Perfect Enough to Sleep? Perfectionism and Actigraphy-Determined Markers of Insomnia.

OBJECTIVES: Perfectionism is an important factor in insomnia development and maintenance. Previous studies exploring the relationship between perfectionism and insomnia have predominantly relied on self-reported sleep measures. Therefore, this study sought to assess whether actigraphy-measured sleep parameters were associated with perfectionism. METHODS: Sixty adults (85% females, mean age 30.18 ± 11.01 years) were sampled from the Australian general population. Actigraphy-derived objective sleep measures, subjective sleep diary measures, the Frost Multidimensional Perfectionism Scale (FMPS), Hewitt-Flett Multidimensional Perfectionism Scale (HFMPS) and Depression, Anxiety and Stress Scale 21 (DASS-21) were collected. RESULTS: High perfectionism levels were associated with poor sleep, but these relationships differed between objective and subjective measures. Perfectionism via FMPS total score and subscales of Concern over Mistakes, Doubts about Actions, Personal Standards and Self-oriented Perfectionism correlated with subjective sleep onset latency and sleep efficiency with moderate effects (r = .26 to .88). In contrast, perfectionism via HFMPS total score and subscales of Socially Prescribed Perfectionism and Parental Expectations predicted objective sleep onset latency and sleep efficiency. Additionally, stress mediated the relationships between objective sleep efficiency and Concern over Mistakes and Doubts about Actions. CONCLUSIONS: Perfectionism demonstrated stronger associations with subjective than objective sleep measures. Higher Parental Expectations and Socially Prescribed Perfectionism may increase one's vulnerability to objectively measured poor sleep. Therefore, perfectionism may be important in preventing and treating insomnia.

Prevalence of subclinical lung cancer detected at autopsy: a systematic review.

BACKGROUND: Lung cancer screening in high-risk populations with low-dose computed tomography is supported by international associations and recommendations. Overdiagnosis is considered a risk of screening with associated harms. The aim of this paper is to determine the prevalence of subclinical lung cancer diagnosed post-mortem to better understand the reservoir of subclinical lung cancer. METHODS: We searched EMBASE, PubMed, and MEDLINE databases from inception until March 2022 with no language restrictions. We considered all studies with ≥100 autopsies in adults. Two reviewers independently assessed eligibility of studies, extracted data, and assessed risk of bias of included studies. We performed a meta-analysis using a random-effects model for prevalence of subclinical lung cancer diagnosed post-mortem with sensitivity and subgroup analyses. RESULTS: A total of 13 studies with 16 730 autopsies were included. Pooled prevalence was 0.4% (95% CI 0.20 to 0.82%, I2 = 84%, tau2 = 1.19, low certainty evidence,16 730 autopsies). We performed a sensitivity analysis excluding studies which did not specify exclusion of children in their cohort, with a pooled prevalence of subclinical lung cancer of 0.87% (95% CI 0.48 to 1.57%, I2 = 71%, tau2 = 0.38, 6998 autopsies, 8 studies). CONCLUSIONS: This is the first published systematic review to evaluate the prevalence of post-mortem subclinical lung cancer. Compared to autopsy systematic reviews in breast, prostate and thyroid cancers, the pooled prevalence is lower in lung cancer for subclinical cancer. This result should be interpreted with caution due to the included studies risk of bias and heterogeneity, with further high-quality studies required in target screening populations.

Prevalence of Blood-Borne Viruses and Predictors of Risk in Potential Organ Donors in Australia.

Internationally, the designation of a patient as an increased viral risk organ donor has been associated with lower utilisation rates. The actual prevalence of blood borne viruses in Australian potential organ donors, and the predictive performance of questionnaires administered to stratify this risk, remains unknown. We conducted a retrospective review of all patients who commenced workup for donation on the national database between 2014-2020. The prevalence of HIV, Active HBV and Active HCV in 3650 potential organ donors was 0.16%, 0.9%, and 2.2%, respectively. The behavioural risk profile was assessed in a subset of 3633 patients. Next-of-kin reported increased risk behaviours were associated with an increased prevalence of HCV but not of HIV or HBV (OR 13.8, p < 0.01, OR 0.3. p = 0.42, OR 1.5, p = 0.14). Furthermore, the majority of HIV and HBV infections occurred in potential donors without a disclosed history of increased risk behaviours. In this series, donors had a higher prevalence of HCV, and similar rates of HBV and HIV to the broader community. Behavioural transmission risks were poorly predictive of HIV and HBV. Rather than pre-transplantation behavioural risk screening, routine post-transplant recipient screening may provide a more powerful tool in mitigating the consequences of unexpected viral transmission.

Cost-effectiveness analysis of home-based rehabilitation compared to usual care for people with inoperable lung cancer.

OBJECTIVE: Few economic evaluations of lung cancer rehabilitation exist. The aim of this study was to assess the cost-effectiveness of providing home-based rehabilitation for inoperable lung cancer. METHODS: A cost-utility analysis alongside a randomised controlled trial (RCT) of rehabilitation compared with usual care. The primary outcome was quality-adjusted life years (QALYs) gained. The incremental cost-effectiveness ratio [ICER (95% CI)] and the net monetary benefit are reported. Value of information (VOI) analysis assessed the need/value of more research. RESULTS: Seventy participants (34 intervention and 36 usual care), average (SD) age 63.0 (12.0) years, 32 (45.7%) stage IV. The average intervention cost was AU$3421 (AU$5352 usual care), and effect (QALY) was 0.30 (0.31 usual care). The ICER was AU$228,197 (-1,173,194 to 1,101,450) per QALY gained. The net monetary benefit was AU$1508, favouring the intervention. The probability that the intervention was more cost-effective than usual care, at a willingness to pay threshold of AU$50,000, was 75%. VOI analysis showed that additional research to resolve decision uncertainty is potentially worthwhile. CONCLUSION: A high degree of uncertainty exists regarding the cost-effectiveness of lung cancer rehabilitation. Further RCTs, powered for economic evaluations and utilising rehabilitation sensitive outcomes, are required to support translation of evidence into clinical practice.

Ten-year trends in catheter ablation for ventricular tachycardia vs other interventional procedures in Australia.

AIMS: Major technological and procedural advancements have reinvigorated catheter ablation as adjunctive therapy for drug-refractory ventricular tachycardia (VT). We examined temporal trends in VT ablations as compared to other interventional cardiovascular procedures namely, percutaneous coronary intervention (PCI) and atrial fibrillation (AF) ablation in Australia. METHODS AND RESULTS: A retrospective review of procedural numbers for VT ablations, AF ablations, and PCI was performed from 2008/09-2016/17 the Australian Institute of Health, Welfare and Aging (AIHW), and Medicare Australia (MA) databases. Linear regression models were fitted to compare the trends in population-adjusted procedural numbers over the 10-year period. Data from the AIHW and MA sources respectively showed that (a) PCI had a 1.3% (AIHW data P = .15) and 1.8% (MA data P < .001) population-adjusted increment per year, (b) AF ablations had a 12.7% (P < .001) and 11.7% (P < .001) per year population-adjusted increment, and (c) VT ablations showed an 18% (P < .001) and 12.7% (P < .001) per year population-adjusted increment. Growth of PCI was increasing at a lower rate than AF ablations (P < .001 for both AIHW and MA sources). Growth of VT ablation was significantly higher than AF ablations and PCI (AIHW: 18% vs 12.7% [P = .004] and 1.3% per year [P < .001]). CONCLUSION: Catheter-based VT ablation has increased significantly in Australia over the last decade, consistent with worldwide trends, and now surpassing all ablation procedures, including AF ablation and PCI for CAD. This data highlight the provision of additional resources to match the increasing demand for VT ablation procedures in Australia.

Common clinical findings identified in working equids in low- and middle-income countries from 2005 to 2021.

Despite several millions of working equids worldwide, there are few published studies regarding the epidemiology of their health and welfare. Data collected by non-governmental organisations (NGOs) operating in the working equid sphere therefore have important epidemiological value and could be used towards animal health surveillance. The aim of this study was to identify common clinical findings and mortality patterns of working equids in low- and middle-income countries and investigate their epidemiology using data collected from an international NGO. A retrospective analysis was conducted to determine the proportion of clinical findings and mortality risk by equid species, year and region. Negative binomial regression models were generated to investigate differences in mortality risk and proportion of key clinical findings between equid species, hemispheres and calendar month. A total of 4,313,606 presentations were reported from 14 countries between January 2005 and March 2021 (mean 22,121; SD ± 7,858 per month). Wounds and abscesses were the most reported clinical finding for all equid species (mean proportion 35%; SD ±0.19 of all findings). A higher proportion of wounds (mean proportion 41.7%; SD±0.2) was recorded in donkeys than mules or horses (P<0.001). Mules had higher reported mortality risk (1.2%; 95% CI 0.94-1.46%) than horses (0.4%; 95% CI 0.36-0.55%; p<0.001) or donkeys (0.2%; 95% CI 0.14-0.22%). Work-related wounds were the predominant finding in working equids, particularly so in donkeys. Prevention strategies should focus on improvements to work equipment and practices for all equids. Future investigations required include refinement of diagnostic approaches for donkeys and investigation of risk factors to understand the higher mortality in mules. Routine monitoring of clinical findings reported by national or international NGOs could be included in animal health surveillance strategies, although standardisation of data for this purpose is needed so that changes in prevalence following implementation of prevention strategies can be monitored.

Contact with Mature Cows and Access to Pasture during Early Life Shape Dairy Heifer Behaviour at Integration into the Milking Herd.

This study aimed to determine the effects of early-life physical and social enrichment on the ability of dairy heifers to integrate into a herd of mature cows. Fifty heifer calves were reared from the ages of 2-13 weeks in one of three treatments: (1) Hand-reared and group-housed in sheds (CC); (2) Hand-reared and group-housed at pasture (-S); or (3) Hand-reared and group-housed at pasture, with 3 non-familial dry cows per group (+S). At 23 months of age, these heifers were introduced in groups to small herds of cows (Cows) at pasture. Social interactions were recorded continuously for two 1-h periods. Feeding, ruminating and resting behaviours of all animals and walking, standing and lying behaviours of 36 heifers only (+S = 14, -S = 13, CC = 9) were recorded for 48 h after mixing. Heifers that were managed as calves according to the CC treatment delivered less agonistic behaviour to other heifers after mixing than those reared in the +S or -S treatments (p = 0.002 and p = 0.041, respectively). On Day 2, +S heifers and cows spent the lowest proportion of time feeding (p = 0.961), with -S heifers spending significantly more time feeding than cows (p = 0.046), while CC heifers spent more time feeding than both +S heifers and cows (p = 0.027 and p < 0.002, respectively). Increasing the complexity of the early-life environment, particularly socially, may aid heifers in integrating into groups of multiparous cows later in life and shape their lifelong social experiences with same-age conspecifics.

Nonsense-mediated decay machinery in Plasmodium falciparum is inefficient and non-essential.

Nonsense-mediated decay (NMD) is a conserved mRNA quality control process that eliminates transcripts bearing a premature termination codon. In addition to its role in removing erroneous transcripts, NMD is involved in post-transcriptional regulation of gene expression via programmed intron retention in metazoans. The apicomplexan parasite Plasmodium falciparum shows relatively high levels of intron retention, but it is unclear whether these variant transcripts are functional targets of NMD. In this study, we use CRISPR-Cas9 to disrupt and epitope-tag the P. falciparum orthologs of two core NMD components: PfUPF1 (PF3D7_1005500) and PfUPF2 (PF3D7_0925800). We localize both PfUPF1 and PfUPF2 to puncta within the parasite cytoplasm and show that these proteins interact with each other and other mRNA-binding proteins. Using RNA-seq, we find that although these core NMD orthologs are expressed and interact in P. falciparum, they are not required for degradation of nonsense transcripts. Furthermore, our work suggests that the majority of intron retention in P. falciparum has no functional role and that NMD is not required for parasite growth ex vivo. IMPORTANCE In many organisms, the process of destroying nonsense transcripts is dependent on a small set of highly conserved proteins. We show that in the malaria parasite, these proteins do not impact the abundance of nonsense transcripts. Furthermore, we demonstrate efficient CRISPR-Cas9 editing of the malaria parasite using commercial Cas9 nuclease and synthetic guide RNA, streamlining genomic modifications in this genetically intractable organism.

Recently Acquired Blood-borne Virus Infections in Australian Deceased Organ Donors: Estimation of the Residual Risk of Unexpected Transmission.

Unexpected donor-derived infections of hepatitis B virus (HBV), hepatitis C virus (HCV), and HIV are rare but important potential complications of deceased organ transplantation. The prevalence of recently acquired (yield) infections has not been previously described in a national cohort of Australian deceased organ donors. Donor yield infections are of particularly significance, as they can be used to gain insights in the incidence of disease in the donor pool and in turn, estimate the risk of unexpected disease transmission to recipients. Methods: We conducted a retrospective review of all patients who commenced workup for donation in Australia between 2014 and 2020. Yield cases were defined by having both unreactive serological screening for current or previous infection and reactive nucleic acid testing screening on initial and repeat testing. Incidence was calculated using a yield window estimate and residual risk using the incidence/window period model. Results: The review identified only a single yield infection of HBV in 3724 persons who commenced donation workup. There were no yield cases of HIV or HCV. There were no yield infections in donors with increased viral risk behaviors. The prevalence of HBV, HCV, and HIV was 0.06% (0.01-0.22), 0.00% (0-0.11), and 0.00% (0-0.11), respectively. The residual risk of HBV was estimated to be 0.021% (0.001-0.119). Conclusions: The prevalence of recently acquired HBV, HCV, and HIV in Australians who commence workup for deceased donation is low. This novel application of yield-case-methodology has produced estimates of unexpected disease transmission which are modest, particularly when contrasted with local average waitlist mortality. Supplemental Visual Abstract; http://links.lww.com/TXD/A503.

Prehabilitation in high-risk patients scheduled for major abdominal cancer surgery: a feasibility study.

BACKGROUND: Patients presenting for major surgery with low cardiorespiratory fitness (deconditioning) and other modifiable risk factors are at increased risk of postoperative complications. This study investigated the feasibility of delivering prehabilitation in high-risk patients scheduled for major abdominal cancer surgery. METHODS: Eligible patients in this single-center cohort study included patients with poor fitness (objectively assessed by cardiopulmonary exercise testing, CPET) scheduled for elective major abdominal cancer surgery. Patients were recruited to participate in a prehabilitation program that spanned up to 6 weeks pre-operatively and comprised aerobic and resistance exercise training, breathing exercise, and nutritional support. The primary outcome assessed pre-specified feasibility targets: recruitment >70%, retention >85%, and intervention adherence >70%. Secondary outcomes were assessed for improved pre-operative functional status and health-related quality of life and for postoperative complications. RESULTS: Eighty-two (34%) out of 238 patients screened between April 2018 and December 2019 were eligible for recruitment. Fifty (61%) patients (52% males) with a median age of 71 (IQR, 63-77) years participated in the study. Baseline oxygen consumption the at anaerobic threshold and at peak exercise (mean±SD: 9.8±1.8 and 14.0±2.9 mL/kg/min, respectively) confirmed the deconditioned state of the study cohort. The retention rate within the prehabilitation program was 84%, with 42 participants returning for repeat CPET testing. While >60% of participants preferred to do home-based prehabilitation, adherence to the intervention was low-with only 12 (28%) and 15 (35%) of patients having self-reported compliance >70% with their exercise prescriptions. CONCLUSION: Our prehabilitation program in high-risk cancer surgery patients did not achieve pre-specified targets for recruitment, retention, and self-reported program adherence. These findings underpin the importance of implementation research and strategies for the prehabilitation programs in major surgery. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry ( ACTRN12620000073909 ) retrospectively registered.

The impact of inter-observer variation in delineation on robustness of radiomics features in non-small cell lung cancer.

Artificial intelligence and radiomics have the potential to revolutionise cancer prognostication and personalised treatment. Manual outlining of the tumour volume for extraction of radiomics features (RF) is a subjective process. This study investigates robustness of RF to inter-observer variation (IOV) in contouring in lung cancer. We utilised two public imaging datasets: 'NSCLC-Radiomics' and 'NSCLC-Radiomics-Interobserver1' ('Interobserver'). For 'NSCLC-Radiomics', we created an additional set of manual contours for 92 patients, and for 'Interobserver', there were five manual and five semi-automated contours available for 20 patients. Dice coefficients (DC) were calculated for contours. 1113 RF were extracted including shape, first order and texture features. Intraclass correlation coefficient (ICC) was computed to assess robustness of RF to IOV. Cox regression analysis for overall survival (OS) was performed with a previously published radiomics signature. The median DC ranged from 0.81 ('NSCLC-Radiomics') to 0.85 ('Interobserver'-semi-automated). The median ICC for the 'NSCLC-Radiomics', 'Interobserver' (manual) and 'Interobserver' (semi-automated) were 0.90, 0.88 and 0.93 respectively. The ICC varied by feature type and was lower for first order and gray level co-occurrence matrix (GLCM) features. Shape features had a lower median ICC in the 'NSCLC-Radiomics' dataset compared to the 'Interobserver' dataset. Survival analysis showed similar separation of curves for three of four RF apart from 'original_shape_Compactness2', a feature with low ICC (0.61). The majority of RF are robust to IOV, with first order, GLCM and shape features being the least robust. Semi-automated contouring improves feature stability. Decreased robustness of a feature is significant as it may impact upon the features' prognostic capability.

Factors Associated With Discharge Destination in Community-Dwelling Adults Admitted to Acute General Medical Units.

BACKGROUND AND PURPOSE: General medical patients often present to the hospital with medical, social, cognitive, and functional issues that may impact discharge destination. The aim of this study was to investigate the association between patient factors at hospital admission and discharge destination in general medical patients. METHODS: This was a prospective, single-site observational study conducted on the general medical wards at a tertiary hospital. Inpatients admitted to the general medical unit and referred to physical therapy were included. Patients admitted from residential care were excluded. MAIN OUTCOME MEASURES: Data were collected a median of 2 days (interquartile range: 1-3) from hospital admission and included demographics, comorbidities (Charlson Comorbidity Index), premorbid physical function (Blaylock Risk Assessment Screening Score, BRASS), current function (de Morton Mobility Index, DEMMI and Alpha Functional Independence Measure, AlphaFIM), and cognition (Rowland Universal Dementia Assessment Scale, RUDAS). RESULTS: Between July 2016 and August 2017, 417 patients were recruited (53% female, median age: 81 years (interquartile range: 76-86). Of these, 245 patients were discharged directly home; 172 were not discharged home of whom 140 were discharged to a subacute temporary facility providing further opportunity for therapy and discharge planning. Patients discharged directly home had higher functional, mobility, and cognitive scores. Data were partitioned into training, validation, and test sets to provide unbiased estimates of sensitivity, specificity, receiver operating characteristic curve, and area under the curve. Models best associated with discharge were "DEMMI and toilet transfers" (sensitivity 82.1%, specificity 66.2%, area under the curve 83.8%, 95% confidence interval: 76.4-91.2) and "AlphaFIM and walking independence" (sensitivity: 66.7%, specificity: 83.1%, area under the curve: 81.5, 95% confidence interval: 73.2-89.7). CONCLUSION: Two models were created that differentiated between discharge home and not home and had similar statistical measures of validity. Although the models require further validation, clinicians should consider whether identification of patients likely to be discharged home or not home is of greater relevance for their clinical setting.

Using proteomics to advance the search for potential biomarkers for preeclampsia: A systematic review and meta-analysis.

BACKGROUND: Preeclampsia (PE) is a leading cause of maternal and perinatal morbidity and mortality worldwide. Although predictive multiparametric screening is being developed, it is not applicable to nulliparous women, and is not applied to low-risk women. As PE is considered a heterogenous disorder, it is unlikely that any single multiparametric screening protocol containing a small group of biomarkers could have the required accuracy to predict all PE subgroups. Given the etiology of PE is complex and not fully understood, it begs the question, whether the search for biomarkers based on the predominant view of impaired placentation involving factors predominately implicated in angiogenesis and inflammation, has been too limiting. Here we highlight the enormous potential of state-of-the-art, high-throughput proteomics, to provide a comprehensive and unbiased approach to biomarker identification. METHODS AND FINDINGS: Our literature search identified 1336 articles; after review, 45 studies with proteomic data from PE women that were eligible for inclusion. From 710 proteins with altered abundance, we identified 13 common circulating proteins, some of which had not been previously considered as prospective biomarkers of PE. An additional search of the literature for original publications testing any of the 13 common proteins using non-proteomic techniques was also undertaken. Strikingly, 9 of these common proteins had been independently evaluated in PE studies as potential biomarkers. CONCLUSION: This study highlights the potential of using high-throughput data sets, which are comprehensive and without bias, to identify a profile of proteins that may improve predictions of PE and understanding of its etiology. We bring to the attention of the medical and research communities that the strengths and advantages of using data from high-throughput studies for biomarker discovery would be increased dramatically, if first and second trimester samples were collected for proteomics, and if standardized guidelines for patient reporting and data collection were implemented.