Helping Others Facilitates Well-Being for Indigenous Peoples Living With HIV/AIDS in Canada.

Research has found that helping others facilitates well-being for Indigenous peoples living with HIV and AIDS, but limited research exists that investigates the mechanism(s) underlying this relationship. Indigenous perspectives posit that helping others facilitates well-being through the development of an individual's spiritual, physical, emotional, and mental aspects (four aspects). Similarly, self-determination theory posits that helping others facilitates well-being by satisfying basic psychological needs. In the present study, we examined if helping others facilitates well-being through the fulfillment of the spiritual, physical, emotional, and mental aspects among Indigenous peoples living with HIV and AIDS. We used a convergent parallel mixed methods design, coupled with a community-engaged approach grounded in the United Nations Greater Involvement of People Living with HIV and AIDS principles and Indigenous and decolonizing research methodologies. Survey (n = 117) and interview data (n = 9) collected by an Indigenous-led HIV/AIDS organization in Canada were employed to examine the relationship between helping, the four aspects, and well-being. Participants were primarily First Nations leaders and mentors who live with HIV/AIDS, with some Métis and Inuit. A parallel multiple mediation model and reflexive thematic analysis were used to analyze the relationship between helping, the four aspects, and well-being. Mixed-methods findings support the idea that helping others promotes well-being by fulfilling the emotional and mental aspects. Qualitative findings demonstrated this relationship for all four aspects. This research may facilitate the development of programs to support Indigenous peoples living with HIV/AIDS well-being and contribute to the literature on integrating Indigenous perspectives and methodologies within psychological research.

Autogenous and efficient acceleration of energetic ions upstream of Earth's bow shock.

Earth and its magnetosphere are immersed in the supersonic flow of the solar-wind plasma that fills interplanetary space. As the solar wind slows and deflects to flow around Earth, or any other obstacle, a 'bow shock' forms within the flow. Under almost all solar-wind conditions, planetary bow shocks such as Earth's are collisionless, supercritical shocks, meaning that they reflect and accelerate a fraction of the incident solar-wind ions as an energy dissipation mechanism1,2, which results in the formation of a region called the ion foreshock3. In the foreshock, large-scale, transient phenomena can develop, such as 'hot flow anomalies'4-9, which are concentrations of shock-reflected, suprathermal ions that are channelled and accumulated along certain structures in the upstream magnetic field. Hot flow anomalies evolve explosively, often resulting in the formation of new shocks along their upstream edges5,10, and potentially contribute to particle acceleration11-13, but there have hitherto been no observations to constrain this acceleration or to confirm the underlying mechanism. Here we report observations of a hot flow anomaly accelerating solar-wind ions from roughly 1-10 kiloelectronvolts up to almost 1,000 kiloelectronvolts. The acceleration mechanism depends on the mass and charge state of the ions and is consistent with first-order Fermi acceleration14,15. The acceleration that we observe results from only the interaction of Earth's bow shock with the solar wind, but produces a much, much larger number of energetic particles compared to what would typically be produced in the foreshock from acceleration at the bow shock. Such autogenous and efficient acceleration at quasi-parallel bow shocks (the normal direction of which are within about 45 degrees of the interplanetary magnetic field direction) provides a potential solution to Fermi's 'injection problem', which requires an as-yet-unexplained seed population of energetic particles, and implies that foreshock transients may be important in the generation of cosmic rays at astrophysical shocks throughout the cosmos.

The sustainability of exercise following colorectal surgery: A qualitative study of participants in the PREPARE-ABC trial.

OBJECTIVE: This study aimed to explore perceptions regarding the sustainability of exercise following participation in a pre- and post-colorectal surgery exercise intervention trial (PREPARE-ABC). DESIGN: Qualitative interview study. Data were analysed using framework analysis and independently coded by two researchers. SETTING: Six United Kingdom National Health Service Trusts. PARTICIPANTS: Eighteen interviews (hospital-based exercise n = 9, home-based exercise n = 3, standard care n = 6) were conducted with patients 12-15 months after being randomised in the trial, after their 12 month appointment. INTERVENTION: Individuals who participated in one of two exercise intervention groups (hospital-supervised or home-supported exercise) or a standard care control group of the PREPARE-ABC trial were invited to interview. RESULTS: The exercise interventions were reported to influence participants' recovery and future sustainability of exercise behaviour change. Several participants continued to engage in exercise over a year after their surgery. Reasons for this included being engaged with exercise prior to diagnosis, psychological benefits of exercise and wanting to be engaged with something to help recovery. Perceptions about the sustainability of active lifestyles were influenced by confidence to engage in structured exercise or physical activity and beliefs about its potential to promote future wellness. CONCLUSIONS: Sustainability varies among individuals and early assessment of physical activity engagement could be beneficial. Physical activity interventions immediately following surgery may be important for future engagement.

Mimicking exercise in vitro: effects of myotube contractions and mechanical stretch on omics.

The number of studies using skeletal muscle (SkM) cell culture models to study exercise in vitro are rapidly expanding. Progressively, more comprehensive analysis methods, such as different omics approaches including transcriptomics, proteomics, and metabolomics have been used to examine the intra- and extracellular molecular responses to exercise mimicking stimuli in cultured myotubes. Among other techniques, exercise-like electrical pulse stimulation (EL-EPS) and mechanical stretch of SkM cells are the two most commonly used methods to mimic exercise in vitro. In this mini-review, we focus on these two approaches and their effects on the omics of myotubes and/or cell culture media. Furthermore, besides traditional two-dimensional (2-D) methods, the use of three-dimensional (3-D) SkM approaches are increasing in the field of in vitro exercise mimicry. Our aim with this mini-review is to provide the reader with an up-to-date overview of the 2-D and 3-D models and the use of omics approaches to study the molecular response to exercise in vitro.

Endophthalmitis following cataract surgery: visual outcomes, microbial spectrum and complications.

PURPOSE OF REVIEW: The aim of this study was to update visual outcomes, microbial spectrum and complications in eyes with endophthalmitis following cataract surgery. RECENT FINDINGS: A single-institution, retrospective review of eyes treated for endophthalmitis following cataract surgery between 2 January 2014 and 10 January 2017. This study included 112 cases of endophthalmitis following cataract surgery, 58 of which were culture-positive (51.8%). The most isolated organisms were coagulase-negative Staphylococci (56.9%). Oral flora were present in 17.2% of cases. At 6 months, 71.7% of patients achieved visual acuity of at least 20/200 and 51.7% achieved at least 20/40 or better. Visual acuity was better in culture-negative vs. culture-positive cases (∼20/290 vs. ∼20/80, P   =  0.03), and in nonoral flora-associated vs. oral flora-associated culture-positive cases (∼CF vs. ∼20/150, P   <  0.01). SUMMARY: Following postcataract surgery endophthalmitis, approximately 70% of eyes achieved vision of 20/200 or better and half achieved vision of 20/40 or better 6 months after treatment. Poor visual outcomes were seen in eyes with positive bacterial cultures and with oral flora.

RISK FACTORS FOR SURGERY OR BLINDNESS IN NEOVASCULAR GLAUCOMA EYES TREATED WITH ANTI-VEGF INJECTIONS BY A RETINA SPECIALIST.

PURPOSE: To determine baseline patient characteristics that predict the need for glaucoma surgery or blindness in eyes with neovascular glaucoma (NVG) despite intravitreal antivascular endothelial growth factor therapy. METHODS: This is a retrospective cohort study of patients with NVG who had not previously received glaucoma surgery and were treated with intravitreal antivascular endothelial growth factor injections at the time of diagnosis, from September 8, 2011, to May 8, 2020, at a large, retina subspecialty practice. RESULTS: Of 301 newly presenting NVG eyes, 31% required glaucoma surgery and 20% progressed to no light perception vision despite treatment. Patients with intraocular pressure >35 mmHg ( P < 0.001), two or more topical glaucoma medications ( P = 0.003), worse than 20/100 vision ( P = 0.024), proliferative diabetic retinopathy ( P = 0.001), eye pain or discomfort ( P = 0.010), and new patient status ( P = 0.015) at the time of NVG diagnosis were at a higher risk of glaucoma surgery or blindness regardless of antivascular endothelial growth factor therapy. The effect of panretinal photocoagulation was not statistically significant in a subgroup analysis of patients without media opacity ( P = 0.199). CONCLUSION: Several baseline characteristics at the time of presentation to a retina specialist with NVG seem to portend a higher risk of uncontrolled glaucoma despite the use of antivascular endothelial growth factor therapy. Prompt referral of these patients to a glaucoma specialist should be strongly considered.

An epidemiological investigation of COVID-19 outbreaks in a group of care homes in Wales, UK: a retrospective cohort study.

BACKGROUND: This study describes the epidemiology of COVID-19 outbreaks in four care homes in terms of spread, severity, presentation and interventions. METHODS: Participants were 100 residents and 102 staff from four co-located care homes in Wales. Data were collected from the homes and Public Health Wales, including demographics, presentations, test status and results, hospital admissions and deaths. Genomic sequencing of confirmed case samples was completed, where possible. Epi-curves, crude attack rates, a Kaplan-Meier survival curve and adjusted hazard ratios were calculated using R. RESULTS: About 14 confirmed and 43 possible resident cases, 23 confirmed and 47 possible staff cases occurred. Crude attack rates of possible and confirmed cases were 57% (residents) and 69% (staff). Genomic sequencing for 10 confirmed case PCR samples identified at least 5 different UK lineages of COVID-19.42 (42%) residents died, 23 (55%) with COVID-19 or suspected COVID-19 recorded on the death certificate. The hazard ratio for death amongst resident possible and confirmed cases compared to null cases, adjusting for age and sex, was 13.26 (95% CI 5.61-31.34). CONCLUSIONS: There were extensive outbreaks of COVID-19 in these homes with high crude attack rates and deaths. Universal testing and early isolation of residents are recommended.

Hydrolysis-Based Small-Molecule Hydrogen Selenide (H2Se) Donors for Intracellular H2Se Delivery.

Hydrogen selenide (H2Se) is a central metabolite in the biological processing of selenium for incorporation into selenoproteins, which play crucial antioxidant roles in biological systems. Despite being integral to proper physiological function, this reactive selenium species (RSeS) has received limited attention. We recently reported an early example of a H2Se donor (TDN1042) that exhibited slow, sustained release through hydrolysis. Here we expand that technology based on the P═Se motif to develop cyclic-PSe compounds with increased rates of hydrolysis and function through well-defined mechanisms as monitored by 31P and 77Se NMR spectroscopy. In addition, we report a colorimetric method based on the reaction of H2Se with NBD-Cl to generate NBD-SeH (λmax = 551 nm), which can be used to detect free H2Se. Furthermore, we use TOF-SIMS (time of flight secondary ion mass spectroscopy) to demonstrate that these H2Se donors are cell permeable and use this technique for spatial mapping of the intracellular Se content after H2Se delivery. Moreover, these H2Se donors reduce endogenous intracellular reactive oxygen species (ROS) levels. Taken together, this work expands the toolbox of H2Se donor technology and sets the stage for future work focused on the biological activity and beneficial applications of H2Se and related bioinorganic RSeS.

Measurement accuracy of prototype non-contrast, compressed sensing-based, respiratory motion-resolved whole heart cardiovascular magnetic resonance angiography for the assessment of thoracic aortic dilatation: comparison with computed tomography angiography.

BACKGROUND: Patients with thoracic aortic dilatation who undergo annual computed tomography angiography (CTA) are subject to repeated radiation and contrast exposure. The purpose of this study was to evaluate the feasibility of a non-contrast, respiratory motion-resolved whole-heart cardiovascular magnetic resonance angiography (CMRA) technique against reference standard CTA, for the quantitative assessment of cardiovascular anatomy and monitoring of disease progression in patients with thoracic aortic dilatation.  METHODS: Twenty-four patients (68.6 ± 9.8 years) with thoracic aortic dilatation prospectively underwent clinical CTA and research 1.5T CMRA between July 2017 and November 2018. Scans were repeated in 15 patients 1 year later. A prototype free-breathing 3D radial balanced steady-state free-precession whole-heart CMRA sequence was used in combination with compressed sensing-based reconstruction. Area, circumference, and diameter measurements were obtained at seven aortic levels by two experienced and two inexperienced readers. In addition, area and diameter measurements of the cardiac chambers, pulmonary arteries and pulmonary veins were also obtained. Agreement between the two modalities was assessed with intraclass correlation coefficient (ICC) analysis, Bland-Altman plots and scatter plots. RESULTS: Area, circumference and diameter measurements on a per-level analysis showed good or excellent agreement between CTA and CMRA (ICCs > 0.84). Means of differences on Bland-Altman plots were: area 0.0 cm2 [- 1.7; 1.6]; circumference 1.0 mm [- 10.0; 12.0], and diameter 0.6 mm [- 2.6; 3.6]. Area and diameter measurements of the left cardiac chambers showed good agreement (ICCs > 0.80), while moderate to good agreement was observed for the right chambers (all ICCs > 0.56). Similar good to excellent inter-modality agreement was shown for the pulmonary arteries and veins (ICC range 0.79-0.93), with the exception of the left lower pulmonary vein (ICC < 0.51). Inter-reader assessment demonstrated mostly good or excellent agreement for both CTA and CMRA measurements on a per-level analysis (ICCs > 0.64). Difference in maximum aortic diameter measurements at baseline vs follow up showed excellent agreement between CMRA and CTA (ICC = 0.91). CONCLUSIONS: The radial whole-heart CMRA technique combined with respiratory motion-resolved reconstruction provides comparable anatomical measurements of the thoracic aorta and cardiac structures as the reference standard CTA. It could potentially be used to diagnose and monitor patients with thoracic aortic dilatation without exposing them to radiation or contrast media.

THE EFFECT OF ENDOPHTHALMITIS ON RECURRENCE OF MACULAR EDEMA IN EYES RECEIVING INTRAVITREAL ANTI-VASCULAR ENDOTHELIAL GROWTH FACTOR.

PURPOSE: Visual outcomes after postinjection endophthalmitis have been well-studied, but the effect of endophthalmitis on the underlying exudative disease process remains unclear. We investigate the need for continued anti-vascular endothelial growth factor injections after endophthalmitis. METHODS: Eyes that developed endophthalmitis after intravitreal injection of anti-vascular endothelial growth factor between January 1, 2016, and May 31, 2018, at a single academic retina practice were identified. Retrospective chart review was performed to determine 1) the proportion of eyes without recurrence of macular edema or subretinal fluid after endophthalmitis and 2) the proportion achieving a 12-week or greater interval between anti-vascular endothelial growth factor injections or exudation after endophthalmitis compared with internal controls before endophthalmitis. RESULTS: Of 50 eyes with endophthalmitis, seven (14.0%) had no fluid recurrence at a mean of 98.1 week. Of 43 eyes with recurrence, 48.0% achieved a >12-week recurrence-free interval after endophthalmitis (vs. 8.3% before endophthalmitis; P < 0.0001). Eyes with compared to those without choroidal neovascularization were more likely to achieve this interval (60.5% vs. 8.3%, respectively; P = 0.002). CONCLUSION: Endophthalmitis after anti-vascular endothelial growth factor injection is associated with relative stability of the underlying exudation. Further research is necessary to elucidate the mechanism, which may be useful in developing strategies and targets for the treatment of exudative macular diseases.

Photodiagnostic services in the UK and Republic of Ireland: a British Photodermatology Group Workshop Report.

BACKGROUND: Photodiagnostic investigations are essential for the accurate diagnosis of abnormal cutaneous photosensitivity and provide important information for the management of patients with photodermatoses (cutaneous photosensitivity disorders). Although photodiagnosis has been undertaken since the early 1970s, specialist services in the United Kingdom (UK) and Republic of Ireland are limited and there is no formal guidance on diagnostic approach. Indeed, there is a limited literature in this area of methodology and diagnostic practice. OBJECTIVES: The primary objective was to undertake a British Photodermatology Group Workshop to review the role and activities of specialist centres in the UK and Republic of Ireland in order to ascertain whether there were consensus practices. Secondary objectives were to identify key priorities for service, training and research. METHODS: An initial detailed survey review of current activities was undertaken prior to the Workshop and data from this survey were used to inform discussion at the Workshop, which was attended by key photodermatology experts from the UK and Republic of Ireland. RESULTS/CONCLUSIONS: We have undertaken a detailed review of current Photodiagnostic Services in the UK and Republic of Ireland and report on our findings from the 12 centres and we have identified key areas of consensus practice. This is an important step in the process of standardising and optimising procedures and protocols and defining minimum clinical standards for photodiagnostic investigations, which are of such diagnostic importance in Dermatology.

Delayed Retinal Breaks and Detachments after Acute Posterior Vitreous Detachment.

PURPOSE: To determine the incidence and timing of delayed retinal breaks and retinal detachments (RDs) after acute posterior vitreous detachment (PVD) and associated risk factors. DESIGN: Retrospective case-control study. PARTICIPANTS: Acute PVD eyes treated between October 2015 and August 2018 at a single academic retina practice. METHODS: Eyes with a PVD diagnosis and history of extended ophthalmoscopic examination on presentation were identified using diagnostic billing codes. The number of eyes with a history of laser retinopexy, cryotherapy for retinal tear, or RD repair was determined using procedural billing codes, and the duration between initial and treatment visits was measured. Records of eyes with a delayed retinal break or RD and of a reference group comprising the first 100 presenting eyes with no initial or delayed retinal break or RD were reviewed to determine and compare the presence of select risk factors on initial examination. MAIN OUTCOME MEASURES: Development of a delayed retinal break or RD. RESULTS: Of 7999 eyes with acute PVD, 1280 (16.0%) showed a retinal break and 499 (6.2%) showed an RD on presentation. Delayed retinal breaks and RDs were found in 209 (2.6%) and 80 (1.0%) eyes, respectively. Of delayed breaks, 116 (55.5%) were found in 6 weeks or less and 93 (44.5%) were found more than 6 weeks after presentation. Of delayed RDs, 26 (32.5%) were found in 6 weeks or less and 54 (67.5%) were found more than 6 weeks after presentation. Compared with the reference group, vitreous hemorrhage (hazard ratio, 2.53 [P < 0.001] and 2.80 [P = 0.001]) and male gender (hazard ratio, 1.36 [P = 0.03] and 1.87 [P = 0.02]) were risk factors for delayed retinal breaks and RDs, respectively. Pseudophakia (hazard ratio, 2.10; P = 0.004) was also a risk factor for delayed RD; older age (odds ratio, 0.96; P = 0.01) was slightly protective. Vitreous hemorrhage was a risk factor for earlier retinal breaks (≤6 weeks vs. >6 weeks; odds ratio, 3.58; P < 0.001). CONCLUSIONS: Clinically significant rates of newly detected retinal breaks and RDs may occur after acute PVD, suggesting that repeat examination may be prudent in these patients.

Long-term cost-effectiveness of screening for fracture risk in a UK primary care setting: the SCOOP study.

Community-based screening and treatment of women aged 70-85 years at high fracture risk reduced fractures; moreover, the screening programme was cost-saving. The results support a case for a screening programme of fracture risk in older women in the UK. INTRODUCTION: The SCOOP (screening for prevention of fractures in older women) randomized controlled trial investigated whether community-based screening could reduce fractures in women aged 70-85 years. The objective of this study was to estimate the long-term cost-effectiveness of screening for fracture risk in a UK primary care setting compared with usual management, based on the SCOOP study. METHODS: A health economic Markov model was used to predict the life-time consequences in terms of costs and quality of life of the screening programme compared with the control arm. The model was populated with costs related to drugs, administration and screening intervention derived from the SCOOP study. Fracture risk reduction in the screening arm compared with the usual management arm was derived from SCOOP. Modelled fracture risk corresponded to the risk observed in SCOOP. RESULTS: Screening of 1000 patients saved 9 hip fractures and 20 non-hip fractures over the remaining lifetime (mean 14 years) compared with usual management. In total, the screening arm saved costs (£286) and gained 0.015 QALYs/patient in comparison with usual management arm. CONCLUSIONS: This analysis suggests that a screening programme of fracture risk in older women in the UK would gain quality of life and life years, and reduce fracture costs to more than offset the cost of running the programme.

Screening for high hip fracture risk does not impact on falls risk: a post hoc analysis from the SCOOP study.

A reduction in hip fracture incidence following population screening might reflect the effectiveness of anti-osteoporosis therapy, behaviour change to reduce falls, or both. This post hoc analysis demonstrates that identifying high hip fracture risk by FRAX was not associated with any alteration in falls risk. INTRODUCTION: To investigate whether effectiveness of an osteoporosis screening programme to reduce hip fractures was mediated by modification of falls risk in the screening arm. METHODS: The SCOOP study recruited 12,483 women aged 70-85 years, individually randomised to a control (n = 6250) or screening (n = 6233) arm; in the latter, osteoporosis treatment was recommended to women at high risk of hip fracture, while the control arm received usual care. Falls were captured by self-reported questionnaire. We determined the influence of baseline risk factors on future falls, and then examined for differences in falls risk between the randomisation groups, particularly in those at high fracture risk. RESULTS: Women sustaining one or more falls were slightly older at baseline than those remaining falls free during follow-up (mean difference 0.70 years, 95%CI 0.55-0.85, p < 0.001). A higher FRAX 10-year probability of hip fracture was associated with increased likelihood of falling, with fall risk increasing by 1-2% for every 1% increase in hip fracture probability. However, falls risk factors were well balanced between the study arms and, importantly, there was no evidence of a difference in falls occurrence. In particular, there was no evidence of interaction (p = 0.18) between baseline FRAX hip fracture probabilities and falls risk in the two arms, consistent with no impact of screening on falls in women informed to be at high risk of hip fracture. CONCLUSION: Effectiveness of screening for high FRAX hip fracture probability to reduce hip fracture risk was not mediated by a reduction in falls.

Observational Evidence for Stochastic Shock Drift Acceleration of Electrons at the Earth's Bow Shock.

The first-order Fermi acceleration of electrons requires an injection of electrons into a mildly relativistic energy range. However, the mechanism of injection has remained a puzzle both in theory and observation. We present direct evidence for a novel stochastic shock drift acceleration theory for the injection obtained with Magnetospheric Multiscale observations at the Earth's bow shock. The theoretical model can explain electron acceleration to mildly relativistic energies at high-speed astrophysical shocks, which may provide a solution to the long-standing issue of electron injection.

Characteristics associated with significantly worse quality of life in mycosis fungoides/Sézary syndrome from the Prospective Cutaneous Lymphoma International Prognostic Index (PROCLIPI) study.

BACKGROUND: Mycosis fungoides (MF) and Sézary Syndrome (SS) are the most common cutaneous T-cell lymphomas. MF/SS is accompanied by considerable morbidity from pain, itching and disfigurement. AIM: To identify factors associated with poorer health-related quality of life (HRQoL) in patients newly diagnosed with MF/SS. METHODS: Patients enrolled into Prospective Cutaneous Lymphoma International Prognostic Index (PROCLIPI; an international observational study in MF/SS) had their HRQoL assessed using the Skindex-29 questionnaire. Skindex-29 scores were analysed in relation to patient- and disease-specific characteristics. RESULTS: The study population consisted of 237 patients [60·3% male; median age 60 years, (interquartile range 49-70)], of whom 179 had early MF and 58 had advanced MF/SS. In univariate analysis, HRQoL, as measured by Skindex-29, was worse in women, SS, late-stage MF, those with elevated lactate dehydrogenase, alopecia, high modified Severity Weighted Assessment Tool and confluent erythema. Linear regression models only identified female gender (ß = 8·61; P = 0·003) and alopecia (ß = 9·71, P = 0·02) as independent predictors of worse global HRQoL. Item-level analysis showed that the severe impairment in symptoms [odds ratio (OR) 2·14, 95% confidence interval (CI) 1·19-3·89] and emotions (OR 1·88, 95% CI 1·09-3·27) subscale scores seen in women was caused by more burning/stinging, pruritus, irritation and greater feelings of depression, shame, embarrassment and annoyance with their diagnosis of MF/SS. CONCLUSIONS: HRQoL is significantly more impaired in newly diagnosed women with MF/SS and in those with alopecia. As Skindex-29 does not include existential questions on cancer, which may cause additional worry and distress, a comprehensive validated cutaneous T-cell lymphoma-specific questionnaire is urgently needed to more accurately assess disease-specific HRQoL in these patients. What's already known about this topic? Cross-sectional studies of mixed populations of known and newly diagnosed patients with mycosis fungoides (MF)/Sézary syndrome (SS) have shown significant impairment in health-related quality of life (HRQoL). Previous studies on assessing gender-specific differences in HRQoL in MF/SS are conflicting. More advanced-stage disease and pruritus is associated with poorer HRQoL in patients with MF/SS. What does this study add? This is the first prospective study to investigate HRQoL in a homogenous group of newly diagnosed patients with MF/SS. In patients newly diagnosed with MF/SS, HRQoL is worse in women and in those with alopecia and confluent erythema. MF/SS diagnosis has a multidimensional impact on patient HRQoL, including a large burden of cutaneous symptoms, as well as a negative impact on emotional well-being.

Identification and characterization of HIV positive Ethiopian elite controllers in both Africa and Israel.

OBJECTIVES: HIV elite controllers (ECs) are a unique subgroup of HIV-positive patients who are long-term virologically suppressed in the absence of antiretroviral treatment (ART). The prevalence of this subgroup is estimated to be < 1%. Various cohorts of ECs have been described in developed countries, most of which have been demographically heterogeneous. The aim of this study was to identify ECs in two large African cohorts and to estimate their prevalence in a relatively genetically homogenous population. METHODS: We screened two cohorts of HIV-positive Ethiopian patients. The first cohort resided in Mekelle, Ethiopia. The second was comprised of HIV-positive Ethiopian immigrants in Israel. In the Mekelle cohort, ART-naïve subjects with stable CD4 counts were prospectively screened using two measurements of viral load 6 months apart. Subjects were defined as ECs when both measurements were undetectable. In the Israeli cohort, subjects with consistently undetectable viral loads (mean of 17 viral load measurements/patient) and stable CD4 count > 500 cells/µL were defined as ECs. RESULTS: In the Mekelle cohort, 16 of 9515 patients (0.16%) fitted the definition of EC, whereas seven of 1160 (0.6%) in the Israeli cohort were identified as ECs (P = 0.011). CONCLUSIONS: This is the first large-scale screening for HIV-positive ECs to be performed in entirely African cohorts. The overall prevalence of ECs is within the range of that previously described in developing countries. The significant difference in prevalence between the two cohorts of similar genetic background is probably a consequence of selection bias but warrants further investigation into possible environmental factors which may underlie the EC state.

Rhegmatogenous Retinal Detachment after Intravitreal Injection of Anti-Vascular Endothelial Growth Factor.

PURPOSE: To report the rate, risk factors, and outcomes of rhegmatogenous retinal detachment (RRD) after intravitreal injection of anti-vascular endothelial growth factor medications. DESIGN: Single-center, retrospective, consecutive review. PARTICIPANTS: All patients receiving ranibizumab, bevacizumab, or aflibercept for neovascular age-related macular degeneration or retinal vein occlusion between October 1, 2014, and October 1, 2017. METHODS: The total number of eyes and injections were determined from billing codes. Rhegmatogenous retinal detachment patients were determined from billing records and confirmed with chart review. MAIN OUTCOME MEASURES: Rate of retinal detachment and visual acuity outcomes. RESULTS: A total of 180 671 intravitreal injections in 12 718 unique patients were included. An RRD occurred in 24 patients within 3 months after injection, giving a rate of 1 RRD per 7532 intravitreal injections (0.013%) and 1 RRD per 530 patients (0.19%). No association was found between RRD risk after injection and diagnosis (P = 0.54), physician experience (P = 0.23), injection site (P = 0.41), caliper use (P = 0.75), or 31- versus 30-gauge needle use (P = 0.18). A retinal tear was found located in the quadrant of the injection site (within 1.5 clock hours of the injection) in 15 of 24 patients (62.5%; P < 0.0001). At the time of RRD diagnosis, the macula was attached in 9 patients (37.5%). Interventions for RRD repair included pars plana vitrectomy (PPV; 15 patients), combined scleral buckle and PPV (4 patients), pneumatic retinopexy (3 patients), and laser or cryotherapy alone (2 patients). Single-surgery success rate was 54.2%, with 54.5% of recurrent detachments caused by proliferative vitreoretinopathy. Average loss from visual acuity recorded at the visit before diagnosis of RRD was 1.0 line for macula-on detachments versus 6.8 lines for macula-off detachments (P = 0.027) at final follow-up (average, 16.3 months). CONCLUSIONS: Retinal detachment after intravitreal injection is uncommon, with a rate of approximately 1 in 7500 injections. Macular status at the time of RRD diagnosis significantly affects visual outcomes.

The PROCLIPI international registry of early-stage mycosis fungoides identifies substantial diagnostic delay in most patients.

BACKGROUND: Survival in mycosis fungoides (MF) is varied and may be poor. The PROCLIPI (PROspective Cutaneous Lymphoma International Prognostic Index) study is a web-based data collection system for early-stage MF with legal data-sharing agreements permitting international collaboration in a rare cancer with complex pathology. Clinicopathological data must be 100% complete and in-built intelligence in the database system ensures accurate staging. OBJECTIVES: To develop a prognostic index for MF. METHODS: Predefined datasets for clinical, haematological, radiological, immunohistochemical, genotypic, treatment and quality of life are collected at first diagnosis of MF and annually to test against survival. Biobanked tissue samples are recorded within a Federated Biobank for translational studies. RESULTS: In total, 430 patients were enrolled from 29 centres in 15 countries spanning five continents. Altogether, 348 were confirmed as having early-stage MF at central review. The majority had classical MF (81·6%) with a CD4 phenotype (88·2%). Folliculotropic MF was diagnosed in 17·8%. Most presented with stage I (IA: 49·4%; IB: 42·8%), but 7·8% presented with enlarged lymph nodes (stage IIA). A diagnostic delay between first symptom development and initial diagnosis was frequent [85·6%; median delay 36 months (interquartile range 12-90)]. This highlights the difficulties in accurate diagnosis, which includes lack of a singular diagnostic test for MF. CONCLUSIONS: This confirmed early-stage MF cohort is being followed-up to identify prognostic factors, which may allow better management and improve survival by identifying patients at risk of disease progression. This study design is a useful model for collaboration in other rare diseases, especially where pathological diagnosis can be complex.

Modified calcium subtraction in dual-energy CT angiography of the lower extremity runoff: impact on diagnostic accuracy for stenosis detection.

OBJECTIVES: To investigate the diagnostic accuracy of a modified three-material decomposition calcium subtraction (CS) algorithm for the detection of arterial stenosis in dual-energy CT angiography (DE-CTA) of the lower extremity runoff compared to standard image reconstruction, using digital subtraction angiography (DSA) as the reference standard. METHODS: Eighty-eight patients (53 males; mean age, 65.9 ± 11 years) with suspected peripheral arterial disease (PAD) who had undergone a DE-CTA examination of the lower extremity runoff between May 2014 and May 2015 were included in this IRB-approved, HIPAA-compliant retrospective study. Standard linearly blended and CS images were reconstructed and vascular contrast-to-noise ratios (CNR) were calculated. Two independent observers assessed subjective image quality using a 5-point Likert scale. Diagnostic accuracy for ≥ 50% stenosis detection was analyzed in a subgroup of 45 patients who had undergone additional DSA. Diagnostic accuracy parameters were estimated with a random-effects logistic regression analysis and compared using generalized estimating equations. RESULTS: CS datasets showed higher CNR (15.3 ± 7.3) compared to standard reconstructions (13.5 ± 6.5, p < 0.001). Both reconstructions showed comparable qualitative image quality scores (CS, 4.64; standard, 4.57; p = 0.220). Diagnostic accuracy (sensitivity, specificity, positive and negative predictive values) for CS reconstructions was 96.5% (97.5%, 95.6%, 90.9%, 98.1) and 93.1% (98.8%, 90.4%, 82.3%, 99.1%) for standard images. CONCLUSIONS: A modified three-material decomposition CS algorithm provides increased vascular CNR, equivalent qualitative image quality, and greater diagnostic accuracy for the detection of significant arterial stenosis of the lower extremity runoff on DE-CTA compared with standard image reconstruction. KEY POINTS: • Calcified plaques may lead to overestimation of stenosis severity and false positive results, requiring additional invasive digital subtraction angiography (DSA). • A modified three-material decomposition algorithm for calcium subtraction provides greater diagnostic accuracy for the detection of significant arterial stenosis of the lower extremity runoff compared with standard image reconstruction. • The application of this algorithm in patients with heavily calcified vessels may be helpful to potentially reduce inconclusive CT angiography examinations and the need for subsequent invasive DSA.