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Wrexham Maelor Hospital

Hospital / health systemWrexham, United Kingdom

Research output, citation impact, and the most-cited recent papers from Wrexham Maelor Hospital (United Kingdom). Aggregated across the NobleBlocks index of 300M+ scholarly works.

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1.9K
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Wrexham Maelor Hospital

Top-cited papers from Wrexham Maelor Hospital

Validation of a modified Early Warning Score in medical admissions
Christian P Subbe
2001· QJM1.8Kdoi:10.1093/qjmed/94.10.521

The Early Warning Score (EWS) is a simple physiological scoring system suitable for bedside application. The ability of a modified Early Warning Score (MEWS) to identify medical patients at risk of catastrophic deterioration in a busy clinical area was investigated. In a prospective cohort study, we applied MEWS to patients admitted to the 56-bed acute Medical Admissions Unit (MAU) of a District General Hospital (DGH). Data on 709 medical emergency admissions were collected during March 2000. Main outcome measures were death, intensive care unit (ICU) admission, high dependency unit (HDU) admission, cardiac arrest, survival and hospital discharge at 60 days. Scores of 5 or more were associated with increased risk of death (OR 5.4, 95%CI 2.8-10.7), ICU admission (OR 10.9, 95%CI 2.2-55.6) and HDU admission (OR 3.3, 95%CI 1.2-9.2). MEWS can be applied easily in a DGH medical admission unit, and identifies patients at risk of deterioration who require increased levels of care in the HDU or ICU. A clinical pathway could be created, using nurse practitioners and/or critical care physicians, to respond to high scores and intervene with appropriate changes in clinical management.

The U.K. Working Party's Diagnostic Criteria for Atopic Dermatitis..
Hywel C Williams, Peter Burney, Roderick J. Hay, Corey Archer +4 more
1994· British Journal of Dermatology1.3Kdoi:10.1111/j.1365-2133.1994.tb08530.x

A working party of 13 dermatologists, two family practitioners and a paediatrician was assembled, with the aim of developing a minimum list of reliable discriminators for atopic dermatitis. Each physician was asked to select 10 consecutive new cases of unequivocal mild to moderate atopic dermatitis and 10 controls with other inflammatory dermatoses. Each subject was examined by two independent observers, who were blind to the clinical diagnosis and study aim, with regard to 31 clinically useful diagnostic features for atopic dermatitis. Two hundred and twenty-four patients were studied (120 cases and 102 controls). Using the key physician's clinical diagnosis as a gold standard, the sensitivity and specificity of each of the 31 diagnostic criteria were tested. Using multiple logistic regression techniques, a minimum set of diagnostic criteria for atopic dermatitis was derived. These were: history of flexural involvement, history of a dry skin, onset under the age of 2, personal history of asthma, history of a pruritic skin condition, and visible flexural dermatitis. Adjustment for age, sex, region, social class and ethnic group did not alter the choice of final criteria. The discriminatory value of these criteria was also satisfactory when tested against a further sample of 150 patients drawn from the community, who did not have skin disease.

Mapping the human genetic architecture of COVID-19
COVID-19 Host Genetics Initiative, COVID-19 Host Genetics InitiativeLeadership, Mari Niemi, Juha Karjalainen +4 more
2021· Nature1.1Kdoi:10.1038/s41586-021-03767-x

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.

The Children's Dermatology Life Quality Index (CDLQI): initial validation and practical use
M.S. Lewis‐Jones, A.Y. Finlay
2010· British Journal of Dermatology1.1Kdoi:10.1111/j.1365-2133.1995.tb16953.x

Skin disease can cause severe disability and handicap in children. Measurement of the impact of skin disease on the quality of life is required to aid clinical decision‐making, for clinical research, for audit of paediatric dermatology services, and for political reasons, to aid arguments for more resources for the care of children with skin disease. Adult measures are inappropriate, as the lives of children differ markedly from those of adults. The purpose of this study was to create and initially validate a simple practical questionnaire for use in children. One hundred and sixty‐nine children, aged 3–16 years, attending a paediatric dermatology clinic, wrote down, with the help of their parents, all the ways in which their skin disease affected their lives. One hundred and eleven different aspects were identified; 10 questions were composed to cover these aspects, using a structure similar to the Adult Dermatology Life Quality Index. This draft questionnaire was piloted on two series, totalling 40 children, and minor alterations were made to improve clarity. The Children's Dermatology Life Quality Index (CDLQI) questionnaire (maximum score 30) was then given to a further 233 dermatology paediatric out‐patients (CDLQI mean = 5.1, SD = 4.9), 47 normal controls (mean 0.4, 0.7) and 55 control patients attending a general paediatric clinic (mean 0.7, 2.5). The CDLQI scores for eczema (mean = 7.7, 5.6, n = 47), psoriasis (5.4, 5.0, n = 25) and acne (5.7, 4.4, n = 40), were all highly significantly greater than for moles and naevi (2.3, 2.9, n = 29). The highest mean score was that for scabies (mean = 9.5, 10.5, n = 6). Overall, the highest scoring questions (each maximum score 3) related to symptoms (mean = 1.05, n = 233), feelings (0.90), swimming and sports (0.51), sleep (0.49) and treatment effects (0.47), with the question on effects on friendships (0.18) scoring least. Forty‐six additional patients completed the CDLQI on two occasions, with a 4‐day interval to check reliability of test‐retesting. The standard deviation of the differences between pairs (2.5) was substantially less than the standard deviation of the measurements themselves (before = 4.79, after = 5.08). confirming acceptable repeatability. This study has confirmed the major impact of widespread inflammatory skin disease, in particular atopic eczema, on the quality of life of children. Although further validation is required, the CLDQI provides a new technique for comparative purposes.

Is increased time to diagnosis and treatment in symptomatic cancer associated with poorer outcomes? Systematic review
Richard D Neal, Puvan Tharmanathan, B France, N Din +4 more
2015· British Journal of Cancer1.0Kdoi:10.1038/bjc.2015.48

BACKGROUND: It is unclear whether more timely cancer diagnosis brings favourable outcomes, with much of the previous evidence, in some cancers, being equivocal. We set out to determine whether there is an association between time to diagnosis, treatment and clinical outcomes, across all cancers for symptomatic presentations. METHODS: Systematic review of the literature and narrative synthesis. RESULTS: We included 177 articles reporting 209 studies. These studies varied in study design, the time intervals assessed and the outcomes reported. Study quality was variable, with a small number of higher-quality studies. Heterogeneity precluded definitive findings. The cancers with more reports of an association between shorter times to diagnosis and more favourable outcomes were breast, colorectal, head and neck, testicular and melanoma. CONCLUSIONS: This is the first review encompassing many cancer types, and we have demonstrated those cancers in which more evidence of an association between shorter times to diagnosis and more favourable outcomes exists, and where it is lacking. We believe that it is reasonable to assume that efforts to expedite the diagnosis of symptomatic cancer are likely to have benefits for patients in terms of improved survival, earlier-stage diagnosis and improved quality of life, although these benefits vary between cancers.

Effect of introducing the Modified Early Warning score on clinical outcomes, cardio‐pulmonary arrests and intensive care utilisation in acute medical admissions*
Christian P Subbe, R. G. Davies, Elizabeth M. Williams, Peter Rutherford +1 more
2003· Anaesthesia451doi:10.1046/j.1365-2044.2003.03258.x

The effects of introducing Modified Early Warning scores to identify medical patients at risk of catastrophic deterioration have not been examined. We prospectively studied 1695 acute medical admissions. All patients were scored in the admissions unit. Patients with a Modified Early Warning score > 4 were referred for urgent medical and critical care outreach team review. Data was compared with an observational study performed in the same unit during the proceeding year. There was no change in mortality of patients with low, intermediate or high Modified Early Warning scores. Rates of cardio-pulmonary arrest, intensive care unit or high dependency unit admission were similar. Data analysis confirmed respiratory rate as the best discriminator in identifying high-risk patient groups. The therapeutic interventions performed in response to abnormal scores were not assessed. We are convinced that the Modified Early Warning score is a suitable scoring tool to identify patients at risk. However, outcomes in medical emergency admissions are influenced by a multitude of factors and so it may be difficult to demonstrate the score's benefit without further standardizing the response to abnormal values.

The family impact of childhood atopic dermatitis: the Dermatitis Family Impact questionnaire
Lawson, Lewis-Jones, A.Y. Finlay, Reid +1 more
1998· British Journal of Dermatology436doi:10.1046/j.1365-2133.1998.02034.x

Little information is available about the effect of childhood atopic dermatitis (AD) on family function. The aim of this study was to identify the areas of family life most affected and their perceived importance. Intensive qualitative interviews with 34 families were conducted and 11 basic problem areas were identified. A detailed questionnaire was prepared, part of which addressed the perceived importance of particular issues using the framework of multi-attribute utility theory. The results from using this questionnaire in 41 families were analysed and a shorter 10-question one-page Dermatitis Family Impact (DFI) questionnaire designed (maximum score = 30). In affected families the mean DFI score was 9.6 +/- 7.0 (range 0-27, n = 56) and in unaffected families the mean score was 0.4 +/- 0.9 (range 0-3, n = 26, P < 0.0001). The DFI could potentially be used as an extra measure in clinical studies, or to help guide appropriate management of AD.

Total serum homocysteine in senile dementia of Alzheimer type
Andrew McCaddon, Gareth Davies, Peter Hudson, Stephen Tandy +1 more
1998· International Journal of Geriatric Psychiatry401doi:10.1002/(sici)1099-1166(199804)13:4<235::aid-gps761>3.0.co;2-8

OBJECTIVE: The main hypothesis was that subtle vitamin B12 deficiencies occur more commonly in senile dementia of Alzheimer type (SDAT) that in healthy elderly individuals, and may be revealed by elevated total serum homocysteine (tHcy). A subsidiary hypothesis was that such deficiencies would be nutritionally independent as determined by retinol binding protein (RBP). DESIGN: A prospective case-controlled survey. SETTING: A Welsh urban psychogeriatric assessment centre and local general practice. PATIENTS: Thirty patients, aged 65 or over, seen consecutively in 1994 with features compatible with DSM-III-R criteria for primary degenerative dementia of Alzheimer type and 30 cognitively intact age-matched control subjects. MEASURES: Diagnosis was assessed using the CAMDEX. Cognitive scores were evaluated with the CAMCOG scale for patients and MMSE scores for control subjects. THcy was measured using high performance liquid chromatography (HPLC), and RBP assayed by a radial immunodiffusion method. RESULTS: Patients had a highly significant elevation of tHcy compared with control (p < 0.0001). Multiple regression highlighted the interrelated effects of tHcy and total serum cobalamin on cognitive scores. RBP did not differ between groups. Macrocytosis was absent, and neutrophil hypersegmentation uncommon, in hyperhomocysteinaemic patients. CONCLUSIONS: SDAT patients have significantly elevated tHcy. This is independent of RBP determined nutritional status. 'Classical' haematological changes of cobalamin or folate deficiency are poor predictors of tHcy in these patients. Aberrant cobalamin tissue delivery appears to contribute to SDAT cognitive decline. Relative contributions of other tHcy determinants require further investigation.

Toxic bile acids in gastro-oesophageal reflux disease: influence of gastric acidity
D Nehra, Pauline Howell, C P Williams, J K Pye +1 more
1999· Gut393doi:10.1136/gut.44.5.598

BACKGROUND: Bile acid toxicity has been shown in the gastric, colonic, and hepatic tissues; the effect on oesophageal mucosa is less well known. AIMS: To determine the spectrum of bile acids refluxing in patients with gastro-oesophageal reflux disease and its relation to oesophageal pH using a new technique of combined oesophageal aspiration and pH monitoring. METHODS: Ten asymptomatic subjects and 30 patients with symptoms of gastro-oesophageal reflux disease (minimal mucosal injury, erosive oesophagitis (grade 2 or 3 Savary-Miller), Barrett's oesophagus/stricture; n=10 in each group) underwent 15 hour continuous oesophageal aspiration with simultaneous pH monitoring. Bile acid assay of the oesophageal samples was performed using modified high performance liquid chromatography. RESULTS: The peak bile acid concentration and DeMeester acid scores were significantly higher in the patients with oesophagitis (median bile acid concentration 124 micromol/l; acid score 20.2) and Barrett's oesophagus/stricture (181 micromol/l; 43. 3) than patients with minimal injury (14 micromol/l; 12.5) or controls (0 micromol/l; 11.1). The predominant bile acids detected were cholic, taurocholic, and glycocholic acids but there was a significantly greater proportion of secondary bile acids, deoxycholic and taurodeoxycholic acids, in patients with erosive oesophagitis and Barrett's oesophagus/stricture. Although bile acid reflux episodes occurred at variable pH, a temporal relation existed between reflux of taurine conjugates and oesophageal acid exposure (r=0.58, p=0.009). CONCLUSION: Toxic secondary bile acid fractions have been detected in patients with extensive mucosal damage. Mixed reflux is more harmful than acid reflux alone with possible toxic synergism existing between the taurine conjugates and acid.

Survival of Functionally Anuric Patients on Automated Peritoneal Dialysis
Edwina A. Brown, Simon Davies, Peter Rutherford, Frédérique Meeus +4 more
2003· Journal of the American Society of Nephrology380doi:10.1097/01.asn.0000092146.67909.e2

The European APD Outcome Study (EAPOS) is a 2-yr, prospective, multicenter study of the feasibility and clinical outcomes of automated peritoneal dialysis (APD) in anuric patients. A total of 177 patients were enrolled with a median age of 54 yr (range, 21 to 91 yr). Previous median total time on dialysis was 38 mo (range, 1.6 to 259 mo), and 36% of patients had previously been on hemodialysis for >90 d. Diabetes and cardiovascular disease were present in 17% and 46% of patients, respectively. The APD prescription was adjusted at physician discretion to aim for creatinine clearance (Ccrea) >/=60 L/wk per 1.73 m(2) and ultrafiltration (UF) >/=750 ml/24 h during the first 6 mo. Baseline solute transport status (D/P) was determined by peritoneal equilibration test. At 1 yr, 78% and 74% achieved Ccrea and UF targets, respectively; median drained dialysate volume was 16.2 L/24 h with 50% of patients using icodextrin. Baseline D/P was not related to UF achieved at 1 yr. At 2 yr, patient survival was 78% and technique survival was 62%. Baseline predictors of poor survival were age (>65 yr; P = 0.006), nutritional status (Subjective Global Assessment grade C; P = 0.009), diabetic status (P = 0.008), and UF (<750 ml/24 h; P = 0.047). Time-averaged analyses showed that age, Subjective Global Assessment grade C and diabetic status predicted patient survival with UF the next most significant variable (risk ratio, 0.5/L per d; P = 0.097). Baseline Ccrea, time-averaged Ccrea, and baseline D/P had no effect on patient or technique survival. This study shows that anuric patients can successfully use APD. Baseline UF, not Ccrea or membrane permeability, is associated with patient survival.

Whole-genome sequencing reveals host factors underlying critical COVID-19
Athanasios Kousathanas, Erola Pairo‐Castineira, Konrad Rawlik, A. Stuckey +4 more
2022· Nature351doi:10.1038/s41586-022-04576-6

after infection with SARS-CoV-2. The GenOMICC (Genetics of Mortality in Critical Care) study enables the comparison of genomes from individuals who are critically ill with those of population controls to find underlying disease mechanisms. Here we use whole-genome sequencing in 7,491 critically ill individuals compared with 48,400 controls to discover and replicate 23 independent variants that significantly predispose to critical COVID-19. We identify 16 new independent associations, including variants within genes that are involved in interferon signalling (IL10RB and PLSCR1), leucocyte differentiation (BCL11A) and blood-type antigen secretor status (FUT2). Using transcriptome-wide association and colocalization to infer the effect of gene expression on disease severity, we find evidence that implicates multiple genes-including reduced expression of a membrane flippase (ATP11A), and increased expression of a mucin (MUC1)-in critical disease. Mendelian randomization provides evidence in support of causal roles for myeloid cell adhesion molecules (SELE, ICAM5 and CD209) and the coagulation factor F8, all of which are potentially druggable targets. Our results are broadly consistent with a multi-component model of COVID-19 pathophysiology, in which at least two distinct mechanisms can predispose to life-threatening disease: failure to control viral replication; or an enhanced tendency towards pulmonary inflammation and intravascular coagulation. We show that comparison between cases of critical illness and population controls is highly efficient for the detection of therapeutically relevant mechanisms of disease.

International genome-wide meta-analysis identifies new primary biliary cirrhosis risk loci and targetable pathogenic pathways
Heather J. Cordell, Younghun Han, George Mells, Yafang Li +4 more
2015· Nature Communications311doi:10.1038/ncomms9019

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.

Cyclosporin for severe childhood atopic dermatitis: short course versus continuous therapy
John Harper, I. Ahmed, G R Barclay, M Lacour +4 more
2000· British Journal of Dermatology283doi:10.1046/j.1365-2133.2000.03241.x

Cyclosporin (CyA) has been shown to be highly effective and well tolerated in the short-term treatment of severe childhood atopic dermatitis; however, there is limited experience in its longer-term use. The aim of this study was to compare multiple short courses of CyA with continuous therapy for 1 year, with respect to efficacy, safety, tolerability and quality of life. Children aged 2-16 years, with a diagnosis of severe atopic dermatitis refractory to topical steroid therapy, were randomly assigned to receive short course therapy (multiple courses of 12 weeks) or continuous therapy. The starting dose and maximum dose for all patients was 5 mg/kg per day. Disease activity was monitored using the Six Area Six Sign Atopic Dermatitis score and the 'Rule of Nines' area score. Pruritus, sleep disturbance and irritability were measured using visual analogue scales, and topical therapy was monitored. Safety measurements included monitoring of serum creatinine, blood pressure and adverse events. Forty patients were included in the efficacy analysis, 21 of whom were randomized to the short course group (of whom six were withdrawn) and 19 to the continuous group (of whom five were withdrawn). Significant improvements were seen in all efficacy parameters at every time-point. There were no significant differences between groups, although the improvement was more consistent in the continuous arm. In the short course arm, 7 out of 21 patients could be managed by at least two short courses. The remaining 14 patients includes 12 who could not be controlled by at least two short courses, one patient who failed to return after week 12 and another patient who was withdrawn at week 4 due to an adverse event. Quality of life improved for both the children and their families. Tolerability was considered good or very good in at least 80% of the patients at week 12 and at the end of the study. No clinically significant change was seen in mean serum creatinine and no change was seen in mean blood pressure in either group. CyA is effective in controlling severe atopic dermatitis in children over a 1-year period and is well tolerated. More consistent control is achieved with continuous treatment; however, short course therapy was adequate for some patients, indicating that treatment should be tailored to the individual patient's needs. Short course treatment may produce prolonged remission in some cases and reduce the cumulative exposure to the drug.

Levetiracetam versus phenytoin for second-line treatment of paediatric convulsive status epilepticus (EcLiPSE): a multicentre, open-label, randomised trial
Mark D Lyttle, Naomi Rainford, Carrol Gamble, Shrouk Messahel +4 more
2019· The Lancet252doi:10.1016/s0140-6736(19)30724-x

BACKGROUND: Phenytoin is the recommended second-line intravenous anticonvulsant for treatment of paediatric convulsive status epilepticus in the UK; however, some evidence suggests that levetiracetam could be an effective and safer alternative. This trial compared the efficacy and safety of phenytoin and levetiracetam for second-line management of paediatric convulsive status epilepticus. METHODS: This open-label, randomised clinical trial was undertaken at 30 UK emergency departments at secondary and tertiary care centres. Participants aged 6 months to under 18 years, with convulsive status epilepticus requiring second-line treatment, were randomly assigned (1:1) using a computer-generated randomisation schedule to receive levetiracetam (40 mg/kg over 5 min) or phenytoin (20 mg/kg over at least 20 min), stratified by centre. The primary outcome was time from randomisation to cessation of convulsive status epilepticus, analysed in the modified intention-to-treat population (excluding those who did not require second-line treatment after randomisation and those who did not provide consent). This trial is registered with ISRCTN, number ISRCTN22567894. FINDINGS: Between July 17, 2015, and April 7, 2018, 1432 patients were assessed for eligibility. After exclusion of ineligible patients, 404 patients were randomly assigned. After exclusion of those who did not require second-line treatment and those who did not consent, 286 randomised participants were treated and had available data: 152 allocated to levetiracetam, and 134 to phenytoin. Convulsive status epilepticus was terminated in 106 (70%) children in the levetiracetam group and in 86 (64%) in the phenytoin group. Median time from randomisation to cessation of convulsive status epilepticus was 35 min (IQR 20 to not assessable) in the levetiracetam group and 45 min (24 to not assessable) in the phenytoin group (hazard ratio 1·20, 95% CI 0·91-1·60; p=0·20). One participant who received levetiracetam followed by phenytoin died as a result of catastrophic cerebral oedema unrelated to either treatment. One participant who received phenytoin had serious adverse reactions related to study treatment (hypotension considered to be immediately life-threatening [a serious adverse reaction] and increased focal seizures and decreased consciousness considered to be medically significant [a suspected unexpected serious adverse reaction]). INTERPRETATION: Although levetiracetam was not significantly superior to phenytoin, the results, together with previously reported safety profiles and comparative ease of administration of levetiracetam, suggest it could be an appropriate alternative to phenytoin as the first-choice, second-line anticonvulsant in the treatment of paediatric convulsive status epilepticus. FUNDING: National Institute for Health Research Health Technology Assessment programme.

British Association of Dermatologists’ guidelines for the management of pemphigus vulgaris 2017
Kristyn Harman, D. Brown, L.S. Exton, Richard Groves +4 more
2017· British Journal of Dermatology247doi:10.1111/bjd.15930

Plain language summary available online

Cardiac Rehabilitation Availability and Density around the Globe
Karam Turk-Adawi, Marta Supervía, Francisco López-Jiménez, Ella Pesah +4 more
2019· EClinicalMedicine233doi:10.1016/j.eclinm.2019.06.007

Background Despite the epidemic of cardiovascular disease and the benefits of cardiac rehabilitation (CR), availability is known to be insufficient, although this is not quantified. This study ascertained CR availability, volumes and its drivers, and density. Methods A survey was administered to CR programs globally. Cardiac associations and local champions facilitated program identification. Factors associated with volumes were assessed using generalized linear mixed models, and compared by World Health Organization region. Density (i.e. annual ischemic heart disease [IHD] incidence estimate from Global Burden of Disease study divided by national CR capacity) was computed. Findings CR was available in 111/203 (54.7%) countries; data were collected in 93 (83.8% country response; N = 1082 surveys, 32.1% program response rate). Availability by region ranged from 80.7% of countries in Europe, to 17.0% in Africa (p < .001). There were 5753 programs globally that could serve 1,655,083 patients/year, despite an estimated 20,279,651 incident IHD cases globally/year. Volume was significantly greater where patients were systematically referred (odds ratio [OR] = 1.36, 95% confidence interval [CI] = 1.35–1.38) and programs offered alternative models (OR = 1.05, 95%CI = 1.04–1.06), and significantly lower with private (OR = .92, 95%CI = .91–.93) or public (OR = .83, 95%CI = .82–84) funding compared to hybrid sources. Median capacity (i.e., number of patients a program could serve annually) was 246/program (Q25-Q75 = 150–390). The absolute density was one CR spot per 11 IHD cases in countries with CR, and 12 globally. Interpretation CR is available in only half of countries globally. Where offered, capacity is grossly insufficient, such that most patients will not derive the benefits associated with participation.

GWAS and meta-analysis identifies 49 genetic variants underlying critical COVID-19
Erola Pairo‐Castineira, Konrad Rawlik, Andrew D. Bretherick, Ting Qi +4 more
2023· Nature218doi:10.1038/s41586-023-06034-3

Abstract Critical illness in COVID-19 is an extreme and clinically homogeneous disease phenotype that we have previously shown 1 to be highly efficient for discovery of genetic associations 2 . Despite the advanced stage of illness at presentation, we have shown that host genetics in patients who are critically ill with COVID-19 can identify immunomodulatory therapies with strong beneficial effects in this group 3 . Here we analyse 24,202 cases of COVID-19 with critical illness comprising a combination of microarray genotype and whole-genome sequencing data from cases of critical illness in the international GenOMICC (11,440 cases) study, combined with other studies recruiting hospitalized patients with a strong focus on severe and critical disease: ISARIC4C (676 cases) and the SCOURGE consortium (5,934 cases). To put these results in the context of existing work, we conduct a meta-analysis of the new GenOMICC genome-wide association study (GWAS) results with previously published data. We find 49 genome-wide significant associations, of which 16 have not been reported previously. To investigate the therapeutic implications of these findings, we infer the structural consequences of protein-coding variants, and combine our GWAS results with gene expression data using a monocyte transcriptome-wide association study (TWAS) model, as well as gene and protein expression using Mendelian randomization. We identify potentially druggable targets in multiple systems, including inflammatory signalling ( JAK1 ), monocyte–macrophage activation and endothelial permeability ( PDE4A ), immunometabolism ( SLC2A5 and AK5 ), and host factors required for viral entry and replication ( TMPRSS2 and RAB2A ).

Comparison of cancer diagnostic intervals before and after implementation of NICE guidelines: analysis of data from the UK General Practice Research Database
Richard D Neal, N Din, William Hamilton, Obioha C. Ukoumunne +3 more
2013· British Journal of Cancer212doi:10.1038/bjc.2013.791

BACKGROUND: The primary aim was to use routine data to compare cancer diagnostic intervals before and after implementation of the 2005 NICE Referral Guidelines for Suspected Cancer. The secondary aim was to compare change in diagnostic intervals across different categories of presenting symptoms. METHODS: Using data from the General Practice Research Database, we analysed patients with one of 15 cancers diagnosed in either 2001-2002 or 2007-2008. Putative symptom lists for each cancer were classified into whether or not they qualified for urgent referral under NICE guidelines. Diagnostic interval (duration from first presented symptom to date of diagnosis in primary care records) was compared between the two cohorts. RESULTS: In total, 37,588 patients had a new diagnosis of cancer and of these 20,535 (54.6%) had a recorded symptom in the year prior to diagnosis and were included in the analysis. The overall mean diagnostic interval fell by 5.4 days (95% CI: 2.4-8.5; P<0.001) between 2001-2002 and 2007-2008. There was evidence of significant reductions for the following cancers: (mean, 95% confidence interval) kidney (20.4 days, -0.5 to 41.5; P=0.05), head and neck (21.2 days, 0.2-41.6; P=0.04), bladder (16.4 days, 6.6-26.5; P≤0.001), colorectal (9.0 days, 3.2-14.8; P=0.002), oesophageal (13.1 days, 3.0-24.1; P=0.006) and pancreatic (12.6 days, 0.2-24.6; P=0.04). Patients who presented with NICE-qualifying symptoms had shorter diagnostic intervals than those who did not (all cancers in both cohorts). For the 2007-2008 cohort, the cancers with the shortest median diagnostic intervals were breast (26 days) and testicular (44 days); the highest were myeloma (156 days) and lung (112 days). The values for the 90th centiles of the distributions remain very high for some cancers. Tests of interaction provided little evidence of differences in change in mean diagnostic intervals between those who did and did not present with symptoms specifically cited in the NICE Guideline as requiring urgent referral. CONCLUSION: We suggest that the implementation of the 2005 NICE Guidelines may have contributed to this reduction in diagnostic intervals between 2001-2002 and 2007-2008. There remains considerable scope to achieve more timely cancer diagnosis, with the ultimate aim of improving cancer outcomes.

Homocysteine and Cognitive Decline in Healthy Elderly
Andrew McCaddon, Peter Hudson, Gareth Davies, Alan Hughes +2 more
2001· Dementia and Geriatric Cognitive Disorders210doi:10.1159/000051275

Serum homocysteine is increased, and correlates inversely with cognitive scores, in Alzheimer's disease (AD), vascular dementia and "age-associated memory impairment". Elevated levels might signal accelerated cognitive decline, although this remains to be established. We therefore repeated Mini-Mental State Examinations, together with additional ADAS-Cog assessments, in 32 healthy elderly individuals to determine whether prior homocysteine levels predicted cognitive changes over a 5-year period. Homocysteine predicted follow-up cognitive scores and rate of decline in cognitive performance independently of age, sex, education, renal function, vitamin B status, smoking and hypertension (p < 0.001). Homocysteine predicted word recall (p = 0.01), orientation (p = 0.02) and constructional praxis scores (p < 0.0001). One subject, with the second highest initial homocysteine, had developed probable AD at follow-up. Fasting total serum homocysteine appears to be an independent predictor of cognitive decline in healthy elderly and exerts a maximal effect on spatial copying skills.

Antipsychotic treatment of primary delusional parasitosis
Peter Lepping, Ian Russell, Roland W. Freudenmann
2007· The British Journal of Psychiatry193doi:10.1192/bjp.bp.106.029660

BACKGROUND: Little is known about the treatment of delusional parasitosis with typical and atypical antipsychotics. AIMS: To evaluate the effectiveness of typical and atypical antipsychotics in primary delusional parasitosis (delusional disorder, somatic type). METHOD: A systematic review was conducted. RESULTS: No randomised trials were found and hence we collected the best evidence from 16 other trials and case reports, separating primary from other forms of delusional parasitosis. Studies using typical antipsychotics showed partial or full remission in between 60 and 100% of patients. Analysis of selected patients with primary delusional parasitosis showed that typical and atypical antipsychotics were effective in the majority, but that remission rates did not differ significantly between typical and atypical antipsychotics. CONCLUSIONS: In the absence of controlled trials there is limited evidence that antipsychotics are effective in primary delusional parasitosis. Rigorous studies are needed to evaluate their effectiveness and to compare typical and atypical antipsychotics directly.