Safety and Efficacy of Mucograft Porcine Collagen Bioengineered Acellular Dermal Matrix as a Spacer Graft in Lower Eyelid Elevation Surgery.

Background: Recent regulatory changes have limited the access to a widely used commercially available bioengineered acellular dermal matrix (BADM) product as a spacer graft in the surgical correction of lower eyelid retraction. We report our off-label usage of Mucograft, a porcine BADM, as an alternative BADM. Methods: A retrospective review was conducted of patients undergoing bilateral lower lid surgery with Mucograft (12 eyes) at a single institution. Results: For the six patients, there was a mean lower lid elevation of 1.93 mm, without any serious complications. There was greater elevation of the lower lid position for the Mucograft group compared with four septo-retractor control patients (1.93 versus 0.94mm, P = 0.008). Conclusion: Mucograft performed satisfactorily, and further investigation is warranted regarding its longer-term safety and efficacy.

Translating the potential of the urine steroid metabolome to stage NAFLD (TrUSt-NAFLD): study protocol for a multicentre, prospective validation study.

INTRODUCTION: Non-alcoholic fatty liver disease (NAFLD) affects approximately one in four individuals and its prevalence continues to rise. The advanced stages of NAFLD with significant liver fibrosis are associated with adverse morbidity and mortality outcomes. Currently, liver biopsy remains the 'gold-standard' approach to stage NAFLD severity. Although generally well tolerated, liver biopsies are associated with significant complications, are resource intensive, costly, and sample only a very small area of the liver as well as requiring day case admission to a secondary care setting. As a result, there is a significant unmet need to develop non-invasive biomarkers that can accurately stage NAFLD and limit the need for liver biopsy. The aim of this study is to validate the use of the urine steroid metabolome as a strategy to stage NAFLD severity and to compare its performance against other non-invasive NAFLD biomarkers. METHODS AND ANALYSIS: The TrUSt-NAFLD study is a multicentre prospective test validation study aiming to recruit 310 patients with biopsy-proven and staged NAFLD across eight centres within the UK. 150 appropriately matched control patients without liver disease will be recruited through the Oxford Biobank. Blood and urine samples, alongside clinical data, will be collected from all participants. Urine samples will be analysed by liquid chromatography-tandem mass spectroscopy to quantify a panel of predefined steroid metabolites. A machine learning-based classifier, for example, Generalized Matrix Relevance Learning Vector Quantization that was trained on retrospective samples, will be applied to the prospective steroid metabolite data to determine its ability to identify those patients with advanced, as opposed to mild-moderate, liver fibrosis as a consequence of NAFLD. ETHICS AND DISSEMINATION: Research ethical approval was granted by West Midlands, Black Country Research Ethics Committee (REC reference: 21/WM/0177). A substantial amendment (TrUSt-NAFLD-SA1) was approved on 26 November 2021. TRIAL REGISTRATION NUMBER: ISRCTN19370855.

Preliminary results from the Australian Genetics of Bipolar Disorder Study: A nation-wide cohort.

OBJECTIVE: The Australian Genetics of Bipolar Disorder Study is a nation-wide cohort of adults living with bipolar disorder. The study aims to detect the relationships between genetic risk, symptom severity, and the lifetime prevalence of bipolar disorder, treatment response and medication side effects, and patterns and costs of health care usage. METHODS: A total of 6682 participants (68.3% female; aged 44.8 ± 13.6 years [range = 18-90]) were recruited in three waves: a nation-wide media campaign, a mail-out based on prescriptions for lithium carbonate and through the Australian Genetics of Depression Study. Participants completed a self-report questionnaire. A total of 4706 (70%) participants provided a saliva sample and were genotyped and 5506 (82%) consented to record linkage of their Pharmaceutical and Medicare Benefits Schedule data. RESULTS: Most participants were living with bipolar I disorder (n = 4068) while 1622 participants were living with bipolar II disorder and 992 with sub-threshold bipolar disorder. The mean age of bipolar disorder diagnosis was 32.7 ± 11.6 years but was younger in bipolar I (p = 2.0E-26) and females (p = 5.7E-23). Excluding depression with onset prior to bipolar disorder diagnosis, 64.5% of participants reported one or more co-occurring psychiatric disorders: most commonly generalised anxiety disorder (43.5%) and posttraumatic stress disorder (20.7%). Adverse drug reactions were common and resulted in discontinuation rates ranging from 33.4% for lithium to 63.0% for carbamazepine. CONCLUSION: Our findings highlight the high rate of comorbidities and adverse drug reactions among adults living with bipolar disorder in the general Australian population. Future genomic analyses focus on identifying genetic variants influencing pharmacotherapy treatment response and side effects.

Predictors of Return to Activity at 2 Years After Anterior Cruciate Ligament Reconstruction Among Patients With High Preinjury Marx Activity Scores: A MOON Prospective Cohort Study.

BACKGROUND: Predictors of return to activity after anterior cruciate ligament reconstruction (ACLR) among patients with relatively high preinjury activity levels remain poorly understood. PURPOSE/HYPOTHESIS: The purpose of this study was to identify predictors of return to preinjury levels of activity after ACLR, defined as achieving a Marx activity score within 2 points of the preinjury value, among patients with Marx activity scores of 12 to 16 who had been prospectively enrolled in the Multicenter Orthopaedic Outcomes Network (MOON) cohort. We hypothesized that age, sex, preinjury activity level, meniscal injuries and/or procedures, and concurrent articular cartilage injuries would predict return to preinjury activity levels at 2 years after ACLR. STUDY DESIGN: Cohort study; Level of evidence, 2. METHODS: All unilateral ACLR procedures from 2002 to 2008 performed in patients enrolled in the MOON, with preinjury Marx activity scores ranging from 12 to 16, were evaluated with a specific focus on return to preinjury activity levels at 2 years postoperatively. Return to activity was defined as a Marx activity score within 2 points of the preinjury value. The proportion of patients able to return to preinjury activity levels was calculated, and multivariable modeling was performed to identify risk factors for patients' inability to return to preinjury activity levels. RESULTS: A total of 1188 patients were included in the final analysis. The median preinjury Marx activity score was 16 (interquartile range, 12-16). Overall, 466 patients (39.2%) were able to return to preinjury levels of activity, and 722 patients (60.8%) were not able to return to preinjury levels of activity. Female sex, smoking at the time of ACLR, fewer years of education, lower 36-Item Short Form Health Survey Mental Component Summary scores, and higher preinjury Marx activity scores were predictive of patients' inability to return to preinjury activity levels. Graft type, revision ACLR, the presence of medial and/or lateral meniscal injuries, a history of meniscal surgery, the presence of articular cartilage injuries, a history of articular cartilage treatment, and the presence of high-grade knee laxity were not predictive of a patient's ability to return to preinjury activity level. CONCLUSION: At 2 years after ACLR, most patients with high preinjury Marx activity scores did not return to their preinjury level of activity. The higher the preinjury Marx activity score that a patient reported at the time of enrollment, the less likely he/she was able to return to preinjury activity level. Smoking and lower mental health at the time of ACLR were the only modifiable risk factors in this cohort that predicted an inability to return to preinjury activity levels. Continued effort and investigation are required to maximize functional recovery after ACLR in patients with high preinjury levels of activity.

Meta-analysis: Enhanced liver fibrosis test to identify hepatic fibrosis in chronic liver diseases.

BACKGROUND & AIMS: Patients with liver disease can be stratified for risk of liver-related ill health by degree of hepatic fibrosis. The Enhanced liver fibrosis (ELF) test was developed to quantify hepatic fibrosis non-invasively and is widely used. The objective of this review was to identify and synthesise the evidence on the diagnostic accuracy of the ELF test for staging of hepatic fibrosis. APPROACH & RESULTS: Searches of PubMed and EMBASE were conducted between October 2020 and November 2021 to identify studies reporting the diagnostic accuracy of the ELF test compared to histology in liver disease patients. QUADAS-2 was used to assess risk of bias in each study. Meta-analysis using the multiple thresholds model described by Steinhauser S, Schumacher M, Rücker G. Modelling multiple thresholds in meta-analysis of diagnostic test accuracy studies. BMC Med. Res. Methodol. 2016;16. 10.1186/s12874-016-0196-1 allowed synthesis of 2 × 2 data at different cut-offs. Sixty-three studies were included in this review. These studies included 19,285 patients with or at risk of liver disease from viral hepatitis, Non-Alcoholic Fatty Liver Disease, Alcohol-related Liver Disease and other mixed chronic liver diseases. The prevalence of significant fibrosis, advanced fibrosis and cirrhosis was 47.5%, 39.2% and 4.4%, respectively. Cut-offs with maximal Youden index were generated with AUROC = 0.811 (95% CI: 0.736-0.870), 0.812 (95% CI: 0.758-0.856) and 0.810 (95% CI: 0.694-0.888) to detect significant fibrosis, advanced fibrosis or cirrhosis, respectively. Diagnostic accuracy of the ELF test varied between different liver diseases and cut-offs to detect each stage with 95% sensitivity or specificity were also generated. CONCLUSIONS: Meta-analysis revealed considerable variability in the ability of ELF to stage fibrosis across disease aetiologies. Research has mostly focused on viral hepatitis and NAFLD. There is currently a lack of data on the value of the ELF test in Alcohol-related liver disease and patients in primary care settings.

Extra-hepatic morbidity and mortality in alcohol-related liver disease: Systematic review and meta-analysis.

BACKGROUND: Alcohol use increases the risk of many conditions in addition to liver disease; patients with alcohol-related liver disease (ALD) are therefore at risk from both extra-hepatic and hepatic disease. AIMS: This review synthesises information about non-liver-related mortality in persons with ALD. METHODS: A systematic literature review was performed to identify studies describing non-liver outcomes in ALD. Information about overall non-liver mortality was extracted from included studies and sub-categorised into major causes: cardiovascular disease (CVD), non-liver cancer and infection. Single-proportion meta-analysis was done to calculate incidence rates (events/1000 patient-years) and relative risks (RR) compared with control populations. RESULTS: Thirty-seven studies describing 50 302 individuals with 155 820 patient-years of follow-up were included. Diabetes, CVD and obesity were highly prevalent amongst included patients (5.4%, 10.4% and 20.8% respectively). Outcomes varied across the spectrum of ALD: in alcohol-related fatty liver the rate of non-liver mortality was 43.4/1000 patient-years, whereas in alcoholic hepatitis the rate of non-liver mortality was 22.5/1000 patient-years. The risk of all studied outcomes was higher in ALD compared with control populations: The RR of death from CVD was 2.4 (1.6-3.8), from non-hepatic cancer 2.2 (1.6-2.9) and from infection 8.2 (4.7-14.3). CONCLUSION: Persons with ALD are at high risk of death from non-liver causes such as cardiovascular disease and non-hepatic cancer.

The Natural History of Advanced Chronic Liver Disease Defined by Transient Elastography.

BACKGROUND & AIMS: The clinical course of cirrhosis does not follow a predictable trajectory. Transient elastography (TE) is commonly used in clinical practice to diagnose liver fibrosis and increasingly to risk stratify patients. The aim of this study was to assess the natural history of advanced chronic liver disease (ACLD) defined by TE using electronic health record (EHR) data in a multistate framework. METHODS: TE data were collected between 2008 and 2019. Patients with a liver stiffness measurement (LSM) >10 kPa were included. Disease and procedure code information held in EHR was analyzed. Clinical events including decompensation, hepatocellular carcinoma (HCC), and death were identified. Outcomes were described in a multistate model using flexible parametric survival methods including LSM and the albumin bilirubin (ALBI) score. RESULTS: Three thousand and twenty eight patients were included. Median follow up was 3.1 years. LSM and ALBI were associated with the development of varices and decompensation, and ALBI, age, sex, and viral liver disease were associated with the development of HCC from the compensated state. The cumulative incidence of HCC before decompensation was low for patients with alcohol-related liver disease (3.8%) and nonalcoholic fatty liver disease (1.3%) at 5 years after TE. Importantly, death was predicted to occur before decompensation or HCC in most cases. CONCLUSIONS: Liver stiffness, ALBI score, and disease etiology are each associated with outcomes in a large contemporary cohort with ACLD. EHR data can be used to define clinical progression in these patients, facilitating large clinical effectiveness trials and cost-effectiveness analyses.

Do Patellar Tendon Repairs Have Better Outcomes than Quadriceps Tendon Repairs? A Prospective Cohort Analysis.

Patellar tendon (PT) and quadriceps tendon (QT) ruptures represent significant injuries and warrant surgical intervention in most patients. Outcome data are predominantly retrospective analyses with low sample sizes. There are also minimal data comparing QT and PT repairs and the variables impacting patient outcomes. The level of evidence of the study is level II (prognosis). From the prospective OME cohort, 189 PT or QT repairs were performed between February 2015 and October 2019. Of these, 178 were successfully enrolled (94.2%) with 1-year follow-up on 141 (79.2%). Baseline demographic data included age, sex, race, BMI, years of education, smoking status, and baseline VR-12 MCS score. Surgical and follow-up data included surgeon volume, fixation technique, baseline, and 1-year Knee Injury and Osteoarthritis Outcome Score-Pain (KOOS-Pain), Knee Injury and Osteoarthritis Outcome Score-Physical Function (KOOS-PS), and 1-year Patient Acceptable Symptom State (PASS) scores and complications. Multivariable regression analysis was utilized to identify prognosis and significant risk factors for outcomes-specifically, whether KOOS-Pain or KOOS-PS were different between QT versus PT repairs. There were 59 patients in the PT cohort and 82 patients in QT cohort. Baseline demographic data demonstrated that PT cohort was younger (45.1 vs. 59.5 years, p <0.001), included significantly fewer patients of White race (51.7 vs. 80.0%, p = 0.001), lesser number of years of education (13.9 vs. 15.2 years, p = 0.020), a higher percentage of "high" surgeon volume (72.9% vs. 43.9%, p = 0.001) and 25.4% of PT repairs had supplemental fixation (QT had zero, p <0.001). Multivariable analysis identified gender (female-worse, p = 0.001), years of education (higher-better, p = 0.02), and baseline KOOS-Pain score (higher-better, p <0.001) as the risk factors that significantly predicted KOOS-Pain score. The risk factors that significantly predicted KOOS-PS were gender (female worse, p = 0.033), race (non-White-worse, p <0.001), baseline VR-12 MCS score (higher-better, p <0.001), and baseline KOOS-PS score (higher better, p = 0.029). KOOS-Pain and KOOS-PS scores improved after both QT and PT repairs. Patient reported pain and function at 1 year were similar between PT and QT repairs after adjusting for known risk factors. Multivariable analysis identified female gender and low baseline KOOS scores as predictors for worse outcomes.

Outcomes After Liver Transplantation With Incidental Cholangiocarcinoma.

Cholangiocarcinoma (CCA) is currently a contraindication to liver transplantation (LT) in the United Kingdom (UK). Incidental CCA occurs rarely in some patients undergoing LT. We report on retrospective outcomes of patients with incidental CCA from six UK LT centres. Cases were identified from pathology records. Data regarding tumour characteristics and post-transplant survival were collected. CCA was classified by TNM staging and anatomical location. 95 patients who underwent LT between 1988-2020 were identified. Median follow-up after LT was 2.1 years (14 days-18.6 years). Most patients were male (68.4%), median age at LT was 53 (IQR 46-62), and the majority had underlying PSC (61%). Overall median survival after LT was 4.4 years. Survival differed by tumour site: 1-, 3-, and 5-year estimated survival was 82.1%, 68.7%, and 57.1%, respectively, in intrahepatic CCA (n = 40) and 58.5%, 42.6%, and 30.2% in perihilar CCA (n = 42; p = 0.06). 1-, 3-, and 5-year estimated survival was 95.8%, 86.5%, and 80.6%, respectively, in pT1 tumours (28.2% of cohort), and 65.8%, 44.7%, and 31.1%, respectively, in pT2-4 (p = 0.018). Survival after LT for recipients with incidental CCA is inferior compared to usual outcomes for LT in the United Kingdom. LT for earlier stage CCA has similar survival to LT for hepatocellular cancer, and intrahepatic CCAs have better survival compared to perihilar CCAs. These observations may support LT for CCA in selected cases.

Pela urgente e definitiva inclusão dos campos de identidade de gênero e orientação sexual nos sistemas de informação em saúde do SUS: o que podemos aprender com o surto de monkeypox? / A call for the urgent and definitive inclusion of gender identity and sexual orientation data in the Brazilian health information systems: what can we learn from the monkeypox outbreak?

Resumo Neste documento trazemos um posicionamento para a comunidade científica e a sociedade civil acerca do desafio imposto à vigilância e às ações em saúde no Brasil relacionadas à monkeypox. Apresentamos pontos e encaminhamentos que podem subsidiar os aprendizados e os avanços a partir do atual cenário.

Abstract In this document, we present to the scientific community a proposal on how to deal with the challenge imposed on surveillance and health actions in Brazil regarding monkeypox, including points and directions that have the potential to support learning and enable advances in the current scenario.

Evaluation of Health Care Disparities in Patients With Anterior Cruciate Ligament Injury: Does Race and Insurance Matter?

Background: It is unknown whether race- or insurance-based disparities in health care exist regarding baseline knee pain, knee function, complete meniscal tear, or articular cartilage damage in patients who undergo anterior cruciate ligament reconstruction (ACLR). Hypothesis: Black patients and patients with Medicaid evaluated for ACLR would have worse baseline knee pain, worse knee function, and greater odds of having a complete meniscal tear. Study Design: Cross-sectional study; Level of evidence, 3. Methods: A cohort of patients (N = 1463; 81% White, 14% Black, 5% Other race; median age, 22 years) who underwent ACLR between February 2015 and December 2018 was selected from an institutional database. Patients who underwent concomitant procedures and patients of undisclosed race or self-pay status were excluded. The associations of race with preoperative Knee injury and Osteoarthritis Outcome Score (KOOS) Pain subscale, KOOS Function subscale, and intraoperatively assessed complete meniscal tear (tear that extended through both the superior and the inferior meniscal surfaces) were determined via multivariate modeling with adjustment for age, sex, insurance status, years of education, smoking status, body mass index (BMI), meniscal tear location, and Veterans RAND 12-Item Health Survey Mental Component Score (VR-12 MCS). Results: The 3 factors most strongly associated with worse KOOS Pain and KOOS Function were lower VR-12 MCS score, increased BMI, and increased age. Except for age, the other two factors had an unequal distribution between Black and White patients. Univariate analysis demonstrated equal baseline median KOOS Pain scores (Black, 72.2; White, 72.2) and KOOS Function scores (Black, 68.2; White, 68.2). After adjusting for confounding variables, there was no significant difference between Black and White patients in KOOS Pain, KOOS Function, or complete meniscal tears. Insurance status was not a significant predictor of KOOS Pain, KOOS Function, or complete meniscal tear. Conclusion: There were clinically significant differences between Black and White patients evaluated for ACLR. After accounting for confounding factors, no difference was observed between Black and White patients in knee pain, knee function, or complete meniscal tear. Insurance was not a clinically significant predictor of knee pain, knee function, or complete meniscal tear.

Posteromedial Tibial Bone Bruise After Anterior Cruciate Ligament Injury: An MRI Study of Bone Bruise Patterns in 208 Patients.

Background: Bone bruise patterns after anterior cruciate ligament (ACL) rupture may predict the presence of intra-articular pathology and help explain the mechanism of injury. Lateral femoral condyle (LFC) and lateral tibial plateau (LTP) bone bruises are pathognomic to ACL rupture. There is a lack of information regarding medial tibial plateau (MTP) and medial femoral condyle (MFC) bone bruises. Purpose: To summarize the prevalence and location of MTP bone bruises with acute ACL rupture and to determine the predictors of MTP bone bruises. Study Design: Cross-sectional study; Level of evidence, 3. Methods: Inclusion criteria were patients who underwent ACL reconstruction between February 2015 and November 2017, magnetic resonance imaging (MRI) within 90 days of injury, and participation in the database. Exclusion criteria included previous ipsilateral surgery, multiligamentous injuries, and incomplete imaging. Due to the large number of cases remaining (n = 600), 150 patients were selected randomly from each year included in the study, for a total of 300 patients. Two readers independently reviewed injury MRI scans using the Costa-Paz bone bruise grading system. Logistic regression was used to identify factors associated with MTP bone bruises. Results: Included were 208 patients (mean age, 23.8 years; mean body mass index, 25.6). The mechanism of injury was noncontact in 59% of injuries, with over half from soccer, basketball, and football. The median time from injury to MRI scan was 12 days. Of the 208 patients, 98% (203/208) had a bone bruise, 79% (164/208) had an MTP bone bruise, and 83% (172/208) had bruises in both medial and lateral compartments. The most common pattern, representing 46.6% of patients (97/208), was a bruise in all 4 locations (MFC, LFC, MTP, and LTP). Of the 164 MTP bruises, 160 (98%) involved the posterior third of the plateau, and 161 were grade 1. The presence of an MFC bruise was the only independent risk factor for an MTP bruise (odds ratio, 3.71). The resulting nomogram demonstrated MFC bruise, sport, and mechanism of injury were the most important predictors of an MTP bruise. Conclusion: MTP bruise after acute ACL rupture was as prevalent as lateral bruises. The presence of a posterior MTP bruise suggested anterior tibial translation at the time of injury and could portend more medial compartment pathology at the time of injury than previously recognized.

Intra-articular Hip Injuries in National Basketball Association Players: A Descriptive Epidemiological Study.

Background: Since the most recent epidemiologic study of injuries in National Basketball Association (NBA) players was completed in 2012, the understanding and diagnosis of intra-articular hip injury has advanced. Purpose: To report the epidemiology of intra- versus extra-articular hip injuries in NBA players with regard to missed games, risk factors for injury, and treatment types. Study Design: Cohort study; Level of evidence, 3. Methods: The NBA injury database was queried for all reported hip and groin injuries from 2013 to 2017. The injuries were then divided into intra-articular and extra-articular types. Variables compared between injury types included player age, NBA tenure, season schedule (preseason or offseason), onset type, injury mechanism, roster position, games missed, time to return to play, and need for surgery. Results: A total of 224 athletes sustaining 353 total hip pathologies were identified. Of these injuries, 216 (61.2%) were sustained during game competition and affected 156 (69.6%) of the athletes. Intra-articular injuries represented 39 (11.0%) cases and involved 36 (16.1%) players. The time to return to play was significantly longer after intra-articular versus extra-articular injury (44.6 ± 96.0 vs 11.8 ± 32.0 days; P = .03), and the number of games missed was significantly greater after intra-articular versus extra-articular injury (8.0 ± 18.7 vs 1.54 ± 4.9 games; P = .03). Patients with intra-articular hip injuries were more likely to undergo surgery (odds ratio, 5.5 [95% CI, 1.8-16.7]; P = .005). There was no statistically significant difference in the number of games missed due to surgery (35.2 ± 8.3 [intra-articular] vs 35.4 ± 11.6 [extra-articular]; P = .42) or nonoperative treatment (4.2 ± 3.4 [intra-articular] vs 1.3 ± 0.5 [extra-articular]; P = .11). Years of NBA tenure were not significantly different between intra-articular and extra-articular injuries (7.1 ± 3.7 vs 6.3 ± 4.0 years). For both types of hip injury, there was no correlation between player age and either days to return to play or number of games missed (R 2 = 0.014). Conclusion: NBA players with intra-articular hip injuries underwent surgery more frequently and had a longer return-to-play time compared with those with extra-articular hip injuries. NBA tenure and player age were not correlated with the risk of developing hip injury or the need for surgery.

Does a screening checklist for complex health and social care needs have potential clinical usefulness for predicting unplanned hospital readmissions in intensive care survivors: development and prospective cohort study.

OBJECTIVES: Intensive care (ICU) survivors are at high risk of long-term physical and psychosocial problems. Unplanned hospital readmission rates are high, but the best way to triage patients for interventions is uncertain. We aimed to develop and evaluate a screening checklist to help predict subsequent readmissions or deaths. DESIGN: A checklist for complex health and social care needs (CHSCNs) was developed based on previous research, comprising six items: multimorbidity; polypharmacy; frequent previous hospitalisations; mental health issues; fragile social circumstances and impaired activities of daily living. Patients were considered to have CHSCNs if two or more were present. We prospectively screened all ICU discharges for CHSCNs for 12 months. SETTING: ICU, Royal Infirmary, Edinburgh, UK. PARTICIPANTS: ICU survivors over a 12-month period (1 June 2018 and 31 May 2019). INTERVENTIONS: None. OUTCOME MEASURE: Readmission or death in the community within 3 months postindex hospital discharge. RESULTS: Of 1174 ICU survivors, 937 were discharged alive from the hospital. Of these 253 (27%) were classified as having CHSCNs. In total 28% (266/937) patients were readmitted (N=238) or died (N=28) within 3 months. Among CHSCNs patients 45% (n=115) patients were readmitted (N=105) or died (N=10). Patients without CHSCNs had a 22% readmission (N=133) or death (N=18) rate. The checklist had: sensitivity 43% (95% CI 37% to 49%), specificity 79% (95% CI 76% to 82%), positive predictive value 45% (95% CI 41% to 51%), and negative predictive value 78% (95% CI 76% to 80%). Relative risk of readmission/death for patients with CHSCNs was 2.06 (95% CI 1.69 to 2.50), indicating a pretest to post-test probability change of 28%-45%. The checklist demonstrated high inter-rater reliability (percentage agreement ≥87% for all domains; overall kappa, 0.84). CONCLUSIONS: Early evaluation of a screening checklist for CHSCNs at ICU discharge suggests potential clinical usefulness, but this requires further evaluation as part of a care pathway.

Australian Parkinson's Genetics Study (APGS): pilot (n=1532).

PURPOSE: Parkinson's disease (PD) is a neurodegenerative disorder associated with progressive disability. While the precise aetiology is unknown, there is evidence of significant genetic and environmental influences on individual risk. The Australian Parkinson's Genetics Study seeks to study genetic and patient-reported data from a large cohort of individuals with PD in Australia to understand the sociodemographic, genetic and environmental basis of PD susceptibility, symptoms and progression. PARTICIPANTS: In the pilot phase reported here, 1819 participants were recruited through assisted mailouts facilitated by Services Australia based on having three or more prescriptions for anti-PD medications in their Pharmaceutical Benefits Scheme records. The average age at the time of the questionnaire was 64±6 years. We collected patient-reported information and sociodemographic variables via an online (93% of the cohort) or paper-based (7%) questionnaire. One thousand five hundred and thirty-two participants (84.2%) met all inclusion criteria, and 1499 provided a DNA sample via traditional post. FINDINGS TO DATE: 65% of participants were men, and 92% identified as being of European descent. A previous traumatic brain injury was reported by 16% of participants and was correlated with a younger age of symptom onset. At the time of the questionnaire, constipation (36% of participants), depression (34%), anxiety (17%), melanoma (16%) and diabetes (10%) were the most reported comorbid conditions. FUTURE PLANS: We plan to recruit sex-matched and age-matched unaffected controls, genotype all participants and collect non-motor symptoms and cognitive function data. Future work will explore the role of genetic and environmental factors in the aetiology of PD susceptibility, onset, symptoms, and progression, including as part of international PD research consortia.

Bayesian methods in palliative care research: cancer-induced bone pain.

OBJECTIVE: To show how a simple Bayesian analysis method can be used to improve the evidence base in patient populations where recruitment and retention are challenging. METHODS: A Bayesian conjugate analysis method was applied to binary data from the Thermal testing in Bone Pain (TiBoP) study: a prospective diagnostic accuracy/predictive study in patients with cancer-induced bone pain (CIBP). This study aimed to evaluate the clinical utility of a simple bedside tool to identify who was most likely to benefit from palliative radiotherapy (XRT) for CIBP. RESULTS: Recruitment and retention of patients were challenging due to the frail population, with only 27 patients available for the primary analysis. The Bayesian method allowed us to make use of prior work done in this area and combine it with the TiBoP data to maximise the informativeness of the results. Positive and negative predictive values were estimated with greater precision, and interpretation of results was facilitated by use of direct probability statements. In particular, there was only 7% probability that the true positive predictive value was above 80%. CONCLUSIONS: Several advantages of using Bayesian analysis are illustrated in this article. The Bayesian method allowed us to gain greater confidence in our interpretation of the results despite the small sample size by allowing us to incorporate data from a previous similar study. We suggest that this method is likely to be useful for the analysis of small diagnostic or predictive studies when prior information is available.

The Placebo Response in Randomized Trials in Nonalcoholic Steatohepatitis Simply Explained.

BACKGROUND & AIMS: Liver histology is the primary endpoint in phase III trials in nonalcoholic steatohepatitis (NASH). There is an appreciable response to placebo that confounds endpoint assessment. The aim of this study was to quantify contributors to the placebo response and its impact on liver fibrosis improvement. METHODS: Estimates of fibrosis improvement in placebo-treated participants were made using probabilistic simulation. Each simulated trial included 120 participants. Parameters considered in the model included sampling and observer variability, regression to the mean, and net fibrosis progression calibrated to reported trial outcomes. RESULTS: In large phase IIb and III trials, 22% of placebo-treated participants with fibrosis stage 2 or 3 NASH at baseline improved by at least 1 fibrosis stage with minimal net disease progression. Estimates of sampling and observer variability in simultaneous biopsy studies highlighted an imbalance where apparent fibrosis improvement was more likely than worsening. Using these estimates and known trial outcomes, net fibrosis progression was estimated at 0.05 stages per year. Simulations of the placebo response rate showed a rate of 22% with 80% of trials falling between 15 and 30%, in keeping with trials reported to date. Additional increases in observer variability further increased the placebo response. CONCLUSIONS: The analyses presented simply define the placebo response in liver fibrosis in trials in NASH in terms of sampling and observer variability, regression to the mean, and fibrosis progression. Factors relating to liver biopsy are largely unmodifiable, and the variation in placebo response rates, both simulated and observed, challenges the role of biopsy in trial endpoint assessment.

Large-scale fabrication of structurally coloured cellulose nanocrystal films and effect pigments.

Cellulose nanocrystals are renewable plant-based colloidal particles capable of forming photonic films by solvent-evaporation-driven self-assembly. So far, the cellulose nanocrystal self-assembly process has been studied only at a small scale, neglecting the limitations and challenges posed by the continuous deposition processes that are required to exploit this sustainable material in an industrial context. Here, we addressed these limitations by using roll-to-roll deposition to produce large-area photonic films, which required optimization of the formulation of the cellulose nanocrystal suspension and the deposition and drying conditions. Furthermore, we showed how metre-long structurally coloured films can be processed into effect pigments and glitters that are dispersible, even in water-based formulations. These promising effect pigments are an industrially relevant cellulose-based alternative to current products that are either micro-polluting (for example, non-biodegradable microplastic glitters) or based on carcinogenic, unsustainable or unethically sourced compounds (for example, titania or mica).

Intact Removal of Orbital Lobe Tumors of the Lacrimal Gland, With or Without Lateral Wall Osteotomy.

PURPOSE: To examine the necessity for lateral osteotomy for intact removal of tumors within the orbital lobe of the lacrimal gland. METHODS: Patients who, between 1992 and 2020, were scheduled for intact excision of well-defined masses within the orbital lobe of the lacrimal gland were identified from an orbital database. A retrospective review of the clinical records was performed and details of the tumor size obtained from histopathological reports. The first patients in the series had lateral osteotomy, whereas later, there was a shift toward osteotomy-free tumor excision through a skin-crease incision. The latter approach required isolation of the gland's orbital lobe on an intact sheet of periosteum, an anterior "flip" of the mass (out of the orbit, past the orbital rim) "hinged" at the isthmus between the orbital and palpebral lobes, and finally a division of the isthmus to release the intact mass. RESULTS: Clinical details were available for 100 patients (50 male), with 56 tumors removed using lateral osteotomy and 44 without. The mean age at surgery was 50.3 years with osteotomy (median, 51.8; range, 19-85 years) and 51.1 years without (median, 50.3; range, 11-81 years; P = 0.81). There were no postoperative complications in either group. Although the range of tumor volumes was similar in the two groups (1.6-15.0 ml with osteotomy; 0.9-15.1 ml without), the average volume was somewhat greater in those having osteotomy (mean, 6.4 ml) as compared with those without (mean, 4.6 ml; P = 0.0016). Inadvertent rupture of the tumor occurred once in each group, with tumors of similar small size. CONCLUSIONS: In many cases, large masses within the orbital lobe of the lacrimal gland can be safely removed intact, using the described flip technique without the need for lateral wall osteotomy.

Refazendo a prevenção ao HIV na 5ª década da epidemia: lições da história social da Aids / Remaking HIV prevention in the 5th decade of the epidemic: lessons from the social history of AIDS

RESUMO A chegada da 5ª década da epidemia de Aids sob o impacto da pandemia da Covid-19 trouxe importantes desafios para a prevenção do HIV/Aids. Este ensaio buscou sistematizar as reflexões produzidas em projeto desenvolvido pela Associação Brasileira Interdisciplinar de Aids que conjugou debates sobre o momento presente das respostas à epidemia com o resgate da história social da Aids e da prevenção. Trata-se da história social da epidemia de Aids nos seus 40 anos e abordaram-se lições no campo da prevenção relevantes para repensar a prevenção na 5ª década. Apresentam-se princípios ético-políticos que fundamentaram respostas bem-sucedidas à Aids no Brasil, bem como apontam-se caminhos futuros, recomendando abordagens a serem adotadas e um pacote mínimo de recursos preventivos de acesso universal. Para evitar o desperdício da rica experiência acumulada ao longo da história social da Aids, propõe-se valorizar e recuperar lições aprendidas ao longo da história da prevenção, como a articulação de estratégias culturais e estruturais - fundamentadas em direitos e mobilização social - às estratégias de prevenção biomédicas e comportamentais e a combinação dos conceitos de vulnerabilidade e de direitos humanos, instrumentais para analisar os determinantes da epidemia e propor intervenções social e culturalmente apropriadas.

ABSTRACT The arrival of the 5th decade of the AIDS epidemic under the impact of the COVID-19 pandemic has brought important challenges for HIV/AIDS prevention. This essay sought to systematize the reflections produced in a project developed by the Brazilian Interdisciplinary AIDS Association that combined current debates on the responses to the epidemic with the rescue of the social history of AIDS and prevention. We deal with the social history of the AIDS epidemic in its 40 years and address lessons in the field of prevention that are relevant to rethinking prevention in the 5th decade. We present ethical-political principles that underpin successful responses to AIDS in Brazil, as well as point out future paths, recommending approaches to be adopted and a minimum package of preventive resources for universal access. To avoid wasting the rich experience accumulated throughout the social history of AIDS, we propose to value and recover lessons learned throughout the history of prevention, such as the articulation of cultural and structural strategies - based on rights and social mobilization - with biomedical and behavioral prevention strategies and the combination of the concepts of vulnerability and human rights, instrumental in analyzing the determinants of the epidemic and proposing socially and culturally appropriate interventions.