Development of clinical tools to estimate the breathing effort during high-flow oxygen therapy: A multicenter cohort study.

INTRODUCTION AND OBJECTIVES: Quantifying breathing effort in non-intubated patients is important but difficult. We aimed to develop two models to estimate it in patients treated with high-flow oxygen therapy. PATIENTS AND METHODS: We analyzed the data of 260 patients from previous studies who received high-flow oxygen therapy. Their breathing effort was measured as the maximal deflection of esophageal pressure (ΔPes). We developed a multivariable linear regression model to estimate ΔPes (in cmH2O) and a multivariable logistic regression model to predict the risk of ΔPes being >10 cmH2O. Candidate predictors included age, sex, diagnosis of the coronavirus disease 2019 (COVID-19), respiratory rate, heart rate, mean arterial pressure, the results of arterial blood gas analysis, including base excess concentration (BEa) and the ratio of arterial tension to the inspiratory fraction of oxygen (PaO2:FiO2), and the product term between COVID-19 and PaO2:FiO2. RESULTS: We found that ΔPes can be estimated from the presence or absence of COVID-19, BEa, respiratory rate, PaO2:FiO2, and the product term between COVID-19 and PaO2:FiO2. The adjusted R2 was 0.39. The risk of ΔPes being >10 cmH2O can be predicted from BEa, respiratory rate, and PaO2:FiO2. The area under the receiver operating characteristic curve was 0.79 (0.73-0.85). We called these two models BREF, where BREF stands for BReathing EFfort and the three common predictors: BEa (B), respiratory rate (RE), and PaO2:FiO2 (F). CONCLUSIONS: We developed two models to estimate the breathing effort of patients on high-flow oxygen therapy. Our initial findings are promising and suggest that these models merit further evaluation.

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.

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.

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.

Systematic review with network meta-analysis: comparative efficacy and safety of budesonide and mesalazine (mesalamine) for Crohn's disease.

BACKGROUND: Budesonide and mesalazine (mesalamine) are commonly used in the medical management of patients with mild to moderate Crohn's disease. AIM: To assess their comparative efficacy and harm using the methodology of network meta-analysis. METHODS: A comprehensive search of Medline, Embase, the Cochrane Library and ClinicalTrials.gov, through October 2014, was performed to identify randomised controlled trials (RCTs) that recruited adult patients with active or quiescent Crohn's disease, and compared budesonide or mesalazine with placebo, or against each other, or different dosing strategies of one drug. RESULTS: Twenty-five RCTs were combined using Bayesian network meta-analysis. Budesonide 9 mg/day, or at higher doses (15 or 18 mg/day), was shown superior to placebo for induction of remission [odds ratio (OR), 2.93; 95% credible interval (CrI), 1.52-5.39, and OR, 3.28; CrI, 1.46-7.55 respectively] and ranks at the top of the hierarchy of the competing treatments. For maintenance of remission, budesonide 6 mg/day demonstrated superiority over placebo (OR, 1.69; CrI, 1.05-2.75), being also at the best ranking position among all compared treatment strategies. No other comparisons (i.e. different doses of mesalazine vs. placebo or budesonide, for induction or maintenance of remission) reached significance. The occurrence of withdrawals due to adverse events was not shown different between budesonide, mesalazine and placebo, in both the induction and maintenance phases. CONCLUSIONS: Budesonide, at the doses of 9 mg/day, or higher, for induction of remission in active mild or moderate Crohn's disease, and at 6 mg/day for maintenance of remission, appears to be the best treatment choice.

Effect of angiotensin converting enzyme gene I/D polymorphism and its expression on clinical outcome in acute respiratory distress syndrome.

BACKGROUND: The role of the D allele of the angiotensin-converting enzyme (ACE) gene I/D polymorphism in the clinical outcomes of patients with acute lung injury and acute respiratory distress syndrome (ALI/ARDS) remains controversial. Our aim was to assess simultaneously the effect of the ACE I/D polymorphisms as well as the serum and BALF ACE levels on prognosis of patients with ARDS. METHODS: Sixty-nine mechanically ventilated patients with ALI/ARDS were recruited. ACE activity levels both in serum and BALF were assessed by chemical methods. Patients were genotyped for ACE I/D polymorphisms. Time-to-event analysis evaluated the variables associated with the 28-day and 90-day mortality. Finally, we performed a meta-analysis of studies examining the association between ACE I/D polymorphisms and mortality of ALI/ARDS patients. RESULTS: In the multivariable model, age, lung compliance, serum lactate and serum ACE levels were significantly associated with both 28- and 90-day mortality. No significant correlation was found between serum and BALF ACE levels (Spearman's rho=0.054; P=0.66). Serum ACE concentrations were significantly higher (P=0.046) in patients with D/D genotype versus the two other groups combined (I/D and I/I genotypes). The meta-analysis of 6 studies (including ours) provided evidence that D allele is significantly associated with increased mortality in ALI/ARDS patients, yielding a per-allele odds ratio of 1.76 (95% CI: 1.19, 2.59). CONCLUSION: Serum ACE levels appear to be affected by the I/D polymorphism and are correlated with prognosis in patients with ALI/ARDS indicating that further investigation of the clinical significance of the ACE in ARDS might be of value.

Antiviral drugs in the prophylaxis of HBV infection.

Reactivation of hepatitis B infection (HBV) is known to occur in liver graft recipients and in chronic carriers of the surface antigen of HBV who receive immunosuppressive therapy. The use of hepatitis B immune globulin alone or in combination with antiviral agents such as lamivudine, adefovir, tenofovir, entecavir, famciclovir, ganciclovir, as prophylaxis in HBV liver transplants, has been well documented. In terms of HBV positive carriers undergoing cytotoxic chemotherapy, the preemptive use of nucleoside or nucleotide analogues seems to be effective. Monotherapy or combination of antiviral drugs, as well as the optimal duration of HBV prophylaxis, is to be determined.

Antiretrovirals for HIV Exposure Prophylaxis.

Infection with Human Immunodeficiency Virus (HIV) remains a global public health problem. Although the epidemic has not been completely controlled, there was considerable progress in HIV prevention and treatment during the last 30 years. The modern prevention approaches are multi-component including also the administration of combinations of potent antiretroviral agents as a prophylaxis after occupational or non-occupational exposures to HIV. The aim of the current review is to present the chemical and pharmacological characteristics of antiretroviral drugs used in HIV prophylaxis and to describe briefly the medical management of exposures to potentially infectious body fluids.

Antivirals used for influenza chemoprophylaxis.

Current data about the role of adamantanes and neuraminidase inhibitors (NIs) in the chemoprophylaxis against influenza viruses were reviewed. We found significant evidence favouring the role of NIs in the chemoprophylaxis of influenza. Awareness and prudent use are necessary, due to recent evidence of gradually increasing resistance of several influenza strains to these agents. On the other hand, the role of adamantanes appears to have decreased over the last decade. Both pre-pandemic and the novel pandemic A/H1N1 2009 strains exhibited either increasing rates of resistance or no susceptibility to adamantanes. Adamantanes currently only have a theoretical role in influenza chemoprophylaxis given the likelihood of the occurrence of an epidemic due to a susceptible strain. In conclusion, changes in antiviral susceptibility will affect future guidance in prophylaxis against influenza. Further investigation of novel medications with new mechanisms of action is important in this regard. Meanwhile, implementing strategies to conserve our current antivirals is necessary.

Recent advances in the treatment of HIV/HBV and HIV/HCV co-infection.

Concurrent infection with hepatitis B virus (HBV) and hepatitis C virus (HCV) in patients positive for human immunodeficiency virus (HIV) is relatively common. The treatment of co-infected individuals is rather complex because the anti-viral therapy may be associated with drug-resistance, hepatotoxicity and lack of response. Herein, we present a summary of the available compounds and the recent recommendations concerning the therapeutic management of HIV/HBV and HIV/HCV co-infections.

High-burden epidemics in Greece in the era of economic crisis. Early signs of a public health tragedy.

BACKGROUND: Economic hardships have unleashed epidemics of infectious diseases in many countries in the past. In the era of the current financial crisis in Greece, it is interesting to assess the preliminary evidence concerning outbreaks of infectious diseases. METHODS: Description and evaluation of published surveillance data. RESULTS: Greece has been suffering a high burden of different large-scale epidemics during the last three years. These include the increased mortality of influenza during the pandemic and the first post-pandemic seasons, the emergence and spread of West Nile virus, the appearance of clusters of non-imported malaria and the outbreak of Human Immunodeficiency Virus infection among people who inject drugs. CONCLUSION: The economic turmoil in Greece seems to impact the infectious disease dynamics. It is essential to safeguard and even bolster budgetary allocations to the public health sector, in order to alleviate the effects of the economic downturn.

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.

Autochthonous Plasmodium vivax malaria in Greece, 2011.

Between May and September 2011, twenty cases of Plasmodium vivax infection were reported in Greek citizens without reported travel history. The vast majority of those cases were confined to a delimited agricultural area of Evrotas, Lakonia. Conditions favouring locally acquired transmission of malaria, including the presence of competent vectors and migrants from endemic countries exist in Greece, underscoring the need for the development of an integrated preparedness and response plan for malaria prevention.

Ongoing outbreak of West Nile virus infection in humans, Greece, July to August 2011.

Between 16 July and 21 August 2011, 31 cases of West Nile neuroinvasive disease were reported from four regions in Greece. Of these, 17 occurred in districts that had not been affected in 2010. The reoccurrence of human cases in two consecutive years (following the large 2010 outbreak) and the spread of the virus in new areas suggest that West Nile virus is established in Greece, and its transmission may continue to occur in the future.

A waterborne Campylobacter jejuni outbreak on a Greek island.

A case-control and a case-crossover study were performed to investigate a Campylobacter jejuni outbreak in Crete in 2009. Most cases originated from rural areas, served by a different water-supply system from that of the adjacent town. Thirty-seven cases and 79 controls were interviewed; cases were interviewed for two different time periods for the case-crossover study. Stool cultures, PFGE and MLST subtyping were run in human samples. Univariately, consumption of tap water was associated with C. jejuni infection. Stratified analysis revealed that water-supply system was an effect modifier of this association. In the multivariable analysis, the rural areas' water supplier and drinking tap water were risk factors. No risk factors were revealed in the case-crossover study. No Campylobacter were isolated in the tested water samples. There is strong epidemiological evidence that tap water was the vehicle of the outbreak.

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.