The Otolaryngology Consultant Workforce in England: A Survey Update and Future Repercussions.

INTRODUCTION: Effective medical staffing is pivotal for a successful healthcare system, demanding strategic planning to ensure a high-quality service. Although the UK's doctor to population ratio has improved over time, it remains below global averages. The COVID-19 pandemic has exacerbated existing challenges, resulting in an unprecedented NHS waiting list with Ear, Nose, and Throat (ENT) surgeries ranking third highest in waiting times amongst all specialties. METHODS: This study utilized a national jotform survey to gather data from ENTUK members, primarily focusing on consultant staffing within ENT departments across the UK. Additional information collected encompassed registration status, part-time roles, gender, vacancies, locum roles, associate specialists, registrars and other junior doctors, and advanced nurse practitioners. When survey responses were inadequate, direct communication was established with departmental consultants or secretaries, followed by Freedom of Information requests as necessary. All data were compiled using Microsoft Excel. RESULTS: Among the 65 responses to the ENTUK survey, 53 individual trusts were identified. These included 41 English acute trusts, with supplementary participation from Scotland, Wales, and Northern Ireland. Data from 749 consultants across 115 English acute trusts were collected in combination with a Freedom of Information request. CONCLUSION: Despite an increased number of ENT consultants, the persistence of unfilled posts coincides with mounting waiting lists. The pandemic's effects, including early retirements and part-time roles, emphasise the urgency of expanding training positions to counterbalance these shifts. Local and national interventions are essential to fortify and diversify the ENT workforce through a variety of strategies.

Examining the role of community resilience and social capital on mental health in public health emergency and disaster response: a scoping review.

The ability of the public to remain psychologically resilient in the face of public health emergencies and disasters (such as the COVID-19 pandemic) is a key factor in the effectiveness of a national response to such events. Community resilience and social capital are often perceived as beneficial and ensuring that a community is socially and psychologically resilient may aid emergency response and recovery. This review presents a synthesis of literature which answers the following research questions: How are community resilience and social capital quantified in research?; What is the impact of community resilience on mental wellbeing?; What is the impact of infectious disease outbreaks, disasters and emergencies on community resilience and social capital?; and, What types of interventions enhance community resilience and social capital?A scoping review procedure was followed. Searches were run across Medline, PsycInfo, and EMBASE, with search terms covering both community resilience and social capital, public health emergencies, and mental health. 26 papers met the inclusion criteria.The majority of retained papers originated in the USA, used a survey methodology to collect data, and involved a natural disaster. There was no common method for measuring community resilience or social capital. The association between community resilience and social capital with mental health was regarded as positive in most cases. However, we found that community resilience, and social capital, were initially negatively impacted by public health emergencies and enhanced by social group activities.Several key recommendations are proposed based on the outcomes from the review, which include: the need for a standardised and validated approach to measuring both community resilience and social capital; that there should be enhanced effort to improve preparedness to public health emergencies in communities by gauging current levels of community resilience and social capital; that community resilience and social capital should be bolstered if areas are at risk of disasters or public health emergencies; the need to ensure that suitable short-term support is provided to communities with high resilience in the immediate aftermath of a public health emergency or disaster; the importance of conducting robust evaluation of community resilience initiatives deployed during the COVID-19 pandemic.

On the post-pandemic travel boom: How capacity building and smart tourism technologies in rural areas can help - evidence from Iran.

While there have been numerous studies investigating the impact of the COVID-19 pandemic on tourism, few research projects have examined the impact of the outbreak on using smart tourism technologies (STT), especially in developing countries. This study adopted thematic analysis, with data collected using in-person interviews. The participants for the study were selected using the snow-balling technique. We explored the process of developing smart technologies during the pandemic and its impact on smart rural tourism technology development upon travel restart. The subject was investigated by focusing on five selected villages in central Iran which have tourism dependent economies. Overall, the results indicated that the pandemic partially changed the government's resistance towards the fast development of smart technologies. Thus, the role of smart technologies in curbing the virus spread was officially recognized. This change of policy led to the implementation of Capacity Building (CB) programs to improve digital literacy and minimize the digital gap that exists between urban and rural areas in Iran. Implementing CB programs during the pandemic directly and indirectly contributed to the digitalization of rural tourism. Implementing such programs enhanced tourism stakeholders' individual and institutional capacity to gain access to and creatively use STT in rural area. The results of this study improve our understanding and knowledge of the impact of crises on the degree of acceptability and use of STT in traditional rural societies.

Is walking or riding your bike when a tourist different? Applying VAB theory to better understand active transport behavior.

Active transport (walking and biking) has significant environmental, health, and social benefits. Despite the importance of active transport, theoretically framed research has not sufficiently considered what makes consumers walk or bike based on activity types, particularly in an Asian context. This is an important topic as it helps provides a basis for better targeted marketing and promotion to encourage greater public engagement with active transport. To fill this knowledge gap, this work applied the value-attitude-behavior (VAB) theory to understand walkers and bikers' behaviors in comparing tourism, leisure, and work activity. Results indicate that value on attitude has the greatest influence, followed by personal, and then social norm. Behavior for active transport is significantly influenced by personal norm, followed by attitude and social norm. Interestingly, from the three types of activities, the tourism group has the strongest relationship of value and attitude and the highest prediction for attitude and behavior.

Synchrotron CT of an equine digit at the Australian Synchrotron Imaging and Medical Beamline.

Laminitis is an extremely painful and debilitating condition of horses that can affect their athletic ability and even quality of life. The current gold standard for assessment of laminar tissue is histology, which is the only modality that enables detailed visualization of the lamina. Histology requires dissection of the hoof and therefore can only represent one specific time point. The superior spatial and contrast resolution of synchrotron computed tomography (sCT), when compared with readily available imaging modalities, such as radiographs and conventional CT, provides an opportunity for detailed studies of the lamina without the need for hoof dissection and histological assessment. If the resolution of histology can be matched or even approached, dynamic events, such as laminar blood flow, could also be studied on the microscopic tissue level. To investigate this possible application of sCT further, two objectives are presented: (i) to develop a protocol for sCT of an equine digit using cadaver limbs and (ii) to apply the imaging protocol established during (i) for sCT imaging of the vasculature within the foot using an ex vivo perfusion system to deliver the vascular contrast. The hypotheses were that sCT would allow sufficient resolution for detailed visualization to the level of the secondary lamellae and associated capillaries within the equine digit. Synchrotron CT enabled good visualization of the primary lamellae (average length 3.6 mm) and the ex vivo perfusion system was able to deliver vascular contrast agent to the vessels of the lamina. The individual secondary lamellae (average length 0.142 mm) could not be seen in detail, although differentiation between primary and secondary lamellae was achieved. This approaches, but does not yet reach, the current gold standard, histology, for assessment of the lamellae; however, with further refinement of this imaging technique, improved resolution may be accomplished in future studies.

iRFP (near-infrared fluorescent protein) imaging of subcutaneous and deep tissue tumours in mice highlights differences between imaging platforms.

BACKGROUND: In vivo imaging using fluorescence is used in cancer biology for the detection, measurement and monitoring of tumours. This can be achieved with the expression of fluorescent proteins such as iRFP, which emits light at a wavelength less attenuated in biological tissues compared to light emitted by other fluorescent proteins such as GFP or RFP. Imaging platforms capable of detecting fluorescent tumours in small animals have been developed but studies comparing the performance of these platforms are scarce. RESULTS: Through access to three platforms from Xenogen, Bruker and Li-Cor, we compared their ability to detect iRFP-expressing subcutaneous tumours as well as tumours localised deeper within the body of female NSG mice. Each platform was paired with proprietary software for image analyse, but the output depends on subjective decisions from the user. To more objectively compare platforms, we developed an 'in house' software-based approach which results in lower measured variability between mice. CONCLUSIONS: Our comparisons showed that all three platforms allowed for reliable detection and monitoring of subcutaneous iRFP tumour growth. The biggest differences between platforms became apparent when imaging deeper tumours with the Li-Cor platform detecting most tumours and showing the highest dynamic range.

Planned surgery in the COVID-19 pandemic: a prospective cohort study from Nottingham.

PURPOSE: Globally planned surgical procedures have been deferred during the current COVID-19 pandemic. The study aimed to report the outcomes of planned urgent and cancer cases during the current pandemic using a multi-disciplinary prioritisation group. METHODS: A prospective cohort study of patients having urgent or cancer surgery at a NHS Trust from 1st March to 30th April 2020 who had been prioritised by a multi-disciplinary COVID Surgery group. Rates of post-operative PCR positive and suspected COVID-19 infections within 30 days, 30-day mortality and any death related to COVID-19 are reported. RESULTS: Overall 597 patients underwent surgery with a median age of 65 years (interquartile range (IQR) 54-74 years). Of these, 86.1% (514/597) had a current cancer diagnosis. During the period, 60.8% (363/597) of patients had surgery at the NHS Trust whilst 39.2% (234/597) had surgery at Independent Sector hospitals. The incidence of COVID-19 in the East Midlands was 193.7 per 100,000 population during the study period. In the 30 days following surgery, 1.3% (8/597) of patients tested positive for COVID-19 with all cases at the NHS site. Overall 30-day mortality was 0.7% (4/597). Following a PCR positive COVID-19 diagnosis, mortality was 25.0% (2/8). Including both PCR positive and suspected cases, 3.0% (18/597) developed COVID-19 infection with 1.3% at the independent site compared to 4.1% at the NHS Trust (p=0.047). CONCLUSIONS: Rates of COVID-19 infection in the post-operative period were low especially in the Independent Sector site. Mortality following a post-operative diagnosis of COVID-19 was high.

Weather and climate in the assessment of tourism-related walkability.

Walking is an important outdoor recreational and tourism activity, both in natural surroundings and in urban settings. Walkability is the extent to which the built environment promotes walking, and addresses issues such as comfort, connectivity, safety and aesthetic values. The paper explores a relatively overlooked domain of recreation- and tourism-related walkability: the extent to which weather and climatic conditions are incorporated into assessments of walkability and their influence on walking behaviour. Following a discussion of the assessment of walkability, the results of a scoping review of weather- and climate-related variables in walkability articles published up to June 2018 are presented. The review indicates there is little research on walkability from a tourist perspective, although there is substantial interest in walking for leisure and recreation. Four major themes were identified. The descriptive theme focuses on the general importance of weather and climate to walkability; the passive analyses the weather and climate conditions as barriers to, or as promoters of, walking; proactive studies refer to adapting to and managing weather, such as provision of shade or snow-clearing. The proactive perspective gains less attention than the passive analysis. Finally, statistical controlling was only employed by a minority of studies that adjusted their results to the impacts of weather conditions. The work concludes that the sub-field has been poorly served with respect to concept and variable definition and consistency of use mean that present knowledge is of limited scientific value. Strategies for future research are suggested.

Mental health of staff working in intensive care during Covid-19.

BACKGROUND: Staff working in intensive care units (ICUs) have faced significant challenges during the COVID-19 pandemic which have the potential to adversely affect their mental health. AIMS: To identify the rates of probable mental health disorder in staff working in ICUs in nine English hospitals during June and July 2020. METHODS: An anonymized brief web-based survey comprising standardized questionnaires examining depression, anxiety symptoms, symptoms of post-traumatic stress disorder (PTSD), well-being and alcohol use was administered to staff. RESULTS: Seven hundred and nine participants completed the surveys comprising 291 (41%) doctors, 344 (49%) nurses and 74 (10%) other healthcare staff. Over half (59%) reported good well-being; however, 45% met the threshold for probable clinical significance on at least one of the following measures: severe depression (6%), PTSD (40%), severe anxiety (11%) or problem drinking (7%). Thirteen per cent of respondents reported frequent thoughts of being better off dead, or of hurting themselves in the past 2 weeks. Within the sample used in this study, we found that doctors reported better mental health than nurses across a range of measures. CONCLUSIONS: We found substantial rates of probable mental health disorders, and thoughts of self-harm, amongst ICU staff; these difficulties were especially prevalent in nurses. Whilst further work is needed to better understand the real level of clinical need amongst ICU staff, these results indicate the need for a national strategy to protect the mental health, and decrease the risk of functional impairment, of ICU staff whilst they carry out their essential work during COVID-19.

Do value-attitude-behavior and personality affect sustainability crowdfunding initiatives?

Crowdfunding is an innovative financial measure that is increasingly important in supporting sustainability initiatives. However, little research-based theory has been devoted to crowdfunding in light of the Sustainable Development Goals (SDGs). To bridge this gap, this study utilizes theories of value-attitude-behavior (VAB) model and personality to investigate Korean consumer crowdfunding behavior for sustainability initiatives in relation to the United Nations 17 SDGs. Seven hypotheses related to value, attitude, personal norm, and social norm on sustainability, and participation in sustainability crowdfunding are offered, with personality as a moderator. The findings revealed that value has substantial impacts on attitude, personal norm, and social norm. Attitude, personal norm, and social norm on source are found to have positive impacts on participation. Conscientiousness, extraversion, agreeableness, and neuroticism have partial moderating effects on the VAB model. These results offer theoretical and empirical contributions to sustainability crowdfunding in light of the SDGs.

Measurement of the Spectral Shape of the ß-Decay of

We report on a comparison between the theoretically predicted and experimentally measured spectra of the first-forbidden nonunique ß-decay transition ^{137}Xe(7/2^{-})→^{137}Cs(7/2^{+}). The experimental data were acquired by the EXO-200 experiment during a deployment of an AmBe neutron source. The ultralow background environment of EXO-200, together with dedicated source deployment and analysis procedures, allowed for collection of a pure sample of the decays, with an estimated signal to background ratio of more than 99 to 1 in the energy range from 1075 to 4175 keV. In addition to providing a rare and accurate measurement of the first-forbidden nonunique ß-decay shape, this work constitutes a novel test of the calculated electron spectral shapes in the context of the reactor antineutrino anomaly and spectral bump.

World Trade Center exposure, post-traumatic stress disorder, and subjective cognitive concerns in a cohort of rescue/recovery workers.

OBJECTIVE: To determine whether World Trade Center (WTC)-exposure intensity and post-traumatic stress disorder (PTSD) are associated with subjective cognitive change in rescue/recovery workers. METHOD: The population included 7875 rescue/recovery workers who completed a subjective cognition measure, the Cognitive Function Instrument (CFI), between 3/1/2018 and 2/28/2019 during routine monitoring, indicating whether they had experienced cognitive and functional difficulties in the past year. Higher scores indicated greater self-perceived cognitive change. Probable PTSD, depression, and alcohol abuse were evaluated by validated mental health screeners. Logistic regression assessed the associations of WTC exposure and current PTSD with top-quartile (≥2) CFI score, and of early post-9/11 PTSD with top-quartile CFI in a subpopulation (N = 6440). Models included demographics, smoking, depression, and alcohol abuse as covariates. RESULTS: Mean age at CFI completion was 56.7 ± 7.7 (range: 36-81). Participants with high-intensity WTC exposure had an increased likelihood of top-quartile CFI score (odds ratio[OR] vs. low exposure: 1.32, 95%CI: 1.07-1.64), controlling for covariates. Current and early PTSD were both associated with top-quartile CFI (OR: 3.25, 95%CI: 2.53-4.19 and OR: 1.56, 95%CI: 1.26-1.93) respectively. CONCLUSIONS: High-intensity WTC exposure was associated with self-reported cognitive change 17 years later in rescue/recovery workers, as was PTSD. Highly WTC-exposed subgroups may benefit from additional cognitive evaluation and monitoring of cognition over time.

Development and evaluation of an online education tool on attention deficit hyperactivity disorder for general practitioners: the important contribution of co-production.

BACKGROUND: Attention deficit hyperactivity disorder (ADHD) is underdiagnosed in the UK and the assessment and diagnosis pathway often involves a general practitioner (GP) referral to secondary care services. GPs' levels of knowledge and understanding about ADHD is often a significant barrier in patients accessing care. The development of an online education resource could improve GPs knowledge of ADHD and optimise appropriate referrals. Involving end-users in co-creating interventions may enhance their clinical utility and impact routine clinical practice. However, there is limited published evidence describing how to meaningfully involve stakeholders in both the design and development components of co-production. METHOD: We report a step wise, co-production approach towards developing an online ADHD education intervention for GPs. Preparatory work highlighted the relevant topics to be included in the intervention, from which educational videos were then developed. Workshops were then conducted with GPs, leading to further refinement of the video content and subsequently the final intervention. A pilot usability study (n = 10 GPs) was then conducted to assess the intervention's acceptability, feasibility and accessibility. RESULTS: The development of the online intervention was greatly facilitated by the involvement of GPs. Having a co-production development process ensured the consistent adaptation of the intervention to meet GPs' needs. The usability study showed that the content of the intervention was suitable, easily accessible, engaging and delivered at an acceptable level of intensity, validating the development approach taken. CONCLUSION: While further studies are needed to evaluate the efficacy of the developed intervention, preliminary findings demonstrated that it was acceptable and well received. The importance of co-development was highlighted in developing an intervention that addresses specific needs for GPs. This development approach may be useful for other researchers and developers of clinical interventions.

Glucose Variability as Measured by Inter-measurement Percentage Change is Predictive of In-patient Mortality in Aneurysmal Subarachnoid Hemorrhage.

BACKGROUND: Critically ill aneurysmal subarachnoid hemorrhage (aSAH) patients suffer from systemic complications at a high rate. Hyperglycemia is a common intensive care unit (ICU) complication and has become a focus after aggressive glucose management was associated with improved ICU outcomes. Subsequent research has suggested that glucose variability, not a specific blood glucose range, may be a more appropriate clinical target. Glucose variability is highly correlated to poor outcomes in a wide spectrum of critically ill patients. Here, we investigate the changes between subsequent glucose values termed "inter-measurement difference," as an indicator of glucose variability and its association with outcomes in patients with aSAH. METHODS: All SAH admissions to a single, tertiary referral center between 2002 and 2016 were screened. All aneurysmal cases who had more than 2 glucose measurements were included (n = 2451). We calculated several measures of variability, including simple variance, the average consecutive absolute change, average absolute change by time difference, within subject variance, median absolute deviation, and average or median consecutive absolute percentage change. Predictor variables also included admission Hunt and Hess grade, age, gender, cardiovascular risk factors, and surgical treatment. In-patient mortality was the main outcome measure. RESULTS: In a multiple regression analysis, nearly all forms of glucose variability calculations were found to be correlated with in-patient mortality. The consecutive absolute percentage change, however, was most predictive: OR 5.2 [1.4-19.8, CI 95%] for percentage change and 8.8 [1.8-43.6] for median change, when controlling for the defined predictors. Survival to ICU discharge was associated with lower glucose variability (consecutive absolute percentage change 17% ± 9%) compared with the group that did not survive to discharge (20% ± 15%, p < 0.01). Interestingly, this finding was not significant in patients with pre-admission poorly controlled diabetes as indicated by HbA1c (OR 0.45 [0.04-7.18], by percentage change). The effect is driven mostly by non-diabetic patients or those with well-controlled diabetes. CONCLUSIONS: Reduced glucose variability is highly correlated with in-patient survival and long-term mortality in aSAH patients. This finding was observed in the non-diabetic and well-controlled diabetic patients, suggesting a possible benefit for personalized glucose targets based on baseline HbA1c and minimizing variability. The inter-measure percentage change as an indicator of glucose variability is not only predictive of outcome, but is an easy-to-use tool that could be implemented in future clinical trials.

Do Health Promoting Compounds of Flaxseed Attenuate Weight Gain Via Modulation of Obesity Gene Expression?

Diet-induced obesity (DIO) has been shown to increase DNA methyltransferases (DNMTs) expression and DNMTs binding at obesity-associated genes. Natural compounds have the potential to reverse obesity-associated gene expression via the regulation of DNA methylation. The objective of this study was to determine the effect of health promoting compounds of flaxseed on DNMTs and obesity-associated gene expression and weight gain. Sixty C57BL/6J male mice were randomly assigned into one of the following diet groups and fed for eight weeks: 45% kcal fat; 45% kcal fat+10% whole flaxseed; 45% kcal fat+6% defatted flaxseed; 45% kcal fat+4% flaxseed oil; and 16% kcal fat. DNMT1, DNMT3a, DNMT3b, leptin, and peroxisome proliferator-activated receptor (PPAR)-α expressions in adipose and muscle tissues were determined by real-time PCR. The health promoting compounds of flaxseed affected selected gene expression and attenuated weight gain. Further research is needed to identify the specific mechanisms modulating leptin or PPAR-α expression during DIO development.

Search for Neutrinoless Double-ß Decay with the Complete EXO-200 Dataset.

A search for neutrinoless double-ß decay (0νßß) in ^{136}Xe is performed with the full EXO-200 dataset using a deep neural network to discriminate between 0νßß and background events. Relative to previous analyses, the signal detection efficiency has been raised from 80.8% to 96.4±3.0%, and the energy resolution of the detector at the Q value of ^{136}Xe 0νßß has been improved from σ/E=1.23% to 1.15±0.02% with the upgraded detector. Accounting for the new data, the median 90% confidence level 0νßß half-life sensitivity for this analysis is 5.0×10^{25} yr with a total ^{136}Xe exposure of 234.1 kg yr. No statistically significant evidence for 0νßß is observed, leading to a lower limit on the 0νßß half-life of 3.5×10^{25} yr at the 90% confidence level.

Results of a Search for Sub-GeV Dark Matter Using 2013 LUX Data.

The scattering of dark matter (DM) particles with sub-GeV masses off nuclei is difficult to detect using liquid xenon-based DM search instruments because the energy transfer during nuclear recoils is smaller than the typical detector threshold. However, the tree-level DM-nucleus scattering diagram can be accompanied by simultaneous emission of a bremsstrahlung photon or a so-called "Migdal" electron. These provide an electron recoil component to the experimental signature at higher energies than the corresponding nuclear recoil. The presence of this signature allows liquid xenon detectors to use both the scintillation and the ionization signals in the analysis where the nuclear recoil signal would not be otherwise visible. We report constraints on spin-independent DM-nucleon scattering for DM particles with masses of 0.4-5 GeV/c^{2} using 1.4×10^{4} kg day of search exposure from the 2013 data from the Large Underground Xenon (LUX) experiment for four different classes of mediators. This analysis extends the reach of liquid xenon-based DM search instruments to lower DM masses than has been achieved previously.

Higher risk breast screening: cancer detection rates, recall rates, and attendance rates in Northern Ireland.

AIM: To evaluate the outcomes of higher risk screening in Northern Ireland (NI) and compare with the UK National Health Service Breast Screening Programme (NHSBSP). MATERIALS AND METHODS: Higher risk breast screening commenced in NI in April 2013. Data on the programme were audited retrospectively through the Higher Risk screening centre. As there are no national standards for attendance rates and cancer detection rates, screening data and standards from the NHSBSP were used as a baseline for comparison. RESULTS: Attendance rates for the higher risk screening population have increased each of the last 3 years up to 77.7%. Recall rates have improved year on year from initial 14.2%-8.6%. Cancer detection rates have varied each year with a range from 21.5 per 1,000 women screened to 30.9 per 1,000 women screened. CONCLUSION: The Higher Risk Breast Screening Programme in NI represents a success story in risk stratified screening. Performance outcomes are excellent. The data outcomes may be used to inform standards of acceptable practice in the wider NHSBSP.

Testicular hyperthermia increases blood flow that maintains aerobic metabolism in rams.

There is a paradigm that testicular hyperthermia fails to increase testicular blood flow and that an ensuing hypoxia impairs spermatogenesis. However, in our previous studies, decreases in normal and motile spermatozoa after testicular warming were neither prevented by concurrent hyperoxia nor replicated by hypoxia. The objective of the present study was to determine the effects of increasing testicular temperature on testicular blood flow and O2 delivery and uptake and to detect evidence of anaerobic metabolism. Under general anaesthesia, the testicular temperature of nine crossbred rams was sequentially maintained at ~33°C, 37°C and 40°C (±0.5°C; 45min per temperature). As testicular temperature increased from 33°C to 40°C there were increases in testicular blood flow (13.2±2.7 vs 17.7±3.2mLmin-1 per 100g of testes, mean±s.e.m.; P<0.05), O2 extraction (31.2±5.0 vs 47.3±3.1%; P<0.0001) and O2 consumption (0.35±0.04 vs 0.64±0.06mLmin-1 per 100g of testes; P<0.0001). There was no evidence of anaerobic metabolism, based on a lack of change in lactate, pH, HCO3- and base excess. In conclusion, these data challenge the paradigm regarding scrotal-testicular thermoregulation, as acute testicular hyperthermia increased blood flow and tended to increase O2 delivery and uptake, with no indication of hypoxia or anaerobic metabolism.

Characterization of demographics and NS5A genetic diversity for hepatitis C virus genotype 4-infected patients with or without cirrhosis treated with ombitasvir/paritaprevir/ritonavir.

Hepatitis C virus (HCV) genotype 4 (GT4) is genetically diverse with 17 confirmed and 4 provisional subtypes. In this report, HCV GT4-infected patient samples from Phase 2/3 clinical studies were analysed to characterize global demographics and genetic diversity of GT4 infection among patients treated with ombitasvir (OBV, NS5A inhibitor) plus paritaprevir/r (NS3/4A inhibitor codosed with ritonavir). Among 17 subtypes isolated from GT4-infected patients in the PEARL-I and AGATE-I studies, subtype prevalence by country of enrolment and country of origin suggested that subtypes 4a and 4d were likely circulating in Europe, while heterogeneous GT4 subtypes and a portion of GT4a detected in European and North American countries were likely due to immigration of HCV-infected patients from Africa. The distributions of birth cohort and race were also significantly different across GT4 subtypes 4a, 4d, and non-4a/4d. In addition, phylogenetic analyses of NS5A sequences revealed clustering within subtype 4a which segregated by the patient-reported country of origin and the presence of the L30R/S polymorphism. HCV NS5A sequences derived from GT4a-infected patients who originated from Europe and the United States clustered separately from sequences derived from patients who originated from Egypt, suggesting that genetically distinct strains of subtype 4a may be circulating globally. Finally, NS5A baseline polymorphisms were frequently detected at amino acid positions of interest for the inhibitor-class and OBV retained activity against 37 of 39 NS5A GT4 clinical isolates, with no impact on treatment outcome in the PEARL-I and AGATE-I studies.