Prognostication for prelabor rupture of membranes and the time of delivery in nationwide insured women: development, validation, and deployment ImportancePrognostic predictions of prelabor rupture of membranes lack proper sample sizes and external validation.

ObjectiveTo develop, validate, and deploy statistical and/or machine learning prediction models using medical histories for prelabor rupture of membranes and the time of delivery.

DesignA retrospective cohort design within 2-year period (2015 to 2016) of a single-payer, government-owned health insurance database covering 75.8% individuals in a country

SettingNationwide healthcare providers (n=22,024) at primary, secondary, and tertiary levels

Participants12-to-55-year-old women that visit healthcare providers using the insurance from [~]1% random sample of insurance holders stratified by healthcare provider and category of family: (1) never visit; (2) visit only primary care; and (3) visit all levels of care

PredictorsMedical histories of diagnosis and procedure (International Classification of Disease version 10) before the latest visit of outcome within the database period

Main Outcomes and MeasuresPrelabor rupture of membranes prognostication (area under curve, with sensitivity, specificity, and likelihood ratio), the time of delivery estimation (root mean square error), and inference time (minutes), with 95% confidence interval

ResultsWe selected 219,272 women aged 33 {+/-} 12 years. The best prognostication achieved area under curve 0.73 (0.72 to 0.75), sensitivity 0.494 (0.489 to 0.500), specificity 0.816 (0.814 to 0.818), and likelihood ratio being positive 2.68 (2.63 to 2.75) and negative 0.62 (0.61 to 0.63). This outperformed models from previous studies according to area under curve of an external validation set, including one using a biomarker (area under curve 0.641; sensitivity 0.419; sensitivity 0.863; positive likelihood ratio 3.06; negative likelihood ratio 0.67; n=1177). Meanwhile, the best estimation achieved {+/-} 2.2 and 2.6 weeks respectively for predicted events and non-events. Our web application only took 5.14 minutes (5.11 to 5.18) per prediction.

Conclusions and RelevancePrelabor rupture of membranes and the time of delivery were predicted by medical histories; but, an impact study is required before clinical application.

Key PointsO_ST_ABSQuestionC_ST_ABSCan we use medical histories of diagnosis and procedure in electronic health records to predict prelabor rupture of membranes and the time of delivery before the day in nationwide insured women?

FindingsIn this prognostic study applying retrospective cohort paradigm, a significant predictive performance was achieved and validated. The area under receiver operating characteristics curve was 0.73 with the estimation errors of {+/-} 2.2 and 2.6 weeks for the time of delivery.

MeaningPreliminary prediction can be conducted in a wide population of insured women to predict prelabor rupture of membranes and estimate the time of delivery.
Molecular analysis suggests oligoclonality and metastasis of endometriosis lesions across anatomically defined subtypes. Endometriosis symptoms are heterogeneous with controversy on whether it constitutes a single disease or multiple distinct types. Our previous work found recurrent somatic cancer-driver alterations in endometriosis; however, these have not been found ubiquitously. A handful of cases spread across studies also suggest mutations might be shared (clonal) between lesions of the same type. As current classification systems correlate poorly with symptoms or outcomes, somatic genomics may improve the current system. Here, we investigate heterogeneity of somatic cancer-driver mutations within patients and across endometriosis types. We examined anatomically distinct types of endometriosis (ovarian, deep infiltrating, and superficial endometriosis) in 27 individual patients all of whom had at least two types of endometriosis. Specimens were analyzed using high-sensitivity targeted sequencing with orthogonal validation from droplet digital PCR and mutation-surrogate immunohistochemistry. Results found 13/27 patients had informative somatic driver mutation in endometriosis, 9/13 had identical mutations across distinct lesions. Endometriomas tended to have a higher mutational complexity, with functionally redundant driver mutations in same gene and within the same lesions.

Our data are consistent with clonality across endometriosis lesions regardless of subtype. Further the finding of redundancy in mutations with the same gene and lesions is also consistent with endometriosis representing an oligoclonal disease with dissemination likely to consist of multiple epithelial clones travelling together. This suggests the current anatomically defined classification of endometriosis does not fully recognize the etiology of the disease. A novel classification should take into account genomic and other molecular features. These findings could further contribute to development of a more personalized endometriosis diagnosis and care.
Feasibility of an online Langerian mindfulness program for stroke survivors and caregivers BackgroundMindfulness is promising for individuals with neurological disorders and their caregivers to improve psychological well-being. The potential application of a Langerian mindfulness intervention, focused on attention to variability, however, is still unknown.

ObjectiveTo determine the feasibility (usability, satisfaction, and potential effectiveness on psychological well-being) of an online mindfulness intervention for stroke survivors and caregivers.

MethodologyUsing mixed-methods, 11 stroke survivors and 3 caregivers participated in a 3-week, online, Langerian mindfulness intervention. A semi-structured interview assessed the interventions usability and gathered feedback. Self-reported measures about psychological well-being were documented remotely three times (pre, post, one-month follow-up).

ResultsQualitatively, participants were highly satisfied with the intervention, reported subjective benefits, but the usability of the online platform was poor. None of the self-reported measures changed over time.

ConclusionThis study provided evidence of feasibility of an online Langerian mindfulness intervention in a new population: stroke survivors and caregivers. A Randomised Trial of a Wearable UV dosimeter for Skin Cancer Prevention BackgroundNon-melanoma skin cancer (NMSC) is the most prevalent cancer in the United States, affecting 5 million people and costing $8.1 billion per year. Despite well-defined guidelines on ultraviolet radiation (UVR) avoidance, it remains difficult for people to assess their individual exposure, as UVR is invisible and the onset of symptoms due to UVR damage are delayed.

MethodsIn a prospective, randomized-controlled trial, 97 patients with a history of actinic keratoses were enrolled from March 2018 to July 2018 and followed over 6 months. 50 patients were given a wearable device that measured UV exposure and a smartphone application that provided both real-time and cumulative UV exposure information, and 47 patients were provided with UV protection counseling by a dermatologist.

ResultsWe observed a significant decrease in the incidence rate of NMSC in the intervention group compared to the control group over 3 months (p = 0.02). We did not observe a significant decrease in the incidence rate of actinic keratoses (AK) in the intervention group compared to the control group. The observed clinical benefit was not accompanied by psychological side effects such as anxiety and depression.

ConclusionsThis study suggests that providing real-time UV exposure data using a wearable UV dosimeter is a safe and effective behavioral change strategy to prevent NMSC. (Funded by the National Cancer Institute, contract HHSN261201700005C; ClinicalTrials.gov number NCT03315286.) Complementary frailty and mortality prediction models on older patients as a tool for assessing palliative care needs BackgroundPalliative care (PC) has demonstrated benefits for life-limiting illnesses. Cancer patients have mainly accessed these services, but there is growing consensus about the importance of promoting access for patients with non-malignant disease. Bad survival prognosis and patients frailty are usual dimensions to decide PC inclusion.

ObjectivesThe main aim of this work is to design and evaluate three quantitative models based on machine learning approaches to predict frailty and mortality on older patients in the context of supporting PC decision making: one-year mortality, survival regression and one-year frailty classification.

MethodsThe dataset used in this study is composed of 39,310 hospital admissions for 19,753 older patients (age >= 65) from January 1st, 2011 to December 30th, 2018. All prediction models were based on Gradient Boosting Machines. From the initial pool of variables at hospital admission, 20 were selected by a recursive feature elimination algorithm based on the random forests GINI importance criterion. Besides, we run an independent grid search to find the best hyperparameters in each model. The evaluation was performed by 10-fold cross-validation and area under the receiver operating characteristic curve and mean absolute error were reported. The Cox proportional-hazards model was used to compare our proposed approach with classical survival methods.

ResultsThe one-year mortality model achieved an AUC ROC of 0.87 {+/-} 0.01; the mortality regression model achieved an MAE of 329.97 {+/-} 5.24 days. The one-year frailty classification reported an AUC ROC of 0.9 {+/-} 0.01. The Spearmans correlation between the admission frailty index and the survival time was -0.1, while the point-biserial correlation between one-year frailty index and survival time was -0.16.

ConclusionsOne-year mortality model performance is at a state-of-the-art level. Frailty Index used in this study behaves coherently with other works in the literature. One-year frailty classifier demonstrated that frailty status within the year could be predicted accurately. To our knowledge, this is the first study predicting one-year frailty status based on a frailty index. We found mortality and frailty as two weakly correlated and complementary PC needs assessment criteria. Predictive models are available online at http://demoiapc.upv.es. Characterising SARS-CoV-2 viral clearance kinetics to improve the design of antiviral pharmacometric studies A consensus methodology for pharmacometric assessment of candidate SARS-CoV-2 antiviral drugs would be useful for comparing trial results and improving trial design. The time to viral clearance, assessed by serial qPCR of nasopharyngeal swab samples, has been the most widely reported measure of virological response in clinical trials, but it has not been compared formally with other metrics, notably model-based estimates of the rate of viral clearance. We analysed prospectively gathered viral clearance profiles from 280 infection episodes in vaccinated and unvaccinated individuals. We fitted different phenomenological pharmacodynamic models (single exponential decay, bi-exponential, penalised splines) and found that the clearance rate, estimated from a mixed effects single exponential decay model, is a robust pharmacodynamic summary of viral clearance. The rate of viral clearance, estimated from viral densities during the first week following peak viral load, provides increased statistical power (reduced type 2 error) compared with time to clearance. We recommend that pharmacometric antiviral assessments should be conducted in early illness with serial qPCR samples taken over one week. High-resolution portability of 245 polygenic scores when derived and applied in the same cohort The low portability of polygenic scores (PGS) across global populations is a major concern that must be addressed before PGS can be used for everyone in the clinic. Indeed, prediction accuracy has been shown to decay as a function of the genetic distance between the training and test cohorts. However, such cohorts differ not only in their genetic distance but also in their geographical distance and their data collection and assaying, conflating multiple factors. In this study, we examine the extent to which PGS are transferable between ancestries by deriving polygenic scores for 245 curated traits from the UK Biobank data and applying them in nine ancestry groups from the same cohort. By restricting both training and testing to the UK Biobank data, we reduce the risk of environmental and genotyping confounding from using different cohorts. We define the nine ancestry groups at a high-resolution, country-specific level, based on a simple, robust and effective method that we introduce here. We then apply two different predictive methods to derive polygenic scores for all 245 phenotypes, and show a systematic and dramatic reduction in portability of PGS trained in the inferred ancestral UK population and applied to the inferred ancestral Polish - Italian - Iranian - Indian - Chinese - Caribbean - Nigerian - Ashkenazi populations, respectively. These analyses, performed at a finer scale than the usual continental scale, demonstrate that prediction already drops off within European ancestries and reduces globally in proportion to PC distance, even when all individuals reside in the same country and are genotyped and phenotyped as part of the same cohort. Our study provides high-resolution and robust insights into the PGS portability problem. Deceased donor kidney degradomics indicates cytoskeletal proteolytic alterations impacting post-transplant function. BackgroundIn brain death, cerebral injury contributes to systemic biological dysregulation, causing significant cellular stress in donor kidneys that adversely impacts the quality of grafts. Here, we hypothesized that DBD kidneys may undergo proteolytic processes that renders grafts susceptible to post-transplant dysfunction.

Material & MethodsUsing mass spectrometry and immunoblotting analyses, we profiled degradation patterns of cytoskeletal proteins in deceased (n=55) and living (n=10) donor kidneys.

ResultsWe found that in DBD kidneys, key podocyte cytoskeletal proteins had been proteolytically cleaved. Generated degradation profiles were not associated to donor related demographic and clinical factors but were associated to suboptimal post-transplant function. Strikingly, -actinin -4 and Talin-1 degradation profiles were not observed in circulatory-death or living-donor kidneys. As Talin-1 is a specific proteolytic target of Calpain-1, we investigated a potential trigger of Calpain activation and Talin-1 degradation using ex-vivo precision-cut human kidney slices and in-vitro immortalised human podocytes. Notably, we found that Transforming-Growth Factor-{beta} (TGF-{beta}) activated Calpain-1 and proteolytically cleaved Talin-1 to generate distinct peptide fragments. These peptide fragments were of similar size and matched the degradation patterns observed in DBD kidneys. Talin-1 degradation was prevented in vitro by Calpain-1 inhibition.

ConclusionsHere, we provide initial evidence that DBD kidneys are susceptible to cytoskeletal protein degradation that impacts posttransplant kidney function. Subsequent studies should aim to further investigate the link between brain death and activation of proteolytic pathways exploring new therapeutic opportunities. RELATIONSHIP BETWEEN ADVERSE EVENTS PREVALENCE, PATIENT SAFETY CULTURE AND PATIENT SAFETY PERCEPTION IN A SINGLE SAMPLE OF PATIENTS: A CROSS-SECTIONAL AND CORRELATIONAL STUDY ObjectiveTo assess the relationship between Adverse Events Prevalence, Patient Safety Culture and Patient Safety Perception.

DesignCross-sectional, ex post facto comparative study on a single sample of patients.

SettingFour medium-high-level hospitals were included in the study -- two public and two private from Zulia State in Venezuela.

Participants556 medical records and patients were studied for the prevalence and patient safety perception study, and 397 of the healthcare providers involved in the care of these patients were surveyed for the patient safety culture study, at two public and two private hospitals.

Outcome measurementThe primary outcome of this study was the Association between Adverse Events Prevalence, Patient Safety Culture and Patient Safety Perception, and according to hospital funding type, private and public.

ResultsAn inverse association was observed between Adverse Events Prevalence and its severity and Patient Safety Culture Index (PSCI: rho=-0.8 p=0.5) (95% CI=0.26-0.10) and Patient Safety Perception Index (PSPI: rho=-0.6 p=0.18) (95% CI=0.10-0.28), which were protective factors for patient safety. No association was identified between Patient Safety Culture and Patient Safety Perception (rho=0.0001). No statistical differences were identified by hospital type (p=0.93) (95% CI=0.70-1.2).

ConclusionsThe analysis of the variable correlations studied (AEP, PSC and PSP) within the same sample offers an interesting and useful perspective. In this sample, although no correlation was observed between the three variables as an interacting set, some correlation patterns were observed between pairs of variables that could guide further studies.

Strengths and limitations of this studyO_LIThe association analysis of the three main variables (adverse events prevalence, patient safety culture and patient safety perception) in the same sample of patients and health professionals and over the same time period during which the care process and, consequently, the adverse events took place is an unprecedented and innovative approach, which contributes to the body of knowledge on this field of study.
C_LIO_LIThe relational theoretical framework produced provides a "map" that can facilitate decision-taking and which establishes the variables that should be considered a priority. As a result, it is highly likely to have an impact on the clinical efficiency and safety of healthcare institutions and services.
C_LIO_LIThe study was carried out at both private and public hospitals, enabling the behaviour of the aforementioned variables to be compared and analysed at each type of institution. The literature to date on this approach is scarce and offers little information.
C_LIO_LIAlthough the sample of hospitals selected is not representative of Venezuela, it is representative of the hospitals of one of the most productive and populated states in the country.
C_LIO_LIDuring stages 1 and 2, some resistance to collaborating with and completing the evaluation instruments was identified among the health professionals.
C_LI Vaccine Effectiveness against Referral to Hospital and Severe Lung Injury Associated with COVID-19: A Population-Based Case-Control Study in St. Petersburg, Russia BackgroundResults of a randomised trial showed the safety and efficacy of Gam-COVID-Vac against COVID-19. However, compared to other vaccines used across the globe, the real-world data on the effectiveness of Gam-COVID-Vac, especially against the disease caused by Delta variant of concern, was not available. We aimed to assess the effectiveness of vaccination mainly conducted with Gam-COVID-Vac in St. Petersburg, Russia.

MethodsWe designed a case-control study to assess the vaccine effectiveness (VE) against lung injury and referral to hospital. Self-reported vaccination status was collected for individuals with confirmed SARS-CoV-2 infection who were referred for initial low-dose computed tomography triage in two outpatient centres in July 3 - August 9, 2021 in St. Petersburg, Russia. We used logistic regression models to estimate the adjusted (for age, sex, and triage centre) VE for complete (>14 days after the second dose) vaccination. We estimated the VE against referral for hospital admission, COVID-19-related lung injury assessed with LDCT, and decline in oxygen saturation.

ResultsIn the final analysis, 13,893 patients were included, 1,291 (9.3%) of patients met our criteria for complete vaccination status, and 495 (3.6%) were referred to hospital. In the primary analysis, the adjusted VE against referral to hospital was 81% (95% CI: 68-88) for complete vaccination. The VE against referral to hospital was more pronounced in women (84%, 95% CI: 66-92) compared to men (76%, 95% CI: 51-88). Vaccine protective effect increased with increasing lung injury categories, from 54% (95% CI: 48-60) against any sign of lung injury to 76% (95% CI: 59-86) against more than 50% lung involvement. A sharp increase was observed in the probability of hospital admission with age for non-vaccinated patients in relation to an almost flat relationship for the completely vaccinated group.

ConclusionsCOVID-19 vaccination was effective against referral to hospital in patients with symptomatic SARS-CoV-2 infection in St. Petersburg, Russia. This protection is probably mediated through VE against lung injury associated with COVID-19. Analysis of MRI-derived spleen iron in the UK Biobank identifies genetic variation linked to iron homeostasis and erythrocyte morphology Aging, and the pathogenesis of many common diseases, involves iron homeostasis. A key role in iron homeostasis is played by the spleen, which is the largest filter of the blood and performs iron reuptake from old or damaged erythrocytes. Despite this important role, spleen iron content has not been measured previously in a large, population-based cohort. In this study, we quantify spleen iron in 41,764 participants of the UK Biobank using magnetic resonance imaging (MRI). We find that epidemiologic and environmental factors such as increased age, higher red meat consumption and lower alcohol intake correlate with higher spleen iron. Through genome-wide association study, we identify genetic associations between spleen iron and common variation at seven loci, including in two hereditary spherocytosis (HS) genes, ANK1 and SPTA1. HS-causing mutations in these genes are associated with lower reticulocyte volume and increased reticulocyte percentage, while our common alleles are associated with increased expression of ANK1 and SPTA1 in blood and with larger reticulocyte volume and reduced reticulocyte percentage. As genetic modifiers, these common alleles may explain mild spherocytosis phenotypes observed in some HS allele carriers. Further, we identify an association between spleen iron and MS4A7, which colocalizes with a quantitative trait locus for MS4A7 alternative splicing in whole blood, and with monocyte count and fraction. Through quantification of spleen iron in a large human cohort, we extend our understanding of epidemiological and genetic factors associated with iron recycling and erythrocyte morphology. Cohort profile: The Australian Parkinson's Genetics Study (APGS) - pilot (N=1,532) PurposeParkinsons 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 Parkinsons Genetics Study (APGS) 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.

ParticipantsIn the pilot phase reported here, 1,819 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 (PBS) records. The average age at the time of the questionnaire was 64 {+/-} 6 years. We collected patient-reported PD information and socio-demographic variables via an online (93% of the cohort) or paper-based (7%) questionnaire. One thousand five hundred thirty-two participants (84.2%) met all inclusion criteria, and 1,499 provided a DNA sample via traditional post.

Findings to date65% of participants were male, 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 plansWe plan to recruit sex- 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.

Article summaryO_ST_ABSStrengths and limitations of this studyC_ST_ABSO_LIWe used a time- and cost-effective recruitment method that enabled us to reach out to a random sample of individuals who have been prescribed medications for Parkinsons disease across all over Australia to invite them to participate in this study.
C_LIO_LIThe identities of letter recipients remained private and confidential and were not shared with the researchers. However, those recipients who were interested and willing to participate were directed to a website where they could sign up and provide informed consent.
C_LIO_LIThe source database only captures individuals who have been prescribed medications to treat Parkinsons disease in Australia and who are eligible for Medicare. Those without an official diagnosis, not receiving treatment, or not eligible for government subsidies are not included.
C_LIO_LIWe collected a wide range of patient-reported variables relevant to disease onset, diagnosis, symptoms, medical comorbidities, lifestyle, and family history in a large cohort of participants. However, some variables might not be as accurate as when measured by a specialist clinician.
C_LIO_LIGiven the 9% response rate to our single-letter invitation, there is a substantial risk of self-selection bias. Thus, patient characteristics for this cohort might differ from those of the typical population of individuals with Parkinsons disease in Australia.
C_LI Macular vascular complexity analysis of diabetes mellitus by swept-source optical coherence tomographic angiography PurposeTo evaluate the associations of retinal vascular complexity features, including fractal dimension (FD) and blood vessel tortuosity (BVT), with the severity of diabetic retinopathy (DR) by using noninvasive optical coherence tomographic angiography (OCTA).

MethodsThis prospective cross-sectional study recruited ocular-treatment-naive patients with type 2 diabetes mellitus (DM) registered in the community of Guangzhou, China. OCTA was used to obtain the measurements of FD and BVT in the superficial capillary plexus (SCP) and the deep capillary plexus (DCP). Univariate and multivariate linear regression was used to analyse the correlation of FD and BVT in different layers with DR severity.

ResultsA total of 1282 patients with DM (1282 eyes), with a mean age of 64.2{+/-}7.8 years, were included. FD in the DCP decreased and BVT in the DCP increased in DR patients compared to non-DR patients, even after adjusting for confounding factors (P< 0.05). Trend analysis showed a significant decrease in the FD values as the DR progressed, while the BVT progressively increased with worsening DR severity (P< 0.01). The FD in DCP had a statistically significant positive correlation with FD in SCP and a negative correlation with BVT in SCP and BVT in DCP in all of the participants, including the non-DR group, moderate DR group and severe DR group (P< 0.01).

ConclusionFD and BVT determined using OCTA might be useful parameters for objectively distinguishing DR from non-DR and indicating DR progression. Subpopulation-specific Machine Learning Prognosis for Underrepresented Patients with Double Prioritized Bias Correction Many clinical datasets are intrinsically imbalanced, dominated by overwhelming majority groups. Off-the-shelf machine learning models that optimize the prognosis of majority patient types (e.g., healthy class) may cause substantial errors on the minority prediction class (e.g., disease class) and demographic subgroups (e.g., Black or young patients). For example, our work found that missed death cases are 3.14 times higher than missed survival cases in a mortality prediction model. In the typical one-machine-learning-model-fits-all paradigm, racial and age disparities are likely to exist, but unreported. What makes it worse is the deceptive nature of widely used whole-population metrics, such as AUC-ROC. We show that some metrics fail to reflect serious prediction deficiencies. To mitigate representational biases, we design a double prioritized (DP) bias correction technique. Our method trains customized models for specific ethnicity or age groups, a substantial departure from the one-model-predicts-all convention. We report our findings on four prognosis tasks over two imbalanced clinical datasets. DP reduces relative disparities among race and age groups, 5.6% to 86.8% better than the 8 existing sampling solutions being compared, in terms of the minority class' recall. Decision curve analysis to identify optimal candidates of liver resection for intermediate-stage hepatocellular carcinoma with hepatitis B cirrhosis：A cohort study BackgroundThe selection criterion for liver resection (LR) in intermediate-stage (IM) hepatocellular carcinoma (HCC) is still controversial. This study aims to compare LR and transarterial chemoembolization in the range of predicted death risk

MethodsThe multivariable Cox regression model (MVR) was estimated to predict mortality at 5yr. The cut-off values were determined by a two-piece-wise linear regression model, decision curve analysis with MVR model, and hazard ratio curve for treatment plotted against the predicted mortality.

Results825 IM-HCC with hepatitis B cirrhosis were included for analysis (TACE, n=622; LR, n=203). The 5-yr overall survival rate of LR patients was higher than the TACE group (52.8% vs. 20.8%; P<0.0001). The line of LR and TACE were crossing with predicted death risk at 100% (P for interaction =0.008). The benefit of LR versus TACE decreased progressively as predicted death risk>0.55 (95%CI: 0.45,0.62). When predicted death risk over 0.7, decision curve analysis suggested that LR and TACE did not increase net benefit. Patients were then divided into four subgroups by the cut-off values (<0.45, 0.45[&ge;] /<0.62, 0.62[&ge;] /<0.7, [&ge;] 0.7). The stratified analysis of treatment in different subgroups, hazard ratios were 0.39 (95%CI: 0.27, 0.56), 0.36 (95%CI: 0.23, 0.56), 0.51 (95%CI: 0.27, 0.98), and 0.46 (95%CI: 0.27, 0.80), respectively.

ConclusionsLR reached the maximal relative utility in the interval of 0.45 to 0.62, and both LR and TACE did not increase net benefit at the 5-yr death risk over 0.7. The incidence of delirium in an acute geriatric community hospital: an observational cohort feasibility study. ObjectivesDelirium in hospitalised older adults is associated with negative health outcomes. Admission to an alternative care setting may lower the incidence of delirium. The Acute Geriatric Community Hospital (AGCH) was recently opened in the Netherlands and uses a multi-component non-pharmacological intervention strategy to prevent delirium. The objective of this study was to describe the incidence of delirium at the AGCH and compare this incidence to existing rates from literature. If a possible effect on delirium is seen in this comparison this would support conducting a larger prospectively controlled study on delirium in this new care setting.

DesignProspective cohort feasibility study; exploratory meta-analysis of proportions.

Setting and ParticipantsThe AGCH is an acute geriatric unit in a skilled nursing facility for patients aged >65 years with acute medical conditions.

MethodsDelirium assessment using the Confusion Assessment Method (CAM) upon admission and on day one, two and three or until delirium had resolved. Patients charts were reviewed if CAM was missing. In an linear mixed-effects model, the delirium incidence rate in AGCH was compared to pooled delirium incidence rates from six studies found in a high-quality review.

Results214 patients from the AGCH (mean age 81.9 years, 47% male, 12% with a history of dementia) were included in the analysis. Delirium developed in 8% (18/214) (95% confidence interval [CI] 5-13%) of patients during AGCH admission compared to 16% (95% CI 12-21%) in hospitals. Admission to the AGCH was associated with a decreased delirium incidence rate compared to the hospital control group (OR[odds ratio]= 0.49, 95% CI 0.24-0.98, p-value=0.044).

Conclusions and implicationsThe delirium incidence in the AGCH was low compared to those incidences found in general hospitals in literature. Based on these findings a controlled observational or randomized study measuring delirium in this care setting is recommended. COVID-19 mRNA Vaccination in Lactation: Assessment of adverse effects and transfer of anti-SARS-CoV2 antibodies from mother to child BackgroundData regarding adverse events observed in the lactating mother-infant dyad and their immune response to COVID-19 mRNA vaccination during lactation are needed to inform vaccination guidelines.

MethodsFrom a prospective cohort of 50 lactating individuals who received mRNA-based vaccines for COVID-19 (mRNA-1273 and BNT162b2), blood and milk samples were collected prior to first vaccination dose, immediately prior to 2nd dose, and 4-10 weeks after 2nd dose. Symptoms in mother and infant were assessed by detailed questionnaires. Anti-SARS-CoV-2 antibody levels in blood and milk were measured by Pylon 3D automated immunoassay and ELISA. In addition, vaccine-related PEGylated proteins in milk were measured by ELISA. Blood samples were collected from a subset of infants whose mothers received the vaccine during lactation (4-15 weeks after mothers 2nd dose).

ResultsNo severe maternal or infant adverse events were reported in this cohort. Two mothers and two infants were diagnosed with COVID-19 during the study period. PEGylated proteins, were not found at significant levels in milk after vaccination. After vaccination, levels of anti-SARS-CoV-2 IgG and IgM significantly increased in maternal plasma and there was significant transfer of anti-SARS-CoV-2-Receptor Binding Domain (anti-RBD) IgA and IgG antibodies to milk. Milk IgA levels after the 2nd dose were negatively associated with infant age. Anti-SARS-CoV-2 IgG antibodies were not detected in the plasma of infants whose mothers were vaccinated during lactation.

ConclusionsCOVID-19 mRNA vaccines generate robust immune responses in plasma and milk of lactating individuals without severe adverse events reported. Public-private partnership to strengthening COVID-19 response in Kisumu, Kenya INTRODUCTIONIn Kenya approximately half of healthcare services are delivered through private sector providers. In line with our experience building rapid responses to HIV and to support and accelerate the public sectors COVID-19 response, we initiated a PPP project in Kisumu County, Kenya. In this manuscript we demonstrate this PPPs performance using digital tools as a replicable model for scaling the response to COVID-19 in similar resource-poor settings.

METHODSCOVID-19 diagnostic testing formed the basis for a PPP between KEMRI, Department of Health Kisumu County, PharmAccess Foundation, and local faith-based and private healthcare facilities, thus naming our PPP: COVID-Dx. COVID-Dx was implemented from June 01, 2020, to March 31, 2021, in Kisumu County, Kenya. Trained laboratory technologists in participating healthcare facilities collected nasopharyngeal and oropharyngeal samples from patients meeting the Kenyan MoH COVID-19 case definition. Samples were tested using RT-PCR at the central reference laboratory in KEMRI. Healthcare workers in participating facilities collected patient clinical data using a digitized MoH COVID-19 Case Identification Form. We shared aggregated results from these data via (semi-) live dashboard to all relevant stakeholders. We did descriptive statistical analyses using Stata 16 to inform project processes.

ResultsNine facilities participated in the project. A detailed collaboration schedule was developed, supported by a semi-real time digital dashboard. A total of 4,324 PCR tests for SARS-CoV-2 were added to the public response, with 425 positives. Geo-mapped and time-tagged information on incident cases was collected and fed back to policymakers. At the beginning of the pandemic, there a heavy focus on health workers within Kisumu County, with a total of 1009 tested consisting about 43% of all County health workforce.

CONCLUSIONWe demonstrate feasibility to rapidly increase the public health sector response to a COVID-19 epidemic outbreak in a resource-poor setting. Our complementary public-private intervention in Kisumu, Kenya was based on a joint testing strategy and demonstrated that digitalization of the healthcare system can gain efficiencies, link public and private healthcare efforts, increase transparency and inform local policy makers with semi-real time data supporting targeting interventions. The Kisumu model is currently being scaled to 13 additional western Kenyan counties. Factors affecting first return to work following arthroscopic rotator cuff repair: A retrospective observational study in an occupational medicine clinic and single-surgeon practice BackgroundReturn to work (RTW) following arthroscopic rotator cuff repair (aRCR) within New South Wales (NSW), Australia, under compensable schemes has not been reported.

AimsDetermine factors affecting RTW status and time in patients treated with aRCR under state-based compensation schemes, compared to those outside such schemes.

MethodsPatients undergoing aRCR by one surgeon with minimum 1-year follow-up were grouped into those under (CP) or outside (non-CP) workers or vehicle accident compensation schemes, matched by age and gender. RTW status and time were assessed using chi-square analysis and multivariable linear regression.

ResultsOf 1054 available patients, 90 CP patients were identified with 29 consented and matched to non-CP (N=29). A higher proportion of CP patients (17.2 vs 0%, P<0.001) never returned to work and a lower proportion resumed pre-injury duties at first RTW (3 vs 52%, P<0.01). Median time to first RTW did not differ between CP and non-CP groups (5.1 vs 4.4, P=0.86). Smoking (P=0.007) and post-injury activity level (P=0.004) were significantly associated with longer time to first RTW, whereas compensation status was not.

ConclusionsCP patients undergoing aRCR in NSW are at risk of not returning to work. For those that return, there is no significant difference compared to non-CP in time to first RTW. Particularly, patient and management factors associated with extended time to first RTW have been identified. Interventions aimed at modifiable factors such as smoking cessation and increasing preoperative activity may improve future outcomes.

What is already known about this subjectO_LIWork-related injury and disease present a significant financial burden to the Australian economy ($AUD61.8billion per annum), with shoulder conditions due to body stressing accounting for 7% of this total cost (>$AUD4.2billion)
C_LIO_LIPatients receiving compensation appear to have poorer outcomes and take longer to return to work than their non-compensated counterparts, but the degree to which this occurs is variably reported in the literature
C_LIO_LIThe effect of modifiable factors on return to work status and time remain unclear, and have not previously been reported for the Australian population under the New South Wales workers compensation scheme
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What this study addsO_LIPatients receiving arthroscopic rotator cuff repair under a compensable scheme in New South Wales are at increased risk of not returning to work compared to patients presenting outside of a compensable scheme and patients in equivalent schemes internationally
C_LIO_LIPatients reporting a longer duration of symptoms and smokers are at increased risk of extended time to first return to work
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What impact this may have on practice or policyO_LIThe study has identified smoking and pre-surgery activity levels as key targets for intervention in patients receiving arthroscopic rotator cuff repair under a workers compensation scheme in New South Wales
C_LIO_LIBy further investigating whether interventions designed to modify these factors are able to favourably affect patient outcomes, there is potential to return patients to their preoperative level of work sooner
C_LI The CT Scan Lung Severity Score and Vaccination Status in COVID-19 patients in India: Perspective of an Independent Radiology Practice BackgroundThe COVID-19 patients often undergo a high-resolution CT scan to determine extent of their lung involvement. The aim of this study was to determine lung involvement in confirmed/suspected COVID-19 patients (encountered at an independent radiology practice) and its correlation to vaccination status amidst the second COVID-19 wave in India.

MethodsWe retrospectively queried our data since April 2021 to identify adult patients (>17 years) who had confirmed (positive RT-PCR or antigen test) or suspected COVID-19 (classic symptoms but negative RT-PCR) and received a high-resolution CT scan to determine the extent of their lung involvement using the CT severity (CT-SS) score. Patients were classified in 3 groups based on their vaccination status to determine its correlation with the CT-SS score: fully vaccinated, partially vaccinated, and unvaccinated. Basic descriptive statistics, univariate tests and multivariate linear regression analysis were used.

ResultsWe identified 229 patients (median age 45 years, 60% male) of which 205 (89%) had confirmed COVID-19 (positive RT-PCR) and 24 had suspected disease (negative RT-PCT but classic symptoms). Of the 229 patients 29 (13%) had complete vaccination, 38 (17%) had partial vaccination and 162 (70%) had no vaccination. The CT score of the completely vaccinated patients was significantly lower compared to partially or unvaccinated patients (median 0 v. 3.5 v. 10, respectively p<.01). A multivariate linear regression model showed that partial or fully vaccinated patients had lower CT severity score compared to unvaccinated patients (adjusted R squared = 0.47).

ConclusionWe present here the real-world findings from an independent radiology practice (a unique and common practice model), in India amid the second COVID-19 wave showing significantly lower CT severity score in fully or partially vaccinated patients compared to unvaccinated patients. Complete vaccination in patients could be critical in preventing severe lung disease. Molecular mapping of urinary complement peptides in kidney diseases Defective complement activation has been associated with various types of kidney disease. This led to the hypothesis that specific urine complement fragments may be associated with kidney disease etiologies, and disease progression may be reflected by changes in these complement fragments. We investigated the occurrence of complement fragments in urine, their association with kidney function, proteinuria and disease etiology. Mass spectrometry based peptidomics data from the Human Urinary Proteome/Peptidome Database were extracted and the distribution of complement peptides in the different kidney disease etiologies and controls was investigated. All datasets with informations on disease/health status and detectable complement peptides were included (n=16027). Twenty-three different urinary peptides derived from complement proteins could be identified, originating from the complement proteins C3, C4 and complement factor B. For most C3-derived peptides an inverse association with eGFR was observed, while the majority of peptides derived from CFB demonstrated positive association with eGFR. Highest levels of significant C3 excretion relative to controls were seen in minimal change disease (MCD), focal segmental glomerulosclerosis (FSGS), membranous glomerulonephritis (MGN), lupus nephritis (LN), diabetic kidney disease (DKD), IgAN, membranoproliferative glomerulonephritis (MPGN), and C3-glomerulonephritis. In conclusion, several peptides derived from the complement proteins C3, C4 and factor B are significantly associated with specific kidney disease etiologies. These peptides may depict disease-specific complement activation, as well as damage to the glomerular basement membrane. Further targeted investigation of these peptides may provide new insight into disease pathophysiology and could possibly guide therapeutic decisions, especially when targeting complement factors. Effects of repeated injection of 1% lidocaine vs. radial extra-corporeal shock wave therapy for treating myofascial trigger points: a randomized controlled trial Background and ObjectivesThis study tested the hypothesis that treatment of myofascial trigger points (MTrPs) in the upper trapezius muscle (UTM) with repeated injection of 1% lidocaine results in better alleviation of muscular stiffness and soreness as well as improved metabolism in the hypercontracted MTrP area than treatment with radial extracorporeal shock wave therapy (rESWT).

Materials and MethodsA single-blinded, prospective, randomized controlled trial was conducted on patients suffering from MTrPs in the UTM. Thirty patients were treated with repeated injection of 2 ml of 1% lidocaine (three injections; one injection per week). Another 30 patients were treated with rESWT (three treatment sessions; one treatment session per week; 2000 radial extracorporeal shock waves per treatment session; positive energy flux density = 0.10 mJ/mm2). The primary outcome measure was pain severity using the VAS score. The secondary outcome measures included muscle elasticity index, pressure pain threshold and neck disability index. Evaluation was performed at baseline (T1), 15-30 minutes after the first treatment in order to register immediate treatment effects (T2), before the second treatment (i.e., one week after baseline) (T3) and one week after the third treatment (i.e., four weeks after baseline) (T4).

ResultsThere were no statistically significant differences in the primary and secondary outcome measures between the patients in the lidocaine arm and the patients in the rESWT arm at T1 and T4. Within the arms, the mean differences of all outcomes were statistically significant (P < 0.001) when comparing the data obtained at T1 with the data obtained at T3 and the data obtained at T4.

ConclusionsThe results of this pilot study suggest that the use of rESWT in patients with MTrPs in the UTM is safe and leads to reduced pain and improved muscle elasticty, pressure pain threshold and neck disability index, without adverse effects. Larger trials are necessary to verify this. Clinicians should consider rESWT instead of injections of lidocaine in the treatment of MTrPs in the UTM. Hyperactive immature state and differential CXCR2 expression of neutrophils in severe COVID-19 Neutrophils are vital in defence against pathogens but excessive neutrophil activity can lead to tissue damage and promote acute respiratory distress syndrome (ARDS). COVID-19 is associated with systemic expansion of immature neutrophils but the functional consequences of this shift to immaturity are not understood. We used flow cytometry to investigate activity and phenotypic diversity of circulating neutrophils in COVID-19. First, we demonstrate hyperactivation of immature CD10- subpopulations in severe disease, with elevated degranulation of secondary granule markers. Partially activated immature neutrophils are detectable three months post symptom onset, indication long term myeloid dysregulation in convalescent COVID-19 patients. Second, we demonstrate that neutrophils from moderately ill patients downregulate the chemokine receptor CXCR2, while neutrophils from severely ill individuals failed to do so, suggesting altered ability for organ trafficking. CD10- and CXCR2hi neutrophil subpopulations were enriched in severe disease and may represent biomarkers for early identification of individuals at high risk of progressing to severe COVID-19. Engagement in leisure activities and depression in older adults in the United States: Longitudinal evidence from the Health and Retirement Study ObjectivesReceptive cultural engagement (e.g., attending theaters and museums) can reduce depression in older adults. However, whether specific participatory leisure activities are associated with lower rates of depression remains unknown. We aimed to test whether engagement in a diverse range of leisure activities, all of which could involve artistic or creative elements, was associated with concurrent and subsequent depression.

MethodsUsing longitudinal data from 19,134 participants aged over 50 in the Health and Retirement Study, engagement in leisure activities was measured every four years, and depression every two years, between 2008 and 2016. Leisure activities included: reading books, magazines, or newspapers; writing; baking/cooking something special; making clothes, knitting, or embroidery (sewing); working on hobbies/projects; going to sport, social, or other clubs; and attending non-religious organization meetings. A score of three or more on the Center for Epidemiologic Studies Depression Scale indicated depression. We fitted population-averaged panel data models using generalized estimating equations with a logit link.

ResultsEngaging in some leisure activities, such as clubs, hobbies/projects, and baking/cooking was associated with reduced depression, independent of confounders. Concurrently, spending time on hobbies/projects (monthly OR = 0.80, 95% CI = 0.72-0.88; weekly OR = 0.81, 95% CI = 0.73-0.89) and clubs (monthly OR = 0.85, 95% CI = 0.77-0.94; weekly OR = 0.78, 95% CI = 0.69-0.88) was associated with lower odds of depression versus not engaging. Longitudinally, the odds of depression two years later were reduced amongst people engaging in weekly baking/cooking (OR = 0.85, 95% CI = 0.75- 0.95), hobbies (OR = 0.81, 95% CI = 0.71-0.92), and clubs (OR = 0.82, 95% CI = 0.71-0.94). Writing, reading, sewing, and attending non-religious organizations were not consistently associated with depression.

DiscussionEngagement in some leisure activities is associated with reduced odds of depression. We should consider how older adults can be supported to actively participate in leisure activities as health-promoting behaviors.