The impact of the COVID-19 pandemic on the performance of the Rapid Access Lung Cancer Clinic.

BACKGROUND: The Rapid Access Lung Cancer Clinic (RALC) experienced fewer referrals during the COVID-19 pandemic in Ireland. AIMS: Our aim was to determine the impact of the pandemic on the key performance indicators (KPIs) of the Cork University Hospital (CUH) RALC, using a retrospective chart review of the referrals and attendances. METHODS: The medical charts of patients referred to CUH-RALC from 03/2019 to 02/2020 (period I), and from 03/2020 to 02/2021 (period II) were reviewed. Performance of the RALC was determined based on average wait time from referral to 1] acquisition of the first CT scan, 2] consultation, and 3] receiving a cancer diagnosis, and compared between periods I and II. RESULTS: Average monthly referrals (57.3 vs 42.1, p = 0.0078) and RALC reviews (24.3 vs 22, p = 0.0310) were lower in period II compared to period I. However, no difference was seen in the length of time from referral to review at RALC or time to receive cancer diagnosis. There were shorter wait times from referral to CT scan (11.2 vs. 8.7 days, p = 0.0011) and to surgery (109.0 vs 79.3 days, p = 0.0236) in period II. CONCLUSIONS: The COVID-19 pandemic had minimal impact on the performance of RALC at our institution. Fewer referrals to RALC in period II may relate to hesitancy in attending general practitioner (GP) and/or GPs raising the thresholds for referrals to RALC during the early lockdown period of the pandemic. A national evaluation will be required to fully determine the impact of this pandemic on lung cancer in Ireland.

Association Between Chronic Hypertension and the Risk of 12 Cardiovascular Diseases Among Parous Women: The Role of Adverse Pregnancy Outcomes.

BACKGROUND: Evidence on the association between chronic hypertension and the risk of cardiovascular disease (CVD) in mothers with adverse pregnancy outcomes (APOs) is limited. We investigated the association between chronic hypertension and risk of CVD, considering the role of APOs. METHODS: We used linked electronic health records in the CALIBER platform to define a UK cohort of women with recorded births between 1997 and 2016. We conducted multivariable Cox regression to estimate the association between chronic hypertension, with and without APOs, and 12 subsequent CVD events. RESULTS: The study cohort comprised 1 784 247 births (1.2 million women); of these 12 698 (0.71%) records had chronic hypertension, and 16 499 women had incident CVD during follow-up, of which 66% occurred in women under 40 years. Chronic hypertension (versus no chronic hypertension) was associated with a 2-fold higher risk of first subsequent CVD (adjusted hazard ratios, 2.22 [95% CI, 2.03-2.42]). Compared to normotensive women without APOs, the associations were the strongest in women with chronic hypertension and APOs across the 12 CVD outcomes, varying from 9.65 (5.96-15.6) for heart failure to 2.66 (2.17-3.26) for stable angina. In women with chronic hypertension without APOs, adjusted hazard ratios varied from 5.25 (3.47-7.94) for subarachnoid hemorrhage to 1.26 (0.59-2.67) for peripheral arterial disease. In women with APOs, but without chronic hypertension, adjusted hazard ratios varied from 3.27 (2.48-4.31) for intracerebral hemorrhage to 1.33 (1.26-1.41) for stable angina. CONCLUSIONS: We found strong associations between chronic hypertension and the risk of premature CVD, with greater risk in women who additionally had APOs. Intervention programs focused on these groups might lower their risk of subsequent CVD.

Chemsex, Anxiety and Depression Among Gay, Bisexual and Other Men Who have Sex with Men Living with HIV.

Chemsex is common among gay, bisexual and other men who have sex with men (gbMSM). Although not always categorised as problematic, a link with psychological distress has been reported and might be exacerbated amongst gbMSM living with HIV, as HIV has been associated with anxiety and depression. A cross-sectional online survey of gbMSM living with HIV (n = 359) was performed incorporating the Hospital Anxiety and Depression Scale and sociodemographic variables including, HIV characteristics, chemsex and sexual behaviours. Logistic regression analysis was used to find associations with anxiety or depression. Many participants engaged in chemsex (48.5%, n = 174). Chemsex was associated with lower odds of depression (aOR 0.45, 95% CI 0.23-0.85) and not associated with anxiety (aOR 0.66, CI 0.40-1.09). Although chemsex is a public health concern; we found it was associated with lower levels of depression in gbMSM living with HIV. However, causal inference is not possible, as gbMSM with higher levels of depression might engage in chemsex less.

Compliance with local travel restrictions and face masks during first phase of COVID-19 pandemic in Ireland: a national survey.

BACKGROUND: This study examines compliance with local travel restrictions and assesses early uptake of mask wearing, during the initial phase of the coronavirus disease of 2019 (COVID-19) pandemic in Ireland, to inform the ongoing outbreak response. METHODS: A series of four nationally representative telephone surveys were developed. Information was collected at a household level and from primary respondents. Multivariable logistic regression estimated the association between sociodemographic characteristics and compliance with the local travel restriction and with mask use in primary respondents. RESULTS: Household compliance with local travel restrictions was similar by region, household size and social position. 73.4% of all household members complied, with high levels maintained over time. Higher proportions reported travelling for non-permitted reasons with time. Older age, female gender and attending higher education were independently associated with compliance to local travel restrictions. Among primary respondents, no factors were independently associated with mask use. CONCLUSION: High compliance with local travel restrictions during the early stages of the pandemic demonstrates the engagement of the population with public health guidance. Although high compliance with local travel restrictions was generally maintained over time, non-permitted activities increased. Early adoption of mask use before required by national policy or legislation provides further evidence of the responsiveness of the population.

Enhancing referral processes within an integrated fall prevention pathway for older people: a mixed-methods study.

OBJECTIVES: Multifactorial interventions, which involve assessing an individual's risk of falling and providing treatment or onward referral, require coordination across settings. Using a mixed-methods design, we aimed to develop a process map to examine onward referral pathways following falls risk assessment in primary care. SETTING: Primary care fall risk assessment clinics in the South of Ireland. PARTICIPANTS: Focus groups using participatory mapping techniques with primary care staff (public health nurses (PHNs), physiotherapists (PT),and occupational therapists (OT)) were conducted to plot the processes and onward referral pathways at each clinic (n=5). METHODS: Focus groups were analysed in NVivo V.12 using inductive thematic analysis. Routine administrative data from January to March 2018 included details of client referrals, assessments and demographics sourced from referral and assessment forms. Data were analysed in Stata V.12 to estimate the number, origin and focus of onward referrals and whether older adults received follow-up interventions. Quantitative and qualitative data were analysed separately and integrated to produce a map of the service. RESULTS: Nine staff participated in three focus groups and one interview (PHN n=2; OT n=4; PT n=3). 85 assessments were completed at five clinics (female n=69, 81.2%, average age 77). The average number of risk factors was 5.4 out of a maximum of 10. Following assessment, clients received an average of three onward referrals. Only one-third of referrals (n=135/201, 33%) had data available on intervention receipt. Primary care staff identified variations in how formally onward referrals were managed and barriers, including a lack of client information, inappropriate referral and a lack of data management support. CONCLUSION: Challenges to onward referral manifest early in an integrated care pathway, such as clients with multiple risk factors sent for initial assessment and the lack of an integrated IT system to share information across settings.

Association between social deprivation and incidence of first seizures and epilepsy: A prospective population-based cohort.

OBJECTIVE: Epidemiologic studies have investigated whether social deprivation is associated with a higher incidence of epilepsy, and results are conflicting, especially in children. The mechanisms underlying a potential association are unclear. This study examines whether there is an association between social deprivation and the incidence of first seizures (unprovoked and provoked) and new diagnosis of epilepsy by comparing incidence across an area-level measure of deprivation in a population-based cohort. METHODS: Multiple methods of case identification followed by individual case validation and classification were carried out in a defined geographical area (population 542 868) to identify all incident cases of first provoked and first unprovoked seizures and new diagnosis of epilepsy presenting during the calendar year 2017. An area-level relative deprivation index, based on 10 indicators from census data, was assigned to each patient according to registered address and categorized into quintiles from most to least deprived. RESULTS: The annual incidence of first unprovoked seizures (n = 372), first provoked seizures (n = 189), and new diagnosis of epilepsy (n = 336) was highest in the most deprived areas compared to the least deprived areas (incidence ratios of 1.79 [95% confidence interval (CI) = 1.26-2.52], 1.55 [95% CI = 1.04-2.32], and 1.83 [95% CI = 1.28-2.62], respectively). This finding was evident in both adults and children and in those with structural and unknown etiologies of epilepsy. SIGNIFICANCE: The incidence of first seizures and new diagnosis of epilepsy is associated with more social deprivation. The reason for this higher incidence is likely multifactorial.

Role of Antihypertensive Treatment and Blood Pressure Control in the Occurrence of Adverse Pregnancy Outcomes: a Population-Based Study of Linked Electronic Health Records.

BACKGROUND: Chronic hypertension (CH) adversely impacts pregnancy. It remains unclear whether antihypertensive treatment alters these risks. We examined the role of antihypertensive treatment in the association between CH and adverse pregnancy outcomes. METHODS: Electronic health records from the UK Caliber and Clinical Practice Research Datalink were used to define a cohort of women delivering between 1997 and 2016. Primary outcomes were preeclampsia, preterm birth (PTB), and fetal growth restriction (FGR). We used multivariable logistic regression to compare outcomes in women with CH to women without CH and propensity score matching to compare antihypertensive agents. RESULTS: The study cohort consisted of 1 304 679 women and 1 894 184 births. 14 595 (0.77%) had CH, and 6786 (0.36%) were prescribed antihypertensive medications in pregnancy. Overall, women with CH (versus no CH), had higher odds of preeclampsia (adjusted odds ratio [aOR], 5.74 [95% CI, 5.44-6.07]); PTB (aOR, 2.53 [2.39-2.67]); and FGR (aOR, 2.51 [2.31-2.72]). Women with CH prescribed treatment (versus untreated women) had higher odds of preeclampsia (aOR, 1.17 [1.05-1.30]), PTB (1.25 [1.12-1.39]), and FGR (1.80 [1.51-2.14]). Women prescribed methyldopa (versus ß-blockers) had higher odds of preeclampsia (aOR, 1.43 [1.19-1.73]); PTB (1.59 [1.30-1.93]), but lower odds of FGR (aOR, 0.66 [0.48-0.90]). Odds of adverse outcomes were similar in relation to calcium channel blockers (versus ß-blockers) except for PTB (aOR, 1.94 [1.15-3.27]). Among women prescribed treatment, lower average blood pressure (<135/85 mm Hg) was associated with better pregnancy outcomes. CONCLUSIONS: Treatment with antihypertensive agents and control of hypertension ameliorates some effects but higher risks of adverse outcomes persist. ß-Blockers versus methyldopa may be associated with better pregnancy outcomes except for FGR. Powered trials are needed to inform optimal treatment of CH during pregnancy.

Chronic kidney disease and adverse pregnancy outcomes: a systematic review and meta-analysis.

OBJECTIVE: Limited evidence exists on the role that the cause of chronic kidney disease plays in determining pregnancy outcomes. The aim of this systematic review and meta-analysis was to examine the association between chronic kidney disease and adverse pregnancy outcomes by the cause and severity of chronic kidney disease where reported. The protocol was registered under the International Prospective Register of Systematic Reviews (CRD42020211925). DATA SOURCES: PubMed, Embase, and Web of Science were searched until May 24, 2021, supplemented with reference list checking. STUDY ELIGIBILITY CRITERIA: Studies that compared the pregnancy outcomes in women with or without chronic kidney disease were included. Two reviewers independently screened titles, abstracts, and full-text articles according to a priori defined inclusion criteria. METHODS: Data extraction and quality appraisal were performed independently by 3 reviewers. The grading of recommendations, assessment, development, and evaluation approach was used to assess the overall certainty of the evidence. Random-effects meta-analyses were used to calculate the pooled estimates using the generic inverse variance method. The primary outcomes included preeclampsia, cesarean delivery, preterm birth (<37 weeks' gestation), and small for gestational age babies. RESULTS: Of 4076 citations, 31 studies were included. Prepregnancy chronic kidney disease was significantly associated with a higher odds of preeclampsia (pooled crude odds ratio, 8.13; [95% confidence interval, 4.41-15], and adjusted odds ratio, 2.58; [1.33-5.01]), cesarean delivery (adjusted odds ratio, 1.65; [1.21-2.25]), preterm birth (adjusted odds ratio, 1.73; [1.31-2.27]), and small for gestational age babies (adjusted odds ratio, 1.93; [1.06-3.52]). The association with stillbirth was not statistically significant (adjusted odds ratio, 1.67; [0.96-2.92]). Subgroup analyses indicated that different causes of chronic kidney disease might confer different risks and that the severity of chronic kidney disease is associated with a risk of adverse pregnancy outcomes, as pregnancies with later stages of chronic kidney disease had higher odds of preeclampsia, preterm birth, and small for gestational age babies than those at earlier stages. The grading of recommendations, assessment, development, and evaluation certainty of the evidence overall was "very low". CONCLUSION: This meta-analysis quantified the associations between prepregnancy chronic kidney disease and adverse pregnancy outcomes, both overall and according to the cause and severity of the disease. These findings might support the clinicians aiming to counsel women having chronic kidney disease by allowing them to tailor their advice according to cause and severity of the chronic kidney disease. We identified the gaps in the literature, and further studies examining the effect of specific kidney diseases and other clinical characteristics (eg, proteinuria, hypertension) on adverse pregnancy outcomes are warranted.

Causes and classification of first unprovoked seizures and newly-diagnosed epilepsy in a defined geographical area- an all-comers analysis.

PURPOSE: The ILAE recently updated the operational definition of epilepsy and the classifications of seizures and epilepsy incorporating aetiology into the classification framework. To date, these classifications have not been applied in any whole population incidence study. METHODS: Multiple overlapping methods of case identification were applied to a defined geographical area (population 542,868 adults and children) to identify all first unprovoked seizures and new diagnosis of epilepsy presenting during the calendar year 2017. The 2017 ILAE classification frameworks were applied. Incidence was age-standardised to the 2013 Standard European Population. RESULTS: The annual incidence per 100,000 population was 44 for focal epilepsy, 6.8 for generalized epilepsy and 10.9 for unclassified epilepsy (age standardized 56, 6.9 and 11.4, respectively). Focal epilepsy was diagnosed in all age groups, though incidence increased in those ≥55 years of age. Primary generalised epilepsy accounted for 10% (n = 32) of newly diagnosed epilepsy. The most frequently diagnosed aetiology was structural (54%, n = 182). In 30% (n = 102) of newly diagnosed epilepsy, aetiology was not established. CONCLUSION: We report on the causes of incident first unprovoked seizures and epilepsy in accordance with recently updated ILAE definitions and classification systems employing standard diagnostic investigations. We report a higher proportion of structural aetiology than previous studies, which may reflect incorporation of imaging in aetiology classification. Despite improved access to diagnostic testing, aetiology of a large fraction of first seizures and newly diagnosed epilepsy remains unknown.

Prediagnostic Neurofilament Light Chain Levels in Amyotrophic Lateral Sclerosis.

OBJECTIVE: To assess whether plasma neurofilament light chain (NfL) levels are elevated before ALS diagnosis and to evaluate whether pre-diagnostic NfL levels are associated with metabolic alterations. METHODS: We conducted a matched case-control study nested in three large prospective US cohorts (the Nurses' Health Study, the Health Professionals Follow-up Study, and the Multiethnic Cohort Study), and identified 84 individuals who developed ALS during follow-up and had available plasma samples prior to disease diagnosis. For each ALS case, we randomly selected controls from those who were alive at the time of the case diagnosis and matched on birth year, sex, race/ethnicity, fasting status, cohort, and time of blood draw. We measured NfL in the plasma samples and used conditional logistic regression to estimate rate ratios (RRs) and 95% confidence intervals (CIs) for ALS, adjusting for body mass index, smoking, physical activity, and urate levels. RESULTS: Higher NfL levels were associated with a higher ALS risk in plasma samples collected within 5 years of the ALS diagnosis (RR per 1 standard deviation [SD] increase: 2.68, 95% CI: 1.18-6.08), but not in samples collected further away from the diagnosis (RR per 1 SD increase 1.16, 95% CI: 0.78-1.73). A total of 21 metabolites were correlated with pre-diagnostic NfL levels in ALS cases (p < 0.05), but none of these remained significant after multiple comparison adjustments. CONCLUSIONS: Plasma NfL levels were elevated in pre-diagnostic ALS cases, indicating that NfL may be a useful biomarker already in the earliest stages of the disease. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that plasma NfL levels are elevated in pre-diagnostic ALS patients.

Impact of Chronic Hypertension and Antihypertensive Treatment on Adverse Perinatal Outcomes: Systematic Review and Meta-Analysis.

Background Maternal chronic hypertension is associated with adverse pregnancy outcomes. Previous studies examined the association between either chronic hypertension or antihypertensive treatment and adverse pregnancy outcomes. We aimed to synthesize the evidence on the effect of chronic hypertension/antihypertensive treatment on adverse pregnancy outcomes. Methods and Results Medline/PubMed, EMBASE, and Web of Science were searched; we included observational studies and assessed the effect of race/ethnicity, where possible, following a registered protocol (CRD42019120088). Random-effects meta-analyses were used. A total of 81 studies were identified on chronic hypertension, and a total of 16 studies were identified on antihypertensive treatment. Chronic hypertension was associated with higher odds of preeclampsia (adjusted odd ratio [aOR], 5.43; 95% CI, 3.85-7.65); cesarean section (aOR, 1.87; 95% CI, 1.6-2.16); maternal mortality (aOR, 4.80; 95% CI, 3.04-7.58); preterm birth (aOR, 2.23; 95% CI, 1.96-2.53); stillbirth (aOR, 2.32; 95% CI, 2.22-2.42); and small for gestational age (SGA) (aOR, 1.96; 95% CI, 1.6-2.40). Subgroup analyses indicated that maternal race/ethnicity does not influence the observed associations. Women with chronic hypertension on antihypertensive treatment (versus untreated) had higher odds of SGA (aOR, 1.86; 95% CI, 1.38-2.50). Conclusions Chronic hypertension is associated with adverse pregnancy outcomes, and these associations appear to be independent of maternal race/ethnicity. In women with chronic hypertension, those on treatment had a higher risk of SGA, although the number of studies was limited. This could result from a direct effect of the treatment or because severe hypertension during pregnancy is a risk factor for SGA and women with severe hypertension are more likely to be treated. The effect of antihypertensive treatment on SGA needs to be further tested with large randomized controlled trials.

Pregnancy outcomes in women with chronic kidney disease and chronic hypertension: a National cohort study.

BACKGROUND: Maternal chronic kidney disease and chronic hypertension have been linked with adverse pregnancy outcomes. We aimed to examine the association between these conditions and adverse pregnancy outcomes over the last 3 decades. OBJECTIVE: We conducted this national cohort study to assess the association between maternal chronic disease (CH, CKD or both conditions) and adverse pregnancy outcomes with an emphasis on the effect of parity, maternal age, and BMI on these associations over the last three decades. We further investigated whether different subtypes of CKD had differing effects. STUDY DESIGN: We used data from the Swedish Medical Birth Register, including 2,788,490 singleton births between 1982 and 2012. Women with chronic kidney disease and chronic hypertension were identified from the Medical Birth Register and National Patient Register. Logistic regression models were performed to assess the associations between maternal chronic disease (chronic hypertension, chronic kidney disease, or both conditions) and pregnancy outcomes, including preeclampsia, in-labor and prelabor cesarean delivery, preterm birth, small for gestational age, and stillbirth. RESULTS: During the 30-year study period, 22,397 babies (0.8%) were born to women with chronic kidney disease, 13,279 (0.48%) to women with chronic hypertension and 1079 (0.04%) to women with both conditions. Associations with chronic hypertension were strongest for preeclampsia (adjusted odds ratio, 4.57; 95% confidence interval, 4.33-4.84) and stillbirth (adjusted odds ratio, 1.65; 95% confidence interval, 1.35-2.03) and weakest for spontaneous preterm birth (adjusted odds ratio, 1.07; 95% confidence interval, 0.96-1.20). The effect of chronic kidney disease varied from (adjusted odds ratio, 2.05; 95% confidence interval, 1.92-2.19) for indicated preterm birth to no effect for stillbirth (adjusted odds ratio, 1.16; 95% confidence interval, 0.95-1.43). Women with both conditions had the strongest associations for in-labor cesarean delivery (adjusted odds ratio, 1.86; 95% confidence interval, 1.49-2.32), prelabor cesarean delivery (adjusted odds ratio, 2.68; 95% confidence interval, 2.18-3.28), indicated preterm birth (adjusted odds ratio, 9.09; 95% confidence interval, 7.61-10.7), and small for gestational age (adjusted odds ratio, 4.52; 95% confidence interval, 3.68-5.57). The results remained constant over the last 3 decades. Stratified analyses of the associations by parity, maternal age, and body mass index showed that adverse outcomes remained independently higher in women with these conditions, with worse outcomes in multiparous women. All chronic kidney disease subtypes were associated with higher odds of preeclampsia, in-labor cesarean delivery, and medically indicated preterm birth. Different subtypes of chronic kidney disease had differing risks; strongest associations of preeclampsia (adjusted odds ratio, 3.98; 95% confidence interval, 2.98-5.31) and stillbirth (adjusted odds ratio, 2.73; 95% confidence interval, 1.13-6.59) were observed in women with congenital kidney disease, whereas women with diabetic nephropathy had the most pronounced increase odds of in-labor cesarean delivery (adjusted odds ratio, 3.54; 95% confidence interval, 2.06-6.09), prelabor cesarean delivery (adjusted odds ratio, 7.50; 95% confidence interval, 4.74-11.9), and small for gestational age (adjusted odds ratio, 4.50; 95% confidence interval, 2.92-6.94). In addition, women with renovascular disease had the highest increased risk of preterm birth in both spontaneous preterm birth (adjusted odds ratio, 3.01; 95% confidence interval, 1.57-5.76) and indicated preterm birth (adjusted odds ratio, 8.09; 95% confidence interval, 5.73-11.4). CONCLUSION: Women with chronic hypertension, chronic kidney disease, or both conditions are at an increased risk of adverse pregnancy outcomes which were independent of maternal age, body mass index, and parity. Multidisciplinary management should be provided with intensive clinical follow-up to support these women during pregnancy, particularly multiparous women. Further research is needed to evaluate the effect of disease severity on adverse pregnancy outcomes.

Pre-diagnostic plasma lipid levels and the risk of amyotrophic lateral sclerosis.

OBJECTIVE: To assess whether pre-diagnostic lipid levels are associated with Amyotrophic lateral sclerosis (ALS) risk. Methods: We conducted a matched case-control study nested in five large prospective US cohorts (the Nurses' Health Study, the Health Professionals Follow-up Study, the Cancer Prevention Study II Nutrition Cohort, the Multiethnic Cohort Study, and the Women's Health Initiative), and identified 275 individuals who developed ALS during follow-up and had provided blood samples before disease diagnosis. For each ALS case, we randomly selected two controls who were alive at the time of the case diagnosis and matched on cohort, birth year (±1 year), sex, race/ethnicity, fasting status, and time of blood draw. We measured total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and triglyceride (TG) levels in the plasma samples, and used conditional logistic regression to estimate associations between lipid levels and ALS risk. Results: Higher levels of HDL-C were associated with higher ALS risk in an analysis adjusted for the matching factors (risk ratio [RR] Q4 vs. Q1: 1.78, 95% confidence interval [CI]: 1.18-2.69, p trend: 0.007). The estimate remained similar in a multivariable analysis additionally adjusted for body mass index, physical activity, smoking, alcohol intake, plasma urate levels, and use of cholesterol-lowering drugs (RR Q4 vs. Q1: 1.71, 95% CI: 1.07-2.73, p trend: 0.02). Plasma levels of TC, LDL-C, and TG were not associated with ALS risk. Conclusions: Higher pre-diagnostic HDL-C levels, but not levels of other lipids, were associated with a higher risk of ALS.

Covid-19 Estimating the burden of symptomatic disease in the community and the impact of public health measures on physical, mental and social wellbeing: a study protocol.

Introduction: Covid-19 was declared a pandemic in March 2020. Since then, governments have implemented unprecedented public health measures to contain the virus. This study will provide evidence to inform responses to the pandemic by: i) estimating population prevalence and trends of self-reported symptoms of Covid-19 and the proportions of symptomatic individuals and household contacts testing positive for Covid-19; ii) describing acceptance and compliance with physical-distancing measures, explore effects of public health measures on physical, mental and social wellbeing; iii) developing a mathematical network model to inform decisions on the optimal levels of physical distancing measures. Methods: Two cross-sectional nationally-representative telephone surveys will be conducted in Ireland using random digit-dialling, with response rates estimates based on proportion of non-operational and non-answering numbers. The first survey with four waves in May and June will address adherence to social distancing measures and whether the respondent or other household members are or have been unwell during the preceding two weeks with one or more symptoms of Covid-19. The second survey with three waves in June, July and September will address knowledge, attitudes, and compliance towards physical-distancing measures and physical, mental and social wellbeing. The mathematical network model will be developed for all-Ireland (on various levels of spatial granularity including the scale of counties and electoral divisions) based on outputs from both cross-sectional surveys and relevant publicly available data to inform decisions on optimal levels and duration of physical distancing measures. Discussion: This study will contribute to our understanding of the impact and sustainability of public health measures of the Covid-19 pandemic. Findings will have long-lasting benefits, informing decision-making on the best levels, and duration of physical-distancing measures, balancing a range of factors including capacity of the health service with the effects on individuals' wellbeing and economic disruption. Findings will be shared with key policy-makers.

Incidence of first seizures, epilepsy, and seizure mimics in a geographically defined area.

OBJECTIVE: To determine the incidence of first seizures, epilepsy, and seizure mimics in a geographically defined area using the updated 2014 International League Against Epilepsy (ILAE) definition, which allows an epilepsy diagnosis after a single seizure when the risk of further seizures over the next 10 years is ≈60% or greater. This replaced the 1993 definition by which epilepsy was diagnosed when a person had ≥2 seizures separated by 24 hours. METHODS: Using multiple overlapping methods of case ascertainment followed by individual case classification by an epileptologist, we identified all first seizures, new diagnosis of epilepsy, and seizure mimics occurring in a defined geographic area (population 542,868) from January 1, 2017, to December 31, 2017. Incidence was age standardized to the Standard European Population. We compared incidence rates using the 2014 and 1993 ILAE definitions. RESULTS: When the 2014 ILAE definition of epilepsy was applied, the incidence of new diagnosis of epilepsy was 62 per 100,000 (age standardized 74) compared to 41 per 100,000 (age standardized 48) when the 1993 definition was applied, and the difference was more pronounced at older ages. The incidence of all first seizures and of seizure mimics was 102 per 100,000 (age standardized 123) and 94 per 100,000 (age standardized 111), respectively. The most frequently encountered seizure mimic was syncope. CONCLUSION: Application of the 2014 ILAE definition of epilepsy resulted in a higher incidence of new diagnosis of epilepsy compared to the 1993 definition. The incidence of seizure mimics almost equals that of all first seizures. Seizures, epilepsy, and seizure mimics represent a significant burden to health care systems.

Long-Term Use of Antibiotics and Risk of Parkinson's Disease in the Nurses' Health Study.

OBJECTIVE: Antibiotic use is one of the strongest environmental predictors of an altered and less diverse gut microbiome, which has been linked to Parkinson's disease. To our knowledge, no prior study has examined the association between long-term antibiotic use and Parkinson's disease. DESIGN: We conducted a prospective study of 59,637 women in the Nurses' Health Study who reported total duration of antibiotic use at ages 20-39, 40-59, 60 +, or during the past 4 years. We used Cox Proportional Hazard regression to estimate hazard ratios and 95% confidence intervals for the association between categories of antibiotic use and risk of PD. RESULTS: One hundred and eighty cases of PD were confirmed during the follow-up. Self-reported antibiotic use at ages 20-39, 40-59, and 60 +, as assessed in 2004, was not significantly associated with PD risk in our cohort. The hazard ratio comparing participants who used antibiotics for 2 or more months vs. 1-14 days at age 20-39 was 0.98 (95% CI: 0.54, 1.78), at age 40-59 was 1.44 (95% CI: 0.88, 2.33), and at age 60 +was 0.88 (95% CI: 0.53, 1.47). Antibiotic use during the past four years, as assessed in 2008, was also not associated with future risk of PD (HR: 1.14, 95% CI: 0.62, 2.10). CONCLUSION: In this cohort study, we did not observe a significant association between antibiotic use and incidence PD. A major limitation of our study is assessment of exposure, which required many participants to recall their antibiotic use decades in the past. Thus, although the results of this study do not support an effect of antibiotic use on PD risk, larger investigations relying on records of antibiotic prescriptions would provide more definitive evidence.

Augmented exercise in hospital improves physical performance and reduces negative post hospitalization events: a randomized controlled trial.

BACKGROUND: To measure the effects of an augmented prescribed exercise programme versus usual care, on physical performance, quality of life and healthcare utilisation for frail older medical patients in the acute setting. METHODS: This was a parallel single-blinded randomised controlled trial. Within 2 days of admission, older medical inpatients with an anticipated length of stay ≥3 days, needing assistance/aid to walk, were blindly randomly allocated to the intervention or control group. Until discharge, both groups received twice daily, Monday-to-Friday half-hour assisted exercises, assisted by a staff physiotherapist. The intervention group completed tailored strengthening and balance exercises; the control group performed stretching and relaxation exercises. Length of stay was the primary outcome measure. Blindly assessed secondary measures included readmissions within 3 months, and physical performance (Short Physical Performance Battery) and quality of life (EuroQOL-5D-5 L) at discharge and at 3 months. Time-to-event analysis was used to measure differences in length of stay, and regression models were used to measure differences in physical performance, quality of life, adverse events (falls, deaths) and negative events (prolonged hospitalisation, institutionalisation). RESULTS: Of the 199 patients allocated, 190 patients' (aged 80 ± 7.5 years) data were analysed. Groups were comparable at baseline. In intention-to-treat analysis, length of stay did not differ between groups (HR 1.09 (95% CI, 0.77-1.56) p = 0.6). Physical performance was better in the intervention group at discharge (difference 0.88 (95% CI, 0.20-1.57) p = 0.01), but lost at follow-up (difference 0.45 (95% CI, - 0.43 - 1.33) p = 0.3). An improvement in quality of life was detected at follow-up in the intervention group (difference 0.28 (95% CI, 0.9-0.47) p = 0.004). Overall, fewer negative events occurred in the intervention group (OR 0.46 (95% CI 0.23-0.92) p = 0.03). CONCLUSION: Improvements in physical performance, quality of life and fewer negative events suggest that this intervention is of value to frail medical inpatients. Its effect on length of stay remains unclear. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02463864, registered prospectively 26.05.2015.

Prediagnostic plasma polyunsaturated fatty acids and the risk of amyotrophic lateral sclerosis.

OBJECTIVE: To examine the association between prediagnostic plasma polyunsaturated fatty acids levels (PUFA) and amyotrophic lateral sclerosis (ALS). METHODS: We identified 275 individuals who developed ALS while enrolled in 5 US prospective cohorts, and randomly selected 2 controls, alive at the time of the case diagnosis, matched on cohort, birth year, sex, ethnicity, fasting status, and time of blood draw. We measured PUFA, expressed as percentages of total fatty acids, using gas liquid chromatography and used conditional logistic regression to estimate risk ratios (RR) and 95% confidence intervals (CI) for the association between PUFA and ALS. RESULTS: There was no association between total, n-3, and n-6 PUFA, eicosapentaenoic acid, or docosapentaenoic acid levels and ALS. Higher plasma α-linolenic acid (ALA) in men was associated with lower risk of ALS in age- and matching factor-adjusted analyses (top vs bottom quartile: RR = 0.21 [95% CI 0.07, 0.58], p for trend = 0.004). In women, higher plasma arachidonic acid was associated with higher risk (top vs bottom quartile: RR = 1.65 [95% CI 0.99, 2.76], p for trend = 0.052). Multivariable adjustment, including correlated PUFA, did not change the findings for ALA and arachidonic acid. In men and women combined, higher plasma docosahexaenoic acid (DHA) was associated with higher risk of ALS (top vs bottom quartile: RR = 1.56 [95% CI 1.01, 2.41], p for trend = 0.054), but in multivariable models the association was only evident in men. CONCLUSIONS: The majority of individual PUFAs were not associated with ALS. In men, ALA was inversely and DHA was positively related to risk of ALS, while in women arachidonic acid was positively related. These findings warrant confirmation in future studies.

Substitution of sugar-sweetened beverages for other beverages and the risk of developing coronary heart disease: Results from the Harvard Pooling Project of Diet and Coronary Disease.

Sugar-sweetened beverage (SSB) intake is associated with metabolic disorders. The reduction of SSB intake has been promoted to prevent death and disability from chronic diseases. We investigated the association between SSB intake and the risk of coronary events and death, and assessed if substitution of coffee, tea, milk, fruit juice and artificially-sweetened beverages (ASB) for SSBs was associated with a reduced risk of coronary events and death. This was a follow-up study in which data from six studies were pooled and standard observational analyses were performed. Diet intake was assessed at baseline by food-frequency questionnaires. Hazard ratios (HRs) with 95% confidence intervals for the incidence of coronary events and deaths were calculated by Cox proportional hazards regression. The effect of substituting another beverage for SSBs was calculated by taking the difference in the individual effect estimates. During the median 8.2-year follow-up, 4248 coronary events and 1630 coronary deaths were documented among 284,345 individuals. 355 ml daily increase of SSB intake was associated with an increased risk of coronary events (HR: 1.08; 95%CI: 1.02, 1.14) and possibly coronary death (HR: 1.05; 95%CI: 0.96, 1.16). Substitution analyses suggested that replacing SSBs with coffee (HR: 0.93; 95%CI: 0.87, 1.00) or ASB (HR: 0.89; 95%CI: 0.83, 0.97), might be associated with a lower risk of developing coronary events. We found that SSB intake was associated with an increased risk of coronary events and possibly coronary death. Our findings also suggest that replacing SSB's with ASBs or coffee may lower the risk of developing CHD.

Application of Recent International Epidemiological Guidelines to a Prospective Study of the Incidence of First Seizures, Newly-Diagnosed Epilepsy and Seizure Mimics in a Defined Geographic Region in Ireland.

Studies adherent to international guidelines and epilepsy classification are needed to accurately record the incidence of isolated seizures, epilepsy and seizure-mimics within a population. Because the diagnosis of epilepsy is largely made through clinical assessment by experienced physicians, seizures and epilepsy are susceptible to misdiagnosis. Previous epidemiological studies in epilepsy have not captured "seizure mimics". We therefore sought to quantify the incidence of isolated seizures, epilepsy and seizure-mimics using the International League Against Epilepsy (ILAE) classification system. In this study multiple overlapping methods of case ascertainment were applied to a defined geographic region from January 1 to March 31, 2017 to identify all patients presenting with first seizures (provoked and unprovoked), new diagnoses of epilepsy and seizure mimics. Over a 3 month period, from a population of 542,869 adults and children, 442 potential presentations were identified, and 283 met the inclusion criteria. Radiology databases were the source of the largest number of individual cases (n = 153, 54%), while electroencephalogram (EEG) databases were the source of the highest number of unique-to-source cases (those not identified elsewhere, n = 60, 21%). No single case was picked up in every method of ascertainment. Among the 283 included presentations, 38 (13%) were classed as first provoked seizures, 27 (10%) as first unprovoked seizures, 95 (34%) as new diagnosis of epilepsy and 113 (40%) as seizure mimics. Ten (3%) presentations were indeterminate. We present and apply a rigorous study protocol for investigation of the incidence of first seizures, new diagnosis of epilepsy and seizure mimics in a geographically defined region which is adherent to recently published international guidelines for epidemiologic studies and epilepsy classification. We highlight the challenges in making a diagnosis of new-onset epilepsy in patients presenting with a first seizure using the current ILAE definition of epilepsy, when epilepsy can be diagnosed in situations where the treating physician anticipates the risk of further seizures exceeds 60%.