Antiviral susceptibility profile of influenza A viruses; keep an eye on immunocompromised patients under prolonged treatment.

There was an increase in severe and fatal influenza cases in Greece during the 2011-2015 post-pandemic period. To investigate causality, we determined neuraminidase (NA) inhibitor susceptibility and resistance-conferring NA and hemagglutinin (HA) mutations in circulating influenza type A viruses during the pandemic (2009-2010) and post-pandemic periods in Greece. One hundred thirty-four influenza A(H1N1)pdm09 and 95 influenza A(H3N2) viruses submitted to the National Influenza Reference Laboratory of Southern Greece were tested for susceptibility to oseltamivir and zanamivir. Antiviral resistance was assessed by neuraminidase sequence analysis, as well as the fluorescence-based 50 % inhibitory concentration (IC50) method. Five influenza A(H1N1)pdm09 viruses (2.2 %) showed significantly reduced inhibition by oseltamivir (average IC50 300.60nM vs. 1.19nM) by Gaussian kernel density plot analysis. These viruses were isolated from immunocompromised patients and harbored the H275Y oseltamivir resistance-conferring NA substitution. All A(H1N1)pdm09 viruses were zanamivir-susceptible, and all A(H3N2) viruses were susceptible to both drugs. Oseltamivir-resistant viruses did not form a distinct cluster by phylogenetic analysis. Permissive mutations were detected in immunogenic and non immunogenic NA regions of both oseltamivir- resistant and susceptible viruses in the post-pandemic seasons. Several amino acid substitutions in the HA1 domain of the HA gene of post-pandemic viruses were identified. This study indicated low resistance to NAIs among tested influenza viruses. Antiviral resistance emerged only in immunocompromised patients under long-term oseltamivir treatment. Sequential sample testing in this vulnerable group of patients is recommended to characterise resistance or reinfection and viral evolution.

Influenza surveillance during the post-pandemic influenza 2010/11 season in Greece, 04 October 2010 to 22 May 2011.

In this manuscript, we summarise the experience of Greece during the post-pandemic influenza season 2010/11 from 04 October 2010 to 22 May 2011. The spread of the disease and its impact were monitored using multiple surveillance systems, such as sentinel surveillance, virological surveillance and all-cause mortality surveillance. We also focus on the characteristics of laboratory-confirmed severe influenza cases who required admission to an intensive care unit (ICU) (n=368), and/or with a fatal outcome (n=180). The influenza-like illness rate reported from sentinel surveillance started rising in early January 2011 and peaked between 31 January and 6 February 2011. The total number of ICU admissions was higher in the post-pandemic influenza season than during the pandemic period causing a lot of pressure on ICUs. The overall population mortality rate due to influenza A(H1N1)2009 was higher than during the pandemic period (15.9 vs 13.2 fatal cases per million, p=0.087). Our data suggest that the severity of clinical illness in the first post-pandemic influenza season was comparable or even higher than during the pandemic.

Spotlight on measles 2010: ongoing measles outbreak in Greece, January-July 2010.

A measles outbreak (126 reported cases to date) has been ongoing in Greece, since January 2010, originally related to the recent outbreak in Bulgaria. Cases are mostly unvaccinated, and mainly belong to three groups: Roma population of Bulgarian nationality, Greek Roma population, and Greek non-minority population. In these population groups, 67%, 95%, and 25% of cases respectively were children aged 0-14 years. Measures were taken to raise clinical awareness, and vaccination of specific population groups was undertaken. Policies are necessary to increase routine vaccination uptake of hard-to-reach groups.

Association between type-specific influenza circulation and incidence of severe laboratory-confirmed cases; which subtype is the most virulent?

OBJECTIVES: Excess population mortality during winter is most often associated with influenza A(H3N2), though susceptibility differs by age. We examined differences between influenza types/subtypes in their association with severe laboratory-confirmed cases, overall and by age group, to determine which type is the most virulent. METHODS: We used nine seasons of comprehensive nationwide surveillance data from Greece (2010-2011 to 2018-2019) to examine the association, separately for influenza A(H1N1)pdm09, A(H3N2) and B, between the number of laboratory-confirmed severe cases (intensive care hospitalizations or deaths) per type/subtype and the overall type-specific circulation during the season (expressed as a cumulative incidence proxy). Quasi-Poisson models with identity link were used, and multiple imputation to handle missing influenza A subtype. RESULTS: For the same level of viral circulation and across all ages, influenza A(H1N1)pdm09 was associated with twice as many intensive care hospitalizations as A(H3N2) (rate ratio (RR) 1.89, 95% CI 1.38-2.74) and three times more than influenza B (RR 3.27, 95%CI 2.54-4.20). Similar associations were observed for laboratory-confirmed deaths. A(H1N1)pdm09 affected adults over 40 years at similar rates, whereas A(H3N2) affected elderly people at a much higher rate than younger persons (≥65 vs. 40-64 years, RR for intensive care 5.42, 95% CI 3.45-8.65, and RR for death 6.19, 95%CI 4.05-9.38). Within the 40-64 years age group, A(H1N1)pdm09 was associated with an approximately five times higher rate of severe disease than both A(H3N2) and B. DISCUSSION: Influenza A(H1N1)pdm09 is associated with many more severe laboratory-confirmed cases, likely due to a more typical clinical presentation and younger patient age, leading to more testing. A(H3N2) affects older people more, with cases less often recognized and confirmed.

Association of malnutrition with surgical site infection following spinal surgery: systematic review and meta-analysis.

BACKGROUND: Surgical site infection (SSI) following spinal surgery is a frequent clinical problem with significant clinical and socio-economic consequences. Malnutrition has been linked with SSI in various other surgical procedures. AIM: To investigate whether malnutrition is a risk factor for SSI following spinal surgery. METHODS: Two electronic databases (PUBMED and SCOPUS) and the Cochrane Library were searched systematically from inception to May 2019. Cohort and case-control studies assessing malnutrition as a risk factor for SSI in patients undergoing spinal procedures were considered eligible. Μalnutrition was defined according to laboratory measurements or by relevant International Classification of Diseases-9 codes. SSI was the outcome of interest. Two reviewers independently abstracted study data and assessed the risk of bias for each study. Pooled effect estimates were calculated using random effects models. FINDINGS: In total, 22 studies (20 retrospective cohort and two case-control) with over 175,000 participants (of whom 2.14% developed postoperative SSI) were analysed. SSIs were more likely to develop in malnourished patients [odds ratio (OR) 2.31, 95% confidence interval (CI) 1.75-3.05]. While pre-operative malnutrition was significantly associated with SSI in patients undergoing thoracolumbar spinal and sacral surgery, no significant difference was seen in patients undergoing cervical spinal surgery. In subgroup analyses, similar results were observed for both hospital-based (OR 3.16, 95% CI 1.84-5.43) and population-based (OR 2.00, 95% CI 1.63-2.46) studies. CONCLUSIONS: Malnutrition is associated with increased risk of developing SSI after spinal surgery. Further high-quality research is warranted to investigate whether improvement of pre-operative nutritional status can decrease SSI rates.

Enhanced surveillance of influenza A(H1N1)v in Greece during the containment phase.

Following the emergence of a novel influenza virus (influenza A(H1N1)v) with pandemic potential in late April 2009, public health measures were put in place in an effort to contain disease spread in Greece. These included enhanced surveillance of infections due to influenza A(H1N1)v virus, in order to continuously ascertain the situation and guide further public health action. On 15 July, Greece moved to mitigation phase. This report summarises surveillance findings in Greece during the delaying (or containment) phase, from 30 April to 14 July 2009.

Association of malnutrition with periprosthetic joint and surgical site infections after total joint arthroplasty: a systematic review and meta-analysis.

BACKGROUND: A growing body of evidence associates malnutrition with several adverse outcomes. AIM: To investigate the link between malnutrition with surgical site and periprosthetic joint infections (SSIs and PJIs) following total knee and hip arthroplasty (TKA and THA) through a comprehensive meta-analysis of observational studies. METHODS: A systematic search was conducted on PubMed and Scopus databases through December 2018, and recent proceedings of major orthopaedic meetings. Data from eligible studies were extracted and synthesized; pooled odds ratios (ORs) with 95% confidence intervals (CIs) were estimated. FINDINGS: Seven publications were included, reporting eight independent cohort studies with >250,000 subjects. SSIs and PJIs were more likely to develop in malnourished patients (OR: 2.49; 95% CI: 2.13-2.90; and 3.62; 2.33-5.64, respectively). The association of SSI with malnutrition was evident both after TKA (2.42; 1.94-3.02) and after THA (2.66; 1.64-4.30). Similarly, PJI was associated with malnutrition after TKA (2.55; 1.10-5.91) and after THA (3.10; 1.84-5.25). Finally, PJI correlated with malnutrition both after primary arthroplasty (3.58; 1.82-7.03) and revision arthroplasty (3.96; 2.47-6.33). The subgroup analysis by study setting confirmed the relationship between PJI and malnutrition in hospital (6.02; 3.07-11.81) and population-based (2.80; 1.76-4.44) studies. CONCLUSION: Malnutrition is associated with PJIs and SSIs after total joint arthroplasty. Further high-quality research is warranted to confirm or refute these findings.

European all-cause excess and influenza-attributable mortality in the 2017/18 season: should the burden of influenza B be reconsidered?

OBJECTIVES: Weekly monitoring of European all-cause excess mortality, the EuroMOMO network, observed high excess mortality during the influenza B/Yamagata dominated 2017/18 winter season, especially among elderly. We describe all-cause excess and influenza-attributable mortality during the season 2017/18 in Europe. METHODS: Based on weekly reporting of mortality from 24 European countries or sub-national regions, representing 60% of the European population excluding the Russian and Turkish parts of Europe, we estimated age stratified all-cause excess morality using the EuroMOMO model. In addition, age stratified all-cause influenza-attributable mortality was estimated using the FluMOMO algorithm, incorporating influenza activity based on clinical and virological surveillance data, and adjusting for extreme temperatures. RESULTS: Excess mortality was mainly attributable to influenza activity from December 2017 to April 2018, but also due to exceptionally low temperatures in February-March 2018. The pattern and extent of mortality excess was similar to the previous A(H3N2) dominated seasons, 2014/15 and 2016/17. The 2017/18 overall all-cause influenza-attributable mortality was estimated to be 25.4 (95%CI 25.0-25.8) per 100,000 population; 118.2 (116.4-119.9) for persons aged 65. Extending to the European population this translates into over-all 152,000 deaths. CONCLUSIONS: The high mortality among elderly was unexpected in an influenza B dominated season, which commonly are considered to cause mild illness, mainly among children. Even though A(H3N2) also circulated in the 2017/18 season and may have contributed to the excess mortality among the elderly, the common perception of influenza B only having a modest impact on excess mortality in the older population may need to be reconsidered.

Systematic review with network meta-analysis: comparative assessment of tofacitinib and biological therapies for moderate-to-severe ulcerative colitis.

BACKGROUND: Biological therapies have improved the care of patients with ulcerative colitis (UC). Tofacitinib, an oral small-molecule Janus kinase inhibitor, is potentially a new treatment option. AIM: To comparatively assess efficacy and harm of tofacitinib and biologics (infliximab, adalimumab, golimumab and vedolizumab) in adult patients not previously exposed to TNF antagonists. METHODS: We performed a comprehensive search of PubMed, Embase, Scopus, clinical trial registries, regulatory authorities' websites and major conference proceedings, through August 2017, to identify randomised, placebo-controlled or head-to-head trials assessing tofacitinib or biologics as induction and/or maintenance therapy in moderate-to-severe UC. Two reviewers independently extracted study data and outcomes, and investigated each trial's risk-of-bias. We used conventional meta-analysis to synthesise direct evidence, and network meta-analysis for adjusted indirect treatment comparisons. RESULTS: Fifteen randomised, double-blind, placebo-controlled trials (n = 3130) contributed data for induction: All treatments are superior to placebo. Indirect treatment comparisons showed that infliximab is better than adalimumab (OR: 2.01, 95% CI: 1.36-2.98) and golimumab (1.67, 1.08-2.59) in clinical response, better than adalimumab (2.10, 1.21-3.64) in clinical remission, and better than adalimumab (1.87, 1.26-2.79) and golimumab (1.75, 1.13-2.73) in mucosal healing. No indirect comparisons between tofacitinib and biologics reached statistical significance. Nine studies (n = 1776) contributed maintenance data showing that all treatments have higher clinical efficacy than placebo. Safety analyses indicated no increased rates of adverse events for the treatments under evaluation (except for infliximab), while vedolizumab may have an advantage regarding the occurrence of serious adverse events. CONCLUSIONS: Tofacitinib and biologics are efficacious and safe for UC. Further high-quality research is warranted to establish the best therapeutic option.

Systematic review with meta-analysis: use of 5-aminosalicylates and risk of colorectal neoplasia in patients with inflammatory bowel disease.

BACKGROUND: The relationship of 5-aminosalicylates' use with the risk of colorectal neoplasia in patients with inflammatory bowel disease (IBD) has been the focus of a growing body of research. AIM: To investigate this association through an updated meta-analysis of observational studies. METHODS: PubMed, Scopus and major conference proceedings were searched up to December 2016. The identified studies were evaluated for publication bias and heterogeneity. Pooled relative risk (RR) estimates were calculated using random-effect models. Detailed subgroup analyses were performed. The GRADE approach was used to assess the quality of evidence. RESULTS: Thirty-one independent observational studies including 2137 cases of colorectal neoplasia (of which 76% were cancers) were incorporated. Between-study heterogeneity was moderate, while strong suspicion of small-study effects was raised. The overall analysis revealed a protective association between 5-aminosalicylates' use and colorectal neoplasia (RR = 0.57, 95% CI: 0.45-0.71). When the analysis was stratified according to study design and setting, the association was significant in cohort (RR = 0.65, 95% CI: 0.43-0.99; n = 10) and case-control studies (RR = 0.53, 95% CI: 0.40-0.70; n = 21), population-based (RR = 0.70, 95% CI: 0.52-0.94; n = 12) and hospital-based studies (RR = 0.46, 95% CI: 0.34-0.61; n = 19). Exposure to 5-aminosalicylates was protective against cancer (RR = 0.58, 95% CI: 0.45-0.74) and dysplasia (RR = 0.54, 95% CI: 0.35-0.84). The reduction in colorectal neoplasia risk was strong in ulcerative colitis (RR = 0.50, 95% CI: 0.38-0.64), but nonsignificant in Crohn's disease (RR = 0.76, 95% CI: 0.43-1.33). Mesalazine (mesalamine) use was protective (RR = 0.70, 95% CI: 0.51-0.94) with evidence of a dose-effect. The effect of sulfasalazine was marginally nonsignificant (RR = 0.72, 95% CI: 0.51-1.01). CONCLUSIONS: Our findings support a potential chemopreventive role of 5-aminosalicylates in IBD. Further, high-quality prospective research is warranted.

Incidence Patterns and Occupational Risk Factors of Human Brucellosis in Greece, 2004-2015.

BACKGROUND: Brucellosis is the most common bacterial zoonosis worldwide. Greece has the highest reported incidence among EU countries. However, occupational risk factors have not been well described. OBJECTIVE: To determine the incidence patterns and exposure risk factors of brucellosis in Greece. METHODS: We used national-level surveillance and occupational denominator data to estimate the incidence patterns and exposure risk factors of brucellosis in Greece, with particular emphasis on occupation. RESULTS: Between November 2003 and December 2015 a total of 2159 human brucellosis cases was reported. The mean incidence rate was 1.62 per 100 000 population per year. A large majority of cases (77.1%) reported consumption of unpasteurized milk or contact with livestock animals. Most cases occured in farmers and livestock breeders (1079 [87.7%] of 1231 cases reporting their occupation), corresponding to an annual incidence of 7.1 per 100 000. However, there were other occupations with a similar or higher risk: butchers and abattoir workers (12.7 per 100 000), laboratory personnel (3.1 per 100 000), while the highest risk was for veterinarians (53.2 per 100 000). CONCLUSION: Brucellosis incidence in specific occupational groups was much higher than in the general population. These results underline the importance of collecting information on occupation, both during the diagnostic process and in the surveillance system. Besides efforts to control brucellosis in animals, organized prevention efforts are needed within an occupational health framework, especially for the most vulnerable workers.