of90% (66-99%).· A questionnaire sent to different microbiologic laboratories revealed a substantialvariation between different geographical areas propensity to perform a throat ornasopharyngeal culture. There was also a large variation between the different areas in theoutcome of these cultures. It could be shown that the variation in outcome of the culturesmakes it difficult to directly apply predictive values calculated from many scientificstudies