Mental health support across the sight loss pathway: a qualitative exploration of eye care patients, optometrists, and ECLOs.

BACKGROUND: The process of becoming visually impaired or blind is undoubtedly a highly emotional experience, requiring practical and psychological support. Information on mental health support provision in the UK across the sight-loss pathway, however, is largely unknown, especially amongst healthcare practitioners that are often sought after for advice: the referring optometrist and eye clinic liaison officer (ECLO). This study aims to ascertain the perceived accessibility and quality of mental health support across the sight-loss pathway. METHODS: Semi-structured individual interviews were conducted with patients with a diagnosed eye condition who had received care from a hospital eye service, referring optometrists, and ECLOs. Following interview transcription, results were synthesised in a narrative analysis. RESULTS: A total of 28 participants were included in the analysis, of which 17 were participants with various eye conditions, five were referring optometrists, and five were ECLOs. After analysis, three broad themes emerged: (1) The emotional trauma of diagnosis (2) Availability of mental health support; (3) The point where mental health support is most needed across the sight-loss pathway. Several patients reporting that they had received no offer of support nor were they signposted to any possible sources. Referring optometrists and ECLO's agreed. CONCLUSION: It is important that referring optometrists are aware of the need for mental health support services and can signpost to local support services including the third sector anytime during the referral process. Future large-scale, UK-wide research into referral practice and signposting for mental health support for patients is warranted, to identify how services can be improved in order to ensure that the wellbeing of patients is maintained.

Pathological eating behaviours and risk of retinopathy in diabetes: a systematic review and meta-analysis.

Background: Diabetes mellitus can cause several long-term macrovascular and microvascular complications including nephropathy, neuropathy, and retinopathy (DR). Several studies have reported positive associations between eating pathologies and DR; however, these studies have not been aggregated and sub-grouped into type of pathological eating behaviour, and the differences in risk according to type of eating behaviour is unknown. The aim of this review, therefore, was to aggregate risks of DR in populations with and without pathological eating behaviours, stratified according to eating behaviour. Methods: A systematic review and meta-analysis was conducted. Major databases and grey literature were search from inception until 1/6/2021. Studies reporting the prevalence of pathological eating behaviours (against a control group with no pathological eating behaviours) in diabetic people with and without DR were included. Odds ratios were calculated from primary data. Results: Seven studies with eight independent outcomes with a total of 1162 participants were included. The odds ratio of DR in the total pooled analysis was 2.94 (95%CI 1.86-4.64; p = <0.001; I2 = 29.59). Two types of eating behaviour yielded enough data for sub-group analysis. Eating disorder not otherwise specified yielded an odds ratio of 2.73 (95%CI 1.81-4.10; p = <0.001; I2 = 0.00), and binge eating disorder yielded an non-significant odds ratio of 0.92 (95%CI 0.31-2.77; p = 0.887;I2 = 0.00). Discussion: The likelihood of DR increases almost three times in the presence of pathological eating behaviours. More studies are required to confirm this in clinical populations stratified by eating disorder. Practitioners working with people with diabetes should closely monitor eating behaviours to preclude this risk. Supplementary Information: The online version contains supplementary material available at 10.1007/s40200-022-00980-x.

Correction: A novel scaling methodology to reduce the biases associated with missing data from commercial activity monitors.

[This corrects the article DOI: 10.1371/journal.pone.0235144.].

A novel scaling methodology to reduce the biases associated with missing data from commercial activity monitors.

BACKGROUND: Commercial physical activity monitors have wide utility in the assessment of physical activity in research and clinical settings, however, the removal of devices results in missing data and has the potential to bias study conclusions. This study aimed to evaluate methods to address missingness in data collected from commercial activity monitors. METHODS: This study utilised 1526 days of near complete data from 109 adults participating in a European weight loss maintenance study (NoHoW). We conducted simulation experiments to test a novel scaling methodology (NoHoW method) and alternative imputation strategies (overall/individual mean imputation, overall/individual multiple imputation, Kalman imputation and random forest imputation). Methods were compared for hourly, daily and 14-day physical activity estimates for steps, total daily energy expenditure (TDEE) and time in physical activity categories. In a second simulation study, individual multiple imputation, Kalman imputation and the NoHoW method were tested at different positions and quantities of missingness. Equivalence testing and root mean squared error (RMSE) were used to evaluate the ability of each of the strategies relative to the true data. RESULTS: The NoHoW method, Kalman imputation and multiple imputation methods remained statistically equivalent (p<0.05) for all physical activity metrics at the 14-day level. In the second simulation study, RMSE tended to increase with increased missingness. Multiple imputation showed the smallest RMSE for Steps and TDEE at lower levels of missingness (<19%) and the Kalman and NoHoW methods were generally superior for imputing time in physical activity categories. CONCLUSION: Individual centred imputation approaches (NoHoW method, Kalman imputation and individual Multiple imputation) offer an effective means to reduce the biases associated with missing data from activity monitors and maximise data retention.

The characteristics of krill swarms in relation to aggregating Antarctic blue whales.

We model the presence of rare Antarctic blue whales (Balaenoptera musculus intermedia) in relation to the swarm characteristics of their main prey species, Antarctic krill (Euphausia superba). A combination of visual observations and recent advances in passive acoustic technology were used to locate Antarctic blue whales, whilst simultaneously using active underwater acoustics to characterise the distribution, size, depth, composition and density of krill swarms. Krill swarm characteristics and blue whale presence were examined at a range of spatiotemporal scales to investigate sub meso-scale (i.e., <100 km) foraging behaviour. Results suggest that at all scales, Antarctic blue whales are more likely to be detected within the vicinity of krill swarms with a higher density of krill, those found shallower in the water column, and those of greater vertical height. These findings support hypotheses that as lunge-feeders of extreme size, Antarctic blue whales target shallow, dense krill swarms to maximise their energy intake. As both Antarctic krill and blue whales play a key role in the Southern Ocean ecosystem, the nature of their predator-prey dynamics is an important consideration, not only for the recovery of this endangered species in a changing environment, but for the future management of Antarctic krill fisheries.

Outcomes of rescue therapy in acute severe ulcerative colitis: data from the United Kingdom inflammatory bowel disease audit.

BACKGROUND: Approximately one third of patients with acute severe ulcerative colitis (ASUC) fail response to steroids. Ciclosporin and anti-TNFα are proven second-line therapies, but evidence of their efficacy has come mainly from tertiary centres and/or selective clinical trial recruitment. AIM: To assess ASUC outcomes in a large unselected cohort. METHODS: UK-wide audits of IBD care were conducted in 2008 (209 hospital sites) and 2010 (198 hospital sites), covering >87% of admitting hospitals. Each site entered data from 20 consecutive UC admissions onto a web-based proforma. Admissions included 852 (2008) and 984 (2010) with ASUC, accounting for 35% and 39% of UC admissions, respectively. RESULTS: ASUC in-hospital mortality was 1.2% in 2008; 0.7% in 2010 (P = 0.22). Response to first-line steroid therapy was 61% (2008); 58% (2010) and mortality was higher in non-responders: 2008: 2.9% (9/315) vs. 0.19% (1/537; P < 0.001); 2010: 1.8% (7/391) vs. 0.0% (0/593; P = 0.002). In 2010, more patients (56%) received second-line medical therapy than in 2008 (47%, P = 0.02). In-hospital mortality was similar to second-line medical therapy vs. surgery without further medical therapy; 2008: 2.7% vs. 2.8%, P = 0.99; 2010: 0.9% vs. 3.1%, P = 0.17. Second-line therapy response was more frequently observed with anti-TNFα than ciclosporin: (2008: 76% vs. 46%, P < 0.001; 2010: 80% vs. 58%, P < 0.001). CONCLUSIONS: Mortality in acute severe ulcerative colitis was low, but higher in steroid non-responders. Patients treated with second-line medical therapies had no higher risk of in-hospital mortality than those undergoing surgery. Second-line 'rescue' medical therapy usage is increasing; however, ciclosporin response rates were relatively low.

Statistical and bioanalytical considerations for establishing a depletion criterion for specificity testing during immunogenicity assessment of a biotherapeutic.

Immunogenicity assessment of fully human monoclonal antibody-based biotherapeutics requires sensitive and specific ligand binding assays. One of the components of specificity is the depletion of signal by a relevant biotherapeutic that is commonly based on an arbitrary depletion criterion of inhibition of the original response or reduction of the signal below the screening assay cut point (ACP). Hence, there is a need to develop a statistically derived physiologically relevant specificity criterion. We illustrate an optimization approach to determine the concentration of biotherapeutic required for the specificity evaluation. Naïve donor sample sets with and without circulating drug and antitherapeutic/drug antibody (ADA) were prepared. Next, a depletion cut point (DCP) using naïve and ADA-containing donor sets with the optimized biotherapeutic concentration was evaluated. A statistically derived design of experiment was used to establish a validated DCP. A reliable DCP requires naïve (no ADA) donors treated only with an optimized concentration of biotherapeutic. The additional DCPs generated using two distinct concentrations of ADA-spiked sample sets led to a physiologically irrelevant criterion that was not necessarily representative of real-time samples. This increased the risk of false positives or negatives. In this study, well-defined bioanalytical and statistical methods were employed to validate a DCP to confirm the presence of biotherapeutic specific ADA in human serum samples. A physiologically relevant and effective strategy to confirm specificity in immune reactive samples, especially those that are close to the ACP, is proposed through this study.

Diet and trophic niche of Antarctic silverfish Pleuragramma antarcticum in the Ross Sea, Antarctica.

The diet of Antarctic silverfish Pleuragramma antarcticum was evaluated by examining stomach contents of specimens collected in the Ross Sea (71°-77° S; 165°-180° E) in January to March 2008. Pleuragramma antarcticum (50-236 mm standard length, L(S)) and prey items were analysed for stable-isotopic composition of carbon and nitrogen. According to index of relative importance (I(RI) ), which incorporates frequency of occurrence, mass and number of prey items, the most important prey items were copepods (81%I(RI) over all specimens), predominantly Metridia gerlachei and Paraeuchaeta sp., with krill and fishes having low I(RI) (2·2 and 5·6%I(RI) overall). According to mass of prey (M) in stomachs, however, fishes (P. antarcticum and myctophids) and krill dominated overall diet (48 and 22%M, respectively), with copepods being a relatively minor constituent of overall diet by mass (9·9%M). Piscivory by P. antarcticum occurred mainly in the extreme south-west of the region and near the continental slope. Krill identified to species level in P. antarcticum stomachs were predominantly Euphausia superba (14·1%M) with some Euphausia crystallophorias (4·8%M). Both DistLM modelling (PRIMER-permanova+) on stomach contents (by I(RI)) and stepwise generalized linear modelling on stable isotopes showed that L(S) and location were significant predictors of P. antarcticum diet. Postlarval P. antarcticum (50-89 mm L(S)) consumed exclusively copepods. Juvenile P. antarcticum (90-151 mm L(S)) consumed predominantly krill and copepods by mass (46 and 30%M, respectively). Small adult P. antarcticum (152-178 mm L(S)) consumed krill, fishes and copepods (37, 36 and 15%M, respectively). Large adult P. antarcticum (179-236 mm L(S)) consumed predominantly fishes and krill (55 and 17%M, respectively), especially in the north (near the Ross Sea slope) and in the SW Ross Sea. Amphipods were occasionally important prey items for P. antarcticum (western Ross Sea, 39%M). General concordance between stomach contents and trophic level of P. antarcticum and prey based on δ(15) N was demonstrated. Pleuragramma antarcticum trophic level was estimated as 3·7 (postlarval fish) and 4·1 (fish aged 3+ years).

Functional constraints on nest characteristics of pebble mounds of breeding male hornyhead chub Nocomis biguttatus.

Breeding male hornyhead chub Nocomis biguttatus constructed nests in areas with relatively high but less than maximum flow rate and greater than average water depth. Nests comprised c. 3000 pebbles for a total mass of 11 kg. Males selected pebbles of smaller diameter but higher density than pebbles in the immediate vicinity. Thus, nests balanced the risk of mound erosion and energetic cost of nest construction with the benefits of protection from egg predators and a stable internal flow rate for oxygenation. These data help establish environmental management goals for the conservation of N. biguttatus and the lotic ecosystems dependent upon them.

LAVIA--an evaluation of the potential safety benefits of the French intelligent speed adaptation project.

This paper presents the potential safety benefits of the experimental French LAVIA Intelligent Speed Adaptation system, according to road network and system mode, based on observed driving speeds, distributions of crash severity and crash injury risk. Results are given for car frontal and side impacts that together, represent 80% of all serious and fatal injuries in France. Of the three system modes tested (advisory, driver select, mandatory), our results suggest that driver select would most significantly reduce serious injuries and death. We estimate this 100% utilization of cars equipped with this type of speed adaptation system would decrease injury rates by 6% to 16% over existing conditions depending on the type of crash (frontal or side) and road environment considered. Some limitations associated with the analysis are also identified. LAVIA is the acronym for Limiteur s'Adaptant à la VItesse Autorisée, a French Intelligent Speed Adaptation (ISA) project that was set up towards the end of 1999. At the time, 1998 French national road safety statistics recorded 8437 road related deaths, a figure which had shown virtually no positive evolution since 1994. Detailed analysis of the contributory factors involved in fatal road crashes highlighted the time-honoured crash and injury causation mechanisms - alcohol, speed and seatbelts. Of the three, excessive speed (over and above the posted speed limit) was a contributory factor in half of all fatal crashes Inappropriate behaviour such as excessive speeding can be dealt with either by legislative or driver-incentive programmes. The first of these two solutions involves the introduction of new legislation and/or the enforcement of existing laws. This is the domain of Public Authorities and will not be discussed in detail here. Alternatively, incentive schemes can involve the implementation of speed related driver assistance systems, categorised according to their voluntary or mandatory character and the degree of autonomy proposed to or imposed on the driver. The LAVIA project set out to address several possible combinations of these two factors. The generic term Intelligent Speed Adaptation (ISA) encompasses a wide range of different technologies aimed at improving road safety by reducing traffic speed and homogenising traffic flow, within the limit of posted speed limits. "Fixed speed limit" systems inform the vehicle of the posted speed limit whereas "variable speed limit" systems take into account certain locations on the road network where a speed below the posted limit is desirable, such as sharp curves, pedestrian crossings or crash black spots. Taken one step further, speed limit systems may also take into account weather and traffic flow conditions. These systems are known as "dynamic speed limit" systems and benefit from real time updates for a specific location. The different ISA systems are generally characterised by the degree of freedom of choice given to the driver in moderating his or her speed. Speed limit technologies may be advisory (informing drivers of the current speed limit and speed limit changes), voluntary (allowing the driver to decide whether or not to implement speed limitation) or mandatory (imposing the current speed limit). The information supplied may be provided by way of the road infrastructure (and associated equipment), may be acquired autonomously by the vehicle or may be based on an interaction between the infrastructure and the vehicle. Even the most basic of these systems should be considered as a very useful driver aid, helping the driver to stay within the posted speed limit, avoiding "unnecessary" speeding fines through inattention, modelling driver behaviour through the long term reduction of speeds and reducing driver workload by limiting visual speedometer controls. Vehicle-based ISA systems should not be confused with internal systems. These latter systems rely upon the driver entering the desired travel speed, which is then maintained by cruise control or set as a maximum value by automatic speed regulators. Although these systems will not be discussed in detail here, it should be noted that the engine management technologies that they employ are a vital component of ISA systems.

A rare complication of pneumonectomy: diagnosis made by a literature search.

This case describes platypnoea-orthodeoxia syndrome in a patient 2 months after a right pneumonectomy for adenocarcinoma of the lung. The patient complained of platypnoea (breathlessness in the upright position) and was noted to have orthodeoxia (arterial desaturation on standing) on clinical examination. This was due to anatomical changes after the pneumonectomy that resulted in direct blood flow from the inferior vena cava through a previously unrecognised atrial septal defect into the left atrium. The closure of this right to left shunt with an Amplatzer occluder produced immediate and striking symptomatic relief in the patient. The authors had no previous experience of this very rare complication of pneumonectomy. The diagnosis was made after a literature search using PubMed/Medline, underlining the direct clinical benefit provided by these databases.

Inclusion of the E3 region in an adenoviral vector decreases inflammation and neointima formation after arterial gene transfer.

Adenoviral vectors are promising agents for vascular gene transfer. Their use, however, is limited by inflammatory host responses, neointima formation, and brevity of transgene expression. Inclusion of the immunomodulatory adenoviral E3 genes in a vector might prevent inflammation and neointima formation and prolong transgene expression. We compared 2 adenoviral vectors in a model of in vivo gene transfer to rabbit arteries. Both vectors expressed a luciferase reporter gene. One vector (AdE3Luc) contained the adenovirus early 3 (E3) region and the other (AdRSVLuc) lacked E3. Expression of E3 genes by AdE3Luc was confirmed in vitro and in vivo. Arteries transduced with AdE3Luc had substantially and significantly less inflammation (fewer T cells and lower levels of vascular cell adhesion molecule-1 and intercellular adhesion molecule 1 expression) and decreased neointima formation 14 days after gene transfer. Luciferase expression from the 2 vectors was equivalent, however, at both 3 and 14 days after gene transfer. Expression of E3 had no systemic immunosuppressive effects, as measured by peripheral blood counts and by assays for serum antibodies to adenovirus. We conclude that expression of E3 significantly decreases adenovirus-induced arterial wall inflammation and neointima formation. Because inflammation and neointima formation are major barriers to the clinical application of adenoviral vectors, use of E3-containing vectors improves the promise of adenovirus-mediated arterial gene transfer.

Do all patients require supplemental oxygen during flexible bronchoscopy?

STUDY OBJECTIVES: Some respiratory units routinely administer supplemental oxygen to all patients during flexible bronchoscopy, but other units give oxygen only to those who desaturate (arterial oxygen saturation [SaO(2)], < 90%). We performed a study to examine both the requirement for supplemental oxygen and the effect of IV midazolam therapy on oxygenation during flexible bronchoscopy for patients with a known FEV(1). DESIGN: Data on the SaO(2) of patients during flexible bronchoscopy were collected prospectively for all procedures performed in our respiratory unit for the period 1992 to 1997. RESULTS: There were 1,051 flexible bronchoscopy procedures performed in which the patient had a known FEV(1) and was not receiving supplemental oxygen before the procedure. Supplemental oxygen was commenced during or immediately after the procedure in 151 cases (14.4%), while a further 101 cases (9.6%) had momentary desaturation (ie, < 20 s) not requiring oxygen therapy. The lower the FEV(1), the greater the risk of significant desaturation and the need for supplemental oxygen (p < 0.0001) [supplemental O(2) therapy was administered in 35% of cases if FEV(1) < 1.0 L, in 14% of cases if FEV(1) was 1.0 to 1.5 L, and in 7% of cases if FEV(1) > 1.5 L]. The use of low-to-moderate doses of midazolam as sedation did not affect the probability of the occurrence of significant desaturation (p = 0.204). CONCLUSIONS: This study supports guidelines that suggest that all patients should be monitored by pulse oximetry during flexible bronchoscopy. Desaturation may occur at any FEV(1) level even without sedation. The majority of our patients did not require routine oxygen supplementation, especially the group with an FEV(1) above 1 L.

New York Chapter History of Military Medicine Award. U.S. Army medical helicopters in the Korean War.

Medical evacuation helicopters are taken for granted in today's military. However, the first use of helicopters for this purpose in the Korean War was not done intentionally but as a result of the necessity of moving patients rapidly over difficult Korean terrain and of the early ebbing of the main battle line. The objective of this essay is to increase the historical awareness of military medical evacuation helicopters in the Korean War during this 50th anniversary year. By describing the many challenges and experiences encountered in implementing the use of helicopters for evacuation, the reader will appreciate how a technology developed for another use helped in the success of evacuating nearly 22,000 patients while contributing to establishing a mortality rate of wounded of 2.4%. The preparation to write this essay included archival research of historical reports, records, and oral histories from the archives of the U.S. Army Center for Military History. Additionally, a search of journal articles written during and after the Korean War was conducted. The result is a comprehensive description of the use of medical evacuation helicopters in the Korean War.

Second-generation adenoviral vectors do not prevent rapid loss of transgene expression and vector DNA from the arterial wall.

The utility of adenoviral vectors for arterial gene transfer is limited by the brevity of their expression and by inflammatory host responses. As a step toward circumventing these difficulties, we used a rabbit model of in vivo arterial gene transfer to test 3 second-generation vectors: a vector containing a temperature-sensitive mutation in the E2A region, a vector deleted of E2A, and a vector that expresses the immunomodulatory 19-kDa glycoprotein (gp19k) from adenovirus 2. Compared with similar first-generation vectors, the second-generation vectors did not significantly prolong beta-galactosidase transgene expression or decrease inflammation in the artery wall. Although cyclophosphamide ablated the immune and inflammatory responses to adenovirus infusion, it only marginally prolonged transgene expression (94% drop in expression between 3 and 14 days). In experiments performed with "null" adenoviral vectors (no transgene), loss of vector DNA from the arterial wall was also rapid (>99% decrease between 1 hour and 14 days), unrelated to dose, and only marginally blunted by cyclophosphamide. Thus, the early loss of transgene expression after adenoviral arterial gene transfer is due primarily to loss of vector DNA, is not correlated with the presence of local vascular inflammation, and cannot be prevented by use of E2A-defective viruses, expression of gp19k, or cyclophosphamide-mediated immunosuppression. Adenovirus-induced vascular inflammation can be prevented by cyclophosphamide treatment or by lowering the dose of infused virus. However, stabilization of adenovirus-mediated transgene expression in the arterial wall is a more elusive goal and will require novel approaches that prevent the early loss of vector DNA.

Expression of Fas ligand in arteries of hypercholesterolemic rabbits accelerates atherosclerotic lesion formation.

Fas ligand (FasL) is expressed by cells of the arterial wall and is present in human atherosclerotic lesions. However, the role of FasL in modifying the initiation and progression of atherosclerosis is unclear. To investigate the role of arterial FasL expression in the development of atherosclerosis, we first established a model of primary lesion formation in rabbit carotid arteries. In this model, infusion of adenoviral vectors into surgically isolated, nondenuded arteries of hypercholesterolemic rabbits leads to the formation of human-like early atherosclerotic lesions. Expression of FasL in arterial endothelium in this model decreased T-cell infiltration and expression of vascular cell adhesion molecule-1 but did not affect expression of intercellular adhesion molecule-1. Intimal lesions grew more rapidly in FasL-transduced arteries than in arteries transduced with a control adenovirus that did not express a transgene. Total intimal macrophage accumulation was increased in FasL-transduced arteries; however, the proportion of lesion area occupied by macrophages was not elevated. The accelerated lesion growth was primarily due to the accumulation of intimal smooth muscle cells with a synthetic proliferative phenotype. There was no significant apoptosis in FasL-transduced or control arteries and no granulocytic infiltrates. Thus, the net result of elevated FasL expression is to accelerate atherosclerotic lesion growth by increasing lesion cellularity. Vascular expression of FasL may contribute to the progression of atherosclerosis.

Optimizing vascular gene transfer of plasminogen activator inhibitor 1.

The vessel wall fibrinolytic system plays an important role in maintaining the arterial phenotype and in regulating the arterial response to injury. Plasminogen activator inhibitor type 1 (PAI-1) regulates tissue fibrinolysis and is expressed in arterial tissue; however, its biological role remains uncertain. To help elucidate the role of PAI-1 in the artery wall, and to begin to clarify whether manipulation of vascular PAI-1 expression might be a target for gene therapy, we used adenoviral vectors to increase expression of rat PAI-1 in rat carotid arteries. Infusion of an adenoviral vector in which PAI-1 expression was driven by a promoter derived from the Rous sarcoma virus (RSV) did not increase PAI-1 expression above endogenous levels. To improve PAI-1 expression, we modified the vector by (1) truncating the 3' untranslated region of PAI-1 to increase the mRNA half-life, (2) substituting the SRalpha or the cytomegalovirus (CMV) promoter for the RSV promoter, (3) including an intron in the expression cassette, and (4) altering the direction of transcription of the transgene cassette. The optimal expression vector, revealed by in vitro studies, contained the CMV promoter, an intron, and a truncated PAI-1 mRNA. This vector increased PAI-1 expression by 30-fold over control levels in vitro and by 1.6 to 2-fold over endogenous levels in vivo. This vector will be useful for elucidating the role of PAI-1 in arterial pathobiology. Because genes that are important in maintaining the vascular phenotype are likely to be expressed in the vasculature, the technical issues of how to increase in vivo expression of endogenous genes are highly relevant to the development of genetic therapies for vascular disease.