Excess mortality in Europe coincides with peaks of COVID-19, influenza and respiratory syncytial virus (RSV), November 2023 to February 2024.

Since the end of November 2023, the European Mortality Monitoring Network (EuroMOMO) has observed excess mortality in Europe. During weeks 48 2023-6 2024, preliminary results show a substantially increased rate of 95.3 (95% CI:  91.7-98.9) excess all-cause deaths per 100,000 person-years for all ages. This excess mortality is seen in adults aged 45 years and older, and coincides with widespread presence of COVID-19, influenza and respiratory syncytial virus (RSV) observed in many European countries during the 2023/24 winter season.

Extended Right-Sided Colon Resection Does Not Reduce the Risk of Colon Cancer Local-Regional Recurrence: Nationwide Population-Based Study From Danish Colorectal Cancer Group Database.

BACKGROUND: It is controversial whether extensive resection of right-sided colon cancer confers oncological benefits. OBJECTIVE: The aim of this study was to evaluate short- and long-term outcomes of extended surgical removal of the mesocolon compared to the conventional approach. DESIGN: This was a retrospective population-based study. SETTING: Study is based on a prospectively maintained Danish Colorectal Cancer Group database. MAIN OUTCOME MEASURES: Primary outcome measures included local-regional recurrence in patients who underwent curative resection for right-sided colon cancer and 30-day postoperative complications. Distant metastasis, unplanned intraoperative adverse events, and 30- and 90-day postoperative mortality were also investigated. Patients who had palliative or compromised resection, emergency surgery, or neoadjuvant chemotherapy were excluded. RESULTS: Of the 12,855 patients with resection of right-sided colon cancer retrieved, 1151 underwent extended right hemicolectomy. Patients who had extended right hemicolectomy were younger males with lower ASA scores, were operated on by colorectal surgeons using a laparoscopic approach, and had a significantly higher number of harvested lymph nodes. The rate of local-regional recurrence was 1.1% (136/12,855), with no difference between conventional right hemicolectomy and extended right hemicolectomy (OR, 1.7; 95% CI, 0.63-2.18). Postoperative medical complications were significantly higher in extended right hemicolectomy even after adjusting for age, comorbidity, access to the abdomen, and other covariates (OR, 1.26; 95% CI, 1.01-1.58). No significant difference was noticed between conventional right hemicolectomy and extended right hemicolectomy in the rates of distant metastasis, unplanned intraoperative adverse events, and mortality. LIMITATIONS: Because it is a register-based study, underreporting cannot be excluded. Extended right hemicolectomy, as defined in this study, does not reflect the extent of lymphatic dissection performed during the surgery. CONCLUSIONS: This large population-based register study showed no difference in local-regional recurrence of right-sided colon cancer between conventional and extended right hemicolectomy with mesenteric resection and ligation of the middle colic vessels. Extended resection was associated with higher rates of postoperative complications. See Video Abstract at http://links.lww.com/DCR/B907 . LA RESECCIN AMPLIADA DEL COLON DERECHO NO REDUCE EL RIESGO DE RECURRENCIA LOCALREGIONAL DEL CNCER DE COLON ESTUDIO POBLACIONAL A NIVEL NACIONAL DE LA BASE DE DATOS DEL GRUPO DANS DE CNCER COLORRECTAL: ANTECEDENTES:Es aun un tema controversial si la resección ampliada del cáncer de colon del lado derecho confiere beneficios oncológicos.OBJETIVOS:El objetivo de este estudio fue examinar los resultados a corto y largo plazo de la resección quirúrgica ampliada del mesocolon en comparación con el enfoque convencional.DISEÑO:Este fue un estudio poblacional de tipo retrospectivo basado en una base de datos del Grupo Danés de Cáncer Colorrectal mantenida de manera prospectiva.AJUSTES:La medida de resultado primaria fue la recurrencia local-regional en pacientes sometidos a resección curativa por cáncer de colon del lado derecho y las medidas de resultado secundarias fueron las complicaciones posoperatorias a los 30 días. También fueron investigadas las metástasis a distancia, los eventos adversos intraoperatorios no planificados y la mortalidad posoperatoria a los 30 y 90 días. Se excluyeron los pacientes sometidos a resección paliativa o comprometida, cirugía de urgencia y quimioterapia neoadyuvante.RESULTADOS:De los 12.855 pacientes recuperados y sometidos a resección de cáncer de colon del lado derecho, 1151 fueron sometidos a hemicolectomía derecha ampliada. Los pacientes sometidos a hemicolectomía derecha ampliada fueron varones más jóvenes con puntuaciones ASA más bajas, operados por cirujanos colorrectales, utilizando la vía laparoscópica, y tuvieron un número significativamente mayor de ganglios linfáticos extraídos. La tasa de recidiva local-regional fue del 1,1% (136 / 12.855) sin diferencia entre la hemicolectomía derecha convencional y la hemicolectomía derecha ampliada (OR 1,7 IC 95% 0,63-2,18). Las complicaciones médicas post operatorias fueron significativamente mayores en la hemicolectomía derecha ampliada incluso después del ajuste por edad, comorbilidad, acceso al abdomen y otras covariables (OR 1,26; IC 95% 1,01-1,58). No se observaron diferencias significativas entre la hemicolectomía derecha convencional y la hemicolectomía derecha ampliada con respecto a las tasas de metástasis a distancia, eventos adversos intraoperatorios no planificados y mortalidad.LIMITACIONES:Es un estudio basado en registros, por lo tanto, no se puede excluir la sub notificación. La hemicolectomía derecha ampliada como se define en este estudio no refleja la extensión de la disección linfática realizada durante la cirugía.CONCLUSIONES:Este gran estudio basado en el registro poblacional no mostró diferencias en la recurrencia local-regional del cáncer de colon del lado derecho entre la hemicolectomía derecha convencional y ampliada con resección mesentérica y ligadura de los vasos cólicos medios. La resección ampliada se asoció con tasas más altas de complicaciones posoperatorias. Consulte Video Resumen en http://links.lww.com/DCR/B907 . (Traducción-Dr. Osvaldo Gauto ).

Comparative effectiveness and durability of COVID-19 vaccination against death and severe disease in an ongoing nationwide mass vaccination campaign.

As national coronavirus disease 2019 (COVID-19) mass vaccination campaigns are rolled out, monitoring real-world Vaccine Effectiveness (VE) and its durability is essential. We aimed to estimate COVID-19 VE against severe disease and death in the Greek population, for all vaccines currently in use. Nationwide active surveillance and vaccination registry data during January-December 2021 were used to estimate VE via quasi-Poisson regression, adjusted for age and calendar time. Interaction terms were included to assess VE by age group, against the "delta" severe acute respiratory syndrome coronavirus 2 variant and waning of VE over time. Two doses of BNT162b2, mRNA-1273, or ChAdOx1 nCov-19 vaccines offered very high (>90%) VE against both intubation and death across all age groups, similar against both "delta" and previous variants, with one-dose Ad26.COV2.S slightly lower. VE waned over time but remained >80% at 6 months, and three doses increased VE again to near 100%. Vaccination prevented an estimated 19 691 COVID-19 deaths (95% confidence interval: 18 890-20 788) over the study period. All approved vaccines offer strong and also durable protection against COVID-19 severe disease and death. Every effort should be made to vaccinate the population with at least two doses, to reduce the mortality and morbidity impact of the pandemic.

Total patient load, regional disparities and in-hospital mortality of intubated COVID-19 patients in Greece, from September 2020 to May 2021.

AIMS: While healthcare services have been expanding capacity during the COVID-19 pandemic, quality of care under increasing patient loads has received less attention. We examined in-hospital mortality of intubated COVID-19 patients in Greece, in relation to total intubated patient load, intensive care unit (ICU) availability and hospital region. METHODS: Anonymized surveillance data were analyzed from all intubated COVID-19 patients in Greece between 1 September 2020 and 6 May 2021. Poisson regression was used to estimate the hazard of dying as a function of fixed and time-varying covariates. RESULTS: Mortality was significantly increased above 400 patients, with an adjusted hazard ratio of 1.25 (95% confidence interval (CI): 1.03-1.51), rising progressively up to 1.57 (95% CI: 1.22-2.02) for 800+ patients. Hospitalization outside an ICU or away from the capital region of Attica were also independently associated with significantly increased mortality. CONCLUSIONS: Our results indicate that in-hospital mortality of severely ill COVID-19 patients is adversely affected by high patient load even without exceeding capacity, as well as by regional disparities. This highlights the need for more substantial strengthening of healthcare services, focusing on equity and quality of care besides just expanding capacity.

Effects of Social Distancing Measures during the First Epidemic Wave of Severe Acute Respiratory Syndrome Infection, Greece.

Greece imposed a nationwide lockdown in March 2020 to mitigate transmission of severe acute respiratory syndrome coronavirus 2 during the first epidemic wave. We conducted a survey on age-specific social contact patterns to assess effects of physical distancing measures and used a susceptible-exposed-infectious-recovered model to simulate the epidemic. Because multiple distancing measures were implemented simultaneously, we assessed their overall effects and the contribution of each measure. Before measures were implemented, the estimated basic reproduction number (R0) was 2.38 (95% CI 2.01-2.80). During lockdown, daily contacts decreased by 86.9% and R0 decreased by 81.0% (95% credible interval [CrI] 71.8%-86.0%); each distancing measure decreased R0 by 10%-24%. By April 26, the attack rate in Greece was 0.12% (95% CrI 0.06%-0.26%), one of the lowest in Europe, and the infection fatality ratio was 1.12% (95% CrI 0.55%-2.31%). Multiple social distancing measures contained the first epidemic wave in Greece.

The coexistence of asthma and COPD: risk factors, clinical history and lung function trajectories.

Patients with concomitant features of asthma and chronic obstructive pulmonary disease (COPD) have a heavy disease burden.Using data collected prospectively in the European Community Respiratory Health Survey, we compared the risk factors, clinical history and lung function trajectories from early adulthood to late sixties of middle-aged subjects with asthma+COPD (n=179), past (n=263) or current (n=808) asthma alone, COPD alone (n=111) or none of these (n=3477).Interview data and pre-bronchodilator forced expiratory volume in 1 s (FEV1) and forced vital capacity (FVC) were obtained during three clinical examinations in 1991-1993, 1999-2002 and 2010-2013. Disease status was classified in 2010-2013, when the subjects were aged 40-68 years, according to the presence of fixed airflow obstruction (post-bronchodilator FEV1/FVC below the lower limit of normal), a lifetime history of asthma and cumulative exposure to tobacco or occupational inhalants. Previous lung function trajectories, clinical characteristics and risk factors of these phenotypes were estimated.Subjects with asthma+COPD reported maternal smoking (28.2%) and respiratory infections in childhood (19.1%) more frequently than subjects with COPD alone (20.9% and 14.0%, respectively). Subjects with asthma+COPD had an impairment of lung function at age 20 years that tracked over adulthood, and more than half of them had asthma onset in childhood. Subjects with COPD alone had the highest lifelong exposure to tobacco smoking and occupational inhalants, and they showed accelerated lung function decline during adult life.The coexistence between asthma and COPD seems to have its origins earlier in life compared to COPD alone. These findings suggest that prevention of this severe condition, which is typical at older ages, should start in childhood.

Active case finding of pulmonary TB in a European refugee camp: lessons learnt from Oinofyta hosting site in Greece.

OBJECTIVES: To report on an active case finding (ACF) intervention that took place in the migrant camp of Oinofyta, Greece, upon suspicion of active TB transmission. METHODS: Upon diagnosis of 3 TB cases among camp residents, an ACF intervention among contacts was implemented. All camp residents were offered two-step screening, that is tuberculin skin testing (TST) followed by chest X-ray in case of positive TST (defined as ≥5 mm). RESULTS: 336 of 379 (89%) camp residents underwent TST testing, of whom 110 (33%) exhibited a positive skin reaction. The rate of positive TST results was particularly high in the elderly and significantly higher in adults than in children. Differences by sex or nationality were not observed. Of the 110 cases with positive TST, only 75 underwent chest X-ray, resulting in the detection of one pulmonary TB case in an adult woman. CONCLUSIONS: In the given intervention context, two-step ACF proved to be operationally cumbersome, with many residents lost to follow-up and a high Number Needed to Screen. Simpler ACF designs should be pilot-tested in similar settings in the future, and blanket screening of all camp residents should be reconsidered. Conclusions drawn by these exercises should pave the way for adopting a comprehensive, context-specific and evidence-based national strategy on TB in migrants.

Lockdowns and the COVID-19 pandemic: What is the endgame?

An overall long-term strategy for managing the coronavirus disease 2019 (COVID-19) pandemic is presented. This strategy will need to be maintained until herd immunity is achieved, hopefully through vaccination rather than natural infection. We suggest that a pure test-trace-isolate strategy is likely not practicable in most countries, and a degree of social distancing, ranging up to full lockdown, is the main public-health tool to mitigate the COVID-19 pandemic. Guided by reliable surveillance data, distancing should be continuously optimised down to the lowest sustainable level that guarantees a low and stable infection rate in order to balance its wide-ranging negative effects on public health. The qualitative mixture of social-distancing measures also needs to be carefully optimised in order to minimise social costs.

Real-time monitoring shows substantial excess all-cause mortality during second wave of COVID-19 in Europe, October to December 2020.

The European monitoring of excess mortality for public health action (EuroMOMO) network monitors weekly excess all-cause mortality in 27 European countries or subnational areas. During the first wave of the coronavirus disease (COVID-19) pandemic in Europe in spring 2020, several countries experienced extraordinarily high levels of excess mortality. Europe is currently seeing another upsurge in COVID-19 cases, and EuroMOMO is again witnessing a substantial excess all-cause mortality attributable to COVID-19.

Environmental Risk Factors for Inflammatory Bowel Diseases: An Umbrella Review of Meta-analyses.

BACKGROUND & AIMS: Multiple environmental factors have been associated with the development of inflammatory bowel diseases (IBDs). We performed an umbrella review of meta-analyses to summarize available epidemiologic evidence and assess its credibility. METHODS: We systematically identified and appraised meta-analyses of observational studies examining environmental factors and risk of IBD (Crohn's disease [CD] or ulcerative colitis [UC]). For each meta-analysis, we considered the random effects estimate, its 95% confidence interval, the estimates of heterogeneity, and small-study effects, and we graded the evidence according to prespecified criteria. Methodologic quality was assessed with AMSTAR (ie, A Measurement Tool to Assess Systematic Reviews) 2. RESULTS: We examined 183 estimates in 53 meta-analyses of 71 environmental factors related to lifestyles and hygiene, surgeries, drug exposures, diet, microorganisms, and vaccinations. We identified 9 factors that increase risk of IBD: smoking (CD), urban living (CD and IBD), appendectomy (CD), tonsillectomy (CD), antibiotic exposure (IBD), oral contraceptive use (IBD), consumption of soft drinks (UC), vitamin D deficiency (IBD), and non-Helicobacter pylori-like enterohepatic Helicobacter species (IBD). We identified 7 factors that reduce risk of IBD: physical activity (CD), breastfeeding (IBD), bed sharing (CD), tea consumption (UC), high levels of folate (IBD), high levels of vitamin D (CD), and H pylori infection (CD, UC, and IBD). Epidemiologic evidence for all of these associations was of high to moderate strength; we identified another 11 factors associated with increased risk and 16 factors associated with reduced risk with weak credibility. Methodologic quality varied considerably among meta-analyses. Several associations were based on findings from retrospective studies, so it is not possible to determine if these are effects of IBD or the results of recall bias. CONCLUSIONS: In an umbrella review of meta-analyses, we found varying levels of evidence for associations of different environmental factors with risk of IBD. High-quality prospective studies with analyses of samples from patients with recent diagnoses of IBD are needed to determine whether these factors cause or are results of IBD and their pathogenic mechanisms.

Excess all-cause mortality during the COVID-19 pandemic in Europe - preliminary pooled estimates from the EuroMOMO network, March to April 2020.

A remarkable excess mortality has coincided with the COVID-19 pandemic in Europe. We present preliminary pooled estimates of all-cause mortality for 24 European countries/federal states participating in the European monitoring of excess mortality for public health action (EuroMOMO) network, for the period March-April 2020. Excess mortality particularly affected ≥ 65 year olds (91% of all excess deaths), but also 45-64 (8%) and 15-44 year olds (1%). No excess mortality was observed in 0-14 year olds.

Effect of Early Oseltamivir Treatment on Mortality in Critically Ill Patients With Different Types of Influenza: A Multiseason Cohort Study.

BACKGROUND: The available evidence on whether neuraminidase inhibitors reduce mortality in patients with influenza is inconclusive and focuses solely on influenza A/H1N1pdm09. We assessed whether early oseltamivir treatment (≤48 hours from symptom onset) decreases mortality compared to late treatment in a large cohort of critically ill patients with influenza of all types. METHODS: The study included all adults with laboratory-confirmed influenza hospitalized in intensive care units (ICUs) in Greece over 8 seasons (2010-2011 to 2017-2018) and treated with oseltamivir. The association of early oseltamivir with mortality was assessed with log-binomial models and a competing risks analysis estimating cause-specific and subdistribution hazards for death and discharge. Effect estimates were stratified by influenza type and adjusted for multiple covariates. RESULTS: A total of 1330 patients were studied, of whom 622 (46.8%) died in the ICU. Among patients with influenza A/H3N2, early treatment was associated with significantly lower mortality (relative risk, 0.69 [95% credible interval {CrI}, .49-.94]; subdistribution hazard ratio, 0.58 [95% CrI, .37-.88]). This effect was purely due to an increased cause-specific hazard for discharge, whereas the cause-specific hazard for death was not increased. Among survivors, the median length of ICU stay was shorter with early treatment by 1.8 days (95% CrI, .5-3.5 days). No effect on mortality was observed for A/H1N1 and influenza B patients. CONCLUSIONS: Severely ill patients with suspected influenza should be promptly treated with oseltamivir, particularly when A/H3N2 is circulating. The efficacy of oseltamivir should not be assumed to be equal against all types of influenza.

Loss of Response to Vedolizumab and Ability of Dose Intensification to Restore Response in Patients With Crohn's Disease or Ulcerative Colitis: A Systematic Review and Meta-analysis.

BACKGROUND & AIMS: Vedolizumab is effective and safe for the treatment of Crohn's disease (CD) and ulcerative colitis (UC). Little is known about the incidence rate of loss of response to vedolizumab maintenance therapy or whether dose intensification restores response to this drug. METHODS: We searched PubMed, Scopus and conference abstracts (Digestive Disease Week, European Crohn's and Colitis Organization, and United European Gastroenterology Week), through December 2017, for experimental or observational cohort studies of vedolizumab use in adult patients with CD or UC; we identified studies that provided sufficient data to determine the incidence rate of loss of response among initial responders and the ability of dose intensification to restore response. Two reviewers independently abstracted study data and outcomes and rated each study's risk of bias. The studies were evaluated for heterogeneity and publication bias. Summary estimates were calculated using random effects models. RESULTS: We analyzed data from 10 eligible cohorts; most patients had received prior treatment with a tumor necrosis factor antagonist. The pooled incidence rates of loss of response were 47.9 per 100 person-years of follow up (95% CI, 26.3‒87.0; I2 = 74%) among patients with CD and 39.8 per 100 person-years of follow up (95% CI, 35.0‒45.3; I2 = 0%) among patients with UC. Dose intensification restored response to the drug in 53.8% of secondary non-responders (95% CI, 21.8%‒82.9%; I2 = 77%). CONCLUSIONS: In a systematic review and meta-analysis, we found high proportions of patients with CD or UC to lose responsiveness to vedolizumab maintenance therapy. Dose intensification restores responsiveness to more than half of these patients. Additional studies are warranted to inform clinical decision making.

Comparative assessment of budesonide-MMX and mesalamine in active, mild-to-moderate ulcerative colitis: A systematic review and network meta-analysis.

AIMS: The comparative efficacy, safety and tolerability of budesonide-MMX and oral mesalamine in active, mild-to-moderate ulcerative colitis (UC) are unclear. We conducted a network meta-analysis to fill this evidence gap. METHODS: We searched PubMed, Scopus, Embase, the Cochrane Library, clinical trial registries, regulatory agencies' websites and international conference proceedings, up to July 2018, to identify randomized controlled trials of adult patients with active, mild-to-moderate UC, comparing budesonide-MMX or mesalamine against placebo, or against each other, or different dosing strategies, for induction of remission. Two reviewers independently abstracted study data and outcomes, and assessed each trial's risk-of-bias. RESULTS: We identified and synthesized evidence from 15 eligible trials including 4083 participants. Budesonide-MMX 9 mg/day and mesalamine >2.4 g/day had similar efficacy for induction of clinical and endoscopic remission (OR = 0.97; 0.59-1.60), both showing superiority over placebo (OR = 2.68; 1.75-4.10, and OR = 2.75; 1.94-3.90, respectively). Furthermore, mesalamine >2.4 g/day was more efficacious than mesalamine 1.6-2.4 g/day (odds ratio = 1.27; 1.03-1.56). Secondary analyses showed that mesalamine >2.4 g/day ranks at the top among comparator treatments regarding safety (serious adverse events; surface under the cumulative ranking area [SUCRA] 79.2%) and tolerability (treatment discontinuations or withdrawals from the study due to adverse events; SUCRA 96.7%). There was no evidence of inconsistency, while heterogeneity between studies and risk of publication bias were low. CONCLUSION: Budesonide-MMX and mesalamine >2.4 g/day had similar efficacy for induction of clinical and endoscopic remission in active, mild-to-moderate UC; however, mesalamine >2.4 g/day showed better tolerability. Further high-quality research is warranted.

Occupational exposures and incidence of chronic bronchitis and related symptoms over two decades: the European Community Respiratory Health Survey.

OBJECTIVES: Chronic bronchitis (CB) is an important chronic obstructive pulmonary disease (COPD)-related phenotype, with distinct clinical features and prognostic implications. Occupational exposures have been previously associated with increased risk of CB but few studies have examined this association prospectively using objective exposure assessment. We examined the effect of occupational exposures on CB incidence in the European Community Respiratory Health Survey. METHODS: Population samples aged 20-44 were randomly selected in 1991-1993, and followed up twice over 20 years. Participants without chronic cough or phlegm at baseline were analysed. Coded job histories during follow-up were linked to the ALOHA Job Exposure Matrix, generating occupational exposure estimates to 12 categories of chemical agents. Their association with CB incidence over both follow-ups was examined with Poisson models using generalised estimating equations. RESULTS: 8794 participants fulfilled the inclusion criteria, contributing 13 185 observations. Only participants exposed to metals had a higher incidence of CB (relative risk (RR) 1.70, 95% CI 1.16 to 2.50) compared with non-exposed to metals. Mineral dust exposure increased the incidence of chronic phlegm (RR 1.72, 95% CI 1.43 to 2.06). Incidence of chronic phlegm was increased in men exposed to gases/fumes and to solvents and in women exposed to pesticides. CONCLUSIONS: Occupational exposures are associated with chronic phlegm and CB, and the evidence is strongest for metals and mineral dust exposure. The observed differences between men and women warrant further investigation.

Cleaning at Home and at Work in Relation to Lung Function Decline and Airway Obstruction.

RATIONALE: Cleaning tasks may imply exposure to chemical agents with potential harmful effects to the respiratory system, and increased risk of asthma and respiratory symptoms among professional cleaners and in persons cleaning at home has been reported. Long-term consequences of cleaning agents on respiratory health are, however, not well described. OBJECTIVES: This study aimed to investigate long-term effects of occupational cleaning and cleaning at home on lung function decline and airway obstruction. METHODS: The European Community Respiratory Health Survey (ECRHS) investigated a multicenter population-based cohort at three time points over 20 years. A total of 6,235 participants with at least one lung function measurement from 22 study centers, who in ECRHS II responded to questionnaire modules concerning cleaning activities between ECRHS I and ECRHS II, were included. The data were analyzed with mixed linear models adjusting for potential confounders. MEASUREMENTS AND MAIN RESULTS: As compared with women not engaged in cleaning (ΔFEV1 = -18.5 ml/yr), FEV1 declined more rapidly in women responsible for cleaning at home (-22.1; P = 0.01) and occupational cleaners (-22.4; P = 0.03). The same was found for decline in FVC (ΔFVC = -8.8 ml/yr; -13.1, P = 0.02; and -15.9, P = 0.002; respectively). Both cleaning sprays and other cleaning agents were associated with accelerated FEV1 decline (-22.0, P = 0.04; and -22.9, P = 0.004; respectively). Cleaning was not significantly associated with lung function decline in men or with FEV1/FVC decline or airway obstruction. CONCLUSIONS: Women cleaning at home or working as occupational cleaners had accelerated decline in lung function, suggesting that exposures related to cleaning activities may constitute a risk to long-term respiratory health.

Mortality attributable to seasonal influenza in Greece, 2013 to 2017: variation by type/subtype and age, and a possible harvesting effect.

IntroductionEstimating the contribution of influenza to excess mortality in the population presents substantial methodological challenges.AimIn a modelling study we combined environmental, epidemiological and laboratory surveillance data to estimate influenza-attributable mortality in Greece, over four seasons (2013/14 to 2016/17), specifically addressing the lag dimension and the confounding effect of temperature.MethodsAssociations of influenza type/subtype-specific incidence proxies and of daily mean temperature with mortality were estimated with a distributed-lag nonlinear model with 30 days of maximum lag, separately by age group (all ages, 15-64 and ≥ 65 years old). Total and weekly deaths attributable to influenza and cold temperatures were calculated.ResultsOverall influenza-attributable mortality was 23.6 deaths per 100,000 population per year (95% confidence interval (CI): 17.8 to 29.2), and varied greatly between seasons, by influenza type/subtype and by age group, with the vast majority occurring in persons aged ≥ 65 years. Most deaths were attributable to A(H3N2), followed by influenza B. During periods of A(H1N1)pdm09 circulation, weekly attributable mortality to this subtype among people ≥ 65 years old increased rapidly at first, but then fell to zero and even negative, suggesting a mortality displacement (harvesting) effect. Mortality attributable to cold temperatures was much higher than that attributable to influenza.ConclusionsStudies of influenza-attributable mortality need to consider distributed-lag effects, stratify by age group and adjust both for circulating influenza virus types/subtypes and daily mean temperatures, in order to produce reliable estimates. Our approach addresses these issues, is readily applicable in the context of influenza surveillance, and can be useful for other countries.

Occupational exposures and 20-year incidence of COPD: the European Community Respiratory Health Survey.

BACKGROUND: Occupational exposures have been associated with an increased risk of COPD. However, few studies have related objectively assessed occupational exposures to prospectively assessed incidence of COPD, using postbronchodilator lung function tests. Our objective was to examine the effect of occupational exposures on COPD incidence in the European Community Respiratory Health Survey. METHODS: General population samples aged 20-44 were randomly selected in 1991-1993 and followed up 20 years later (2010-2012). Spirometry was performed at baseline and at follow-up, with incident COPD defined using a lower limit of normal criterion for postbronchodilator FEV1/FVC. Only participants without COPD and without current asthma at baseline were included. Coded job histories during follow-up were linked to a Job-Exposure Matrix, generating occupational exposure estimates to 12 categories of agents. Their association with COPD incidence was examined in log-binomial models fitted in a Bayesian framework. FINDINGS: 3343 participants fulfilled the inclusion criteria; 89 of them had COPD at follow-up (1.4 cases/1000 person-years). Participants exposed to biological dust had a higher incidence of COPD compared with those unexposed (relative risk (RR) 1.6, 95% CI 1.1 to 2.3), as did those exposed to gases and fumes (RR 1.5, 95% CI 1.0 to 2.2) and pesticides (RR 2.2, 95% CI 1.1 to 3.8). The combined population attributable fraction for these exposures was 21.0%. INTERPRETATION: These results substantially strengthen the evidence base for occupational exposures as an important risk factor for COPD.

Comparative safety of systemic and low-bioavailability steroids in inflammatory bowel disease: Systematic review and network meta-analysis.

AIMS: Oral systemic corticosteroids have been used to induce remission in patients with active inflammatory bowel disease (IBD) for over 50 years; however, the wide array of adverse events (AEs) associated with these drugs prompted the development of steroid compounds with targeted delivery and low systemic bioavailability. This study assessed corticosteroids' comparative harm using network meta-analysis. METHODS: We searched PubMed, Scopus, Embase, the Cochrane Library, clinical trial registries, regulatory authorities' websites and major conference proceedings, through March 2017. Randomized controlled trials that recruited adult IBD patients and compared oral systemic corticosteroids (prednisone/prednisolone) or compounds/formulations with low systemic bioavailability (budesonide, budesonide MMX, and beclomethasone dipropionate) with placebo, or against each other, were considered eligible for inclusion. Two reviewers independently extracted study data and outcomes, and rated each trial's risk-of-bias. RESULTS: We identified and synthesized evidence from 31 trials including 5689 IBD patients. Budesonide MMX was associated with significantly fewer corticosteroid-related AEs than oral systemic corticosteroids [odds ratio (OR): 0.25, 95% confidence interval (CI): 0.13-0.49] and beclomethasone (OR: 0.35, 95% CI: 0.13-1.00), but not significantly fewer AEs than budesonide (OR: 0.64, 95% CI: 0.37-1.11); it performed equally good with placebo. By contrast, the occurrence of serious AEs, and treatment discontinuations due to AEs, did not differ between the comparator treatments. CONCLUSIONS: Budesonide MMX is associated with fewer corticosteroid-related AEs than its comparator steroid treatments for adult IBD patients. Further high-quality research is warranted to illuminate the steroid drugs' comparative safety profiles.

Update of an occupational asthma-specific job exposure matrix to assess exposure to 30 specific agents.

OBJECTIVES: We aimed to update an asthmagen job exposure matrix (JEM) developed in the late 1990s. Main reasons were: the number of suspected and recognised asthmagens has since tripled; understanding of the aetiological role of irritants in asthma and methodological insights in application of JEMs have emerged in the period. METHODS: For each agent of the new occupational asthma-specific JEM (OAsJEM), a working group of three experts out of eight evaluated exposure for each International Standard Classification of Occupations, 1988 (ISCO-88) job code into three categories: 'high' (high probability of exposure and moderate-to-high intensity), 'medium' (low-to-moderate probability or low intensity) and 'unexposed'. Within a working group, experts evaluated exposures independently from each other. If expert assessments were inconsistent the final decision was taken by consensus. Specificity was favoured over sensitivity, that is, jobs were classified with high exposure only if the probability of exposure was high and the intensity moderate-to-high. In the final review, all experts checked assigned exposures and proposed/improved recommendations for expert re-evaluation after default application of the JEM. RESULTS: The OAsJEM covers exposures to 30 sensitisers/irritants, including 12 newly recognised, classified into seven broad groups. Initial agreement between the three experts was mostly fair to moderate (κ values 0.2-0.5). Out of 506 ISCO-88 codes, the majority was classified as unexposed (from 82.6% (organic solvents) to 99.8% (persulfates)) and a minority as 'high-exposed' (0.2% (persulfates) to 2.6% (organic solvents)). CONCLUSIONS: The OAsJEM developed to improve occupational exposure assessment may improve evaluations of associations with asthma in epidemiological studies and contribute to assessment of the burden of work-related asthma.