Epidemiology of COVID-19 in Northern Ireland, 26 February 2020-26 April 2020.

This paper describes the epidemiology of coronavirus disease 2019 (COVID-19) in Northern Ireland (NI) between 26 February 2020 and 26 April 2020, and analyses enhanced surveillance and contact tracing data collected between 26 February 2020 and 13 March 2020 to estimate secondary attack rates (SAR) and relative risk of infection among different categories of contacts of individuals with laboratory confirmed severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) infection. Our results show that during the study period COVID-19 cumulative incidence and mortality was lower in NI than the rest of the UK. Incidence and mortality were also lower than in the Republic of Ireland (ROI), although these observed differences are difficult to interpret given considerable differences in testing and surveillance between the two nations. SAR among household contacts was 15.9% (95% CI 6.6%-30.1%), over 6 times higher than the SAR among 'high-risk' contacts at 2.5% (95% CI 0.9%-5.4%). The results from logistic regression analysis of testing data on contacts of laboratory-confirmed cases show that household contacts had 11.0 times higher odds (aOR: 11.0, 95% CI 1.7-70.03, P-value: 0.011) of testing positive for SARS-CoV-2 compared to other categories of contacts. These results demonstrate the importance of the household as a locus of SARS-CoV-2 transmission, and the urgency of identifying effective interventions to reduce household transmission.

Impact of prediagnostic smoking and smoking cessation on colorectal cancer prognosis: a meta-analysis of individual patient data from cohorts within the CHANCES consortium.

Background: Smoking has been associated with colorectal cancer (CRC) incidence and mortality in previous studies and might also be associated with prognosis after CRC diagnosis. However, current evidence on smoking in association with CRC prognosis is limited. Patients and methods: For this individual patient data meta-analysis, sociodemographic and smoking behavior information of 12 414 incident CRC patients (median age at diagnosis: 64.3 years), recruited within 14 prospective cohort studies among previously cancer-free adults, was collected at baseline and harmonized across studies. Vital status and causes of death were collected for a mean follow-up time of 5.1 years following cancer diagnosis. Associations of smoking behavior with overall and CRC-specific survival were evaluated using Cox regression and standard meta-analysis methodology. Results: A total of 5229 participants died, 3194 from CRC. Cox regression revealed significant associations between former [hazard ratio (HR) = 1.12; 95 % confidence interval (CI) = 1.04-1.20] and current smoking (HR = 1.29; 95% CI = 1.04-1.60) and poorer overall survival compared with never smoking. Compared with current smoking, smoking cessation was associated with improved overall (HR<10 years = 0.78; 95% CI = 0.69-0.88; HR≥10 years = 0.78; 95% CI = 0.63-0.97) and CRC-specific survival (HR≥10 years = 0.76; 95% CI = 0.67-0.85). Conclusion: In this large meta-analysis including primary data of incident CRC patients from 14 prospective cohort studies on the association between smoking and CRC prognosis, former and current smoking were associated with poorer CRC prognosis compared with never smoking. Smoking cessation was associated with improved survival when compared with current smokers. Future studies should further quantify the benefits of nonsmoking, both for cancer prevention and for improving survival among CRC patients, in particular also in terms of treatment response.

Social capital, deprivation and self-rated health: Does reporting heterogeneity play a role? Results from the English Longitudinal Study of Ageing.

Self-rated health (SRH) is commonly assessed in large surveys, though responses can be influenced by different individuals' perceptions of and beliefs about health. Therefore, instead of providing evidence of 'true' health disparities across groups, findings may actually reflect reporting heterogeneity. Using data from participants aged 50 years and older from the English Longitudinal Study of Ageing (ELSA) Wave 3 (2006/07; participation rate = 73%), associations between three dimensions of social capital (local area & trust, social support and social networks), deprivation and SRH were examined using the vignette methodology in 2341 individuals who completed both the self-report and at least one of the 18 vignettes. Analysis employed a hierarchical probit model (HOPIT). Individuals expressing low local area & trust social capital (beta = -0.276, p < 0.001) and those with poor social networks (beta = -0.280, p < 0.001) were more likely to report poor SRH in HOPIT models accounting for reporting heterogeneity, but unadjusted ordered probit analyses still correctly show a negative relationship between low local area & trust social capital (beta = -0.243, p < 0.001) and those with poor social networks (beta = -0.210, p < 0.01), though they somewhat tend to underestimate its strength. Neither social support nor deprivation appeared to have any effect on SRH regardless of reporting heterogeneity. Anchoring vignettes offer a relatively uncomplicated and cost-effective way of identifying and correcting for reporting heterogeneity to improve comparative validity of self-report measures of health. This analysis underlines the need for caution when using unadjusted self-reported measures to study the effects of social capital on health.

Alcoholic beverage preference and diabetes incidence across Europe: the Consortium on Health and Ageing Network of Cohorts in Europe and the United States (CHANCES) project.

BACKGROUND/OBJECTIVES: It is unknown if wine, beer and spirit intake lead to a similar association with diabetes. We studied the association between alcoholic beverage preference and type 2 diabetes incidence in persons who reported to consume alcohol. SUBJECTS/METHODS: Ten European cohort studies from the Consortium on Health and Ageing: Network of Cohorts in Europe and the United States were included, comprising participant data of 62 458 adults who reported alcohol consumption at baseline. Diabetes incidence was based on documented and/or self-reported diagnosis during follow-up. Preference was defined when ⩾70% of total alcohol consumed was either beer, wine or spirits. Adjusted hazard ratios (HRs) were computed using Cox proportional hazard regression. Single-cohort HRs were pooled by random-effects meta-analysis. RESULTS: Beer, wine or spirit preference was not related to diabetes risk compared with having no preference. The pooled HRs were HR 1.06 (95% confidence interval (CI) 0.93, 1.20) for beer, HR 0.99 (95% CI 0.88, 1.11) for wine, and HR 1.19 (95% CI 0.97, 1.46) for spirit preference. Absolute wine intake, adjusted for total alcohol, was associated with a lower diabetes risk: pooled HR per 6 g/day was 0.96 (95% CI 0.93, 0.99). A spirit preference was related to a higher diabetes risk in those with a higher body mass index, in men and women separately, but not after excluding persons with prevalent diseases. CONCLUSIONS: This large individual-level meta-analysis among persons who reported alcohol consumption revealed that the preference for beer, wine, and spirits was similarly associated with diabetes incidence compared with having no preference.

Fruit and vegetable intake and risk of incident of type 2 diabetes: results from the consortium on health and ageing network of cohorts in Europe and the United States (CHANCES).

BACKGROUND/OBJECTIVES: There is limited information to support definitive recommendations concerning the role of diet in the development of type 2 Diabetes mellitus (T2DM). The results of the latest meta-analyses suggest that an increased consumption of green leafy vegetables may reduce the incidence of diabetes, with either no association or weak associations demonstrated for total fruit and vegetable intake. Few studies have, however, focused on older subjects. SUBJECTS/METHODS: The relationship between T2DM and fruit and vegetable intake was investigated using data from the NIH-AARP study and the EPIC Elderly study. All participants below the age of 50 and/or with a history of cancer, diabetes or coronary heart disease were excluded from the analysis. Multivariate logistic regression analysis was used to calculate the odds ratio of T2DM comparing the highest with the lowest estimated portions of fruit, vegetable, green leafy vegetables and cabbage intake. RESULTS: Comparing people with the highest and lowest estimated portions of fruit, vegetable or green leafy vegetable intake indicated no association with the risk of T2DM. However, although the pooled OR across all studies showed no effect overall, there was significant heterogeneity across cohorts and independent results from the NIH-AARP study showed that fruit and green leafy vegetable intake was associated with a reduced risk of T2DM OR 0.95 (95% CI 0.91,0.99) and OR 0.87 (95% CI 0.87,0.90) respectively. CONCLUSIONS: Fruit and vegetable intake was not shown to be related to incident T2DM in older subjects. Summary analysis also found no associations between green leafy vegetable and cabbage intake and the onset of T2DM. Future dietary pattern studies may shed light on the origin of the heterogeneity across populations.

Sir William Wilde: an enlightened editor.

This paper examines Sir William Wilde's peculiar genius as editor, his contribution to the Irish Journal of Medical Science in ensuring its endurance and making it a treasure-house of the history of medicine in Ireland.

18F-FDG PET-CT uptake is a feature of both normal diameter and aneurysmal aortic wall and is not related to aneurysm size.

PURPOSE: Aortic metabolic activity is suggested to correlate with presence and progression of aneurysmal disease, but has been inadequately studied. This study investigates the 2-[(18)F] fluoro-2-deoxy-D-glucose ((18)F-FDG) uptake in a population of infra-renal abdominal aortic aneurysms (AAA), compared to a matched non-aneurysmal control group. METHODS: The Positron Emission Tomography - Computed Tomography (PET/CT) database was searched for infra-renal AAA. Exclusion criteria were prior repair, vasculitis, and saccular/mycotic thoracic or thoraco-abdominal aneurysms. Matching of 159 non-aneurysmal (<3 cm diameter) controls from the same population was assessed. Infra-renal aortic wall FDG uptake was assessed using visual analysis; maximum standardized uptake value (SUVmax) and target to background mediastinal blood pool ratio (TBR) were documented. Predictors of FDG uptake (age, sex, aortic diameter, hypertension, statin use, and diabetes) were assessed using univariate analysis. Follow-up questionnaires were sent to referring clinicians. RESULTS: Aneurysms (n = 151) and controls (n = 159) were matched (p > 0.05) for age, sex, diabetes, hypertension, smoking status, statin use, and indication for PET/CT. Median aneurysm diameter was 5.0 cm (range 3.2-10.4). On visual analysis there was no significant difference in the overall numbers with increased visual uptake 24% (36/151) in the aneurysm group vs. 19% (30/159) in the controls, p = ns. SUVmax was slightly lower in the aneurysm group vs. controls (mean (2 SD) 1.75(0.79) vs. 1.84(0.58), p = 0.02). However there was no difference in TBR between the AAA group and controls (mean (2 SD) 1.03 (0.46) vs. 1.05(0.31), p = 0.36). During a median 18 (interquartile range 8-35) months' follow-up 20 were repaired and four were confirmed ruptured. CONCLUSIONS: The level of metabolic activity as assessed by (18)F-FDG PET/CT in infra-renal AAA does not correlate with aortic size and does not differ between aneurysms and matched controls.

Correlation between Ki-67 immunohistochemistry and 18F-fluorothymidine uptake in patients with cancer: A systematic review and meta-analysis.

BACKGROUND: Positron emission tomography (PET) imaging using the radiotracer 18F-Fluorothymidine (FLT) has been proposed as an imaging biomarker of tumour proliferation. If FLT-PET can be established as such it will provide a non-invasive, quantitative measurement of tumour proliferation across the entire tumour. Results from validation studies have so far been conflicting with some studies confirming a good correlation between FLT uptake and Ki-67 score and others presenting negative results. METHODS: Firstly we performed a systematic review of published studies between 1998 and 2011 that explored the correlation between FLT uptake and Ki-67 score and examined possible variations in the methods used. Studies were eligible if they: (a) included patients with cancer, (b) investigated the correlation between Ki-67 measured by immunohistochemistry and FLT uptake measured with PET scanning, and (c) were published as a full paper in a peer-reviewed scientific journal. Secondly a meta-analysis of the correlation coefficient values reported from each study was performed. Correlation coefficient (r) values were extracted from each study and 95% confidence intervals (CIs) were calculated after applying Fisher's z transformation. For subgroup analysis, studies were classified by the index used to characterise Ki-67 expression (average or maximum expression), the nature of the sample (whole specimen or biopsy) and the cancer type. FINDINGS: Twenty-seven studies were identified as eligible for the meta-analysis. In the studies we examined there were variations in aspects of the methods and reporting. The meta-analysis showed that given an appropriate study design the FLT/Ki-67 correlation is significant and independent of cancer type. Specifically subgroup analysis showed that FLT/Ki-67 correlation was high in studies measuring the Ki-67 average expression regardless of use of surgery or biopsy samples (r=0.70, 95% CI=0.43-0.86, p<0.001). Of the studies that measured Ki-67 maximum expression, only those that used the whole surgical specimen provided a significant r value (r=0.72, 95% CI=0.54-0.84, p<0.001). Studies that used biopsy samples for Ki-67 maximum measurements did not produce a significant r value (r=0.04, 95% CI=-0.18-0.26, p=0.71). In terms of the cancer type subgroup analysis there is sufficient data to support a strong FLT/Ki-67 correlation for brain, lung and breast cancer. No publication bias was detected. INTERPRETATION: This systematic review and meta-analysis highlights the importance of the methods used in validation studies comparing FLT-PET imaging with the biomarker Ki-67. The correlation is significant and independent of cancer type provided a study design that uses Ki-67 average measurements, regardless of nature of sample, or whole surgical samples when measuring Ki-67 maximum expression. Sufficient data to support a strong correlation for brain, lung and breast cancer exist. However, larger, prospective studies with improved study design are warranted to validate these findings for the rest of the cancer types.

The challenges of integrating molecular imaging into the optimization of cancer therapy.

We review novel, in vivo and tissue-based imaging technologies that monitor and optimize cancer therapeutics. Recent advances in cancer treatment centre around the development of targeted therapies and personalisation of treatment regimes to individual tumour characteristics. However, clinical outcomes have not improved as expected. Further development of the use of molecular imaging to predict or assess treatment response must address spatial heterogeneity of cancer within the body. A combination of different imaging modalities should be used to relate the effect of the drug to dosing regimen or effective drug concentration at the local site of action. Molecular imaging provides a functional and dynamic read-out of cancer therapeutics, from nanometre to whole body scale. At the whole body scale, an increase in the sensitivity and specificity of the imaging probe is required to localise (micro)metastatic foci and/or residual disease that are currently below the limit of detection. The use of image-guided endoscopic biopsy can produce tumour cells or tissues for nanoscopic analysis in a relatively patient-compliant manner, thereby linking clinical imaging to a more precise assessment of molecular mechanisms. This multimodality imaging approach (in combination with genetics/genomic information) could be used to bridge the gap between our knowledge of mechanisms underlying the processes of metastasis, tumour dormancy and routine clinical practice. Treatment regimes could therefore be individually tailored both at diagnosis and throughout treatment, through monitoring of drug pharmacodynamics providing an early read-out of response or resistance.

Establishment of a UK-wide network to facilitate the acquisition of quality assured FDG-PET data for clinical trials in lymphoma.

BACKGROUND: Multicentre trials are required to determine how [fluorine-18]-2-fluoro-2-deoxy-D-glucose-positron emission tomography imaging can guide cancer treatment. Consistency in quality control (QC), scan acquisition and reporting is mandatory for high-quality results, which are comparable across sites. METHODS: A national positron emission tomography (PET) clinical trials network (CTN) has been set up with a 'core laboratory' to coordinate QC and interpret scans. The CTN is involved in trials in Hodgkin's lymphoma [Randomised Phase III trial to determine the role of FDG-PET Imaging in Clinical Stages IA/IIA Hodgkin's Disease (RAPID) and Randomised Phase III trial to assess response adapted therapy using FDG-PET imaging in patients with newly diagnosed, advanced Hodgkin lymphoma (RATHL)] and diffuse large B-cell lymphoma [Blinded evaluation of prognostic value of FDG-PET after 2 cycles of chemotherapy in diffuse large B-cell Non-Hodgkins Lymphoma, a sub-study of the R-CHOP-21 vs R-CHOP-14 trial (R-CHOP PET substudy)]. Approval to join requires scanner validation and agreement to follow a standard QC protocol. Scans are transferred to the core laboratory and reported centrally according to predetermined criteria. RESULTS: The qualification procedure was carried out on 15 scanners. All scanners were able to demonstrate the necessary quantitative accuracy, and following modification of image reconstruction where necessary, scanners demonstrated comparable recovery coefficients (RCs) indicating similar performance. The average RC (±1 standard deviation) was 0.56 ± 0.095 for the 13-mm sphere. Reports from 444 of 473 (94%) patients in RAPID and 67 of 73 (92%) patients in RATHL were available for randomisation of therapy. CONCLUSIONS: The CTN has enabled consistent quality assured PET results to be obtained from multiple centres in time for clinical decision making. The results of trials will be significantly strengthened by this system.

Incontinentia pigmenti--ophthalmological observation of a series of cases and review of the literature.

AIM: The aims of this study were to make an inventory of the disease in Ireland, to acquire better knowledge of the relationship between genetic makeup and phenotypic ocular presentation and, finally, through literature review and personal experience, to establish clear guidelines on best practice in the management of children with this rare condition both in terms of screening and follow-up. METHODS: All patients who attended the dermatology and genetic clinic in Our Lady's Hospital for Sick Children, Crumlin, with incontinentia pigmenti (IP) were contacted and invited to attend the eye clinic for ocular assessment. Children who were already attending the ophthalmic services before commencement of the study had their charts reviewed for assessment. RESULTS: 11 of 19 patients agreed to attend the clinic for ocular assessment. Of these patients, nine had genetic testing. The mean age of the patients at the examination was 8 years (3 months to 29 years). In 10 patients, IP was the result of a spontaneous mutation, whereas the condition was inherited from an affected mother in one patient. Of the 11 patients with IP, 5 have visually significant ocular findings (47%). We describe the case history of four of these children briefly to outline the severity of this condition. CONCLUSION: Our patients had a significant percentage of ocular abnormalities (47%). We have outlined an examination schedule for patients with and without retinal pathology and recommend fluorescein angiography in patients with retinal pathology to fully determine the extent of ischaemia. Like other studies, early treatment with peripheral retinal photocoagulation to reduce the risk of retinal detachment is recommended in this study.

Diabetes and bone: advantages and limitations of radiological, radionuclide and hybrid techniques in the assessment of diabetic foot.

A common cause of morbidity and mortality in diabetic patients are foot infection/complications often leading to amputation of lower extremities. Various radiological and radionuclide techniques are available for the assessment of diabetic patients with bone or soft tissue infections. However, there are several advantages and limitations. The major limitation of all these techniques is their inability to accurately differentiate osteomyelitis from charcot's/neuropathic joints. Radiologically, magnetic resonance imaging (MRI) is the technique of choice and a radiolobeled white cell scan is a useful nuclear medicine technique in the evaluation of diabetic patients with suspected foot infection. In this review we discuss the efficacy of radiological and radionuclide techniques in the assessment of diabetic foot infection.

Differentiation between infection in kidney and liver cysts in autosomal dominant polycystic kidney disease: use of PET-CT in diagnosis and to guide management.

Positron emission tomography-computed tomography (PET-CT) is a useful imaging method for localizing infective lesions. We report a case of autosomal dominant polycystic kidney disease in which PET-CT was used to differentiate between infection in the kidney and liver cysts. Localization of infection to the liver rather than to kidney cysts altered patient management. We briefly review the role of PET-CT in localization of an occult focus of infection.

Regression of melanoma metastases following treatment with the n-bisphosphonate zoledronate and localised radiotherapy.

We report a case of regression of pulmonary and bony metastases in a patient with malignant melanoma following palliative treatment with systemic zoledronate and localised radiotherapy to the bone. Zoledronate is a potent new bisphosphonate used for the treatment of metabolic bone diseases including bone metastases due to its inhibitory effect on osteoclasts. In the context of metastatic cancer zoledronate is routinely used to improve bone pain and reduce the frequency of skeletal events. There is also an increasing body of evidence suggesting that bisphosphonates exhibit anti-tumour properties. Bisphosphonates are able to activate Vgamma9Vdelta2 gamma-delta T cells which can be key players in the immune defence against malignant cells. Furthermore bisphosphonates have direct anti-proliferative, anti-metastatic and pro-apoptotic effects on tumour cells. These actions, together with their low side effect profile, may prove to be useful therapeutic tools in the treatment of cancer even in the absence of bone metastases. On the basis of this case report we here review the current literature on present preclinical and clinical studies using bisphosphonates for the treatment of cancer.

Interventions for diabetic macular oedema: a systematic review of the literature.

OBJECTIVES: This review discusses the evolution of the treatment of diabetic macular oedema and gives helpful guidelines in the treatment of diabetic macular oedema based on available evidence to date. METHODS: A literature search of all English articles from the Medline and Cochrane database was performed. The search was limited to only English randomised controlled clinical trials in humans. Overall, 93 articles were cited from 1979 to 2007. Of these, 31 articles corresponded to subject matter. Studies were evaluated on a standardised data extraction form and tabulated for easy review. RESULTS: There is good evidence that laser treatment preserves vision in eyes with diabetic macular oedema (DMO). However, laser is a potentially destructive form of treatment which may be of greater benefit in combination with newer forms of treatment such as intravitreal steroid or intravitreal antiangiogenic agents. Current evidence does not support a clear benefit for surgical intervention in DMO. CONCLUSIONS: Although laser treatment remains the cornerstone of treatment in diabetic macular oedema, the literature is beginning to support combination therapy. Using one or two intravitreal injections to reduce central macular thickness followed by focal or grid laser to give a sustained response may offer an alternative to treatment in DMO.