Primary biliary cholangitis drug evaluation and regulatory approval: Where do we go from here?

Primary biliary cholangitis (PBC) is a chronic cholestatic liver disease. The management landscape was transformed 20 years ago with the advent of ursodeoxycholic acid. Up to 40% of patients do not, however, respond adequately to ursodeoxycholic acid and therefore still remain at risk of disease progression to cirrhosis. The introduction of obeticholic acid as a second-line therapy for patients failing ursodeoxycholic acid has improved outcomes for patients with PBC. There remains, however, a need for better treatment for patients at higher risk. The greatest threat facing our efforts to improve treatment in PBC is, paradoxically, the regulatory approval model providing conditional marketing authorization for new drugs based on biochemical markers on the condition that long-term, randomized placebo-controlled outcome trials are performed to confirm efficacy. As demonstrated by the COBALT confirmatory study with obeticholic acid, it is difficult to retain patients in the required follow-on confirmatory placebo-controlled PBC outcome trials when a licensed drug is commercially available. New PBC therapies in development, such as the peroxisome proliferator-activated receptor agonists, face even greater challenges in demonstrating outcome benefit through randomized placebo-controlled studies once following conditional marketing authorization, as there will be even more treatment options available. A recently published EMA Reflection Paper provides some guidance on the regulatory pathway to full approval but fails to recognize the importance of real-world data in providing evidence of outcome benefit in rare diseases. Here we explore the impact of the EMA reflection paper on PBC therapy and offer pragmatic solutions for generating evidence of long-term outcomes through real-world data collection.

"Problems you can live with" versus emergencies: how community members in rural Ethiopia contend with conditions requiring surgery.

BACKGROUND: 98% of people with surgical conditions living in low- and middle-income countries (LMICs) do not receive safe, timely and affordable surgical and anesthesia care. Research exploring barriers to receiving care has tended to be narrow in focus, often facility-based and ignoring the community beliefs, experiences and behaviours that will be an essential component of closing the gap in surgical care. Using qualitative methods, we captured diverse community perspectives in rural Ethiopia: exploring beliefs, perceptions, knowledge and experiences related to surgical conditions, with the overall aim of (re)constructing explanatory models. METHODS: Our study was nested within a community-based survey of surgical conditions conducted in the Butajira Health and Demographic Surveillance Site, southern Ethiopia, and a follow-up study of people accessing surgical care in two local hospitals. We carried out 24 semi-structured interviews. Participants were community members who needed but did/did not access surgical care, community-based healthcare workers and traditional bone-setters. Interviews were conducted in Amharic, audio-recorded, transcribed, and translated into English. We initially carried out thematic analysis and we recognized that emerging themes were aligned with Kleinman's explanatory models framework and decided to use this to guide the final stages of analysis. RESULTS: We found that community members primarily understood surgical conditions according to severity. We identified two categories: conditions you could live with and those which required urgent care, with the latter indicating a clear and direct path to surgical care whilst the former was associated with a longer, more complex and experimental pattern of help-seeking. Fear of surgery and poverty disrupted help-seeking, whilst community narratives based on individual experiences fed into the body of knowledge people used to inform decisions about care. CONCLUSIONS: We found explanatory models to be flexible, responsive to new evidence about what might work best in the context of limited community resources. Our findings have important implications for future research and policy, suggesting that community-level barriers have the potential to be responsive to carefully designed interventions which take account of local knowledge and beliefs.

Pulmonary emphysema subtypes defined by unsupervised machine learning on CT scans.

BACKGROUND: Treatment and preventative advances for chronic obstructive pulmonary disease (COPD) have been slow due, in part, to limited subphenotypes. We tested if unsupervised machine learning on CT images would discover CT emphysema subtypes with distinct characteristics, prognoses and genetic associations. METHODS: New CT emphysema subtypes were identified by unsupervised machine learning on only the texture and location of emphysematous regions on CT scans from 2853 participants in the Subpopulations and Intermediate Outcome Measures in COPD Study (SPIROMICS), a COPD case-control study, followed by data reduction. Subtypes were compared with symptoms and physiology among 2949 participants in the population-based Multi-Ethnic Study of Atherosclerosis (MESA) Lung Study and with prognosis among 6658 MESA participants. Associations with genome-wide single-nucleotide-polymorphisms were examined. RESULTS: The algorithm discovered six reproducible (interlearner intraclass correlation coefficient, 0.91-1.00) CT emphysema subtypes. The most common subtype in SPIROMICS, the combined bronchitis-apical subtype, was associated with chronic bronchitis, accelerated lung function decline, hospitalisations, deaths, incident airflow limitation and a gene variant near DRD1, which is implicated in mucin hypersecretion (p=1.1 ×10-8). The second, the diffuse subtype was associated with lower weight, respiratory hospitalisations and deaths, and incident airflow limitation. The third was associated with age only. The fourth and fifth visually resembled combined pulmonary fibrosis emphysema and had distinct symptoms, physiology, prognosis and genetic associations. The sixth visually resembled vanishing lung syndrome. CONCLUSION: Large-scale unsupervised machine learning on CT scans defined six reproducible, familiar CT emphysema subtypes that suggest paths to specific diagnosis and personalised therapies in COPD and pre-COPD.

Associations of hiatus hernia with CT-based interstitial lung changes: the MESA Lung Study.

BACKGROUND: Hiatus hernia (HH) is prevalent in adults with pulmonary fibrosis. We hypothesised that HH would be associated with markers of lung inflammation and fibrosis among community-dwelling adults and stronger among MUC5B (rs35705950) risk allele carriers. METHODS: In the Multi-Ethnic Study of Atherosclerosis, HH was assessed from cardiac and full-lung computed tomography (CT) scans performed at Exam 1 (2000-2002, n=3342) and Exam 5 (2010-2012, n=3091), respectively. Percentage of high attenuation areas (HAAs; percentage of voxels with attenuation between -600 and -250 HU) was measured from cardiac and lung scans. Interstitial lung abnormalities (ILAs) were examined from Exam 5 scans (n=2380). Regression models were used to examine the associations of HH with HAAs, ILAs and serum matrix metalloproteinase-7 (MMP-7), and adjusted for age, sex, race/ethnicity, educational attainment, smoking, height, weight and scanner parameters for HAA analysis. RESULTS: HH detected from Exam 5 scans was associated with a mean percentage difference in HAAs of 2.23% (95% CI 0.57-3.93%) and an increase of 0.48% (95% CI 0.07-0.89%) per year, particularly in MUC5B risk allele carriers (p-value for interaction=0.02). HH was associated with ILAs among those <80 years of age (OR for ILAs 1.78, 95% CI 1.14-2.80) and higher serum MMP-7 level among smokers (p-value for smoking interaction=0.04). CONCLUSIONS: HH was associated with more HAAs over time, particularly among MUC5B risk allele carriers, and ILAs in younger adults, and may be a risk factor in the early stages of interstitial lung disease.

QSM Throughout the Body.

Magnetic materials in tissue, such as iron, calcium, or collagen, can be studied using quantitative susceptibility mapping (QSM). To date, QSM has been overwhelmingly applied in the brain, but is increasingly utilized outside the brain. QSM relies on the effect of tissue magnetic susceptibility sources on the MR signal phase obtained with gradient echo sequence. However, in the body, the chemical shift of fat present within the region of interest contributes to the MR signal phase as well. Therefore, correcting for the chemical shift effect by means of water-fat separation is essential for body QSM. By employing techniques to compensate for cardiac and respiratory motion artifacts, body QSM has been applied to study liver iron and fibrosis, heart chamber blood and placenta oxygenation, myocardial hemorrhage, atherosclerotic plaque, cartilage, bone, prostate, breast calcification, and kidney stone.

Effect of Averaging Measurements From Multiple MRI Pulse Sequences on Kidney Volume Reproducibility in Autosomal Dominant Polycystic Kidney Disease.

BACKGROUND: Total kidney volume (TKV) is an important biomarker for assessing kidney function, especially for autosomal dominant polycystic kidney disease (ADPKD). However, TKV measurements from a single MRI pulse sequence have limited reproducibility, ± ~5%, similar to ADPKD annual kidney growth rates. PURPOSE: To improve TKV measurement reproducibility on MRI by extending artificial intelligence algorithms to automatically segment kidneys on T1-weighted, T2-weighted, and steady state free precession (SSFP) sequences in axial and coronal planes and averaging measurements. STUDY TYPE: Retrospective training, prospective testing. SUBJECTS: Three hundred ninety-seven patients (356 with ADPKD, 41 without), 75% for training and 25% for validation, 40 ADPKD patients for testing and 17 ADPKD patients for assessing reproducibility. FIELD STRENGTH/SEQUENCE: T2-weighted single-shot fast spin echo (T2), SSFP, and T1-weighted 3D spoiled gradient echo (T1) at 1.5 and 3T. ASSESSMENT: 2D U-net segmentation algorithm was trained on images from all sequences. Five observers independently measured each kidney volume manually on axial T2 and using model-assisted segmentations on all sequences and image plane orientations for two MRI exams in two sessions separated by 1-3 weeks to assess reproducibility. Manual and model-assisted segmentation times were recorded. STATISTICAL TESTS: Bland-Altman, Schapiro-Wilk (normality assessment), Pearson's chi-squared (categorical variables); Dice similarity coefficient, interclass correlation coefficient, and concordance correlation coefficient for analyzing TKV reproducibility. P-value < 0.05 was considered statistically significant. RESULTS: In 17 ADPKD subjects, model-assisted segmentations of axial T2 images were significantly faster than manual segmentations (2:49 minute vs. 11:34 minute), with no significant absolute percent difference in TKV (5.9% vs. 5.3%, P = 0.88) between scans 1 and 2. Absolute percent differences between the two scans for model-assisted segmentations on other sequences were 5.5% (axial T1), 4.5% (axial SSFP), 4.1% (coronal SSFP), and 3.2% (coronal T2). Averaging measurements from all five model-assisted segmentations significantly reduced absolute percent difference to 2.5%, further improving to 2.1% after excluding an outlier. DATA CONCLUSION: Measuring TKV on multiple MRI pulse sequences in coronal and axial planes is practical with deep learning model-assisted segmentations and can improve TKV measurement reproducibility more than 2-fold in ADPKD. EVIDENCE LEVEL: 2 TECHNICAL EFFICACY: Stage 1.

A health systems intervention to strengthen the integration of tuberculosis and COVID-19 detection: Outcomes of a quasi-experimental study in a high burden tuberculosis district in KwaZulu Natal, South Africa.

OBJECTIVES: The adverse effects of the COVID-19 pandemic on tuberculosis (TB) detection have been well documented. Despite shared symptoms, guidance for integrated screening for TBand COVID-19 are limited, and opportunities for health systems strengthening curtailed by lockdowns. We partnered with a high TB burden district in KwaZulu-Natal, South Africa, to co-develop an integrated approach to assessing COVID-19 and TB, delivered using online learning and quality improvement, and evaluated its performance on TB testing and detection. METHODS: We conducted a mixed methods study incorporating a quasi-experimental design and process evaluation in 10 intervention and 18 control clinics. Nurses in all 28 clinics were all provided access to a four-session online course to integrate TB and COVID-19 screening and testing, which was augmented with some webinar and in-person support at the 10 intervention clinics. We estimated the effects of exposure to this additional support using interrupted time series Poisson regression mixed models. Process evaluation data comprised interviews before and after the intervention. Thematic coding was employed to provide explanations for effects of the intervention. RESULTS: Clinic-level support at intervention clinics was associated with a markedly higher uptake (177 nurses from 10 intervention clinics vs. 19 from 18 control clinics). Lack of familiarity with online learning, and a preference for group learning hindered the transition from face-to-face to online learning. Even so, any exposure to training was initially associated with higher rates of GeneXpert testing (adjusted incidence ratio [IRR] 1.11, 95% confidence interval 1.07-1.15) and higher positive TB diagnosis (IRR 1.38, 1.11-1.71). CONCLUSIONS: These results add to the knowledge base regarding the effectiveness of interventions to strengthen TB case detection during the COVID-19 pandemic. The findings support the feasibility of a shift to online learning approaches in low-resource settings with appropriate support and suggest that even low-intensity interventions are capable of activating nurses to integrate existing disease control priorities during pandemic conditions.

Axillary Lymphadenopathy After a COVID-19 Vaccine Booster Dose: Time to Resolution on Ultrasound Follow-Up and Associated Factors.

BACKGROUND. Because administration of booster doses of COVID-19 vaccines is ongoing, radiologists are continuing to encounter COVID-19 vaccine-related axillary lymphadenopathy on imaging. OBJECTIVE. The purposes of this study were to assess time to resolution of COVID-19 vaccine-related axillary lymphadenopathy identified on breast ultrasound after administration of a booster dose and to assess factors potentially associated with time to resolution. METHODS. This retrospective single-institution study included 54 patients (mean age, 57 years) with unilateral axillary lymphadenopathy ipsilateral to the site of injection of a booster dose of messenger RNA COVID-19 vaccine visualized on ultrasound (whether an initial breast imaging examination or follow-up to prior screening or diagnostic breast imaging) performed between September 1, 2021, and December 31, 2022, and who underwent follow-up ultrasound examinations until resolution of lymphadenopathy. Patient information was extracted from the EMR. Univariable and multivariable linear regression analyses were used to identify predictors of time to resolution. Time to resolution was compared with that in a previously described sample of 64 patients from the study institution that was used to evaluate time to resolution of axillary lymphadenopathy after the initial vaccination series. RESULTS. Six of the 54 patients had a history of breast cancer, and two had symptoms related to axillary lymphadenopathy (axillary pain in both patients). Among the 54 initial ultrasound examinations showing lymphadenopathy, 33 were screening examinations and 21 were diagnostic examinations. Lymphadenopathy had resolved a mean of 102 ± 56 (SD) days after administration of the booster dose and 84 ± 49 days after the initial ultrasound showing lymphadenopathy. Age, vaccine booster type (Moderna vs Pfizer-BioNTech), and history of breast cancer were not significantly associated with time to resolution in univariable or multivariable analyses (all p > .05). Time to resolution after administration of a booster dose was significantly shorter than time to resolution after administration of the first dose in the initial series (mean, 129 ± 37 days) (p = .01). CONCLUSION. Axillary lymphadenopathy after administration of a COVID-19 vaccine booster dose has a mean time to resolution of 102 days, shorter than the time to resolution after the initial vaccination series. CLINICAL IMPACT. The time to resolution after administration of a booster dose supports the current recommendation for a follow-up interval of at least 12 weeks when vaccine-related lymphadenopathy is suspected.

Co-morbid mental health conditions in people with epilepsy and association with quality of life in low- and middle-income countries: a systematic review and meta-analysis.

BACKGROUND: Comorbid mental health conditions are common in people with epilepsy and have a significant negative impact on important epilepsy outcomes, although the evidence is mostly from high-income countries. This systematic review aimed to synthesise evidence on the association between comorbid mental health conditions and quality of life and functioning among people with epilepsy living in low- and middle income countries (LMICs). METHODS: We searched PubMed, EMBASE, CINAHL, Global Index medicus (GID) and PsycINFO databases from their dates of inception to January 2022. Only quantiative observational studies were included. Meta-analysis was conducted for studies that reported the same kind of quality of life and functioning outcome. Cohen's d was calculated from the mean difference in quality-of-life score between people with epilepsy who did and did not have a comorbid depression or anxiety condition. The protocol was registered with PROSPERO: CRD42020161487. RESULTS: The search strategy identified a total of 2,101 articles, from which 33 full text articles were included. Depression was the most common comorbid mental health condition (33 studies), followed by anxiety (16 studies). Meta-analysis was conducted on 19 studies reporting quality of life measured with the same instrument. A large standardized mean effect size (ES) in quality of life score was found (pooled ES = -1.16, 95% confidence interval (CI) - 1.70, - 0.63) between those participants with comorbid depression compared to non-depressed participants. There was significant heterogeneity between studies (I2 = 97.6%, p < 0.001). The median ES (IQR) was - 1.20 (- 1.40, (- 0.64)). An intermediate standard effect size for anxiety on quality of life was also observed (pooled ES = -0.64, 95% CI - 1.14, - 0.13). There was only one study reporting on functioning in relation to comorbid mental health conditions. CONCLUSION: Comorbid depression in people with epilepsy in LMICs is associated with poor quality of life although this evidence is based on highly heterogeneous studies. These findings support calls to integrate mental health care into services for people with epilepsy in LMICs. Future studies should use prospective designs in which the change in quality of life in relation to mental health or public health interventions across time can be measured.

The worldwide costs of dementia in 2019.

INTRODUCTION: Dementia is a leading cause of death and disability globally. Estimating total societal costs demonstrates the wide impact of dementia and its main direct and indirect economic components. METHODS: We constructed a global cost model for dementia, presenting costs as cumulated global and regional costs. RESULTS: In 2019, the annual global societal costs of dementia were estimated at US $1313.4 billion for 55.2 million people with dementia, corresponding to US $23,796 per person with dementia. Of the total, US $213.2 billion (16%) were direct medical costs, US $448.7 billion (34%) direct social sector costs (including long-term care), and US $651.4 billion (50%) costs of informal care. DISCUSSION: The huge costs of dementia worldwide place enormous strains on care systems and families alike. Although most people with dementia live in low- and middle-income countries, highest total and per-person costs are seen in high-income countries. HIGHLIGHTS: Global economic costs of dementia were estimated to reach US $1313.4 in 2019. Sixty-one percent of people with dementia live in low-and middle-income countries, whereas 74% of the costs occur in high-income countries. The impact of informal care accounts for about 50% of the global costs. The development of a long-term care infrastructure is a great challenge for low-and middle-income countries. There is a great need for more cost studies, particularly in low- and middle-income countries. Discussions of a framework for global cost comparisons are needed.

Common perinatal mental disorders and post-infancy child development in rural Ethiopia: A population-based cohort study.

OBJECTIVE: To investigate whether maternal common mental disorders (CMD) in the postnatal period are prospectively associated with child development at 2.5 and 3.5 years in a rural low-income African setting. METHODS: This study was nested within the C-MaMiE (Child outcomes in relation to Maternal Mental health in Ethiopia) population-based cohort in Butajira, Ethiopia, and conducted from 2005 to 2006. The sample comprised of 496 women who had recently given birth to living, singleton babies with recorded birth weight measurements, who were 15 to 44 years of age, and residing in six rural sub-districts. Postnatal CMD measurements were ascertained 2 months after delivery. Language, cognitive, and motor development were obtained from the child 2.5 and 3.5 years after birth using a locally adapted version of the Bayley Scales of Infant Development (3rd Ed). Maternal CMD symptoms were measured using a locally validated WHO Self-Reporting Questionnaire. A linear mixed-effects regression model was used to analyze the relationship between postnatal CMD and child development. RESULTS: After adjusting for confounders, there was no evidence for an association between postnatal CMD and overall child development or the cognitive sub-domain in the preschool period. There was no evidence of effect modification by levels of social support, socioeconomic status, stunting, or sex of the child. CONCLUSIONS: Previous studies from predominantly urban and peri-urban settings in middle-income countries have established a relationship between maternal CMD and child development, which contrasts with the findings from this study. The risk and protective factors for child development may differ in areas characterized by high social adversity and food insecurity. More studies are needed to investigate maternal CMD's impact on child development in low-resource and rural areas.

Treatment and Outcome of Autoimmune Hepatitis (AIH): Audit of 28 UK centres.

BACKGROUND: With few data regarding treatment and outcome of patients with AIH outside of large centres we present such a study of patients with AIH in 28 UK hospitals of varying size and facilities. METHODS: Patients with AIH were identified in 14 University and 14 District General hospitals; incident cases during 2007-2015 and prevalent cases, presenting 2000-2015. Treatment and outcomes were analysed. RESULTS: In 1267 patients with AIH, followed-up for 3.8(0-15) years, 5- and 10-year death/transplant rates were 7.1+0.8% and 10.1+1.3% (all-cause) and 4.0+0.6% and 5.9+1% (liver-related) respectively. Baseline parameters independently associated with death/transplantation for all-causes were: older age, vascular/respiratory co-morbidity, cirrhosis, decompensation, platelet count, attending transplant centre and for liver-related: the last four of these and peak bilirubin All-cause and liver-related death/transplantation was independently associated with: non-treatment with corticosteroids, non-treatment with a steroid-sparing agent (SSA), non-treatment of asymptomatic or non-cirrhotic patients and initial dose of Prednisolone >35mg/0.5mg/kg/day (all-cause only), but not with type of steroid (Prednisolone versus Budesonide) or steroid duration beyond 12-months. Subsequent all-cause and liver-death/transplant rates showed independent associations with smaller percentage fall in serum ALT after 1 and 3-months, but not with failure to normalise levels over 12-months. CONCLUSIONS: We observed higher death/transplant rates in patients with AIH who were untreated with steroids (including asymptomatic or non-cirrhotic sub-groups), those receiving higher Prednisolone doses and those who did not receive an SSA. Similar death/transplant rates were seen in those receiving Prednisolone or Budesonide, those continuing steroids after 12-months and patients attaining normal ALT within 12-months versus not.

Imaging modalities for confirming pulmonary embolism during pregnancy: results from a multicenter international study.

OBJECTIVES: We explored the variations in use of imaging modalities for confirming pulmonary embolism (PE) according to the trimester of pregnancy. METHODS: We included all pregnant patients with confirmed acute PE from RIETE, a prospective registry of patients with PE (03/2001-02/2020). Imaging modalities included computed tomography pulmonary angiography (CTPA), ventilation-perfusion (V/Q) scan, or presence of signs of acute PE along with imaging-confirmed proximal deep vein thrombosis (pDVT) without pulmonary vascular imaging. We compared the imaging modalities to postpartum patients with PE, and other non-pregnant women with PE. RESULTS: There were 157 pregnant patients (age: 32.7 ± 0.5), 228 postpartum patients (age: 33.9 ± 0.5), and 23,937 non-pregnant non-postpartum women (age: 69.5 ± 0.1). CTPA was the most common modality for confirming PE, from 55.7% in first trimester to 58.3% in second trimester, and 70.0% in third trimester. From first trimester to third trimester, V/Q scanning was used in 21.3%, 16.7%, and 18.3% of cases, respectively. Confirmed pDVT along with the presence of signs/symptoms of PE was the confirmatory modality for PE in 21.3% of patients in first trimester, 19.4% in second trimester, and 6.7% in third trimester. The proportion of postpartum patients confirmed with CTPA (85.5%) was comparable to that of non-pregnant non-postpartum women (83.2%). From the first trimester of pregnancy to postpartum period, there was a linear increase in the proportion of patients with PE diagnosed with CTPA (p = 0.039). CONCLUSION: CTPA was the primary modality for confirming PE in all trimesters of pregnancy, although its proportional use was higher in later stages of pregnancy. KEY POINTS: • Computed tomography pulmonary angiography (CTPA) was the primary modality of diagnosis in all trimesters of pregnancy among patients with confirmed pulmonary embolism, even in the first trimester. • From the first trimester of pregnancy to postpartum period, there was a linear increase in the proportion of patients with pulmonary embolism who were diagnosed based on CTPA. • In the postpartum period, use of CTPA as the modality to confirm pulmonary embolism was comparable to non-pregnant patients.

Validation of the Short Version of the 10/66 Dementia Diagnosis in Urdu in Karachi, Pakistan.

The standard 10/66 battery has been translated and validated in Pakistan; however, it takes long to administer it with specialized training for the staff. This study was performed to validate a shorter version of the 10/66. The data for validation of the short version was extracted from the full version study. Ethical approval was taken from the Institutional Review Board of the Aga Khan University. The study was funded by the Aga Khan University, University Research Council Grant. The total number of participants was 257, equally divided between people with dementia and normal cognition. The sensitivity of the short version was 95.7% and 80.5%; specificity was 83.5% and 90.7%; κ was 0.751 and 0.712; and the area under the curve was 0.89 and 0.85 against the standard 10/66 diagnosis and clinician diagnosis, respectively. The short version of 10/66 battery is a valid instrument for diagnosing dementia in the Urdu-speaking Pakistani population.

Time for Resolution of COVID-19 Vaccine-Related Axillary Lymphadenopathy and Associated Factors.

BACKGROUND. The variable clinical course of subclinical lymphadenopathy detected on breast imaging after COVID-19 vaccination creates management challenges and has led to evolving practice recommendations. OBJECTIVE. The purpose of this study was to assess the duration of axillary lymphadenopathy ipsilateral to COVID-19 vaccination detected by breast imaging and to assess factors associated with the time until resolution. METHODS. This retrospective single-center study included 111 patients (mean age, 52 ± 12 years) with unilateral axillary lymphadenopathy ipsilateral to mRNA COVID-19 vaccine administration performed within the prior 8 weeks that was detected on breast ultrasound performed between January 1, 2021, and October 1, 2021, and who underwent follow-up ultrasound examinations at 4- to 12-week intervals until resolution of the lymphadenopathy. Patient information was extracted from medical records. Cortical thickness of the largest axillary lymph node on ultrasound was retrospectively measured and was considered enlarged when greater than 3 mm. Multivariable linear regression analysis was used to identify independent predictors of time until resolution. RESULTS. The mean cortical thickness at the initial ultrasound examination was 4.7 ± 1.2 mm. The lymphadenopathy resolved a mean of 97 ± 44 days after the initial ultrasound examination, 127 ± 43 days after the first vaccine dose, and 2.4 ± 0.6 follow-up ultrasound examinations. A significant independent predictor of shorter time to resolution was Pfizer-BioNTech (rather than Moderna) vaccination (ß = -18.0 [95% CI, -34.3 to -1.7]; p = .03]. Significant independent predictors of longer time to resolution were receipt of the second dose after the initial ultrasound examination (ß = 19.2 [95% CI, 3.1-35.2]; p = .02) and greater cortical thickness at the initial ultrasound examination (ß = 8.0 [95% CI, 1.5-14.5]; p = .02). Patient age, history of breast cancer, and axillary symptoms were not significantly associated with time to resolution (all p > .05). CONCLUSION. Axillary lymphadenopathy detected with breast ultrasound after COVID-19 mRNA vaccination lasts longer than reported in initial vaccine clinical trials. CLINICAL IMPACT. The prolonged time to resolution supports not delaying screening mammography because of recent COVID-19 vaccination. It also supports the professional society recommendation of a follow-up interval of at least 12 weeks when vaccine-related lymphadenopathy is suspected.

Kidney Transplantation From Hepatitis-C Viraemic Donors:Considerations for Practice in the United Kingdom.

Background: Donor hepatitis-C (HCV) infection has historically represented a barrier to kidney transplantation (KT). However, direct-acting antiviral (DAA) medications have revolutionised treatment of chronic HCV infection. Recent American studies have demonstrated that DAA regimes can be used safely peri-operatively in KT to mitigate HCV transmission risk. Methods: To formulate this narrative review, a comprehensive literature search was performed to analyse results of existing clinical trials examining KT from HCV-positive donors to HCV-negative recipients with peri-operative DAA regimes. Results: 13 studies were reviewed (11 single centre, four retrospective). Outcomes for 315 recipients were available across these studies. A sustained virological response at 12 weeks (SVR12) of 100% was achieved in 11 studies. One study employed an ultra-short DAA regime and achieved an SVR12 of 98%, while another achieved SVR12 of 96% due to treatment of a missed mixed genotype. Conclusion: HCV+ KT is safe and may allow increased utilisation of organs for transplantation from HCV+ donors, who often have other favourable characteristics for successful donation. Findings from US clinical trials can be applied to the United Kingdom transplant framework to improve organ utilisation as suggested by the NHSBT vision strategy "Organ Donation and Transplantation 2030: meeting the need".

MR Angiography Series: Abdominal and Pelvic MR Angiography.

This review guides readers through the selection and setup of standardized MR angiography (MRA) protocols for the abdomen and pelvis for common clinical applications. Topics covered include renovascular MRA in potential kidney donors and in patients with hypertension; hepatic and mesenteric MRA in potential liver donors, patients with portal hypertension, and patients with chronic mesenteric ischemia; pelvic MRA for pretreatment planning before uterine fibroid embolization and in patients with pelvic congestion syndrome; and abdominal wall MRA for planning of breast reconstructive surgery. This module is the fifth in a series created on behalf of the Society for Magnetic Resonance Angiography (SMRA), a group of researchers and clinicians who are passionate about the benefits of MRA but understand its challenges. The full digital presentation is available online. ©RSNA, 2022.

Major hemorrhage and mortality in COVID-19 patients on therapeutic anticoagulation for venous thromboembolism.

We observed multiple fatal intracranial hemorrhages shortly after initiating therapeutic anticoagulation for treatment of venous thromboembolism (VTE) in COVID-19 patients suggesting increased anticoagulation risk associated with COVID-19. The objective of this study is to quantify risk of major hemorrhage in hospitalized COVID-19 patients on therapeutic anticoagulation for deep venous thrombosis (DVT) or pulmonary embolism (PE). Hospitalized patients with COVID-19 receiving therapeutic anticoagulation for DVT, PE or both at four New York City hospitals were evaluated for hemorrhagic complications. These were categorized as major (including fatal) or clinically relevant non-major according to the criteria of the International Society of Thrombosis and Haemostasis. Hemorrhagic complications were correlated with clinical and laboratory data, ICD-10 code diagnoses and type of anticoagulation treatment. Minor hemorrhages were excluded. Major/clinically relevant hemorrhages occurred in 36 of 170 (21%) hospitalized COVID-19 patients being treated with therapeutic anticoagulation for VTE including 4 (2.4%) fatal hemorrhages. Hemorrhage was 3.4 times more likely with unfractionated heparin 27/76 (36%) compared to 8/81 (10%) with low molecular weight heparin (p = 0.002). Multivariate analysis showed that major hemorrhage was associated with intubation (p = 0.04) and elevated serum LDH (p < 0.001) and low fibrinogen (p = 0.05). Increased risk of hemorrhagic complications in treating VTE in hospitalized COVID-19 patients should be considered especially when using unfractionated heparin, in intubated patients, with low fibrinogen and/or elevated LDH. Checking serum fibrinogen and LDH before initiating therapeutic anticoagulation and monitoring coagulation parameters frequently may reduce bleeding complications.

Machine Learning Based Prediction Model for Closed-Loop Small Bowel Obstruction Using Computed Tomography and Clinical Findings.

PURPOSE: The aim of the study was to develop a prediction model for closed-loop small bowel obstruction integrating computed tomography (CT) and clinical findings. METHODS: The radiology database and surgical reports from 2 suburban teaching hospitals were retrospectively reviewed for patients undergoing surgery for suspected closed-loop small bowel obstruction (CLSBO). Two observers independently reviewed the CT scans for the presence of imaging features of CLSBO, blinded to the surgically confirmed diagnosis and clinical parameters. Random forest analysis was used to train and validate a prediction model for CLSBO, by combining CT and clinical findings, after randomly splitting the sample into 80% training and 20% test subsets. RESULTS: Surgery confirmed CLSBO in 185 of 223 patients with clinically suspected CLSBO. Age greater than 52 years showed 2.82 (95% confidence interval = 1.13-4.77) times higher risk for CLSBO (P = 0.021). Sensitivity/specificity of CT findings included proximal dilatation (97/5%), distal collapse (96/2%), mesenteric edema (94/5%), pneumatosis (1/100%), free air (1/98%), and portal venous gas (0/100%). The random forest model combining imaging/clinical findings yielded an area under receiver operating curve of 0.73 (95% confidence interval = 0.58-0.94), sensitivity of 0.72 (0.55-0.85), specificity of 0.8 (0.28-0.99), and accuracy of 0.73 (0.57-0.85). Prior surgery, age, lactate, whirl sign, U/C-shaped bowel configuration, and fecalization were the most important variables in predicting CLSBO. CONCLUSIONS: A random forest model found clinical factors including prior surgery, age, lactate, and imaging factors including whirl sign, fecalization, and U/C-shaped bowel configuration are helpful in improving the prediction of CLSBO. Individual CT findings in CLSBO had either high sensitivity or specificity, suggesting that accurate diagnosis requires systematic assessment of all CT signs.

The relationship between common mental disorders (CMDs), food insecurity and domestic violence in pregnant women during the COVID-19 lockdown in Cape Town, South Africa.

PURPOSE: We aimed to explore the relationship between common mental disorders (CMDs), food insecurity and experiences of domestic violence among pregnant women attending public sector midwife obstetric units and basic antenatal care clinics in Cape Town during the COVID-19 lockdown. METHODS: Perinatal women, attending 14 healthcare facilities in Cape Town, were enrolled in the study during baseline data collection before the COVID-19 lockdown. During the lockdown period, fieldworkers telephonically contacted the perinatal women who were enrolled in the study and had provided contact details. The following data were collected from those who consented to the study: socio-demographic information, mental health assessment, food insecurity status and experiences of domestic violence. Poisson regression was used to model the associations of a number of risk factors with the occurrence of CMDs. RESULTS: Of the 2149 women enrolled in the ASSET study, 885 consented to telephonic interviews. We found that 12.5% of women had probable CMDs and 43% were severely food insecure. Psychological distress increased significantly during the lockdown period, compared to before the COVID-19 outbreak. Using multivariate Poisson regression modelling, we showed that the risk of CMDs was increased in women who were severely food insecure or who experienced psychological or sexual abuse. CONCLUSIONS: This study provides evidence of the effect of the COVID-19 lockdown on the mental health status of perinatal women living in low-resource settings in Cape Town and highlights how a crisis such as the COVID-19 lockdown amplifies the psycho-social risk factors associated with CMDs in perinatal women.