Hywel Dda University Health Board

<h3>Importance</h3> Cancer and other noncommunicable diseases (NCDs) are now widely recognized as a threat to global development. The latest United Nations high-level meeting on NCDs reaffirmed this observation and also highlighted the slow progress in meeting the 2011 Political Declaration on the Prevention and Control of Noncommunicable Diseases and the third Sustainable Development Goal. Lack of situational analyses, priority setting, and budgeting have been identified as major obstacles in achieving these goals. All of these have in common that they require information on the local cancer epidemiology. The Global Burden of Disease (GBD) study is uniquely poised to provide these crucial data. <h3>Objective</h3> To describe cancer burden for 29 cancer groups in 195 countries from 1990 through 2017 to provide data needed for cancer control planning. <h3>Evidence Review</h3> We used the GBD study estimation methods to describe cancer incidence, mortality, years lived with disability, years of life lost, and disability-adjusted life-years (DALYs). Results are presented at the national level as well as by Socio-demographic Index (SDI), a composite indicator of income, educational attainment, and total fertility rate. We also analyzed the influence of the epidemiological vs the demographic transition on cancer incidence. <h3>Findings</h3> In 2017, there were 24.5 million incident cancer cases worldwide (16.8 million without nonmelanoma skin cancer [NMSC]) and 9.6 million cancer deaths. The majority of cancer DALYs came from years of life lost (97%), and only 3% came from years lived with disability. The odds of developing cancer were the lowest in the low SDI quintile (1 in 7) and the highest in the high SDI quintile (1 in 2) for both sexes. In 2017, the most common incident cancers in men were NMSC (4.3 million incident cases); tracheal, bronchus, and lung (TBL) cancer (1.5 million incident cases); and prostate cancer (1.3 million incident cases). The most common causes of cancer deaths and DALYs for men were TBL cancer (1.3 million deaths and 28.4 million DALYs), liver cancer (572 000 deaths and 15.2 million DALYs), and stomach cancer (542 000 deaths and 12.2 million DALYs). For women in 2017, the most common incident cancers were NMSC (3.3 million incident cases), breast cancer (1.9 million incident cases), and colorectal cancer (819 000 incident cases). The leading causes of cancer deaths and DALYs for women were breast cancer (601 000 deaths and 17.4 million DALYs), TBL cancer (596 000 deaths and 12.6 million DALYs), and colorectal cancer (414 000 deaths and 8.3 million DALYs). <h3>Conclusions and Relevance</h3> The national epidemiological profiles of cancer burden in the GBD study show large heterogeneities, which are a reflection of different exposures to risk factors, economic settings, lifestyles, and access to care and screening. The GBD study can be used by policy makers and other stakeholders to develop and improve national and local cancer control in order to achieve the global targets and improve equity in cancer care.

Abstract The genetic make-up of an individual contributes to the susceptibility and response to viral infection. Although environmental, clinical and social factors have a role in the chance of exposure to SARS-CoV-2 and the severity of COVID-19 1,2 , host genetics may also be important. Identifying host-specific genetic factors may reveal biological mechanisms of therapeutic relevance and clarify causal relationships of modifiable environmental risk factors for SARS-CoV-2 infection and outcomes. We formed a global network of researchers to investigate the role of human genetics in SARS-CoV-2 infection and COVID-19 severity. Here we describe the results of three genome-wide association meta-analyses that consist of up to 49,562 patients with COVID-19 from 46 studies across 19 countries. We report 13 genome-wide significant loci that are associated with SARS-CoV-2 infection or severe manifestations of COVID-19. Several of these loci correspond to previously documented associations to lung or autoimmune and inflammatory diseases 3–7 . They also represent potentially actionable mechanisms in response to infection. Mendelian randomization analyses support a causal role for smoking and body-mass index for severe COVID-19 although not for type II diabetes. The identification of novel host genetic factors associated with COVID-19 was made possible by the community of human genetics researchers coming together to prioritize the sharing of data, results, resources and analytical frameworks. This working model of international collaboration underscores what is possible for future genetic discoveries in emerging pandemics, or indeed for any complex human disease.

BACKGROUND: The impact of COVID-19 on physical and mental health and employment after hospitalisation with acute disease is not well understood. The aim of this study was to determine the effects of COVID-19-related hospitalisation on health and employment, to identify factors associated with recovery, and to describe recovery phenotypes. METHODS: The Post-hospitalisation COVID-19 study (PHOSP-COVID) is a multicentre, long-term follow-up study of adults (aged ≥18 years) discharged from hospital in the UK with a clinical diagnosis of COVID-19, involving an assessment between 2 and 7 months after discharge, including detailed recording of symptoms, and physiological and biochemical testing. Multivariable logistic regression was done for the primary outcome of patient-perceived recovery, with age, sex, ethnicity, body-mass index, comorbidities, and severity of acute illness as covariates. A post-hoc cluster analysis of outcomes for breathlessness, fatigue, mental health, cognitive impairment, and physical performance was done using the clustering large applications k-medoids approach. The study is registered on the ISRCTN Registry (ISRCTN10980107). FINDINGS: We report findings for 1077 patients discharged from hospital between March 5 and Nov 30, 2020, who underwent assessment at a median of 5·9 months (IQR 4·9-6·5) after discharge. Participants had a mean age of 58 years (SD 13); 384 (36%) were female, 710 (69%) were of white ethnicity, 288 (27%) had received mechanical ventilation, and 540 (50%) had at least two comorbidities. At follow-up, only 239 (29%) of 830 participants felt fully recovered, 158 (20%) of 806 had a new disability (assessed by the Washington Group Short Set on Functioning), and 124 (19%) of 641 experienced a health-related change in occupation. Factors associated with not recovering were female sex, middle age (40-59 years), two or more comorbidities, and more severe acute illness. The magnitude of the persistent health burden was substantial but only weakly associated with the severity of acute illness. Four clusters were identified with different severities of mental and physical health impairment (n=767): very severe (131 patients, 17%), severe (159, 21%), moderate along with cognitive impairment (127, 17%), and mild (350, 46%). Of the outcomes used in the cluster analysis, all were closely related except for cognitive impairment. Three (3%) of 113 patients in the very severe cluster, nine (7%) of 129 in the severe cluster, 36 (36%) of 99 in the moderate cluster, and 114 (43%) of 267 in the mild cluster reported feeling fully recovered. Persistently elevated serum C-reactive protein was positively associated with cluster severity. INTERPRETATION: We identified factors related to not recovering after hospital admission with COVID-19 at 6 months after discharge (eg, female sex, middle age, two or more comorbidities, and more acute severe illness), and four different recovery phenotypes. The severity of physical and mental health impairments were closely related, whereas cognitive health impairments were independent. In clinical care, a proactive approach is needed across the acute severity spectrum, with interdisciplinary working, wide access to COVID-19 holistic clinical services, and the potential to stratify care. FUNDING: UK Research and Innovation and National Institute for Health Research.

The British Thoracic Society (BTS) Home Oxygen Guideline provides detailed evidence-based guidance for the use of home oxygen for patients out of hospital. Although the majority of evidence comes from the use of oxygen in patients with chronic obstructive pulmonary disease, the scope of the guidance includes patients with a variety of long-term respiratory illnesses and other groups in whom oxygen is currently ordered, such as those with cardiac failure, cancer and end-stage cardiorespiratory disease, terminal illness or cluster headache. It explores the evidence base for the use of different modalities of oxygen therapy and patient-related outcomes such as mortality, symptoms and quality of life. The guideline also makes recommendations for assessment and follow-up protocols, and risk assessments, particularly in the clinically challenging area of home oxygen users who smoke. The guideline development group is aware of the potential for confusion sometimes caused by the current nomenclature for different types of home oxygen, and rather than renaming them, has adopted the approach of clarifying those definitions, and in particular emphasising what is meant by long-term oxygen therapy and palliative oxygen therapy. The home oxygen guideline provides expert consensus opinion in areas where clinical evidence is lacking, and seeks to deliver improved prescribing practice, leading to improved compliance and improved patient outcomes, with consequent increased value to the health service.

Primary biliary cirrhosis (PBC) is a classical autoimmune liver disease for which effective immunomodulatory therapy is lacking. Here we perform meta-analyses of discovery data sets from genome-wide association studies of European subjects (n=2,764 cases and 10,475 controls) followed by validation genotyping in an independent cohort (n=3,716 cases and 4,261 controls). We discover and validate six previously unknown risk loci for PBC (Pcombined<5 × 10(-8)) and used pathway analysis to identify JAK-STAT/IL12/IL27 signalling and cytokine-cytokine pathways, for which relevant therapies exist.

Background Many people recovering from coronavirus disease 2019 (COVID-19) experience prolonged symptoms, particularly breathlessness. We urgently need to identify safe and effective COVID-19 rehabilitative strategies. The aim of the current study was to investigate the potential rehabilitative role of inspiratory muscle training (IMT). Methods 281 adults (age 46.6±12.2 years; 88% female) recovering from self-reported COVID-19 (9.0±4.2 months post-acute infection) were randomised 4:1 to an 8-week IMT or a “usual care” waitlist control arm. Health-related quality-of-life and breathlessness questionnaires (King's Brief Interstitial Lung Disease (K-BILD) and Transition Dyspnoea Index (TDI)), respiratory muscle strength, and fitness (Chester Step Test) were assessed pre- and post-intervention. The primary end-point was K-BILD total score, with the K-BILD domains and TDI being key secondary outcomes. Results According to intention to treat, there was no difference between groups in K-BILD total score post-intervention (control: 59.5±12.4; IMT: 58.2±12.3; p&lt;0.05) but IMT elicited clinically meaningful improvements in the K-BILD domains for breathlessness (control: 59.8±12.6; IMT: 62.2±16.2; p&lt;0.05) and chest symptoms (control: 59.2±18.7; IMT: 64.5±18.2; p&lt;0.05), along with clinically meaningful improvements in breathlessness according to TDI (control: 0.9±1.7 versus 2.0±2.0; p&lt;0.05). IMT also improved respiratory muscle strength and estimated aerobic fitness. Conclusions IMT may represent an important home-based rehabilitation strategy for wider implementation as part of COVID-19 rehabilitative strategies. Given the diverse nature of long COVID, further research is warranted on the individual responses to rehabilitation; the withdrawal rate herein highlights that no one strategy is likely to be appropriate for all.

Lung cancer (LC) is the most prevalent cancer worldwide, and responsible for over 1.3 million deaths each year. Currently, LC has a low five year survival rates relative to other cancers, and thus, novel methods to screen for and diagnose malignancies are necessary to improve patient outcomes. Here, we report on a pilot-sized study to evaluate the potential of the sputum microbiome as a source of non-invasive bacterial biomarkers for lung cancer status and stage. Spontaneous sputum samples were collected from ten patients referred with possible LC, of which four were eventually diagnosed with LC (LC+), and six had no LC after one year (LC-). Of the seven bacterial species found in all samples, Streptococcus viridans was significantly higher in LC+ samples. Seven further bacterial species were found only in LC-, and 16 were found only in samples from LC+. Additional taxonomic differences were identified in regards to significant fold changes between LC+ and LC-cases, with five species having significantly higher abundances in LC+, with Granulicatella adiacens showing the highest level of abundance change. Functional differences, evident through significant fold changes, included polyamine metabolism and iron siderophore receptors. G. adiacens abundance was correlated with six other bacterial species, namely Enterococcus sp. 130, Streptococcus intermedius, Escherichia coli, S. viridans, Acinetobacter junii, and Streptococcus sp. 6, in LC+ samples only, which could also be related to LC stage. Spontaneous sputum appears to be a viable source of bacterial biomarkers which may have utility as biomarkers for LC status and stage.

BACKGROUND: Low-dose aspirin has been shown to reduce the incidence of cancer, but its role in the treatment of cancer is uncertain. OBJECTIVES: We conducted a systematic search of the scientific literature on aspirin taken by patients following a diagnosis of cancer, together with appropriate meta-analyses. METHODS: Searches were completed in Medline and Embase in December 2015 using a pre-defined search strategy. References and abstracts of all the selected papers were scanned and expert colleagues were contacted for additional studies. Two reviewers applied pre-determined eligibility criteria (cross-sectional, cohort and controlled studies, and aspirin taken after a diagnosis of cancer), assessed study quality and extracted data on cancer cause-specific deaths, overall mortality and incidence of metastases. Random effects meta-analyses and planned sub-group analyses were completed separately for observational and experimental studies. Heterogeneity and publication bias were assessed in sensitivity analyses and appropriate omissions made. Papers were examined for any reference to bleeding and authors of the papers were contacted and questioned. RESULTS: Five reports of randomised trials were identified, together with forty two observational studies: sixteen on colorectal cancer, ten on breast and ten on prostate cancer mortality. Pooling of eleven observational reports of the effect of aspirin on cause-specific mortality from colon cancer, after the omission of one report identified on the basis of sensitivity analyses, gave a hazard ratio (HR) of 0.76 (95% CI 0.66, 0.88) with reduced heterogeneity (P = 0.04). The cause specific mortality in five reports of patients with breast cancer showed significant heterogeneity (P<0.0005) but the omission of one outlying study reduced heterogeneity (P = 0.19) and led to an HR = 0.87 (95% CI 0.69, 1.09). Heterogeneity between nine studies of prostate cancer was significant, but again, the omission of one study led to acceptable homogeneity (P = 0.26) and an overall HR = 0.89 (95% CI 0.79-0.99). Six single studies of other cancers suggested reductions in cause specific mortality by aspirin, and in five the effect is statistically significant. There were no significant differences between the pooled HRs for the three main cancers and after the omission of three reports already identified in sensitivity analyses heterogeneity was removed and revealed an overall HR of 0.83 (95% CI 0.76-0.90). A mutation of PIK3CA was present in about 20% of patients, and appeared to explain most of the reduction in colon cancer mortality by aspirin. Data were not adequate to examine the importance of this or any other marker in the effect of aspirin in the other cancers. On bleeding attributable to aspirin two reports stated that there had been no side effect or bleeding attributable to aspirin. Authors on the other reports were written to and 21 replied stating that no data on bleeding were available. CONCLUSIONS AND IMPLICATIONS: The study highlights the need for randomised trials of aspirin treatment in a variety of cancers. While these are awaited there is an urgent need for evidence from observational studies of aspirin and the less common cancers, and for more evidence of the relevance of possible bio-markers of the aspirin effect on a wide variety of cancers. In the meantime it is urged that patients in whom a cancer is diagnosed should be given details of this research, together with its limitations, to enable each to make an informed decision as to whether or not to take low-dose aspirin. SYSTEMATIC REVIEW PROTOCOL NUMBER: CRD42015014145.

OBJECTIVES: To measure work-related burnout in all groups of health service staff during the COVID-19 pandemic and to identify factors associated with work-related burnout. DESIGN: Cross-sectional staff survey. SETTING: All staff grades and types across primary and secondary care in a single National Health Service organisation. PARTICIPANTS: 257 staff members completed the survey, 251 had a work-related burnout score and 239 records were used in the regression analysis. PRIMARY AND SECONDARY OUTCOME MEASURES: (1) Work-related burnout as measured by the Copenhagen Burnout Inventory; (2) factors associated with work-related burnout identified through a multiple linear regression model; and (3) factors associated with work-related burnout identified through thematic analysis of free text responses. RESULTS: After adjusting for other covariates (including age, sex, job, being able to take breaks and COVID-19 knowledge), we observed meaningful changes in work-related burnout associated with having different COVID-19 roles (p=0.03), differences in the ability to rest and recover during breaks (p<0.01) and having personal protective equipment concerns (p=0.04). Thematic analysis of the free text comments also linked burnout to changes in workload and responsibility and to a lack of control through redeployment and working patterns. Reduction in non-COVID-19 services has resulted in some members of staff feeling underutilised, with feelings of inequality in workload. CONCLUSIONS: Our analyses support anecdotal reports of staff struggling with the additional pressures brought on by COVID-19. All three of the factors we found to be associated with work-related burnout are modifiable and hence their effects can be mitigated. When we next find ourselves in extraordinary times the ordinary considerations of rest and protection and monitoring of the impact of new roles will be more important than ever.

Frontal fibrosing alopecia (FFA) is a recently described inflammatory and scarring type of hair loss affecting almost exclusively women. Despite a dramatic recent increase in incidence the aetiopathogenesis of FFA remains unknown. We undertake genome-wide association studies in females from a UK cohort, comprising 844 cases and 3,760 controls, a Spanish cohort of 172 cases and 385 controls, and perform statistical meta-analysis. We observe genome-wide significant association with FFA at four genomic loci: 2p22.2, 6p21.1, 8q24.22 and 15q2.1. Within the 6p21.1 locus, fine-mapping indicates that the association is driven by the HLA-B*07:02 allele. At 2p22.1, we implicate a putative causal missense variant in CYP1B1, encoding the homonymous xenobiotic- and hormone-processing enzyme. Transcriptomic analysis of affected scalp tissue highlights overrepresentation of transcripts encoding components of innate and adaptive immune response pathways. These findings provide insight into disease pathogenesis and characterise FFA as a genetically predisposed immuno-inflammatory disorder driven by HLA-B*07:02.

Purpose. To compare the through-focus visual performance in a clinical population of pseudophakic patients implanted with two new trifocal intraocular lenses (IOLs) and one extended depth of focus IOL. Methods. Prospective, nonrandomized, examiner-masked case series. Twenty-three patients received the FineVision® and seven patients received the PanOptix™ trifocal IOLs. Fifteen patients received the Symfony extended depth of focus IOL. Mean age of patients was 63 ± 8 years. Through-focus visual acuity was measured from –3.00 to +1.00 D vergences. Contrast sensitivity was measured with and without a source of glare. Light disturbances were evaluated with the Light Distortion Analyzer. Results. Though-focus evaluation showed that trifocal IOLs performed significantly better at near distance (33 and 40 cm), and extended depth of focus performed significantly better at intermediate distance (1.0 m). Contrast sensitivity function with glare and dysphotopsia was similar between the three IOLs and subjective response to questionnaire showed a significantly higher score (worse performance) for the extended depth of focus IOL compared to both trifocal IOLs in the bothersome subscale (<mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" id="M1"><mml:mi>p</mml:mi><mml:mo>&lt;</mml:mo><mml:mn>0.05</mml:mn></mml:math>). Conclusions . Trifocal IOLs grant better performance at near distance while extended depth of focus IOL performs better at intermediate distance. Objective dysphotopsia measured with the Light Distortion Analyzer is not reduced in extended depth of focus IOL compared to trifocal IOLs.

This review aims to examine the volume and quality of the evidence base which supports the use of acupuncture in the treatment of anxiety disorders. A literature review was conducted using Pubmed, Google scholar, AMED, BMJ, Embase, Psychinfo, Cochrane library, Ingenta connect, and Cinahl databases. Keywords were "anxiety,""anxious,""panic,""stress,""phobia," and "acupuncture" limited to year 2000 onwards and English language where available. The quality of research examining the use of acupuncture in the treatment of anxiety disorders is extremely variable. There is enormous variety regarding points used, number of points used in a session, duration of sessions, frequency of treatment and duration of treatment programme. While the generally poor methodological quality, combined with the wide range of outcome measures used, number and variety of points, frequency of sessions, and duration of treatment makes firm conclusions difficult. Against this, the volume of literature, consistency of statistically significant results, wide range of conditions treated and use of animal test subjects suggests very real, positive outcomes using a treatment method preferred by a population of individuals who tend to be resistant to conventional medicine.

OBJECTIVES: The objectives of this study are twofold. First, to examine the direct effect of psychosocial work characteristics (as measured by job autonomy and work-related pressure) in relation to self-reported psychological morbidity symptoms and early retirement intentions among a sample of hospital consultants in the National Health Service (NHS). Second, to investigate burnout as mediating variable (ie, indirect effect) of these postulated associations. DESIGN: A cross-sectional observational study. PARTICIPANTS: 593 NHS consultants (male=63.1%) from hospitals in England, Scotland and Wales. MEASURES: Self-reported online questionnaires on work-related pressure and job autonomy (Job Demands-Resources Questionnaire); emotional exhaustion and depersonalisation (Maslach Burnout Inventory); depressive and anxiety symptoms (State Trait Personality Inventory) and a single-item on early retirement intention. RESULTS: This study observed high prevalence rates across all adverse health measures: emotional exhaustion (38.7%), depersonalisation (20.7%), anxiety symptoms (43.1%) and depressive symptoms (36.1%). Multiple linear regressions examined the postulated direct and indirect effects. Job autonomy had significant negative direct effects on the frequency of NHS consultants' anxiety and depressive symptoms, and their intention to retire early. Both emotional exhaustion and depersonalisation mediated the relationships that work-related pressure (full mediation) and job autonomy (partial mediation) had with self-reported symptoms of psychological morbidities. Only emotional exhaustion mediated the relationships where early retirement intention was the outcome. In terms of sociodemographic factors, age and years' experience predicted both burnout dimensions and psychological morbidity. CONCLUSIONS: This is the first study to observe job autonomy to be associated with the number of self-reported psychological morbidity symptoms and early retirement intentions in a sample of NHS consultants. Burnout dimensions mediated these relationships, indicating that interventions need to focus on enhancing working conditions and addressing burnout among NHS consultants before more severe symptoms of psychological morbidity are reported. This study has implications for NHS policy makers and senior leadership.

AIMS: It is increasingly recognized that tools are required for assessing and benchmarking quality of care in order to improve it. The European Society of Cardiology (ESC) is developing a suite of quality indicators (QIs) to evaluate cardiovascular care and support the delivery of evidence-based care. This paper describes the methodology used for their development. METHODS AND RESULTS: We propose a four-step process for the development of the ESC QIs. For a specific clinical area with a gap in care delivery, the QI development process includes: (i) the identification of key domains of care by constructing a conceptual framework of care; (ii) the construction of candidate QIs by conducting a systematic review of the literature; (iii) the selection of a final set of QIs by obtaining expert opinions using the modified Delphi method; and (iv) the undertaking of a feasibility assessment by evaluating different ways of defining the QI specifications for the proposed data collection source. For each of the four steps, key methodological areas need to be addressed to inform the implementation process and avoid misinterpretation of the measurement results. CONCLUSION: Detailing the methodology for the ESC QIs construction enables healthcare providers to develop valid and feasible metrics to measure and improve the quality of cardiovascular care. As such, high-quality evidence may be translated into clinical practice and the 'evidence-practice' gap closed.

. Here we profiled 368 plasma proteins in 657 participants ≥3 months following hospitalization. Of these, 426 had at least one long COVID symptom and 233 had fully recovered. Elevated markers of myeloid inflammation and complement activation were associated with long COVID. IL-1R2, MATN2 and COLEC12 were associated with cardiorespiratory symptoms, fatigue and anxiety/depression; MATN2, CSF3 and C1QA were elevated in gastrointestinal symptoms and C1QA was elevated in cognitive impairment. Additional markers of alterations in nerve tissue repair (SPON-1 and NFASC) were elevated in those with cognitive impairment and SCG3, suggestive of brain-gut axis disturbance, was elevated in gastrointestinal symptoms. Severe acute respiratory syndrome coronavirus 2-specific immunoglobulin G (IgG) was persistently elevated in some individuals with long COVID, but virus was not detected in sputum. Analysis of inflammatory markers in nasal fluids showed no association with symptoms. Our study aimed to understand inflammatory processes that underlie long COVID and was not designed for biomarker discovery. Our findings suggest that specific inflammatory pathways related to tissue damage are implicated in subtypes of long COVID, which might be targeted in future therapeutic trials.

BACKGROUND: To estimate global and regional trends from 2000 to 2020 of the number of persons visually impaired by cataract and their proportion of the total number of vision-impaired individuals. METHODS: A systematic review and meta-analysis of published population studies and gray literature from 2000 to 2020 was carried out to estimate global and regional trends. We developed prevalence estimates based on modeled distance visual impairment and blindness due to cataract, producing location-, year-, age-, and sex-specific estimates of moderate to severe vision impairment (MSVI presenting visual acuity <6/18, ≥3/60) and blindness (presenting visual acuity <3/60). Estimates are age-standardized using the GBD standard population. RESULTS: In 2020, among overall (all ages) 43.3 million blind and 295 million with MSVI, 17.0 million (39.6%) people were blind and 83.5 million (28.3%) had MSVI due to cataract blind 60% female, MSVI 59% female. From 1990 to 2020, the count of persons blind (MSVI) due to cataract increased by 29.7%(93.1%) whereas the age-standardized global prevalence of cataract-related blindness improved by -27.5% and MSVI increased by 7.2%. The contribution of cataract to the age-standardized prevalence of blindness exceeded the global figure only in South Asia (62.9%) and Southeast Asia and Oceania (47.9%). CONCLUSIONS: The number of people blind and with MSVI due to cataract has risen over the past 30 years, despite a decrease in the age-standardized prevalence of cataract. This indicates that cataract treatment programs have been beneficial, but population growth and aging have outpaced their impact. Growing numbers of cataract blind indicate that more, better-directed, resources are needed to increase global capacity for cataract surgery.

Purpose: To systematically compare epithelial-off standard (SCXL) to accelerated corneal collagen cross-linking (ACXL) for the treatment of keratoconus. Methods: PubMed, Embase, the Cochrane Library, and the US trial registry were searched for trials comparing SCXL and ACXL for keratoconus up to October 2017. Standardized mean differences (SMDs) with 95% confidence intervals (CIs) were calculated. Primary outcomes were changes in uncorrected distance visual acuity, maximum keratometry (Kmax), and mean keratometry (mean K). Secondary outcomes were changes in corrected distance visual acuity, mean refractive spherical equivalent, central corneal thickness (CCT), and endothelial cell density (ECD). Results: Eleven trials were included. For primary outcomes, SCXL showed a greater reduction in Kmax (SMD 0.32; 95% CI 0.16, 0.48) than ACXL. For secondary outcomes, the decrease in CCT (SMD 0.32; 95% CI 0.03, 0.61) and ECD (SMD 0.26; 95% CI 0.06, 0.46) was less with ACXL than with SCXL. For the other outcomes, there were no statistically significant differences. Conclusions: SCXL has a greater effect in terms of reduction in Kmax than ACXL, while ACXL induces less reduction in CCT and ECD than SCXL. Further well-designed randomized controlled trials comparing ACXL and SCXL are indicated.

BACKGROUND: Patients who are critically ill are at increased risk of hospital acquired pneumonia and ventilator associated pneumonia. Effective evidence based oral care may reduce the incidence of such iatrogenic infection. AIM: To provide an evidence-based British Association of Critical Care Nurses endorsed consensus paper for best practice relating to implementing oral care, with the intention of promoting patient comfort and reducing hospital acquired pneumonia and ventilator associated pneumonia in critically ill patients. DESIGN: A nominal group technique was adopted. A consensus committee of adult critical care nursing experts from the United Kingdom met in 2018 to evaluate and review the literature relating to oral care, its application in reducing pneumonia in critically ill adults and to make recommendations for practice. An elected national board member for the British Association of Critical Care Nurses chaired the round table discussion. METHODS: The committee focused on 5 aspects of oral care practice relating to critically ill adult patients. The evidence was evaluated for each practice within the context of reducing pneumonia in the mechanically ventilated patient or pneumonia in the non-ventilated patient. The five practices included the frequency for oral care; tools for oral care; oral care technique; solutions used and oral care in the non-ventilated patient who is critically ill and is at risk of aspiration. The group searched the best available evidence and evaluated this using the Grading of Recommendations Assessment, Development, and Evaluation system to assess the quality of evidence from high to very low, and to formulate recommendations as strong, moderate, weak, or best practice consensus statement when applicable. RESULTS: The consensus group generated recommendations, delineating an approach to best practice for oral care in critically ill adult patients. Recommendations included guidance for frequency and procedure for oral assessment, toothbrushing, and moisturising the mouth. Evidence on the use of chlorhexidine is not consistent and caution is advised with its routine use. CONCLUSION: Oral care is an important part of the care of critically ill patients, both ventilated and non-ventilated. An effective oral care programme reduces the incidence of pneumonia and promotes patient comfort. RELEVANCE TO CLINICAL PRACTICE: Effective oral care is integral to safe patient care in critical care.

Background and objectives Our aim was to use a national electronic AKI alert to define the incidence and outcome of all episodes of community– and hospital–acquired adult AKI. Design, setting, participants, &amp; measurements A prospective national cohort study was undertaken in a population of 3.06 million. Data were collected between March of 2015 and August of 2015. All patients with adult (≥18 years of age) AKI were identified to define the incidence and outcome of all episodes of community- and hospital-acquired AKI in adults. Mortality and renal outcomes were assessed at 90 days. Results There was a total of 31,601 alerts representing 17,689 incident episodes, giving an incidence of AKI of 577 per 100,000 population. Community-acquired AKI accounted for 49.3% of all incident episodes, and 42% occurred in the context of preexisting CKD (Chronic Kidney Disease Epidemiology Collaboration eGFR); 90-day mortality rate was 25.6%, and 23.7% of episodes progressed to a higher AKI stage than the stage associated with the alert. AKI electronic alert stage and peak AKI stage were associated with mortality, and mortality was significantly higher for hospital-acquired AKI compared with alerts generated in a community setting. Among patients who survived to 90 days after the AKI electronic alert, those who were not hospitalized had a lower rate of renal recovery and a greater likelihood of developing an eGFR&lt;60 ml/min per 1.73 m 2 for the first time, which may be indicative of development of de novo CKD. Conclusions The reported incidence of AKI is far greater than the previously reported incidence in studies reliant on clinical identification of adult AKI or hospital coding data. Although an electronic alert system is Information Technology driven and therefore, lacks intelligence and clinical context, these data can be used to identify deficiencies in care, guide the development of appropriate intervention strategies, and provide a baseline against which the effectiveness of these interventions may be measured.

Background The impact of COVID-19 on physical and mental health, and employment following hospitalisation is poorly understood. Methods PHOSP-COVID is a multi-centre, UK, observational study of adults discharged from hospital with a clinical diagnosis of COVID-19 involving an assessment between two- and seven-months later including detailed symptom, physiological and biochemical testing. Multivariable logistic regression was performed for patient-perceived recovery with age, sex, ethnicity, body mass index (BMI), co-morbidities, and severity of acute illness as co-variates. Cluster analysis was performed using outcomes for breathlessness, fatigue, mental health, cognition and physical function. Findings We report findings of 1077 patients discharged in 2020, from the assessment undertaken a median 5 [IQR4 to 6] months later: 36% female, mean age 58 [SD 13] years, 69% white ethnicity, 27% mechanical ventilation, and 50% had at least two co-morbidities. At follow-up only 29% felt fully recovered, 20% had a new disability, and 19% experienced a health-related change in occupation. Factors associated with failure to recover were female, middle-age, white ethnicity, two or more co-morbidities, and more severe acute illness. The magnitude of the persistent health burden was substantial and weakly related to acute severity. Four clusters were identified with different severities of mental and physical health impairment: 1) Very severe (17%), 2) Severe (21%), 3) Moderate with cognitive impairment (17%), 4) Mild (46%), with 3%, 7%, 36% and 43% feeling fully recovered, respectively. Persistent systemic inflammation determined by C-reactive protein was related to cluster severity, but not acute illness severity. Interpretation We identified factors related to recovery from a hospital admission with COVID-19 and four different phenotypes relating to the severity of physical, mental, and cognitive health five months later. The implications for clinical care include the potential to stratify care and the need for a pro-active approach with wide-access to COVID-19 holistic clinical services. Funding: UKRI and NIHR