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Abstract Background Neonatal mortality remains unacceptably high. Many studies successful at reducing neonatal mortality have failed to realise similar gains at scale. Effective implementation and scale-up of interventions designed to tackle neonatal mortality is a global health priority. Multifaceted programmes targeting the continuum of neonatal care, with sustainability and scalability built into the design, can provide practical insights to solve this challenge. Cambodia has amongst the highest neonatal mortality rates in South-East Asia, with rural areas particularly affected. The primary objective of this study is the design, implementation, and assessment of the Saving Babies’ Lives programme, a package of interventions designed to reduce neonatal mortality in rural Cambodia. Methods This study is a five-year stepped-wedge cluster-randomised trial conducted in a rural Cambodian province with an estimated annual delivery rate of 6615. The study is designed to implement and evaluate the Saving Babies’ Lives programme, which is the intervention. The Saving Babies’ Lives programme is an iterative package of neonatal interventions spanning the continuum of care and integrating into the existing health system. The Saving Babies’ Lives programme comprises two major components: participatory learning and action with community health workers, and capacity building of primary care facilities involving facility-based mentorship. Standard government service continues in control arms. Data collection covering the whole study area includes surveillance of all pregnancies, verbal and social autopsies, and quality of care surveys. Mixed methods data collection supports iteration of the complex intervention, and facilitates impact, outcome, process and economic evaluation. Discussion Our study uses a robust study design to evaluate and develop a holistic, innovative, contextually relevant and sustainable programme that can be scaled-up to reduce neonatal mortality. Trial registration ClinicalTrials.gov: NCT04663620 . Registered on 11th December 2020, retrospectively registered.

Objectives Neonatal mortality remains persistently high in low-income and middle-income countries. In Cambodia, there is a paucity of data on the perception of neonatal health and care-seeking behaviours at the community level. This study aimed to identify influencers of neonatal health and healthcare-seeking behaviour in a rural Cambodian province.Design A qualitative study using focus group discussions and thematic content analysis.Setting Four health centres in a rural province of Northern Cambodia.Participants Twenty-four focus group discussions were conducted with 85 community health workers in 2019.Results Community health workers recognised an improvement in neonatal health over time. Key influencers to neonatal health were identified as knowledge, sociocultural behaviours, finances and transport, provision of care and healthcare engagement. Most influencers acted as both barriers and facilitators, with the exception of finances and transport that only acted as a barrier, and healthcare engagement that acted as a facilitator.Conclusion Understanding health influencers and care-seeking behaviours is recognised to facilitate appropriate community health programmes. Key influencers and care-seeking behaviours have been identified from rural Cambodia adding to the current literature. Where facilitators have already been established, they should be used as building blocks for continued change.

The aim of this review was to determine the factors that impact on doctors' management of patients with acute low back pain. A methodological assessment of databases (Medline, EMBASE, Psychinfo, BIOSIS, CINAHL, and the Cochrane Central Register of Controlled Trials) identified papers which were screened for inclusion criteria by two independent reviewers. Data were extracted from accepted papers, and the internal validity and strength of the evidence were determined using valid and reliable scales. The search generated a total of 28 papers [quantitative (n=27), qualitative (n=1) methodologies]. Themes were identified from the accepted papers: education (n=18), knowledge of clinical guidelines and impact on management (n=7), and doctors' demographics (n=4). There was consistent evidence that doctors did not adhere to clinical guidelines when performing a spinal assessment. There was inconsistent evidence that education increased adherence with acute LBP guideline recommendations in terms of referral rates to physiotherapy, for investigations, to secondary care and for maintaining patients at work. Strategies to address the factors impacting on doctors' management of acute LBP are required; these would lead to improvement in patient outcomes and reduce healthcare costs. [ABSTRACT FROM AUTHOR]

BACKGROUND: Homozygotes for the thermolabile mutation (TT genotype) of the methylenetetrahydrofolate reductase (MTHFR; EC 1.5.1.20) enzyme have elevated plasma concentrations of the cardiovascular disease risk factor homocysteine, particularly if folate depleted. OBJECTIVE: We examined the relations between thermolabile MTHFR, plasma homocysteine, plasma folate, and vascular disease risk. DESIGN: This was a case-control comparison in 711 vascular disease cases and 747 controls from 9 European countries. RESULTS: The TT genotype was associated with higher homocysteine and lower plasma folate than the CC and CT genotypes in both cases and controls and a nonsignificant increase in vascular disease risk (1.26; 95% CI: 0.88, 1.81; P = 0.20). The frequency of the TT genotype in cases was not significantly different from that in controls (12.8% compared with 10.8%). After adjustment for traditional risk factors, the TT genotype was associated with an odds ratio of 1.48 (1.0, 2.20) for risk of vascular disease. This risk was attenuated after further adjustment for homocysteine. In subgroups with homocysteine concentrations >or= 9 micro mol/L, risk tended to be higher in CC than in TT subjects. However, CC subjects were characterized by a higher prevalence of the conventional risk factors associated with both elevated plasma homocysteine and serum creatinine. After adjustment, the risk of vascular disease associated with each genotype was not significantly different. CONCLUSIONS: There was a strong graded association between homocysteine and vascular risk in all genotypes. MTHFR genotype is a key determinant of plasma total homocysteine concentrations. The initially nonsignificant risk estimate associated with the TT genotype was strengthened after adjustment for conventional cardiovascular disease risk factors but was attenuated after adjustment for plasma folate and total homocysteine. The modest risk increase conferred by the TT genotype is mediated mainly by increased total homocysteine and low plasma folate concentrations. [ABSTRACT FROM AUTHOR]

Using data from a recent case-control study, a woman's risk of having a child with a neural tube defect (NTD) was found to be associated with early pregnancy red cell folate levels in a continuous dose-response relationship. These findings were used to calculate the reduction in NTD cases that would be expected under two different strategies to raise folate levels. Targeting high-risk individuals has a small effect on the population prevalence but can substantially change an individual's risk. Targeting the population produces a small change in individual risk but has a large effect on the population prevalence. Supplementation of high-risk women would be the most efficient method to implement the high-risk strategy, while food fortification would be preferable for the population approach. The current guidelines for the prevention of NTD are for an increased folic acid intake of 0.4 mg per day. This would result in a 48% reduction in NTDs, which may be near optimal. The two intervention strategies should be considered complementary in prevention of NTDs. [ABSTRACT FROM AUTHOR]

Abstract Background Suicidal behaviour is known to aggregate in families. Patients with psychiatric disorders are at higher risk for suicide attempts (SA), however protective and risk genetic variants for suicide appear to be independent of underlying psychiatric disorders. Here we investigate genetic variants in genes important for neurobiological pathways linked to suicidal behaviour and/or associated endophenotypes, for association with SA among patients with co-existing psychiatric illness. Selected gene-gene and gene-environment interactions were also tested. Methods DNA was obtained from bloods of 159 patients (76 suicide attempters and 83 non-attempters), who were profiled for DSM-IV Axis I psychiatric diagnosis. Twenty-eight single nucleotide polymorphisms (SNPs) from 18 candidate genes (COMT, 5-HT2A, 5-HT1A, 5-HTR1B, TPH1, MAO-A, TPH2, DBH, CNR1, BDNF, ABCG1, GABRA5, GABRG2, GABRB2, SLC1A2, SLC1A3, NTRK2, CRHR1) were genotyped. Genotyping was performed by KBioscience. Tests of association between genetic variants and SA were conducted using Chi squared and Armitage Trend tests. Binary logistical regression analyses were performed to evaluate the contribution of individual genetic variants to the prediction of SA, and to examine SNPs for potential gene-gene and gene-environment interactions. Results Our analysis identified 4 SNPs (rs4755404, rs2269272, rs6296 and rs1659400), which showed evidence of association with SA compared to a non-attempter control group. We provide evidence of a 3-locus gene-gene interaction, and a putative gene-environment interaction, whereby genetic variation at the NTRK2 locus may moderate the risk associated with history of childhood abuse. Conclusion Preliminary findings suggest that allelic variability in SLC1A2/3, 5-HTR1B and NTRK2 may be relevant to the underlying diathesis for suicidal acts.

Abstract Background Genetic factors are known to contribute to COPD susceptibility and these factors are not fully understood. Conflicting results have been reported for many genetic studies of candidate genes based on their role in the disease. Genome-wide association studies in combination with expression profiling have identified a number of new candidates including IREB2. A meta-analysis has implicated transforming growth factor beta-1 (TGFbeta1) as a contributor to disease susceptibility. Methods We have examined previously reported associations in both genes in a collection of 1017 white COPD patients and 912 non-diseased smoking controls. Genotype information was obtained for seven SNPs in the IREB2 gene, and for four SNPs in the TGFbeta1 gene. Allele and genotype frequencies were compared between COPD cases and controls, and odds ratios were calculated. The analysis was adjusted for age, sex, smoking and centre, including interactions of age, sex and smoking with centre. Results Our data replicate the association of IREB2 SNPs in association with COPD for SNP rs2568494, rs2656069 and rs12593229 with respective adjusted p-values of 0.0018, 0.0039 and 0.0053. No significant associations were identified for TGFbeta1. Conclusions These studies have therefore confirmed that the IREB2 locus is a contributor to COPD susceptibility and suggests a new pathway in COPD pathogenesis invoking iron homeostasis.

Abstract Background Sleep disturbance is becoming increasingly recognised as a clinically important symptom in people with chronic low back pain (CLBP, low back pain >12 weeks), associated with physical inactivity and depression. Current research and international clinical guidelines recommend people with CLBP assume a physically active role in their recovery to prevent chronicity, but the high prevalence of sleep disturbance in this population may be unknowingly limiting their ability to participate in exercise-based rehabilitation programmes and contributing to poor outcomes. There is currently no knowledge concerning the effectiveness of physiotherapy on sleep disturbance in people with chronic low back pain and no evidence of the feasibility of conducting randomized controlled trials that comprehensively evaluate sleep as an outcome measure in this population. Methods/Design This study will evaluate the feasibility of a randomised controlled trial (RCT), exploring the effects of three forms of physiotherapy (supervised general exercise programme, individualized walking programme and usual physiotherapy, which will serve as the control group) on sleep quality in people with chronic low back pain. A presenting sample of 60 consenting patients will be recruited in the physiotherapy department of Beaumont Hospital, Dublin, Ireland, and randomly allocated to one of the three groups in a concealed manner. The main outcomes will be sleep quality (self-report and objective measurement), and self-reported functional disability, pain, quality of life, fear avoidance, anxiety and depression, physical activity, and patient satisfaction. Outcome will be evaluated at baseline, 3 months and 6 months. Qualitative telephone interviews will be embedded in the research design to obtain feedback from a sample of participants' about their experiences of sleep monitoring, trial participation and interventions, and to inform the design of a fully powered future RCT. Planned analysis will explore trends in the data, effect sizes and clinically important effects (quantitative data), and thematic analysis (qualitative data). Discussion This study will evaluate the feasibility of a randomised controlled trial exploring the effects of three forms of physiotherapy (supervised general exercise programme, individualized walking programme and usual physiotherapy, which will serve as the control group) on sleep quality in people with chronic low back pain. Trial Registration Current controlled trial ISRCTN54009836

Abstract Background Genetic factors play a role in chronic obstructive pulmonary disease (COPD) but are poorly understood. A number of candidate genes have been proposed on the basis of the pathogenesis of COPD. These include the matrix metalloproteinase (MMP) genes which play a role in tissue remodelling and fit in with the protease - antiprotease imbalance theory for the cause of COPD. Previous genetic studies of MMPs in COPD have had inadequate coverage of the genes, and have reported conflicting associations of both single nucleotide polymorphisms (SNPs) and SNP haplotypes, plausibly due to under-powered studies. Methods To address these issues we genotyped 26 SNPs, providing comprehensive coverage of reported SNP variation, in MMPs- 1, 9 and 12 from 977 COPD patients and 876 non-diseased smokers of European descent and evaluated their association with disease singly and in haplotype combinations. We used logistic regression to adjust for age, gender, centre and smoking history. Results Haplotypes of two SNPs in MMP-12 (rs652438 and rs2276109), showed an association with severe/very severe disease, corresponding to GOLD Stages III and IV. Conclusions Those with the common A-A haplotype for these two SNPs were at greater risk of developing severe/very severe disease (p = 0.0039) while possession of the minor G variants at either SNP locus had a protective effect (adjusted odds ratio of 0.76; 95% CI 0.61 - 0.94). The A-A haplotype was also associated with significantly lower predicted FEV1 (42.62% versus 44.79%; p = 0.0129). This implicates haplotypes of MMP-12 as modifiers of disease severity.

Abstract Background Ireland is an example of a country that has extensive voluntary fortification with folic acid. After a public consultation process, in 2006, the Food Safety Authority in Ireland FSAI 1 recommended mandatory fortification. However due to safety considerations this decision is now on hold. Before mandatory fortification goes ahead, existing levels of unmetabolised folic acid and their anticipated increase after fortification needs investigation because of the potential of folic acid to mask pernicious anaemia and possibly accelerate the growth of existing cancers. The aim of this study was to examine the levels of circulatory unmetabolised folic acid in Irish adults (both fasted and un-fasted) and new-born infants (fasted) before the proposed implementation of mandatory folic acid fortification. A secondary aim was to predict the increase in circulatory unmetabolised folic acid levels after fortification. Methods Study 1. Setting: Irish Blood Transfusion Service (IBTS). Whole blood samples were collected from blood donors (n = 50) attending for routine blood donation sessions (representing the general population). Subjects were not fasted prior to sampling. Study 2. Setting: Coombe Women's and Infant's University Hospital, Dublin. Whole blood samples were collected by venipuncture from mothers (n = 20), and from their infant's umbilical-cords (n = 20) immediately after caesarean section. All women had been fasted for at least 8 hours prior to the surgery. A questionnaire on habitual and recent dietary intakes of folic acid was administered by an interviewer to all subjects. The data collection period was February to April 2006. Serum samples were analysed for plasma folate, plasma folic acid and red cell folate. Results Blood Donor Group: Circulatory unmetabolised folic acid was present in 18 out of 20 mothers (fasted) (CI: 68.3%–99.8%) comprising 1.31% of total plasma folate, 17 out of 20 babies (fasted) (CI: 62.1%–96.8%), and 49 out of 50 blood donors (unfasted) (CI: 88.0%–99.9%), comprising 2.25% of total plasma folate, Conclusion While the levels of circulatory unmetabolised folic acid reported are low, it is persistently present in women immediately after caesarean section who were fasting indicating that there would be a constant/habitual exposure of existing tumours to folic acid, with the potential for accelerated growth. Mandatory fortification might exacerbate this. This has implications for those with responsibility for drafting legislating in this area.

Abstract Background Chronic low back pain (CLBP) is a persistent disabling condition with rising significant healthcare, social and economic costs. Current research supports the use of exercise-based treatment approaches that encourage people with CLBP to assume a physically active role in their recovery. While international clinical guidelines and systematic reviews for CLBP support supervised group exercise as an attractive first-line option for treating large numbers of CLBP patients at low cost, barriers to their delivery include space and time restrictions in healthcare settings and poor patient attendance. The European Clinical Guidelines have identified the need for research in the use of brief/minimal contact self-activation interventions that encourage participation in physical activity for CLBP. Walking may be an ideally suited form of individualized exercise prescription as it is easy to do, requires no special skills or facilities, and is achievable by virtually all ages with little risk of injury, but its effectiveness for LBP is unproven. Methods and design This study will be an assessor-blinded randomized controlled trial that will investigate the difference in clinical effectiveness and costs of an individualized walking programme and a supervised general exercise programme compared to usual physiotherapy, which will act as the control group, in people with chronic low back pain. A sample of 246 patients will be recruited in Dublin, Ireland through acute general hospital outpatient physiotherapy departments that provide treatment for people with CLBP. Patients will be randomly allocated to one of the three groups in a concealed manner. The main outcomes will be functional disability, pain, quality of life, fear avoidance, back beliefs, physical activity, satisfaction and costs, which will be evaluated at baseline, and 3, 6 and 12 months [follow-up by pre-paid postage]. Qualitative telephone interviews and focus groups will be embedded in the research design to obtain feedback about participants' experiences of the interventions and trial participation, and to inform interpretation of the quantitative data. Planned analysis will be by intention to treat (quantitative data) and thematic analysis (qualitative data) Discussion The trial will evaluate the effectiveness of a walking programme and a supervised general exercise programme compared to usual physiotherapy in people with CLBP. Trial registration Current controlled trial ISRCTN17592092

The present study examined the relationships between CT-derived muscle measurements, systemic inflammation, and survival in advanced cancer patients with good performance status (ECOG-PS 0/1). Data was collected prospectively from patients with advanced cancer undergoing anti-cancer therapy with palliative intent. The CT Sarcopenia score (CT-SS) was calculated by combining the CT-derived skeletal muscle index (SMI) and density (SMD). The systemic inflammatory status was determined using the modified Glasgow Prognostic Score (mGPS). The primary outcome of interest was overall survival (OS). Univariate and multivariate Cox regressions were used for survival analysis. Three hundred and seven patients met the inclusion criteria, out of which 62% (n = 109) were male and 47% (n = 144) were ≥65 years of age, while 38% (n = 118) were CT-SS ≥ 1 and 47% (n = 112) of patients with pre-study blood were inflamed (mGPS ≥ 1). The median survival from entry to the study was 11.1 months (1-68.1). On univariate analysis, cancer type ( p < 0.05) and mGPS ( p < 0.001) were significantly associated with OS. On multivariate analysis, only mGPS ( p < 0.001) remained significantly associated with OS. In patients who were ECOG-PS 0, mGPS was significantly associated with CT-SS ( p < 0.05). mGPS may dominate the prognostic value of CT-derived sarcopenia in good-performance-status patients with advanced cancer.

Background: Although suggestive of dysregulated metabolism, the relationship between serum LDH level, phenotypic/aetiologic diagnostic Global Leadership Initiative on Malnutrition (GLIM) criteria and survival in patients with advanced cancer has yet to examined., Methods: Prospectively collected data from patients with advanced cancer, undergoing anti-cancer therapy with palliative intent, across nine sites in the UK and Ireland between 2011-2016, was retrospectively analysed. LDH values were grouped as <250/250-500/>500 Units/L. Relationships were examined using χ 2 test for linear-by-linear association and binary logistics regression analysis., Results: A total of 436 patients met the inclusion criteria. 46% (n = 200) were male and 59% (n = 259) were ≥65 years of age. The median serum LDH was 394 Units/L and 33.5% (n = 146) had an LDH > 500 Units/L. LDH was significantly associated with ECOG-PS (p < 0.001), NLR (p < 0.05), mGPS (p < 0.05) and 3-month survival (p < 0.001). LDH was significantly associated with 3-month survival independent of weight loss (p < 0.01), BMI (p < 0.05), skeletal muscle mass (p < 0.01), metastatic disease (p < 0.05), NLR (p < 0.05) and mGPS (p < 0.01)., Discussion: LDH was associated with performance status, systemic inflammation and survival in patients with advanced cancer. LDH measurement may be considered as an aetiologic criteria and become a potential therapeutic target in the treatment of cancer cachexia., (© 2022. The Author(s).)

Background & Aims: The nutritional status of cancer patients is highly variable, and known to impact on clinical outcomes. To date, no large study evaluating the nutritional status of Irish cancer patients has been reported. The aim of this study was to describe the nutritional status, using gold standard methods, of a large cohort of ambulatory oncology patients receiving Systemic Anti-Cancer Therapy and to assess the impact of abnormal body composition phenotypes on survival., Methods: A prospective study in adults undergoing Systemic Anti-Cancer Therapy for solid tumours enrolled patients between 2012 and 2016. Baseline details were collected incorporating demographics, cancer pathology, lifestyle, body composition (by computed tomography (CT), and inflammatory status. Skeletal muscle index (SMI) and mean muscle attenuation (MA) were obtained from CT images and categorised to low muscle mass and low MA using previously published sex specific cut points. Survival was monitored for a median of 25 months [IQR:10-46 months]. Survival analyses were conducted using multivariate Cox Proportional Hazards Models., Results: Of 1015 patients recruited, 940 patients with an evaluable CT were included in this analysis. Median age was 64 years [IQR 55-71] and 56% were male. Colorectal cancer (28%) and gastro-oesophageal (16%) were the most common diagnoses and 58% of patients had stage IV disease. Despite 56% being overweight or obese (BMI >25 kg/m 2 ), 52% were weight losing and 17% had lost >10% body weight. Cancer Cachexia (CC) was present in 42%, 39% had low muscle mass (MM) (sarcopenia) and 45% had low MA. Overall, 73% of patients exhibited an abnormal body composition (BC) phenotype (≥1 of CC, low MM/MA). Overall survival was significantly lower in those with abnormal BC phenotype, independent of site, stage, sex, ECOG and mGPS (HR: 1.416 [95% CI: 1.069-1.875], p = 0.015)., Conclusions: Malnutrition and abnormal body composition phenotypes are common in cancer, but are often masked by adiposity. Appropriate screening and diagnostic tools should consider this co-presentation of overweight and obesity, alongside muscle depletion. Given that abnormal body composition phenotypes detectable only via CT are associated with reduced survival, these should be more widely employed to identify patients at risk of poor prognosis, and allow potentially more effective, early intervention., Competing Interests: Declaration of competing interest COIs are detailed in the ICMJE statements attached, although no COI are present for any authors, with the exception of ESS. ESS has received honoraria from Complete Nutrition and is supported by an Enterprise Partnership Scheme Postdoctoral Fellowship (EPSPD/2021/18), awarded by the Irish Research Council, and co-funded by Nualtra Ltd., (Copyright © 2022 European Society for Clinical Nutrition and Metabolism. Published by Elsevier Ltd. All rights reserved.)

Purpose: Taste and smell alterations (TAs and SAs) are often reported by patients with cancer receiving systemic antitumor therapy and can negatively impact food intake and quality of life. This study aimed to examine the occurrence of TAs and SAs and investigate the impact of TAs on overall liking of oral nutritional supplements (ONS) with warming and cooling sensations., Methods: Patients receiving systemic antitumor therapy completed a questionnaire on sensory alterations and evaluated overall liking of 5 prototype flavors of Nutridrink® Compact Protein (hot tropical ginger (HTG), hot mango (HM), cool red fruits (CRF), cool lemon (CL), and neutral (N)) on a 10-point scale via a sip test. Differences between patients with and without TAs were investigated using permutation analysis., Results: Fifty patients with various cancer types and treatments were included. Thirty patients (60%) reported TAs and 13 (26%) experienced SAs. Three flavors were rated highly with a liking score > 6 (CRF 6.8 ± 1.7; N 6.5 ± 1.9; HTG 6.0 ± 2.0). Larger variation in ONS liking scores was observed in patients with TAs with or without SAs (4.5-6.9 and 4.6-7.2, respectively) vs. patients without TAs (5.9-6.5). TAs were associated with increased liking of CRF (Δ = + 0.9) and N (Δ = + 1.0) flavors., Conclusions: TAs and SAs are common in patients with cancer undergoing systemic antitumor therapy. Patients with TAs were more discriminant in liking of ONS flavors compared to patients without TAs, and sensory-adapted flavors appeared to be appreciated. The presence of TAs should be considered when developing or selecting ONS for patients with cancer., Trial Registration: Registration at ClinicalTrials.gov (NCT03525236) on 26 April 2018., (© 2021. The Author(s).)

Background: Poorly performing diagnostic tests can impact patient safety. Clinical investigations must have good precision and diagnostic accuracy before widespread use in clinical practice. Transient elastography (TE) measures liver stiffness, a surrogate marker of liver fibrosis in adults and children. Studies to evaluate its repeatability and reproducibility (precision) in children are limited. Our aim was to determine (i) the normal range of TE measurements and (ii) the repeatability and reproducibility of TE in healthy children., Methods: TE was performed in 257 healthy children, of whom 235 (91%, mean age 11.7 years, standard deviation (SD) 2.51, 107 were males (45.5%)) had two valid TE measurements performed, at least 24 h apart, by two operators under similar circumstances. High-quality TE images were obtained for each examination., Results: The normal range of TE was 2.88-6.52 kPa. The mean difference between paired measurements was 0.044 (SD 0.4). The 95% limits of agreement ranged from -0.8 to +0.76 kPa for repeat measurements. There was a difference of >1 kPa between measurements in 61/235 (25.9%) children. The lack of precision was similar across all age groups., Conclusions: This study demonstrates that TE does not have acceptable precision in healthy children, because random measurement variation results in the lack of agreement between paired measurements., Impact: The precision and diagnostic accuracy of a new technology must be determined before it is deployed in children in order to ensure that appropriate clinical decisions are made, and healthcare resources are not wasted. TE is widely used to diagnose liver disease in children without adequate evaluation of the precision (repeatability) of TE either in healthy children or children with liver disease. This study demonstrates that TE does not have adequate precision in children. This study was performed in accordance with methods previously published for children. Refinements to the test protocol, such as duration of fasting or probe size, will have to be evaluated for their impact on precision and accuracy before the test is deployed in research studies or clinical practice.

Background: Optimizing quality of life (QoL) remains the central tenet of care in patients with incurable cancer; however, determinants of QoL are not clear. The objective of the current study was to examine which factors influence QoL in patients with incurable cancer., Methods: A multicenter study of adult patients with advanced cancer was conducted in Ireland and the United Kingdom between 2011 and 2016. Data were collected from patients at study entry and included patient demographics, Eastern Cooperative Oncology Group performance status (ECOG-PS), nutritional parameters (the percentage weight loss [%WL]), muscle parameters assessed using computed tomography images (skeletal muscle index and skeletal muscle attenuation), inflammatory markers (modified Glasgow Prognostic score [mGPS]), and QoL data (the European Organization for Research and Treatment Quality-of-Life Questionnaire C-30). The relation between clinical, nutritional, and inflammatory parameters with QoL was assessed using the Spearman rank correlation coefficient and multivariate binary logistic regression. Components of the European Organization for Research and Treatment Quality-of-Life Questionnaire C-30 (physical function, fatigue, and appetite loss) and summary QoL scores were mean-dichotomized for the logistic regression analyses., Results: Data were available for 1027 patients (51% men; median age, 66 years). Gastrointestinal cancer was most prevalent (40%), followed by lung cancer (26%) and breast cancer (9%). Distant metastatic disease was present in 87% of patients. The %WL, ECOG-PS, and mGPS were significantly correlated with deteriorating QoL functional and symptom scales (all P < .001). On multivariate regression analysis, >10% WL (odds ratio [OR], 2.69; 95% CI, 1.63-4.42), an ECOG-PS of 3 or 4 (OR, 14.33; 95% CI, 6.76-30.37), and an mGPS of 2 (OR, 1.58; 95% CI, 1.09-2.29) were independently associated with poorer summary QoL scores. These parameters were also independently associated with poorer physical function, fatigue, and appetite loss (all P < .05). Low skeletal muscle attenuation was independently associated with poorer physical functioning (OR, 1.67; 95% CI, 1.09-2.56), but muscle parameters were not independently associated with fatigue, appetite loss, or QoL summary scores., Conclusions: The current findings indicate that QoL is determined (at least in part) by WL, ECOG-PS, and the systemic inflammatory response in patients with advanced cancer. Identifying early predictors of poor QoL may allow the identification of patients who may benefit from early referral to palliative and supportive care, which has been shown to improve QoL., (© 2020 American Cancer Society.)

Cancer remains one of the leading causes of mortality worldwide and the associated reduction in physical function has a marked impact on both quality of life and survival. The aim of the present study was to examine the relationship between Eastern Cooperative Oncology Group-Performance status (ECOG-PS), modified Glasgow Prognostic Score (mGPS), Body Mass Index/ Weight Loss grade (BMI/WL grade), and Computerised Tomography (CT)-derived body composition measurement and physical function in patients with advanced cancer. Nine sites contributed prospective data on patient demographics, ECOG-PS, mGPS, physical function tests, and CT-derived body composition. Categorical variables were analysed using χ 2 test for linear-by-linear association, or χ 2 test for 2-by-2 tables. Associations were analysed using binary logistic regression. A total of 523 cancer patients (266 males, 257 females) were included in the final analysis and most had metastatic disease (83.2%). The median overall survival was 5.6 months. On multivariate binary logistic regression analysis, a high ECOG-PS remained independently associated with a low skeletal muscle index ( p < 0.001), low skeletal muscle density ( p < 0.05), and timed up and go test failure ( p < 0.001). A high mGPS remained independently associated with a low skeletal muscle density ( p < 0.05) and hand grip strength test failure ( p < 0.01). A high BMI/WL grade remained independently associated with a low subcutaneous fat index ( p < 0.05), low visceral obesity ( p < 0.01), and low skeletal muscle density ( p < 0.05). In conclusion, a high ECOG-PS and a high mGPS as outlined in the ECOG-PS/mGPS framework were consistently associated with poorer body composition and physical function in patients with advanced cancer., Competing Interests: There are no conflicts of interest to report.

It has frequently been shown that patients with cancer are one of the largest hospital patient groups with a prevalence for malnutrition. Weight loss is a frequent manifestation of malnutrition in patients with cancer. Several large-scale studies over the past 35 y have reported that involuntary weight loss affects 50% to 80% of these patients with the degree of weight loss dependent on tumor site and type and stage of disease. The aim of this review was to determine the consequences of malnutrition, weight loss, and muscle wasting in relation to chemotherapy tolerance, postoperative complications, quality of life, and survival in patients with cancer. The prognostic impact of weight loss on overall survival has long been recognised with recent data suggesting losses as little as 2.4% predicts survival independent of disease, site, stage or performance score. Recently the use of gold-standard methods of body composition assessment, including computed tomography, have led to an increased understanding of the importance of muscle abnormalities, such as low muscle mass (sarcopenia), and more recently low muscle attenuation, as important prognostic indicators of unfavourable outcomes in patients with cancer. Muscle abnormalities are highly prevalent (ranging from 10-90%, depending on cancer site and the diagnostic criteria used). Both low muscle mass and low muscle attenuation have been associated with poorer tolerance to chemotherapy; increased risk of postoperative complications; significant deterioration in a patients' performance status, and poorer psychological well-being, overall quality of life, and survival., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Advancements in image-based technologies and body composition research over the past decade has led to increased understanding of the importance of muscle abnormalities, such as low muscle mass (sarcopenia), and more recently low muscle attenuation (MA), as important prognostic indicators of unfavourable outcomes in patients with cancer. Muscle abnormalities can be highly prevalent in patients with cancer (ranging between 10 and 90 %), depending on the cohort under investigation and diagnostic criteria used. Importantly, both low muscle mass and low MA have been associated with poorer tolerance to chemotherapy, increased risk of post-operative infectious and non-infectious complications, increased length of hospital stay and poorer survival in patients with cancer. Studies have shown that systemic antineoplastic treatment can exacerbate losses in muscle mass and MA, with reported loss of skeletal muscle between 3 and 5 % per 100 d, which are increased exponentially with progressive disease and proximity to death. At present, no effective medical intervention to improve muscle mass and MA exists. Most research to date has focused on treating muscle depletion as part of the cachexia syndrome using nutritional, exercise and pharmacological interventions; however, these single-agent therapies have not provided promising results. Rehabilitation care to modify body composition, either increasing muscle mass and/or MA should be conducted, and its respective impact on oncology outcomes explored. Although the optimal timing and treatment strategy for preventing or delaying the development of muscle abnormalities are yet to be determined, multimodal interventions initiated early in the disease trajectory appear to hold the most promise.

Background: Malnutrition, weight loss, and muscle wasting are common in patients with foregut cancers (oesophagus, stomach, pancreas, liver, and bile ducts) and are associated with adverse clinical outcomes. However, little is known about the changes in body composition that occur in these patients during chemotherapy and its impacts clinical outcomes., Patients and Methods: A prospective study of adult foregut cancer patients undergoing chemotherapy between 2012 and 2016 was conducted. Computed tomography images were evaluated for cross-sectional skeletal muscle area (SMA) and adipose tissue area (ATA) at two time points [interval 118 days (IQR 92-58 days)]. Longitudinal changes in SMA and ATA were examined using paired t-tests. Sarcopenia and low muscle attenuation (MA) were defined using published cut-points. Cox proportional hazards models were used to estimate mortality hazard ratios for key predictors., Results: A total of 225 foregut cancer patients were included (67% male, median age 66 years). At baseline, 40% were sarcopenic, 49% had low MA, and 62% had cancer cachexia. Longitudinal analysis (n = 163) revealed significant reductions in SMA [-6.1 cm 2 (3.9%)/100 days, P < 0.001]. Patients treated with neoadjuvant chemotherapy experienced greater losses in SMA and skeletal muscle mass compared with patients receiving palliative chemotherapy [-6.6 cm 2 (95%, confidence interval, CI: -10.2 to -3.1), P < 0.001 and -1.2 kg (95% CI: -1.8 to -0.5), P < 0.001, respectively]. Neither sarcopenia nor low MA at baseline was associated with reduced survival. A loss of SMA >6.0%/100 days (highest fourth) independently predicted overall survival in patients receiving palliative chemotherapy [hazard ratio: 2.66, (95% CI: 1.42 to 4.97), P = 0.002]., Conclusions: Patients with foregut cancers, particularly those treated with neoadjuvant chemotherapy, experience significant losses of muscle during chemotherapy. A high level of SMA loss is prognostic of reduced survival in patients treated with palliative chemotherapy. Multimodal interventions to stabilize or increase muscle mass and influence outcome warrant further investigation., (© 2018 The Authors. Journal of Cachexia, Sarcopenia and Muscle published by John Wiley & Sons Ltd on behalf of the Society on Sarcopenia, Cachexia and Wasting Disorders.)

Background: Nutrition screening on admission to hospital is mandated in many countries, but to date, there is no consensus on which tool is optimal in the oncology setting. Wasting conditions such as cancer cachexia (CC) and sarcopenia are common in cancer patients and negatively impact on outcomes; however, they are often masked by excessive adiposity. This study aimed to inform the application of screening in cancer populations by investigating whether commonly used nutritional screening tools are adequately capturing nutritionally vulnerable patients, including those with abnormal body composition phenotypes (CC, sarcopenia, and myosteatosis)., Methods: A prospective study of ambulatory oncology outpatients presenting for chemotherapy was performed. A detailed survey incorporating clinical, nutritional, biochemical, and quality of life data was administered. Participants were screened for malnutrition using the Malnutrition Universal Screening Tool (MUST), Malnutrition Screening Tool (MST), and the Nutritional Risk Index (NRI). Computed tomography (CT) assessment of body composition was performed to diagnose CC, sarcopenia, and myosteatosis according to consensus criteria., Results: A total of 725 patients (60% male, median age 64 years) with solid tumours participated (45% metastatic disease). The majority were overweight/obese (57%). However, 67% were losing weight, and CT analysis revealed CC in 42%, sarcopenia in 41%, and myosteatosis in 46%. Among patients with CT-identified CC, the MUST, MST, and NRI tools categorized 27%, 35%, and 7% of them as 'low nutritional risk', respectively. The percentage of patients with CT-identified sarcopenia and myosteatosis that were categorised as 'low nutritional risk' by MUST, MST and NRI were 55%, 61%, and 14% and 52%, 50%, and 11%, respectively. Among these tools, the NRI was most sensitive, with scores <97.5 detecting 85.8%, 88.6%, and 92.9% of sarcopenia, myosteatosis, and CC cases, respectively. Using multivariate Cox proportional hazards models, NRI score < 97.5 predicted greater mortality risk (hazard ratio 1.8, confidence interval: 1.2-2.8, P = 0.007)., Conclusions: High numbers of nutritionally vulnerable patients, with demonstrated abnormal body composition phenotypes on CT analysis, were misclassified by MUST and MST. Caution should be exercised when categorizing the nutritional risk of oncology patients using these tools. NRI detected the majority of abnormal body composition phenotypes and independently predicted survival. Of the tools examined, the NRI yielded the most valuable information from screening and demonstrated usefulness as an initial nutritional risk grading system in ambulatory oncology patients., (© 2017 The Authors. Journal of Cachexia, Sarcopenia and Muscle published by John Wiley & Sons Ltd on behalf of the Society on Sarcopenia, Cachexia and Wasting Disorders.)

Background: Body composition is an important predictor of drug toxicity and outcome. Ipilimumab (Ipi), a monoclonal antibody used to treat metastatic melanoma, has specific toxicities. No validated biomarkers that predict Ipi toxicity and efficacy exist. Also, the impact of Ipi on body composition has not been established., Methods: Patients with metastatic melanoma treated with Ipi between 2009 and 2015 were included. Body composition was assessed by computed tomography at baseline and after four cycles of Ipi. Sarcopenia and low muscle attenuation (MA) were defined using published cut-points. All adverse events (AEs) and immune-related AEs (irAEs) were recorded (Common Terminology Criteria For Adverse Event V.4.0)., Results: Eighty-four patients were included in this study (62% male, median age 54 years). At baseline, 24% were sarcopenic and 33% had low MA. On multivariate analysis, sarcopenia and low MA were significantly associated with high-grade AEs (OR=5.34, 95% CI: 1.15-24.88, P=0.033; OR=5.23, 95% CI: 1.41-19.30, P=0.013, respectively), and low MA was associated with high-grade irAEs (OR=3.57, 95% CI: 1.09-11.77, P=0.036). Longitudinal analysis (n=59) revealed significant reductions in skeletal muscle area (SMA), total body fat-free mass, fat mass (all P<0.001) and MA (P=0.030). Mean reduction in SMA was 3.3%/100 days (95% CI: -4.48 to -1.79%, P<0.001). A loss of SMA ⩾7.5%/100 days (highest quartile) was a significant predictor of overall survival in multivariable Cox regression analysis (HR: 2.1, 95% CI: 1.02-4.56, P=0.046)., Conclusions: Patients with sarcopenia and low MA are more likely to experience severe treatment-related toxicity to Ipi. Loss of muscle during treatment was predictive of worse survival. Treatments to increase muscle mass and influence outcome warrant further investigation.

Background: Neural tube defects (NTDs) are a major cause of death and disability. Periconceptional folic acid prevents up to 70% of these malformations but public health campaigns to increase use of supplements have had disappointing results: The proposed mandatory fortification of bread products in Ireland has raised concerns about possible side effects. We examined data collected on a cohort of children born with NTDs in an era before fortification/supplementation to illustrate the serious consequences in terms of survival and disability., Methods: All 623 infants born with NTDs in the Dublin area between 1976 and 1987 were included. Information was collected on mortality and length of survival for those who died, and for those who survived at least 5 years, interview-based data were collected on age, place of residence, prevalence of hydrocephalus, degree of disability, schooling, and IQ., Results: Seventy-four births (12%) were stillborn. Of the livebirths only 41% were alive at 5 years. Factors associated with mortality were type of lesion, level of lesion, presence of other defects, hydrocephalus, year of birth, and gestation. Of the children who survived to 5 years or more, 75% had a disability and 56% were severely disabled. Type of lesion and level of lesion influenced disability risk. Of the survivors, 51% of children had mobility limitations, 59% were incontinent, 42% had hydrocephalus, and 17% had intellectual disability., Conclusions: These findings illustrate the devastating consequences of NTDs and underline the importance of effective intervention programs with folic acid for prevention., (Copyright 2008 Wiley-Liss, Inc.)

Introduction: General practitioners and consultants in the Republic of Ireland manage patients with chronic low back pain (LBP), but little is known about the non-clinical factors that impact on their management., Aim: To establish the non-clinical factors that impact on the management of chronic LBP by a cohort of general practitioners and consultants., Methods: Using a multiple case study design, semi-structured interviews were conducted with general practitioners (n = 7) and consultants (n = 7). Interviews were transcribed and analysed qualitatively., Results: Two main themes emerged: policy factors (the health care system, the medico-legal system), and patient factors (need for reassurance, lack of patient adherence)., Conclusions: These factors operate at national and local levels. Nationally, they underscore the lack of resources, and the impact of the medico-legal system. Local issues include changing practice by reassuring patients using evidence-based biopsychosocial strategies to maximise patient care and reduce healthcare costs.

There are no national low back pain (LBP) clinical guidelines in Ireland, and neither the level of adherence of General Practitioners (GPs) to the European guidelines, nor the cost of LBP to the patient and the state, have been investigated. A prospective pilot study was conducted on 54 consenting patients (18M, 36F: mean age (SD): 40.5 (14.3) years) with a new episode of acute LBP (<3 months) attending one of nine participating GPs. Baseline demographic, LBP classification [i.e. simple back ache (SBA), nerve root pain (NRP), serious spinal pathology (SSP)] and primary care management data were recorded over a three month period. Adherence and costs were estimated based on: medication prescription, referral for investigations, treatment or consultations, and wage replacement costs (time signed off work). For both SBA and NRP, medication prescriptions were consistent with European guideline recommendations, but not for referral for further treatment (39% of SBA patients were referred on first visit), secondary care (54% of NRP patients were referred on first visit), or discontinuation of work (50% NRP patients on first GP visit). The average total cost (direct and wage replacement) for a single episode of LBP over 12 weeks was 20,531 Euros (20,300-20,762). Direct costs accounted for 43% [8874.36 Euros, (8643.37-9105.37 Euros)] and wage replacement costs 57% (11,657 Euros). In conclusion, management of acute LBP in a cohort of GPs in Ireland was not consistent with European clinical guideline recommendations, and warrants higher levels of postgraduate education among GPs, as well as restructuring of primary care services, which should improve patient outcome and reduce costs.

Background: To investigate the effects of inhaled beta-agonists on sub-maximal and maximal exercise capacity, breathing pattern, dyspnoea, leg-discomfort and spirometry in patients with cystic fibrosis (CF)., Objectives: Eight patients performed two maximal incremental cycle-ergometry tests on separate days with inhaled placebo or salbutamol (600 microg) administered before each test in a randomized, double-blind, placebo-controlled crossover trial. Primary outcomes were exercise duration (Exdur) in seconds (s) and maximal oxygen uptake (VO2max) in litres/minute (L/min). Forced expiratory volume in 1 s (FEV1) was measured immediately pre-inhaler, post-inhaler and post-exercise. Dyspnoea and leg-discomfort were assessed post-exercise., Results: Within-day FEV1 comparisons demonstrated that the placebo test day FEV1 improved significantly post-exercise (0.11 L, p<0.05) and the salbutamol test day FEV1 improved significantly post-inhaler (0.22 L, p<0.001) and post-exercise (0.07 L, p<0.01). Between-day FEV1 comparisons demonstrated significant improvements in post-inhaler (0.17 L, p<0.05) and post-exercise (0.13 L, p<0.05) FEV1 following salbutamol. Sub-maximal and maximal exercise showed no significant difference as shown by Exdur (547+/-154 s vs. 529+/-127 s) and VO2max (1.9+/-0.5 L/min vs. 1.9+/-0.6 L/min). No significant change in breathing pattern, dyspnoea or leg-discomfort was detected. The study had a power of 92% to detect a 10% improvement in Exdur., Conclusions: In adults with CF, salbutamol improves post-exercise FEV1 and is safe when administered immediately before exercise but does not improve exercise capacity, exercise-induced dyspnoea or leg-discomfort.

Background: Elevated plasma total homocysteine (tHcy) is a known risk factor for vascular disease. Gender, age, and circulating levels of folate, vitamins B(6)and B(12)affect tHcy levels. Objectives To study associations of gender and age with levels of plasma tHcy, and to examine the relationships of tHcy and circulating levels of folate, vitamins B(6)and B(12)with risk of vascular disease in men and women (pre- and post-menopausal)., Material and Methods: In a multicentre case-control study in Europe, 750 patients (544 men, 206 women) with documented vascular disease of the coronary, cerebral, or peripheral vessels and 800 control subjects (570 men, 230 women) were enrolled. Plasma tHcy levels (fasting and after methionine loading) and circulating levels of the vitamins were measured. Adjustment for age and centre was carried out for all statistical analyses, with additional adjustment for serum creatinine and vitamins for the tHcy comparisons between the sexes and between cases and controls. Risk analyses included adjustment for creatinine and traditional risk factors. Relationships between age, gender and tHcy were studied among control subjects only., Results: Fasting tHcy levels were lower in women than in men. Levels of tHcy showed a positive association with age, for both sexes. In the post-menopausal age category, female post-methionine load tHcy levels surpassed levels of men. Elevation of tHcy (defined as >80th percentile of controls) appeared to be at least as strong a risk factor for vascular disease in women as in men, even before the menopause. For post-methionine load tHcy, there was a 40% stronger association with vascular disease in women than in men. In both sexes, but especially in pre-menopausal women, low circulating levels of vitamin B(6)conferred a two- to threefold increased risk of vascular disease, independent of tHcy. In men, but not in women, low (defined as <20th percentile of controls) circulating folate levels were associated with a 50% increased risk of vascular disease., Conclusions: Elevation of tHcy appears to be at least as strong a risk for vascular disease in women as men, even before the menopause. Our data indicate that associations of the various tHcy measurements (and the vitamins that determine them), with risks of vascular disease may differ between the sexes. The tHcy-independent relationship of vitamin B(6)with vascular disease indicates that it will be advisable to test the effects of vitamin B(6)in clinical trials., (Copyright 1999 The European Society of Cardiology.)

The use of confidence intervals has become standard in the presentation of statistical results in medical journals. Calculation of confidence limits can be straightforward using the normal approximation with an estimate of the standard error, and in particular cases exact solutions can be obtained from published tables. However, for a number of commonly used measures in epidemiology and clinical research, formulae either are not available or are so complex that calculation is tedious. The author describes how an approach to confidence interval estimation which has been used in certain specific instances can be generalized to obtain a simple and easily understood method that has wide applicability. The technique is applicable as long as the measure for which a confidence interval is required can be expressed as a monotonic function of a single parameter for which the confidence limits are available. These known confidence limits are substituted into the expression for the measure--giving the required interval. This approach makes fewer distributional assumptions than the use of the normal approximation and can be more accurate. The author illustrates his technique by calculating confidence intervals for Levin's attributable risk, some measures in population genetics, and the "number needed to be treated" in a clinical trial. Hitherto the calculation of confidence intervals for these measures was quite problematic. The substitution method can provide a practical alternative to the use of complex formulae when performing interval estimation, and even in simpler situations it has major advantages.

Helicobacter pylori infection is mainly acquired in childhood, and studies on the epidemiology of this infection depend on the availability of a noninvasive diagnostic test for use in children. The aim of this study was to determine whether the carbon 13-labeled urea breath test (UBT) can be used in children by evaluating: (1) its sensitivity and specificity compared with either culture or both rapid urease test and histologic examination, (2) whether a test meal or a prolonged fast is required, (3) the usefulness after treatment for H. pylori. Eighty-eight children (mean age, 10.6 +/- 4.19 years) who were undergoing upper endoscopy were studied while fasting, not fasting, and after treatment. Children were given 50 mg of 13C-urea if they weighed less than 50 kg or 75 mg of 13C-urea if they weighed more than 50 kg with 50 mg of a glucose polymer solution in 7.5 ml of water. Breath samples were collected at baseline and at 15, 30, 45, and 60 minutes. In 63 fasting children the UBT was 100% sensitive and 97.6% specific at 30 minutes with a cutoff value of 3.5 delta 13CO2 per mil. Nonfasting tests in 23 children, performed between 1 and 2 hours after their usual meal, were 100% sensitive and 91.6% specific. In 13 children fed directly before the UBT, the sensitivity of the test was reduced to 50%. Thirty minutes was the optimal sampling time. There was a significant decrease in specificity when samples were obtained at 15 minutes, possibly caused by the interference of oral urease-producing organisms. The test was 100% sensitive and specific in 20 children after treatment for H. pylori infection. The UBT is a highly sensitive and specific test for the diagnosis of H. pylori infection in children. Neither a prolonged fast nor a test meal is required.

Background: Helicobacter pylori infection of the gastric mucosa is vital in the pathogenesis of duodenal ulcer disease. H pylori will only colonise gastric epithelium and its association with duodenal disease is therefore not easily explained., Aims: To determine if gastric metaplasia in the duodenum increases the risk of duodenal ulcer disease in children infected with H pylori., Patients: All children undergoing upper endoscopy over a 20 month period in a children's hospital in Ireland., Methods: Two biopsy specimens were obtained from the antral mucosa and two from the first part of the duodenum. One antral biopsy specimen was used in a rapid urease test (Clo Test). Biopsy sections were stained with haematoxylin and eosin and also with cresyl violet for identification of H pylori. Periodic acid Schiff (PAS) stain was performed to identify areas of gastric metaplasia., Results: Gastric and duodenal biopsy specimens were obtained from 148 patients (M:F 1:2:1). Twenty five children (17%) had H pylori positive gastritis. Thirty four children (23%) had gastric metaplasia in the duodenum. Nine per cent of children under the age of 8 years had gastric metaplasia compared with 38% in those 12 years of age or over (p < 0.005). Seven children had duodenal ulcer disease. Gastric metaplasia was present in six of seven (86%) children with duodenal ulcer disease compared with 28 of 141 (20%) without ulceration (p < 0.001). While both H pylori and gastric metaplasia were each significant risk factors for duodenal ulcer disease, the combined presence of both factors was associated with a pronounced increase in duodenal ulcer disease. Duodenal ulcer disease occurred in over 50% of children with both H pylori infection and gastric metaplasia. In contrast duodenal disease did not occur in children (0 of 100) when both were absent., Conclusion: The presence of gastric metaplasia in the duodenum is the major risk factor for duodenal ulcer disease in patients colonised by H pylori.

Objective: To assess the use of acute coronary care facilities in the Republic of Ireland with regard to case mix, patient characteristics, mortality and factors associated with mortality, time intervals to admission, utilisation of thrombolysis, and risk factor profiles., Design: A 1 week prospective census of all hospitals admitting acute coronary cases. These comprised 23 coronary care units (CCU) and 17 combined coronary care/intensive care units (CCU/ICU). Data were collected by standardised methods on each new patient "upon whom a cardiac monitor was placed"., Results: Acute coronary heart disease was confirmed in 185 (44.9%) of 412 patients. Of these 109 (26.4%) had a confirmed myocardial infarction and 76 (18.4%) unstable angina. Women were significantly older than men in all groups. Of those with proven acute coronary heart disease, 42.6% were current smokers, 23.1% were aware of having a raised cholesterol concentration, and 42.3% gave a history of prior hypertension. Only 44% were transported by ambulance. Median delay time from the onset of symptoms to admission was 6 h in Dublin and 4 h elsewhere. 34.9% of patients with a confirmed myocardial infarction received thrombolysis. Mortality of patients with myocardial infarction CCU/ICU at 7 days was 10.9 %., Conclusions: There is potential for considerable improvement in the management of coronary heart disease in the Republic of Ireland through a reduction in delay times to admission to hospital, increased use of thrombolytic treatment, and intensification of advice on primary and secondary risk factors.

The aim of this study was to determine prospectively whether Helicobacter pylori-associated gastritis is associated with specific symptoms by evaluating whether these symptoms are relieved by treatment of the infection. Symptoms resolved after the eradication of H. pylori in only three of eight children with H. pylori-associated gastritis alone, in comparison with all six children with duodenal ulcer disease.

The general practitioner often requires a simple and reliable method of determining the potential risks of surgical intervention. We derived and tested a simple clinical scoring system for the preoperative prediction of 30-day mortality after coronary artery bypass surgery. From a national register of all open heart operations in the Republic of Ireland 1984-1989, we identified 4276 male patients who had primary isolated non-emergency coronary artery bypass surgery. Using logistic regression, we derived a clinical scoring system to predict operative (30-day) mortality in patients operated on between 1984 and 1987. We then prospectively evaluated the score on patients seen over the next two years. Variables identified for our scoring system were age, recent myocardial infarction, left ventricular failure, extensive distal coronary artery disease and body surface area. Five risk categories were defined; mortality in the high-risk group was 9.7-fold (95% CI: 4.6-20.7) greater than in the low-risk group. When tested on new patients, the relative mortality between the two risk groups was 15.2 (4.6-50.5). The observed and predicted mortalities in each risk group showed close agreement. This clinical scoring system, easily used by a general practitioner, can predict operative mortality in males for whom primary isolated coronary artery bypass surgery is contemplated.

Blood was taken at the first antenatal clinic from 56,049 pregnant women. Neural tube defect (NTD) pregnancies (81) were compared to controls (247) for plasma vitamin B12 (B12) (ng/l), plasma folate (microgram/l), and red cell folate (RCF) (microgram/l). Median values were significantly different and were, respectively, 243 and 296 (p = 0.001); 3.47 and 4.59 (p = 0.002); and 269 and 338 (p < 0.001). There was a significant correlation between plasma B12 and RCF in cases (r = 0.31, p = 0.004) but not in controls (r = 0.02, p = 0.725). In cases only, multiple regression showed that both plasma B12 and plasma folate influenced the maternal RCF (multiple r = 0.68, p < 0.001). Plasma folate and plasma B12 were independent risk factors for NTDs, suggesting that the enzyme methionine synthase is involved directly or indirectly in the aetiology. The levels of folate and B12 where increased risk occurred were not those usually associated with deficiency, calling for a re-evaluation of their recommended daily allowances. Whether the aetiology is purely nutritional or a metabolic defect, this study suggests that consideration should be given to including B12 as well as folic acid in any programme of supplementation or food fortification to prevent NTDs.

A randomised trial was initiated in Ireland in 1981 to determine if periconceptional supplementation with either folic acid alone or a multivitamin preparation alone could reduce the recurrence risk of neural tube defects (NTDs) in women with a previously affected pregnancy from 5.0% to 1.0% or less. The trial was concluded before the initial target number of study subjects was reached and without a clear treatment effect being observed. A total of 354 women were randomised to receive one of three treatments: folic acid, multivitamins without folic acid, and folic acid plus multivitamins. At the end of the trial 257 women had had a first trial pregnancy outcome (261 infants/fetuses) where the presence or absence of NTDs was ascertainable. There was one NTD recurrence in the 89 infants/fetuses of women in the multivitamin group and no recurrence in the 172 infants/fetuses of women in the folic acid groups, a non-significant difference. Otherwise eligible women who were pregnant when first contacted constituted a non-randomised control group; there were three recurrences among the 103 infants in this group. The difference in the recurrence rate between the folic acid groups and the non-randomised controls was statistically significant but we have reservations about the validity of this comparison. Although our findings do not provide clear evidence of a protective effect of folic acid supplementation they are consistent with those of the Medical Research Council (MRC) trial which demonstrated the efficacy of folic acid in preventing recurrence of NTDs and they raise the possibility that folic acid may be protective at a much lower dosage than that used in the MRC trial.

The course of postcoronary angina pectoris was examined in 555 men who had survived a first attack of myocardial infarction or unstable angina. Patients were aged less than 60 and were followed up yearly for up to 17 years. Only 25 (4.5%) had coronary artery bypass surgery. Most patients with angina were treated by nitrates alone. One year after infarction 24.1% of survivors (124/515) reported the presence of angina pectoris, and the proportions at five, 10, and 15 years were 29.9%, 30.4%, and 43.5% respectively. Seventeen years after the initial event 35.3% of the survivors had never reported postcoronary anginal symptoms. The patients who experienced anginal symptoms in the year after their coronary attack had a poorer long term survival than the group who were symptom free over the first year. These patients also had longer subsequent periods with angina, though in 41.7% angina resolved before death after a median of 2.9 years. Throughout follow up mortality during periods in which patients experienced angina was higher than in the symptom free periods. This long term follow up study of patients after a coronary event confirms that the presence or absence of angina may vary considerably over time in patients treated medically and that the presence of angina is associated with a poorer prognosis. These findings have important implications when assessing the effects of various treatment modalities on postcoronary angina, including coronary artery bypass surgery.

Subjects who stop smoking cigarettes after myocardial infarction have an improved rate of survival compared with those who continue, but to date it was not known whether the benefit persisted for more than six years. A total of 498 men aged under 60 years who had survived a first episode of unstable angina or myocardial infarction by two years were followed up by life table methods for a further 13 years. Mortality in those who continued to smoke was significantly higher (82.1%) than in those who stopped smoking (36.9%). These differences increased with time. Mortality in those who were non-smokers initially and who continued not to smoke was intermediate (62.1%). The adverse effect of continued smoking was most pronounced in those with unstable angina. Continuing to smoke increased the rate of sudden death to a greater degree in those with less severe initial attacks, while the effect of smoking on fatal reinfarctions was most apparent in those with a more complicated presentation. These findings suggest that stopping cigarette smoking is the most effective single action in the management of patients with coronary heart disease.

Factors related to the occurrence of sudden death were examined in 551 men aged less than 60 years who survived a first attack of unstable angina or myocardial infarction by at least 28 days. There were 301 deaths over an average follow up period of 9.4 years and 138 (46%) of these were sudden. Life table techniques permitted the estimation of mortality up to 18 years after the index event. The proportion of sudden deaths showed a decrease with length of follow up. In those who were non-smokers and in those aged less than 45 years on admission sudden deaths in the first two years were very common (80% (95% confidence interval: 69%-91%) and 79% (95% confidence interval: 68%-90%) respectively). The proportion of sudden deaths in the remaining 16 years of follow up was related inversely to age at initial attack. After the first two years of follow up sudden death rates were similar in those who continued to smoke and those who stopped smoking, although those who continued to smoke had a significantly higher overall mortality. The risk of sudden death should be borne in mind when planning the investigation and rehabilitation of young and non-smoking subjects presenting with a first coronary event.