Reproducibility in Radiomics: A Comparison of Feature Extraction Methods and Two Independent Datasets.

Radiomics involves the extraction of information from medical images that are not visible to the human eye. There is evidence that these features can be used for treatment stratification and outcome prediction. However, there is much discussion about the reproducibility of results between different studies. This paper studies the reproducibility of CT texture features used in radiomics, comparing two feature extraction implementations, namely the MATLAB toolkit and Pyradiomics, when applied to independent datasets of CT scans of patients: (i) the open access RIDER dataset containing a set of repeat CT scans taken 15 min apart for 31 patients (RIDER Scan 1 and Scan 2, respectively) treated for lung cancer; and (ii) the open access HN1 dataset containing 137 patients treated for head and neck cancer. Gross tumor volume (GTV), manually outlined by an experienced observer available on both datasets, was used. The 43 common radiomics features available in MATLAB and Pyradiomics were calculated using two intensity-level quantization methods with and without an intensity threshold. Cases were ranked for each feature for all combinations of quantization parameters, and the Spearman's rank coefficient, rs, calculated. Reproducibility was defined when a highly correlated feature in the RIDER dataset also correlated highly in the HN1 dataset, and vice versa. A total of 29 out of the 43 reported stable features were found to be highly reproducible between MATLAB and Pyradiomics implementations, having a consistently high correlation in rank ordering for RIDER Scan 1 and RIDER Scan 2 (rs > 0.8). 18/43 reported features were common in the RIDER and HN1 datasets, suggesting they may be agnostic to disease site. Useful radiomics features should be selected based on reproducibility. This study identified a set of features that meet this requirement and validated the methodology for evaluating reproducibility between datasets.

Teleradiology and technology innovations in radiology: status in India and its role in increasing access to primary health care.

Background: There is an inequitable distribution of radiology facilities in India. This scoping review aimed at mapping the available technology instruments to improve access to imaging at primary health care; to identify the facilitators and barriers, and the knowledge gaps for widespread adaptation of technology solutions. Methods: A search was conducted using broad inclusive terms non-specific to subtypes of medical imaging devices or informatics. Work published in the English language between 2005 and 2022, conducted primarily in India, and with full manuscripts were included. Two authors independently screened the abstracts against the inclusion criteria for full-text review and a senior author settled discrepancies. Data were extracted using DistillerSR software. Findings: 43 original articles and 52 non-academic materials were finally reviewed. The data was from 10 Indian states with n = 9 from rural settings. The broad trends in original articles were: connectivity using teleradiology (n = 7), mobile digital imaging units (n = 9), artificial intelligence (n = 16); mobile devices and smartphone applications (n = 7); data security (n = 7) and web-based technology (n = 2); public-private partnership (n = 9); cost (n = 2); concordance (n = 19); evaluation (n = 4); implementation (n = 2). Interpretation: Available evidence suggests that teleradiology when combined with AI and mobile digital imaging units can address radiologist shortages; strengthen programs aimed at population screening and emergency care. However, there is insufficient data on the scale of teleradiology networks within India; needs assessment; cost; facilitators, and barriers for implementation of technologies solutions in primary healthcare settings. Regulations governing quality standards, data protection, and confidentiality are unclear. Funding: The authors are The Lancet Citizen's Commission fellows. The Lancet Commission has received financial support from the Lakshmi Mittal and Family South Asia Institute, Harvard University; Christian Medical College, Vellore (CMC), Vellore; Azim Premji Foundation, Infosys; Kirloskar Systems Ltd.; Mahindra & Mahindra Ltd.; Rohini Nilekani Philanthropies; and Serum Institute of India. The views expressed are those of the author(s) and not necessarily those of the Lancet Citizens' Commission or its partners.

Is radiomics a useful addition to magnetic resonance imaging in the preoperative classification of PitNETs?

BACKGROUND: The WHO 2021 introduced the term pituitary neuroendocrine tumours (PitNETs) for pituitary adenomas and incorporated transcription factors for subtyping, prompting the need for fresh diagnostic methods. Current biomarkers struggle to distinguish between high- and low-risk non-functioning PitNETs. We explored if radiomics can enhance preoperative decision-making. METHODS: Pre-treatment magnetic resonance (MR) images of patients who underwent surgery between 2015 and 2019 with available WHO 2021 classification were used. The tumours were manually segmented on the T1w, T1-contrast enhanced, and T2w images using 3D Slicer. One hundred Pyradiomic features were extracted from each MR sequence. Models were built to classify (1) somatotroph and gonadotroph PitNETs and (2) high- and low-risk subtypes of non-functioning PitNETs. Feature were selected independently from the MR sequences and multi-sequence (combining data from more than one MR sequence) using Boruta and Pearson correlation. Support vector machine (SVM), logistic regression (LR), random forest (RF), and multi-layer perceptron (MLP) were the classifiers used. Data imbalance was addressed using the Synthetic Minority Oversampling TEchnique (SMOTE). Performance of the models were evaluated using area under the receiver operating curve (AUC), accuracy, sensitivity, and specificity. RESULTS: A total of 222 PitNET patients (train, n = 149; test, n = 73) were enrolled in this retrospective study. Multi-sequence-based LR model discriminated best between somatotroph and gonadotroph PitNETs, with a test AUC of 0.84, accuracy of 0.74, specificity of 0.81, and sensitivity of 0.70. Multi-sequence-based MLP model perfomed best for the high- and low-risk non-functioning PitNETs, achieving a test AUC of 0.76, accuracy of 0.67, specificity of 0.72, and sensitivity of 0.66. CONCLUSIONS: Utilizing pre-treatment MRI and radiomics holds promise for distinguishing high-risk from low-risk non-functioning PitNETs based on the latest WHO classification. This could assist neurosurgeons in making critical decisions regarding surgery or alternative management strategies for PitNETs after further clinical validation.

UDHAVI Community Support During India's Second COVID-19 Wave: A Descriptive Study on a Tertiary Care Center's Pandemic Response Helpline.

BACKGROUND: In April 2021, during the peak of the second wave of the COVID-19 pandemic in India, hospitals overflowed with COVID-19 patients, and people hesitated to seek necessary care due to fear of contracting the disease. The UDHAVI helpline was set up by a tertiary care hospital in Vellore with the help of district administration, nongovernmental organizations, and various supporting agencies to provide general information, medical advice, counseling, and logistics support to the community. METHODS: This is a retrospective study of all the phone calls made to the UDHAVI helpline between mid-May and mid-June 2021 during the second wave of the COVID-19 pandemic. The calls were electronically captured as part of the process, and the information was subsequently retrieved and analyzed. RESULTS: In all, 677 calls were received. The lines for general information, medical advice, counseling, and logistics support received 168 (25%), 377 (56%), 15 (2%), and 117 (17%) calls, respectively. Home care kits, oxygen concentrators, and food were delivered by volunteers from local nongovernmental organizations and hospitals. CONCLUSION: We believe the details of our experience would be useful in the preparedness and mobilization of resources in the event of any public health emergency. As a result of this initiative, we propose an integrated partnership model for emergency response to any pandemic situation.

Unequally Unequal? Contextual-level status inequality and social cohesion moderating the association between individual-level socioeconomic position and systemic chronic inflammation.

BACKGROUND: Status inequality is hypothesised to increase socioeconomic inequalities in health by creating an environment in which social cohesion erodes and social comparisons intensify. Such an environment may cause systemic chronic inflammation. Although these are often-used explanations in social epidemiology, empirical tests remain rare. METHODS: We analysed data from the West of Scotland Twenty-07 Study. Our sample consisted of 1977 participants in 499 small residential areas. Systemic chronic inflammation was measured by high-sensitivity C-reactive protein (hs-CRP; <10 mg/L). An area-level measurement of status inequality was created using census data and contextual-level social cohesion was measured applying ecometrics. We estimated linear multilevel models with cross-level interactions between socioeconomic position (SEP), status inequality, and social cohesion adjusted for age and gender. Our main analysis on postcode sector-level was re-estimated on three smaller spatial levels. RESULTS: The difference in hs-CRP between disadvantaged and advantaged SEPs (0.806 mg/L; p = 0.063; [95%CI: -0.044; 1.656]) was highest among participants living in areas where most residents were in advantaged SEPs. In these status distributions, high social cohesion was associated with a shallower socioeconomic gradient in hs-CRP and low social cohesion was associated with a steeper gradient. In areas with an equal mix of SEPs or most residents in disadvantaged SEPs, the estimated difference in hs-CRP between disadvantaged and advantaged SEPs was -0.039 mg/L (p = 0.898; [95%CI: 0.644; 0.566]) and -0.257 mg/L (p = 0.568; [95%CI: 1.139; 0.625]) respectively. In these status distributions, the gradient in hs-CRP appeared steeper when social cohesion was high and potentially reversed when social cohesion was low. Results were broadly consistent when using area-levels smaller than postcode sectors. CONCLUSIONS: Inequalities in hs-CRP were greatest among participants living in areas wherein a majority of residents were in advantaged SEPs and social cohesion was low. In other combinations of these contextual characteristics, inequalities in systemic chronic inflammation were not detectable or potentially even reversed.

Multi-centre radiomics for prediction of recurrence following radical radiotherapy for head and neck cancers: Consequences of feature selection, machine learning classifiers and batch-effect harmonization.

Background and purpose: Radiomics models trained with limited single institution data are often not reproducible and generalisable. We developed radiomics models that predict loco-regional recurrence within two years of radiotherapy with private and public datasets and their combinations, to simulate small and multi-institutional studies and study the responsiveness of the models to feature selection, machine learning algorithms, centre-effect harmonization and increased dataset sizes. Materials and methods: 562 patients histologically confirmed and treated for locally advanced head-and-neck cancer (LA-HNC) from two public and two private datasets; one private dataset exclusively reserved for validation. Clinical contours of primary tumours were not recontoured and were used for Pyradiomics based feature extraction. ComBat harmonization was applied, and LASSO-Logistic Regression (LR) and Support Vector Machine (SVM) models were built. 95% confidence interval (CI) of 1000 bootstrapped area-under-the-Receiver-operating-curves (AUC) provided predictive performance. Responsiveness of the models' performance to the choice of feature selection methods, ComBat harmonization, machine learning classifier, single and pooled data was evaluated. Results: LASSO and SelectKBest selected 14 and 16 features, respectively; three were overlapping. Without ComBat, the LR and SVM models for three institutional data showed AUCs (CI) of 0.513 (0.481-0.559) and 0.632 (0.586-0.665), respectively. Performances following ComBat revealed AUCs of 0.559 (0.536-0.590) and 0.662 (0.606-0.690), respectively. Compared to single cohort AUCs (0.562-0.629), SVM models from pooled data performed significantly better at AUC = 0.680. Conclusions: Multi-institutional retrospective data accentuates the existing variabilities that affect radiomics. Carefully designed prospective, multi-institutional studies and data sharing are necessary for clinically relevant head-and-neck cancer prognostication models.

Utility of Mid-treatment DWI in Selecting Pathological Responders to Neoadjuvant Chemoradiotherapy in Locally Advanced Esophageal Cancer.

PURPOSE: Pathological complete response correlates with better clinical outcomes in locally advanced esophageal cancer (LA-EC). However, there is lack of prognostic markers to identify patients in the current setting of neoadjuvant chemoradiotherapy (NACRT) followed by surgery. This study evaluates the utility of mid-treatment diffusion-weighted imaging (DWI) in identifying pathological responders of NACRT. METHODS: Twenty-four patients with LA-EC on NACRT were prospectively recruited and underwent three MRI (baseline, mid-treatment, end-of-RT) scans. DWI-derived apparent diffusion coefficient (ADC) mean and minimum were used as a surrogate to evaluate the treatment response, and its correlation to pathological response was assessed. RESULTS: Mid-treatment ADC mean was significantly higher among patients with pathological response compared to non-responders (p = 0.011). ADC difference (ΔADC) between baseline and mid-treatment correlated with tumor response (p = 0.007). ADC at other time points did not correlate to pathological response. CONCLUSION: In this study, mid-treatment ADC values show potential to be a surrogate for tumor response in NACRT. However, larger trials are required to establish DW-MRI as a definite biomarker for tumor response.

Clinical Measures of Adolescent Softball Players With and Without Upper-Extremity Pain: A Preliminary Study.

CONTEXT: Upper-extremity (UE) pain is a concern among softball adolescent athletes. However, research on preseason screening of demographic characteristics and clinical measures among those with and without UE pain among adolescent softball athletes is underreported. This study sought to present functional outcomes and clinical measures of shoulder and hip complex flexibility, range of motion (ROM), and strength in adolescent softball athletes with and without UE pain. DESIGN: Cross-sectional study. METHODS: Sixty-seven athletes were assessed at the start of the spring season. The Kerlan-Jobe Orthopedic Clinic Shoulder and Elbow Questionnaire was administered to determine UE function. UE measurements included shoulder ROM, flexibility, and strength; lower-extremity measurements included hip ROM and strength. These variables were reported for players with and without UE pain as mean and SD. Independent samples t tests were performed to analyze differences between the groups. RESULTS: Thirteen (19.4%) athletes reported UE pain during preseason screening. Mean Kerlan-Jobe Orthopedic Clinic Shoulder and Elbow Questionnaire score among athletes with UE pain was 58.0 (17.6) compared with 97.1 (6.9) for athletes reporting no UE pain (P < .001). Athletes with UE pain presented with significantly less dominant side external rotation ROM (UE pain: 106.5 [10.4], no UE pain: 114.6 [11.3]) and total ROM (UE pain: 163.7 [14.5], no UE Pain: 174.8 [14.3]). CONCLUSION: These findings inform clinicians on function and preseason clinical measures in adolescent softball athletes who present with or without UE pain. Athletes with UE pain demonstrated lower outcome scores indicating likely impact on overall UE function. These athletes also appeared to demonstrate UE ROM differences compared with athletes without UE pain. Further research is needed to investigate larger sample sizes and positional differences at baseline and throughout the season to determine if clinical measures used in the current study are risk factors for pain and injury.

Improving Intubation Success in Pediatric and Neonatal Transport Using Simulation.

BACKGROUND: Pediatric and neonatal first-pass intubation rates are higher in adult trained retrieval services than in neonatal or pediatric trained services. Some authors have attributed this to more frequent opportunities to practice the skill in the adult population. OBJECTIVE: The aim of this study was to increase the first-pass intubation rate without adverse events by introducing daily intubation simulation at our mixed neonatal and pediatric retrieval service. METHODS: This prospective cohort study performed from July to December 2018 in our mixed neonatal and pediatric retrieval service involved 16 medical staff performing simulated intubation at commencement of their retrieval shift with a retrieval nurse. Checklists for neonatal and pediatric intubation were introduced to the retrieval service for the intervention cohort. Participants were asked to complete questionnaires about intubation performed on retrieval to gather data not routinely collected by the service. RESULTS: Seven hundred and sixty-eight patients were retrieved by the service and 70 patients required intubation by the retrieval team during the intervention period. First-pass intubation rates were higher during the intervention period compared with a historical cohort, despite less intubations being performed overall. First-pass intubation rates improved from 59% to 78% in neonatal patients (P = 0.032), 58% to 65% in pediatric patients (P = 0.68) and from 58% to 74% overall (P = 0.043). There were no severe adverse events detected during the intervention period. Minor adverse events were associated with multiple attempts at intubation (P < 0.001). Overall compliance with simulation protocol was 43.5%, and on average, each doctor completed simulation once per month. CONCLUSIONS: Simulation is a useful adjunct to support neonatal and pediatric intubation training in the current environment of reducing intubation frequency.

Framework for Machine Learning of CT and PET Radiomics to Predict Local Failure after Radiotherapy in Locally Advanced Head and Neck Cancers.

CONTEXT: Cancer Radiomics is an emerging field in medical imaging and refers to the process of converting routine radiological images that are typically qualitatively interpreted to quantifiable descriptions of the tumor phenotypes and when combined with statistical analytics can improve the accuracy of clinical outcome prediction models. However, to understand the radiomic features and their correlation to molecular changes in the tumor, first, there is a need for the development of robust image analysis methods, software tools and statistical prediction models which is often limited in low- and middle-income countries (LMIC). AIMS: The aim is to build a framework for machine learning of radiomic features of planning computed tomography (CT) and positron emission tomography (PET) using open source radiomics and data analytics platforms to make it widely accessible to clinical groups. The framework is tested in a small cohort to predict local disease failure following radiation treatment for head-and-neck cancer (HNC). The predictors were also compared with the existing Aerts HNC radiomics signature. SETTINGS AND DESIGN: Retrospective analysis of patients with locally advanced HNC between 2017 and 2018 and 31 patients with both pre- and post-radiation CT and evaluation PET were selected. SUBJECTS AND METHODS: Tumor volumes were delineated on baseline PET using the semi-automatic adaptive-threshold algorithm and propagated to CT; PyRadiomics features (total of 110 under shape/intensity/texture classes) were extracted. Two feature-selection methods were tested for model stability. Models were built based on least absolute shrinkage and selection operator-logistic and Ridge regression of the top pretreatment radiomic features and compared to Aerts' HNC-signature. Average model performance across all internal validation test folds was summarized by the area under the receiver operator curve (ROC). RESULTS: Both feature selection methods selected CT features MCC (GLCM), SumEntropy (GLCM) and Sphericity (Shape) that could predict the binary failure status in the cross-validated group and achieved an AUC >0.7. However, models using Aerts' signature features (Energy, Compactness, GLRLM-GrayLevelNonUniformity and GrayLevelNonUniformity-HLH wavelet) could not achieve a clear separation between outcomes (AUC = 0.51-0.54). CONCLUSIONS: Radiomics pipeline included open-source workflows which makes it adoptable in LMIC countries. Additional independent validation of data is crucial for the implementation of radiomic models for clinical risk stratification.

Impact of Upper Eyelid Surgery on Symptom Severity and Frequency in Benign Essential Blepharospasm.

OBJECTIVE: To assess the impact of periocular surgery, other than orbicularis stripping, on the severity and frequency of blepharospasm symptoms. METHODS: Consecutive patients with benign essential blepharospasm (BEB) who underwent eyelid/eyebrow surgery with the aim of improving symptoms were retrospectively reviewed over a 5-year period. Patients who had completed the Jankovic Rating Scale (JRS) and Blepharospasm Disability Index (BDI) pre- and at least 3 months postoperatively were included. RESULTS: Twenty-four patients were included. JRS scores significantly improved from 7.0 preoperatively to 4.1 postoperatively (p < 0.001), and BDI scores significantly improved from 18.4 preoperatively to 12.7 postoperatively (p < 0.001); the mean percentage improvements were 41% and 30%, respectively. Patients were followed for a median of 24 months postoperatively. CONCLUSION: Periocular surgery significantly reduced BEB symptoms in the majority (83%) of patients by an average of 33% and may therefore be offered for suitable patients. An important minority (17%) of patients experienced symptom worsening.

Impact of Upper Eyelid Surgery on Symptom Severity and Frequency in Benign Essential Blepharospasm

Objective@#To assess the impact of periocular surgery, other than orbicularis stripping, on the severity and frequency of blepharospasm symptoms. @*Methods@#Consecutive patients with benign essential blepharospasm (BEB) who underwent eyelid/eyebrow surgery with the aim of improving symptoms were retrospectively reviewed over a 5-year period. Patients who had completed the Jankovic Rating Scale (JRS) and Blepharospasm Disability Index (BDI) pre- and at least 3 months postoperatively were included. @*Results@#Twenty-four patients were included. JRS scores significantly improved from 7.0 preoperatively to 4.1 postoperatively (p < 0.001), and BDI scores significantly improved from 18.4 preoperatively to 12.7 postoperatively (p < 0.001); the mean percentage improvements were 41% and 30%, respectively. Patients were followed for a median of 24 months postoperatively. @*Conclusion@#Periocular surgery significantly reduced BEB symptoms in the majority (83%) of patients by an average of 33% and may therefore be offered for suitable patients. An important minority (17%) of patients experienced symptom worsening.

Comparison of regional lung perfusion response on longitudinal MAA SPECT/CT in lung cancer patients treated with and without functional tissue-avoidance radiation therapy.

OBJECTIVE: The effect of functional lung avoidance planning on radiation dose-dependent changes in regional lung perfusion is unknown. We characterized dose-perfusion response on longitudinal perfusion single photon emission computed tomography (SPECT)/CT in two cohorts of lung cancer patients treated with and without functional lung avoidance techniques. METHODS: The study included 28 primary lung cancer patients: 20 from interventional (NCT02773238) (FLARE-RT) and eight from observational (NCT01982123) (LUNG-RT) clinical trials. FLARE-RT treatment plans included perfused lung dose constraints while LUNG-RT plans adhered to clinical standards. Pre- and 3 month post-treatment macro-aggregated albumin (MAA) SPECT/CT scans were rigidly co-registered to planning four-dimensional CT scans. Tumour-subtracted lung dose was converted to EQD2 and sorted into 5 Gy bins. Mean dose and percent change between pre/post-RT MAA-SPECT uptake (%ΔPERF), normalized to total tumour-subtracted lung uptake, were calculated in each binned dose region. Perfusion frequency histograms of pre/post-RT MAA-SPECT were analyzed. Dose-response data were parameterized by sigmoid logistic functions to estimate maximum perfusion increase (%ΔPERFmaxincrease), maximum perfusion decrease (%ΔPERFmaxdecrease), dose midpoint (Dmid), and dose-response slope (k). RESULTS: Differences in MAA perfusion frequency distribution shape between time points were observed in 11/20 (55%) FLARE-RT and 2/8 (25%) LUNG-RT patients (p < 0.05). FLARE-RT dose response was characterized by >10% perfusion increase in the 0-5 Gy dose bin for 8/20 patients (%ΔPERFmaxincrease = 10-40%), which was not observed in any LUNG-RT patients (p = 0.03). The dose midpoint Dmid at which relative perfusion declined by 50% trended higher in FLARE-RT compared to LUNG-RT cohorts (35 GyEQD2 vs 21 GyEQD2, p = 0.09), while the dose-response slope k was similar between FLARE-RT and LUNG-RT cohorts (3.1-3.2, p = 0.86). CONCLUSION: Functional lung avoidance planning may promote increased post-treatment perfusion in low dose regions for select patients, though inter-patient variability remains high in unbalanced cohorts. These preliminary findings form testable hypotheses that warrant subsequent validation in larger cohorts within randomized or case-matched control investigations. ADVANCES IN KNOWLEDGE: This novel preliminary study reports differences in dose-response relationships between patients receiving functional lung avoidance radiation therapy (FLARE-RT) and those receiving conventionally planned radiation therapy (LUNG-RT). Following further validation and testing of these effects in larger patient populations, individualized estimation of regional lung perfusion dose-response may help refine future risk-adaptive strategies to minimize lung function deficits and toxicity incidence.

Naming the Dead: What information do Physical Therapy and Physician Assistant Anatomy Faculty Share With Students?

In this novel study, the researchers quantify cadaver information provided to Physical Therapy (PT) and Physician Assistant (PA) anatomy faculty and ask what portion of that information is then shared with students. Descriptive statistics were used to the describe demographics of the study respondents and to report survey responses. The majority (60% or greater) of faculty who teach anatomy to PT and PA students have clinical degrees matching the student groups they teach. Chi-square analysis showed no appreciable difference (P < 0.001) between PT and PA anatomy faculty in the amount of cadaver information they receive or then share with students. There was a difference in the type of cadaver information (identifying vs. non-identifying) that is received and then shared by these faculty. Faculty are more likely to receive non-identifying cadaver information (93%) than identifying information (40%) (P < 0.0001) and share non-identifying information (83%) than identifying information (26%) with students (P < 0.0003). Interestingly, there is no consensus as to whether sharing cadaver information is respectful or disrespectful to those who donate their bodies for anatomy education and research. Further research is warranted into the reasons anatomy faculty withhold cadaver information from students and in the value, if any, for students knowing more about the cadavers they are learning from.

Association of longitudinal alcohol consumption trajectories with coronary heart disease: a meta-analysis of six cohort studies using individual participant data.

BACKGROUND: Studies have shown that alcohol intake trajectories differ in their associations with biomarkers of cardiovascular functioning, but it remains unclear if they also differ in their relationship to actual coronary heart disease (CHD) incidence. Using multiple longitudinal cohort studies, we evaluated the association between long-term alcohol consumption trajectories and CHD. METHODS: Data were drawn from six cohorts (five British and one French). The combined analytic sample comprised 35,132 individuals (62.1% male; individual cohorts ranging from 869 to 14,247 participants) of whom 4.9% experienced an incident (fatal or non-fatal) CHD event. Alcohol intake across three assessment periods of each cohort was used to determine participants' intake trajectories over approximately 10 years. Time to onset for (i) incident CHD and (ii) fatal CHD was established using surveys and linked medical record data. A meta-analysis of individual participant data was employed to estimate the intake trajectories' association with CHD onset, adjusting for demographic and clinical characteristics. RESULTS: Compared to consistently moderate drinkers (males: 1-168 g ethanol/week; females: 1-112 g ethanol/week), inconsistently moderate drinkers had a significantly greater risk of incident CHD [hazard ratio (HR) = 1.18, 95% confidence interval (CI) = 1.02-1.37]. An elevated risk of incident CHD was also found for former drinkers (HR = 1.31, 95% CI = 1.13-1.52) and consistent non-drinkers (HR = 1.47, 95% CI = 1.21-1.78), although, after sex stratification, the latter effect was only evident for females. When examining fatal CHD outcomes alone, only former drinkers had a significantly elevated risk, though hazard ratios for consistent non-drinkers were near identical. No evidence of elevated CHD risk was found for consistently heavy drinkers, and a weak association with fatal CHD for inconsistently heavy drinkers was attenuated following adjustment for confounding factors. CONCLUSIONS: Using prospectively recorded alcohol data, this study has shown how instability in drinking behaviours over time is associated with risk of CHD. As well as individuals who abstain from drinking (long term or more recently), those who are inconsistently moderate in their alcohol intake have a higher risk of experiencing CHD. This finding suggests that policies and interventions specifically encouraging consistency in adherence to lower-risk drinking guidelines could have public health benefits in reducing the population burden of CHD. The absence of an effect amongst heavy drinkers should be interpreted with caution given the known wider health risks associated with such intake. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03133689 .

Combined Skin and Muscle DNA Priming Provides Enhanced Humoral Responses to a Human Immunodeficency Virus Type 1 Clade C Envelope Vaccine.

Intradermal (i.d.) and intramuscular (i.m.) injections when administered with or without electroporation (EP) have the potential to tailor the immune response to DNA vaccination. This Phase I randomized controlled clinical trial in human immunodeficiency virus type 1-negative volunteers investigated whether the site and mode of DNA vaccination influences the quality of induced cellular and humoral immune responses following the DNA priming phase and subsequent protein boost with recombinant clade C CN54 gp140. A strategy of concurrent i.d. and i.m. DNA immunizations administered with or without EP was adopted. Subtle differences were observed in the shaping of vaccine-induced virus-specific CD4+ and CD8+ T cell-mediated immune responses between groups receiving: i.d.EP + i.m., i.d. + i.m.EP, and i.d.EP + i.m.EP regimens. The DNA priming phase induced 100% seroconversion in all of the groups. A single, non-adjuvanted protein boost induced a rapid and profound increase in binding antibodies in all groups, with a trend for higher responses in i.d.EP + i.m.EP. The magnitude of antigen-specific binding immunoglobulin G correlated with neutralization of closely matched clade C 93MW965 virus and Fc-dimer receptor binding (FcγRIIa and FcγRIIIa). These results offer new perspectives on the use of combined skin and muscle DNA immunization in priming humoral and cellular responses to recombinant protein.

Corneal perforation from peripheral ulcerative keratopathy in patients with rheumatoid arthritis: epidemiological findings of the British Ophthalmological Surveillance Unit.

BACKGROUND/AIMS: This study quantifies the threat to vision and the survival in patients presenting with peripheral ulcerative keratopathy (PUK) corneal perforation associated with rheumatoid arthritis (RA) in the UK. METHODS: New cases of corneal perforation from PUK in patients with RA were prospectively collected from the UK via the British Ophthalmological Surveillance Unit from July 2012 to June 2014. An initial questionnaire collected data on presentation and the first 2 weeks' management, and a follow-up questionnaire collected 1-year data on ocular morbidity and mortality. RESULTS: 30 eyes of 28 patients were identified over 2 years, estimating a UK incidence of 0.234/million/year. 20/27 (74%) were female, with a median age of 68 years (range 41-84). The most common initial management was cyanoacrylate glue with a bandage contact lens, oral steroids, topical and oral antibiotics, and lubricants. Long-term management included corneal grafting in 12/20 (60%) eyes of patients living at 1 year. The 1-year all-cause mortality was 6/25 (24%), which increased to 1/2 (50%) if both eyes had perforated. In the remaining patients alive at 1-year follow-up, there was a 13/20 (65%) poor visual outcome of less than or equal to counting fingers. 8/25 (40%) patients had bilateral PUK, with 2/25 (8%) having bilateral perforation. 5/19 (26%) patients alive at 1-year follow-up were eligible for sight impairment registration. CONCLUSION: This study highlights the serious ocular morbidity and high mortality associated with corneal perforation from PUK in patients with RA despite treatment. The mortality doubled if both eyes perforated, which should serve as a harbinger of impending serious medical problems.

Impact of tumour motion compensation and delineation methods on FDG PET-based dose painting plan quality for NSCLC radiation therapy.

INTRODUCTION: To quantitatively estimate the impact of different methods for both boost volume delineation and respiratory motion compensation of [18F] FDG PET/CT images on the fidelity of planned non-uniform 'dose painting' plans to the prescribed boost dose distribution. METHODS: Six locally advanced non-small cell lung cancer (NSCLC) patients were retrospectively reviewed. To assess the impact of respiratory motion, time-averaged (3D AVG), respiratory phase-gated (4D GATED) and motion-encompassing (4D MIP) PET images were used. The boost volumes were defined using manual contour (MANUAL), fixed threshold (FIXED) and gradient search algorithm (GRADIENT). The dose painting prescription of 60 Gy base dose to the planning target volume and an integral dose of 14 Gy (total 74 Gy) was discretized into seven treatment planning substructures and linearly redistributed according to the relative SUV at every voxel in the boost volume. Fifty-four dose painting plan combinations were generated and conformity was evaluated using quality index VQ0.95-1.05, which represents the sum of planned dose voxels within 5% deviation from the prescribed dose. Trends in plan quality and magnitude of achievable dose escalation were recorded. RESULTS: Different segmentation techniques produced statistically significant variations in maximum planned dose (P < 0.02), as well as plan quality between segmentation methods for 4D GATED and 4D MIP PET images (P < 0.05). No statistically significant differences in plan quality and maximum dose were observed between motion-compensated PET-based plans (P > 0.75). Low variability in plan quality was observed for FIXED threshold plans, while MANUAL and GRADIENT plans achieved higher dose with lower plan quality indices. CONCLUSIONS: The dose painting plans were more sensitive to segmentation of boost volumes than PET motion compensation in this study sample. Careful consideration of boost target delineation and motion compensation strategies should guide the design of NSCLC dose painting trials.