How common is add-on use and how do patients decide whether to use them? A national survey of IVF patients.

STUDY QUESTION: What is the prevalence and pattern of IVF add-on use in Australia? SUMMARY ANSWER: Among women having IVF in the last 3 years, 82% had used one or more IVF add-on, most commonly acupuncture, preimplantation genetic testing for aneuploidy and Chinese herbal medicine. WHAT IS KNOWN ALREADY: IVF add-ons are procedures, techniques or medicines which may be considered nonessential to IVF, but usually used in attempts to improve the probability of conception and live birth. The use of IVF add-ons is believed to be widespread; however, there is little information about the prevalence and patterns of use in different settings. STUDY DESIGN, SIZE, DURATION: An online survey was distributed via social media to women in Australia who had undergone IVF since 2017. Women were excluded if they were gestational surrogates, used a surrogate, or underwent ovarian stimulation for oocyte donation or elective oocyte cryopreservation only. The survey was open from 21 June to 14 July 2020. PARTICIPANTS/MATERIALS, SETTING, METHODS: Survey questions included demographics, IVF and medical history, and use of IVF add-ons including details of the type of add-on, costs and information sources used. Participants were also asked about the relative importance of evidence regarding safety and effectiveness, factors considered in decision-making and decision regret. MAIN RESULTS AND THE ROLE OF CHANCE: A total of 1590 eligible responses were analysed. Overall, 82% of women had used one or more add-ons and these usually incurred an additional cost (72%). Around half (54%) had learned about add-ons from their fertility specialist, and most reported that the decision to use add-ons was equally shared with the specialist. Women placed a high level of importance on scientific evidence for safety and efficacy, and half (49%) assumed that add-ons were known to be safe. Most women experienced some regret at the decision to use IVF add-ons (66%), and this was more severe among women whose IVF was unsuccessful (83%) and who believed that the specialist had a larger contribution to the decision to use add-ons (75%). LIMITATIONS, REASONS FOR CAUTION: This retrospective survey relied on patient recall. Some aspects were particularly prone to bias such as contributions to decision-making. This approach to capturing IVF add-on use may yield different results to data collected directly from IVF clinics or from fertility specialists. WIDER IMPLICATIONS OF THE FINDINGS: There is a very high prevalence of IVF add-on use in Australia which may be generalisable to other settings with similar models of IVF provision. Although women placed high importance on scientific evidence to support add-ons, most add-ons do not have robust evidence of safety and effectiveness. This suggests that IVF patients are not adequately informed about the risks and benefits of IVF add-ons, or are not aware of the paucity of evidence to support their use. STUDY FUNDING/COMPETING INTEREST(S): This research was supported by a McKenzie Postdoctoral Fellowship Grant (University of Melbourne), a Department of Obstetrics and Gynaecology Innovation Grant (University of Melbourne) and an NHMRC Investigator Grant (APP1195189). A.P. declares that he provides fertility services at Melbourne IVF (part of Virtus Health). J.W. reports grants from Wellcome Trust, during the conduct of the study, and that publishing benefits his career. The remaining authors report no conflict of interest. TRIAL REGISTRATION NUMBER: N/A.

Modelling the cost-effectiveness of public awareness campaigns for the early detection of non-small-cell lung cancer.

BACKGROUND: Survival rates in lung cancer in England are significantly lower than in many similar countries. A range of Be Clear on Cancer (BCOC) campaigns have been conducted targeting lung cancer and found to improve the proportion of diagnoses at the early stage of disease. This paper considers the cost-effectiveness of such campaigns, evaluating the effect of both the regional and national BCOC campaigns on the stage distribution of non-small-cell lung cancer (NSCLC) at diagnosis. METHODS: A natural history model of NSCLC was developed using incidence data, data elicited from clinical experts and model calibration techniques. This structure is used to consider the lifetime cost and quality-adjusted survival implications of the early awareness campaigns. Incremental cost-effectiveness ratios (ICERs) in terms of additional costs per quality-adjusted life-years (QALYs) gained are presented. Two scenario analyses were conducted to investigate the role of changes in the 'worried-well' population and the route of diagnosis that might occur as a result of the campaigns. RESULTS: The base-case theoretical model found the regional and national early awareness campaigns to be associated with QALY gains of 289 and 178 QALYs and ICERs of £13 660 and £18 173 per QALY gained, respectively. The scenarios found that increases in the 'worried-well' population may impact the cost-effectiveness conclusions. CONCLUSIONS: Subject to the available evidence, the analysis suggests that early awareness campaigns in lung cancer have the potential to be cost-effective. However, significant additional research is required to address many of the limitations of this study. In addition, the estimated natural history model presents previously unavailable estimates of the prevalence and rate of disease progression in the undiagnosed population.

Guaiac faecal occult blood test performance at initial and repeat screens in the English Bowel Cancer Screening Programme.

BACKGROUND: In many countries, screening for colorectal cancer (CRC) relies on repeat testing using the guaiac faecal occult blood test (gFOBT). This study aimed to compare gFOBT performance measures between initial and repeat screens. METHODS: Data on screening uptake and outcomes from the English Bowel Cancer Screening Programme (BCSP) for the years 2008 and 2011 were used. An existing CRC natural history model was used to estimate gFOBT sensitivity and specificity, and the cost-effectiveness of different screening strategies. RESULTS: The gFOBT sensitivity for CRC was estimated to decrease from 27.35% at the initial screen to 20.22% at the repeat screen. Decreases were also observed for the positive predictive value (8.4-7.2%) and detection rate for CRC (0.19-0.14%). Assuming equal performance measures for both the initial and repeat screens led to an overestimate of the cost effectiveness of gFOBT screening compared with the other screening modalities. CONCLUSIONS: Performance measures for gFOBT screening were generally lower in the repeat screen compared with the initial screen. Screening for CRC using gFOBT is likely to be cost-effective; however, the use of different screening modalities may result in additional benefits. Future economic evaluations of gFOBT should not assume equal sensitivities between screening rounds.

Sea lice monitoring on Atlantic salmon farms in New Brunswick, Canada: comparing audit and farm staff counts.

Sea lice audits were performed by the Atlantic Veterinary College on commercial aquaculture sites in New Brunswick, Canada, in 2011. Although the primary objective was to verify that farms were reporting similar lice counts to third-party counts, more detailed comparisons were made to identify when lice counts were more likely to differ between the audit team and farm employees. A total of 28 sea lice audits were conducted on 16 sites between June and December 2011. During each audit, 10 cages were evaluated per site where possible, with ten fish per cage being evaluated by an audit technician and a further ten by a farm employee. Data analysis included descriptive statistics of lice counts by stage and limits of agreement plots. A random effects negative binomial model that accounted for clustering of cages within sites was applied to assess the effect of counter type and season on lice counts by stage. The results indicate that farms counts were generally in agreement with audit counts. However, when the average counts for chalimus and preadult (male and female) and adult male lice stages were high, farm counters were more likely to report a lower value. Higher lice counts were observed during autumn compared to summer especially for the adult female stage. Finally, there was a significant clustering effect for site and cage, with most of the variation attributable to site.

A fixed-dose approach to conducting emamectin benzoate tolerance assessments on field-collected sea lice, Lepeophtheirus salmonis.

In New Brunswick, Canada, the sea louse, Lepeophtheirus salmonis, poses an on-going management challenge to the health and productivity of commercially cultured Atlantic salmon, Salmo salar. While the in-feed medication, emamectin benzoate (SLICE® ; Merck), has been highly effective for many years, evidence of increased tolerance has been observed in the field since late 2008. Although bioassays on motile stages are a common tool to monitor sea lice sensitivity to emamectin benzoate in field-collected sea lice, they require the collection of large numbers of sea lice due to inherent natural variability in the gender and stage response to chemotherapeutants. In addition, sensitive instruments such as EC(50) analysis may be unnecessarily complex to characterize susceptibility subsequent to a significant observed decline in efficacy. This study proposes an adaptation of the traditional, dose-response format bioassay to a fixed-dose method. Analysis of 657 bioassays on preadult and adult stages of sea lice over the period 2008-2011 indicated a population of sea lice in New Brunswick with varying degrees of susceptibility to emamectin benzoate. A seasonal and spatial effect was observed in the robustness of genders and stages of sea lice, which suggest that mixing different genders and stages of lice within a single bioassay may result in pertinent information being overlooked. Poor survival of adult female lice in bioassays, particularly during May/June, indicates it may be prudent to consider excluding this stage from bioassays conducted at certain times of the year. This work demonstrates that fixed-dose bioassays can be a valuable technique in detecting reduced sensitivity in sea lice populations with varying degrees of susceptibility to emamectin benzoate treatments.

Temperature impacts Atlantic salmon's (Salmo salar) immunological response to infectious salmon anemia virus (ISAv).

Ocean temperatures continue to rise annually due to the ever-growing consequences of global climate change. These temperature changes can have an impact on the immunological robustness of cultured fish, especially cold-water species such as Atlantic salmon. The salmon farming industry already loses hundreds of millions of dollars each year to infectious and non-infectious diseases. One particularly important and WOAH reportable disease is infectious salmon anemia caused by the orthomyxovirus ISAv. Considering the changing environment, it is necessary to find ways to mitigate the effect of diseases on the industry. For this study, 20 Atlantic salmon families were housed in each of 38 different tanks at the AVC, with half of the fish being kept at 10 °C and half being kept at 20 °C. Donor Atlantic salmon IP- injected with a highly virulent ISAv isolate (HPR4; TCID50 of 1 × 105/mL) were added to each tank as the source of co-habitation infection. Both temperatures were sampled at onset of mortality in co-habited fish and at resolution of mortality. Family background and temperature significantly impacted ISAv load, as assessed by qPCR, time to mortality and overall mortality. Mortality was more acute at 20 °C, but overall mortality was higher at 10 °C. Based on percent mortality calculated over the course of the study, different families demonstrated different levels of survival. The three families that demonstrated the highest percent mortality, and the three families with the lowest percent mortality were then assessed for their antiviral responses using relative gene expression. Genes significantly upregulated between the unexposed fish and ISAv exposed fish included mx1, il4/13a, il12rb2, and trim25, and these were further impacted by temperature. Understanding how ISAv resistance is impacted by temperature can help identify seasonal risks of ISAv outbreaks as well as ideal responses to be targeted through immunopotentiation.

Cost-effectiveness of population-based screening for colorectal cancer: a comparison of guaiac-based faecal occult blood testing, faecal immunochemical testing and flexible sigmoidoscopy.

BACKGROUND: Several colorectal cancer-screening tests are available, but it is uncertain which provides the best balance of risks and benefits within a screening programme. We evaluated cost-effectiveness of a population-based screening programme in Ireland based on (i) biennial guaiac-based faecal occult blood testing (gFOBT) at ages 55-74, with reflex faecal immunochemical testing (FIT); (ii) biennial FIT at ages 55-74; and (iii) once-only flexible sigmoidoscopy (FSIG) at age 60. METHODS: A state-transition model was used to estimate costs and outcomes for each screening scenario vs no screening. A third party payer perspective was adopted. Probabilistic sensitivity analyses were undertaken. RESULTS: All scenarios would be considered highly cost-effective compared with no screening. The lowest incremental cost-effectiveness ratio (ICER vs no screening euro 589 per quality-adjusted life-year (QALY) gained) was found for FSIG, followed by FIT euro 1696) and gFOBT (euro 4428); gFOBT was dominated. Compared with FSIG, FIT was associated with greater gains in QALYs and reductions in lifetime cancer incidence and mortality, but was more costly, required considerably more colonoscopies and resulted in more complications. Results were robust to variations in parameter estimates. CONCLUSION: Population-based screening based on FIT is expected to result in greater health gains than a policy of gFOBT (with reflex FIT) or once-only FSIG, but would require significantly more colonoscopy resources and result in more individuals experiencing adverse effects. Weighing these advantages and disadvantages presents a considerable challenge to policy makers.

Reappraisal of the options for colorectal cancer screening in England.

AIM: The aim was to use newly available data to estimate the cost effectiveness and endoscopy requirements of screening options for colorectal cancer (CRC) to inform screening policy in England. METHODS: A state transition model simulated the life experience of a cohort of individuals in the general population of England with normal colon/rectal epithelium through to the development of adenomas and CRC and subsequent death. CRC natural history model parameters and screening test characteristics were estimated simultaneously by a process of model calibration. This process was fitted to observed data on CRC incidence in the absence of screening, data from existing screening programmes, and data from the UK flexible sigmoidoscopy (FS) screening trial. The costs, effects and resource impact were evaluated for a range of screening options involving the guaiac or immunochemical faecal occult blood test (gFOBT/iFOBT) and FS. RESULTS: The model suggests that screening strategies involving FS or iFOBT may produce additional benefits compared with the current policy of biennial gFOBT for 60-74-year-olds. The age at which a single FS screen results in the greatest quality-adjusted life year gain was 55, with similar gains for ages between 52 and 58. Strategies which combined FS and iFOBT showed further benefits and improved economic outcomes. CONCLUSIONS: Strategies which combine different screening modalities may provide greater clinical and economic benefits. The collection of comprehensive screening data using a uniform format will enable comparative analysis across screening programmes in different countries, will improve our understanding of the disease and will allow identification of optimal screening modalities.

Venous and arterial thrombo-embolic complications of hormonal treatment in a male-to-female transgender patient.

We present a male-to-female (MTF) transgender patient admitted with a pulmonary embolism. The patient had been treated with high-dose oestrogens since the age of 16. Following a prolonged period of hypotension, our patient sustained cerebral border zone infarcts. There was evidence of bilateral carotid stenosis on Doppler ultrasound. We discuss the treatment and vascular complications of gender dysphoria.

Longitudinal prevalence and determinants of early mood disorder post-stroke.

BACKGROUND: Early identification of mood disorder post-stroke (MDPS) or its determinants could improve stroke outcomes. However, the natural history, prevalence and determinants of MDPS within the first weeks post-stroke require further investigation. METHODS: Consecutive hospitalised stroke survivors were assessed within 2-5 days of stroke, and at 1 and 3 months post-stroke. Baseline data included demographics, co-morbidities, stroke subtype, pre-stroke disability and cognition. At baseline, 1- and 3-month interviews physical impairment, disability, cognition and social support were assessed. MDPS was defined as a score of >8 on the depression subscale of the Hospital Anxiety Depression Scale. Factors independently associated with MDPS at each time-point were determined using regression analyses. RESULTS: One hundred and twenty-five subjects were included. The prevalence of MDPS within 5 days and at 1 and 3 months post-stroke was 5%, 16% and 21% respectively. The independent determinants for MDPS at 1 month were disability, social support and change in impairment score between initial and 1-month assessments; and at 3 months were disability, social support and institutionalisation. Individuals moved in and out of the subset of depressed patients over time. MDPS was independently associated with mortality at 3 months post-stroke. CONCLUSION: Mood disorder post-stroke increases in prevalence over the initial weeks post-stroke despite an improvement in disability, and is associated with mortality. Patients with MDPS at 1 month were not necessarily affected at 3 months and vice versa, indicating the dynamic nature of MDPS in the early stages.

The crystal structure of the globular domain of sheep prion protein.

The prion protein PrP is a naturally occurring polypeptide that becomes transformed from a normal conformation to that of an aggregated form, characteristic of pathological states in fatal transmissible spongiform conditions such as Creutzfeld-Jacob Disease and Bovine Spongiform Encephalopathy. We report the crystal structure, at 2 A resolution, of residues 123-230 of the C-terminal globular domain of the ARQ allele of sheep prion protein (PrP). The asymmetric unit contains a single molecule whose secondary structure and overall organisation correspond to those structures of PrPs from various mammalian species determined by NMR. The globular domain shows a close association of helix-1, the C-terminal portion of helix-2 and the N-terminal portion of helix-3, bounded by the intramolecular disulphide bond, 179-214. The loop 164-177, between beta2 and helix-2 is relatively well structured compared to the human PrP NMR structure. Analysis of the sheep PrP structure identifies two possible loci for the initiation of beta-sheet mediated polymerisation. One of these comprises the beta-strand, residues 129-131 that forms an intra-molecular beta-sheet with residues 161-163. This strand is involved in lattice contacts about a crystal dyad to generate a four-stranded intermolecular beta-sheet between neighbouring molecules. The second locus involves the region 188-204, which modelling suggests is able to undergo a partial alpha-->beta switch within the monomer. These loci provide sites within the PrPc monomer that could readily give rise to early intermediate species on the pathway to the formation of aggregated PrPSc containing additional intermolecular beta-structure.

Familial paracentric inversion of 1p.

We report a paracentric inversion of 1p in a boy with mild mental retardation. The chromosome aberration was identified by high resolution chromosome banding, and was also present in his phenotypically normal mother and other relatives. The boy's karyotype was considered to be 46,XY,inv(1) (p31,2p36.22) ISCN (1981).

No association of presenilin-1 intronic polymorphism and Alzheimer's disease in Australia.

We screened 703 Australian subjects for an intronic polymorphism in the presenilin-1 (PS-1) gene. PS-1 intronic allele 1 homozygosity was not associated with individuals with early- or late-onset sporadic Alzheimer's disease (EOAD or LOAD). Carriers for the PS-1 intronic allele 1 were also not associated with significantly increased risk for AD regardless of gender. Our results for the Australian population are consistent with those of recent reports for other populations and do not support the conclusion that the PS-1 intronic polymorphism is associated with AD.

Verbal working memory and solvent exposure: a positron emission tomography study.

Neuropsychological studies have documented frontal dysfunction in patients with a history of exposure to organic solvents. The deficits typically observed in these patients appear to be related to working memory (WM). This study used [15O] water positron emission tomography (PET) to examine the pattern of neural activation during verbal working memory in patients with a history of exposure to solvents. Six individuals with solvent exposure were compared with 6 age- and education-matched controls. On the 2 WM tasks examined with PET, with equivalent task performance, participants with solvent exposure demonstrated frontal peaks that were atypical for the tasks, whereas the posterior peaks were typical for the tasks. The results support frontal dysfunction and compensatory use within anterior regions of the WM system in patients with solvent exposure.

Communication failures in the operating room: an observational classification of recurrent types and effects.

BACKGROUND: Ineffective team communication is frequently at the root of medical error. The objective of this study was to describe the characteristics of communication failures in the operating room (OR) and to classify their effects. This study was part of a larger project to develop a team checklist to improve communication in the OR. METHODS: Trained observers recorded 90 hours of observation during 48 surgical procedures. Ninety four team members participated from anesthesia (16 staff, 6 fellows, 3 residents), surgery (14 staff, 8 fellows, 13 residents, 3 clerks), and nursing (31 staff). Field notes recording procedurally relevant communication events were analysed using a framework which considered the content, audience, purpose, and occasion of a communication exchange. A communication failure was defined as an event that was flawed in one or more of these dimensions. RESULTS: 421 communication events were noted, of which 129 were categorized as communication failures. Failure types included "occasion" (45.7% of instances) where timing was poor; "content" (35.7%) where information was missing or inaccurate, "purpose" (24.0%) where issues were not resolved, and "audience" (20.9%) where key individuals were excluded. 36.4% of failures resulted in visible effects on system processes including inefficiency, team tension, resource waste, workaround, delay, patient inconvenience and procedural error. CONCLUSION: Communication failures in the OR exhibited a common set of problems. They occurred in approximately 30% of team exchanges and a third of these resulted in effects which jeopardized patient safety by increasing cognitive load, interrupting routine, and increasing tension in the OR.

Paediatric basic life support: a practical assessment.

Current European Resuscitation Council (ERC) guidelines for paediatric basic life support advocate delivery of 20 cycles/min at a compression rate of 100/min and a compression:ventilation ratio of 5:1 (Resuscitation 1997;34:115-27; Resuscitation 1998;37(2):97-100). We have evaluated whether cardiopulmonary resuscitation (CPR) can be delivered at this rate by hospital providers. We recruited 24 rescuers, all of whom had successfully completed a training course in paediatric life support. Each was asked to perform single rescuer CPR on a Resusci-Junior mannequin (Laerdal, Kent, UK) for 5 min, following the current ERC guidelines. Compressions and ventilations were recorded in real time by inductance plethysmography. Maintenance of the 5:1 ratio was ensured by investigator observation. Cycles of CPR in the first and fifth minutes of resuscitation were counted. The average duration of compression, ventilation and 'transfer time' spent between these two activities was calculated as a percentage of the average duration of a cycle of CPR. All 24 rescuers completed 5 min of resuscitation. Twenty-three of 24 were unable to deliver 20 cycles of CPR in either the first minute (range 8-27; median 11; interquartile range (IQR) 10-13.75) or in the fifth minute (8-26; 11.5; 10-13.75). The median (IQR) duration of a cycle of CPR was 5 s in the first and fifth minutes. Transfer time comprised 30% of total cycle time. In this study, over 95% of single rescuers trained in paediatric life support were unable to deliver 20 cycles of CPR/min. The guidelines make no allowance for time spent moving between compression and ventilation activity. Future consensus statements should take account of this transfer time. Any changes in recommendations should obviously be prospectively audited with Utstein-style reporting and studies of practicability.

Neonatal resuscitation--a practical assessment.

Current European neonatal resuscitation guidelines (Zideman et al. Resuscitation 1998;37:103-110) advocate cardiopulmonary resuscitation (CPR) at 120 compressions per minute in a ratio of 3:1. This is commonly interpreted as a net rate, thus requiring delivery of 40 breaths per minute, which is the upper end of the range of 30-40 breaths per minute suggested in the guidelines. At least one other interpretation is available, but the correct one is not specified. No studies have evaluated whether the rates inferred by the guidelines can be achieved. This study assesses the ability of trained hospital providers to fulfil these criteria in a simulated arrest scenario. A group of anaesthetists, paediatricians, midwives and neonatal nurses was asked to perform CPR either as single rescuers or in pairs, for 5 min, following European Resuscitation Council guidelines. Breaths and compressions delivered were measured by inductance plethysmography. The number of breaths delivered in the first and fifth minute of the scenario were measured, as well as the quality of delivered breaths. Of 33 single resuscitators, none were able to deliver 40 breaths per minute in either the first minute (range 11-34; median 20; interquartile range 14-26) or the fifth (13-35; 19; 15.25-26.5). Of 18 pairs of rescuers, four achieved 40 breaths per minute in the first minute (24-45; 33.5; 29.75-38.25) but only three of 17 were able to sustain this to the fifth minute (21-48; 35; 30.5 39). One pair did not complete 5 min of resuscitation. Single rescuers were unable to achieve the rate of CPR suggested by current guidelines. Only 22% of paired rescuers were able to achieve this standard in the first minute, falling to less than 20% by the fifth minute. We recommend modifying the guidelines to make them unambiguous and practicable, with the emphasis shifted onto the quality of compressions and ventilations, rather than quantity.