Michael N. Mavros

Do Psychological Variables Affect Early Surgical Recovery

Background Numerous studies have examined the effect of psychological variables on surgical recovery, but no definite conclusion has been reached yet. We sought to examine whether psychological factors influence early surgical recovery. Methods We performed a systematic search in PubMed, Scopus and PsycINFO databases to identify studies examining the association of preoperative psychological variables or interventions with objectively measured, early surgical outcomes. Results We identified 16 eligible studies, 15 of which reported a significant association between at least one psychological variable or intervention and an early postoperative outcome. However, most studies also reported psychological factors not influencing surgical recovery and there was significant heterogeneity across the studies. Overall, trait and state anxiety, state anger, active coping, subclinical depression, and intramarital hostility appeared to complicate recovery, while dispositional optimism, religiousness, anger control, low pain expectations, and external locus of control seemed to promote healing. Psychological interventions (guided relaxation, couple support visit, and psychiatric interview) also appeared to favor recovery. Psychological factors unrelated to surgical outcomes included loneliness, perceived social support, anger expression, and trait anger. Conclusion Although the heterogeneity of the available evidence precludes any safe conclusions, psychological variables appear to be associated with early surgical recovery; this association could bear important implications for clinical practice. Large clinical trials and further analyses are needed to precisely evaluate the contribution of psychology in surgical recovery.

Pharmacological Considerations for the Proper Clinical Use of Aminoglycosides

Aminoglycosides constitute one of the oldest classes of antimicrobials. Despite their toxicity, mainly nephrotoxicity and ototoxicity, aminoglycosides are valuable in current clinical practice, since they retain good activity against multidrug-resistant Gram-negative pathogens, such as Pseudomonas aeruginosa and Acinetobacter spp. Time-kill studies have shown a concentration-dependent and partially concentration-dependent bacterial killing against Gram-negative and Gram-positive bacteria, respectively. Pharmacodynamic data gathered over recent decades show that the administration of aminoglycosides by an extended-interval dosing scheme takes advantage of the maximum potential of these agents, with the goal of achieving an area under the concentration-time curve (AUC) of 100 mg • h/L over 24 hours and a peak plasma drug concentration (Cmax) to minimum inhibitory concentration (MIC) ratio of 8–10. Several clinical conditions that are common in seriously ill patients result in expansion of the extracellular space and can lead to a lower than desirable Cmax with the usual loading dose. Extended-interval dosing schemes allow adequate time to decrease bacterial adaptive resistance, a phenomenon characterized by slow concentration-independent killing. Adaptive resistance is minimized by the complete clearance of the drug before the subsequent dose, thus favouring the extended-interval dosing schemes. The efficacy of these schemes is also safeguarded by the observed post-antibiotic sub-MIC effect and post-antibiotic leukocyte enhancement, which inhibit bacterial regrowth when the serum aminoglycoside levels fall below the MIC of the pathogen.In everyday clinical practice, aminoglycosides are usually used empirically to treat severe sepsis and septic shock while awaiting the results of antimicrobial susceptibility testing. The European Committee on Antimicrobial Susceptibility Testing acknowledges the regimen-dependent nature of clinical breakpoints for aminoglycosides, i.e. of MIC values that classify bacterial isolates into sensitive or resistant, and bases its recommendations on extended-interval dosing. To a large extent, the lack of correlation between in vitro antimicrobial susceptibility testing and clinical outcome is derived from the fact that the available clinical breakpoints for aminoglycosides are set based on mean pharmacokinetic parameters obtained in healthy volunteers and not sick patients. The nephrotoxicity associated with once-versus multiple-daily administration of aminoglycosides has been assessed in numerous prospective randomized trials and by several meta-analyses. The once-daily dosing schedule provides a longer time of administration until the threshold for nephrotoxicity is met. Regarding ototoxicity, no dosing regimen appears to be less ototoxic than another. Inactivation of aminoglycosides inside the bacterial pathogens occurs by diverse modifying enzymes and by operation of multidrug efflux systems, making both of these potential targets for inhibition.In summary, despite their use for several decades, the ideal method of administration and the preferred dosing schemes of aminoglycosides for most of their therapeutic indications need further refinement. Individualized pharmacodynamic monitoring has the potential of minimizing the toxicityand the clinical failures of these agents in critically ill patients.

Risk Factors for Mesh-related Infections After Hernia Repair Surgery: A Meta-analysis of Cohort Studies

Mesh infection, although infrequent, is a devastating complication of mesh hernioplasties. The aim of this study was to systematically review and synthesize the available evidence on risk factors for synthetic mesh infection after hernioplasty. A systematic search was performed in PubMed and Scopus databases. The extracted data were synthesized with the methodology of meta-analysis. We identified six eligible studies that reported on 2,418 mesh hernioplasties. The crude mesh infection rate was 5%. Statistically significant risk factors were smoking (risk ratio [RR]xa0=xa01.36 [95% confidence interval (CI): 1.07, 1.73]; 1,171 hernioplasties), American Society of Anesthesiologists (ASA) score ≥3 (RRxa0=xa01.40 [1.15, 1.70]; 1,682 hernioplasties), and emergency operation (RRxa0=xa02.46 [1.56, 3.91]; 1,561 hernioplasties). Also, mesh infections were significantly correlated with patient age (weighted mean difference [WMD]xa0=xa02.63 [0.22, 5.04]; 2,364 hernioplasties), ASA score (WMDxa0=xa00.23 [0.08, 0.38]; 1,682 hernioplasties), and the duration of the hernioplasty (WMDxa0=xa044.92 [25.66, 64.18]; 833 hernioplasties). A trend toward higher mesh infection rates was observed in obese patients (RRxa0=xa01.41 [0.94, 2.11]; 2,243 hernioplasties) and in patients operated on by a resident (in contrast to a consultant; RRxa0=xa01.18 [0.99, 1.40]; 982 hernioplasties). Mesh infections usually resulted in mesh removal, and common pathogens included Staphylococcus spp., Enterococcus spp., and gram-negative bacteria. Patient age, ASA score, smoking, and the duration and emergency setting of the operation were found to be associated with the development of synthetic mesh infection. The heterogeneity of the available evidence should be taken under consideration. Prospective studies with a meticulous follow-up are warranted to further investigate mesh-related infections.

The Impact of Article Length on the Number of Future Citations: A Bibliometric Analysis of General Medicine Journals

Background The number of citations received is considered an index of study quality and impact. We aimed to examine the factors associated with the number of citations of published articles, focusing on the article length. Methods Original human studies published in the first trimester of 2006 in 5 major General Medicine journals were analyzed with regard to the number of authors and of author-affiliated institutions, title and abstract word count, article length (number of print pages), number of bibliographic references, study design, and 2006 journal impact factor (JIF). A multiple linear regression model was employed to identify the variables independently associated with the number of article citations received through January 2012. Results On univariate analysis the JIF, number of authors, article length, study design (interventional/observational and prospective/retrospective), title and abstract word count, number of author-affiliated institutions, and number of references were all associated with the number of citations received. On multivariate analysis with the logarithm of citations as the dependent variable, only article length [regression coefficient: 14.64 (95% confidence intervals: (5.76–23.50)] and JIF [3.37 (1.80–4.948)] independently predicted the number of citations. The variance of citations explained by these parameters was 51.2%. Conclusion In a sample of articles published in major General Medicine journals, in addition to journal impact factors, article length and number of authors independently predicted the number of citations. This may reflect a higher complexity level and quality of longer and multi-authored studies.

Antiviral treatment for severe EBV infections in apparently immunocompetent patients

BACKGROUNDnInfectious mononucleosis usually runs a mild self-limiting course. Complications arise rarely and when so, corticosteroids are the mainstay of their treatment. The role of antivirals in the management of severe EBV infections is debatable.nnnMETHODSnWe sought to review the usage of antivirals for severe EBV infection in apparently immunocompetent patients. For this reason a search in PubMed and Scopus was performed for the time period from 1982 to 2009.nnnRESULTSn45 patients with severe manifestations of infectious mononucleosis received antivirals (as an adjunct to steroids in 26 of them). Specifically 21 patients with CNS involvement (meningoencephalitis, cerebellitis), 4 with peripheral nervous system involvement (Guillain-Barré, myeloradiculitis, facial nerve palsy), 5 with hepatitis and 15 with other afflictions (including adult respiratory distress syndrome, thrombocytopenia, aplastic anemia, acute renal failure, ulcerations, myocarditis, and frosted branch vasculitis) received antiviral medications. Thirty-nine out of these 45 patients had a favourable outcome (27 were cured and 12 showed clinical improvement) while 6 patients died. The most commonly prescribed antiviral regimen was acyclovir monotherapy (35 patients). Three patients received combinations of acyclovir with other antivirals and 1 received famciclovir. Three patients received ganciclovir monotherapy, 1 ganciclovir plus foscarnet, 1 foscarnet and 1 vidarabine.nnnCONCLUSIONnThe available data derive from case reports and case series and thus the deduction of conclusions regarding the effect, if any, of antiviral treatment is debatable. However, physicians may consider using antiviral agents in severe manifestations of EBV infections in immunocompetent patients as an adjunct to steroid treatment.

Efficacy and Safety of Telavancin in Clinical Trials: A Systematic Review and Meta-Analysis

Introduction The epidemiology and antibiotic resistance of Staphylococcus aureus have evolved, underscoring the need for novel antibiotics, particularly against methicillin-resistant S. aureus (MRSA). Telavancin is a bactericidal lipoglycopeptide with potent activity against Gram-positive pathogens. Objective To systematically review and synthesize the available evidence from randomized controlled trials (RCTs) evaluating telavancin in the treatment of patients with infections due to Gram-positive organisms with the methodology of meta-analysis. Results Six RCTs comparing telavancin with vancomycin were included; 4 (2229 patients) referred to complicated skin and soft tissue infections (cSSTIs) and 2 (1503 patients) to hospital-acquired pneumonia (HAP). Regarding cSSTIs, telavancin and vancomycin showed comparable efficacy in clinically evaluable patients (odds ratio [OR]u200a=u200a1.10 [95% confidence intervals: 0.82–1.48]). Among patients with MRSA infection, telavancin showed higher eradication rates (ORu200a=u200a1.71 [1.08–2.70]) and a trend towards better clinical response (ORu200a=u200a1.55 [0.93–2.58]). Regarding HAP, telavancin was non-inferior to vancomycin in terms of clinical response in two Phase III RCTs; mortality rates for the pooled trials were comparable with telavancin (20%) and vancomycin (18.6%). Pooled data from cSSTIs and HAP studies on telavancin 10 mg/kg indicated higher rates of serum creatinine increases (ORu200a=u200a2.22 [1.38–3.57]), serious adverse events (ORu200a=u200a1.53 [1.05–2.24]), and adverse event-related withdrawals (ORu200a=u200a1.49 [1.14–1.95]) among telavancin recipients. Conclusion Telavancin might be an alternative to vancomycin in cases of difficult-to-treat MRSA infections. The potent antistaphylococcal activity of telavancin should be weighted against the potential for nephrotoxicity.

Safety of Hepatitis B, Pneumococcal Polysaccharide and Meningococcal Polysaccharide Vaccines in Pregnancy

Immunization during pregnancy has the potential to protect the mother and the newborn from preventable diseases. Current recommendations suggest that inactivated vaccines might be considered during pregnancy when the benefits outweigh the risks.In this review, we aimed to evaluate the safety of hepatitis B (HB) vaccine, pneumococcal polysaccharide vaccine (PPSV) and meningococcal polysaccharide vaccine (MPSV) administration during pregnancy by systematically reviewing the available evidence in PubMed and Scopus databases, as well as postmarketing surveillance data (including the Vaccine Adverse Event Reporting System [VAERS] database). A total of 18 studies were eligible for inclusion in the review. Six studies provided data on HB vaccine, six on PPSV and three on MPSV; three additional studies compared PPSV with MPSV. Additionally, 91 reports on vaccinations of pregnant women were identified from postmarketing surveillance data (88 on HB vaccine, 2 on PPSV, 1 on MPSV). The most common complaints were local reactions, including tenderness and swelling. Overall, immunization during pregnancy did not seem to be associated with a teratogenic effect on the fetus, preterm labour or spontaneous abortion. However, the lack of randomized, placebo-controlled trials, or even large cohort studies, in addition to the inherent limitations of the reviewed observational studies with small statistical power, precluded safe conclusions. Large, prospective, population-based cohort studies are needed to elucidate this issue.

H1N1v influenza vaccine in Greek medical students.

BACKGROUNDnWe sought to investigate the penetration of the H1N1v vaccine in Greek medical students, as well as their approach to the vaccination.nnnMETHODSnA survey was conducted among the students of the University of Athens, School of Medicine, 1 month after the initiation of the vaccination programme. Participants were asked to fill in a questionnaire regarding their status of vaccination and their approach to the H1N1v vaccine.nnnRESULTSnWe handed a questionnaire to 1000 students (out of 1700 officially enrolled in the medical school) and retrieved 922 answers. Only 74 (8%) medical students had been vaccinated and 78 (9%) planned to (probably or definitely) do so in the future, while 641 (67%) would (probably or definitely) not get vaccinated. The highest coverage was among the sixth year students (37/234, 16%). The most common reasons for not having received the vaccine were perception of the disease as mild (387/848, 46%), and concern regarding long-term adverse events (370/848, 44%). Thirty percent (258/848) of the students doubted the vaccines effectiveness, and 197 (23%) worried about possible short-term adverse events. One hundred and thirty-three respondents (16%) believed the whole story is a conspiracy while 102 (12%) reported to have had the flu. Almost half (43%) of the participants considered their knowledge on the subject inadequate.nnnCONCLUSIONnOur findings confirmed the low penetration of the H1N1 vaccine in Greece, as in most European countries, even in medical students. Better education of the students and the public might aid in increasing the immunization rates.

In Vitro Antimicrobial Susceptibility to Isepamicin of 6,296 Enterobacteriaceae Clinical Isolates Collected at a Tertiary Care University Hospital in Greece

ABSTRACT The reevaluation of “forgotten” antibiotics can identify new therapeutic options against extensively drug-resistant Gram-negative pathogens. We sought to investigate isepamicin in this regard. We retrospectively evaluated the antimicrobial susceptibility to isepamicin of Enterobacteriaceae sp. isolates from unique patients, collected at the microbiological laboratory of the University Hospital of Heraklion, Crete, Greece, from 2004 to 2009. Susceptibility testing was done with the automated Vitek 2 system. The breakpoints for susceptibility to isepamicin, tigecycline, and other antibiotics were those proposed by the Comité de lAntibiogramme de la Société Française de Microbiologie (CA-SFM), the FDA, and the CLSI, respectively. A total of 6,296 isolates were studied, including primarily 3,401 (54.0%) Escherichia coli, 1,040 (16.5%) Klebsiella pneumoniae, 590 (9.4%) Proteus mirabilis, and 460 (7.3%) Enterobacter sp. isolates. Excluding the species with intrinsic resistance to each antibiotic, antimicrobial susceptibility was highest for colistin (5,275/5,441 isolates [96.9%]) and isepamicin (6,103/6,296 [96.9%]), followed by meropenem (5,890/6,296 [93.6%]), imipenem (5,874/6,296 [93.3%]), and amikacin (5,492/6,296 [87.2%]). The antimicrobial susceptibility of the 1,040 K. pneumoniae isolates was highest for isepamicin (95.3%), followed by colistin (89.3%) and meropenem (63.0%). Regarding resistant K. pneumoniae isolates, susceptibility to isepamicin was observed for 91.1% of the 392, 87.7% of the 375, and 85.6% of the 111 isolates that were nonsusceptible to the carbapenems, all other aminoglycosides, and colistin, respectively. Isepamicin exhibited high in vitro activity against almost all of the Enterobacteriaceae species. It could particularly serve as a last-resort therapeutic option for carbapenem-resistant K. pneumoniae in our region, where it is endemic, as it does not show considerable cross-resistance with other aminoglycosides.

Adhesive strips for the closure of surgical incisional sites: a systematic review and meta-analysis.

Background. The authors evaluated the available evidence regarding the use of adhesive strips for the management of surgical incisions and compared them with sutures and other closure materials. Study design. Systematic review and meta-analysis of randomized controlled trials (RCTs). Results. Twelve RCTs studying 1317 incisions in 1023 patients were included. No difference was found regarding the development of infection (odds ratio [OR] = 0.47; 95% Confidence interval [CI] = 0.12-1.85), dehiscence (OR = 1.22; 95% CI = 0.32-4.64), and overall cosmetic result (standardized mean difference = 0.01; 95% CI = −0.19 to 0.20). Closure with strips resulted in significantly lower incidence of redness (OR = 0.57; 95% CI = 0.37-0.89). The available data on pain, need for resuturing, swelling, patient satisfaction, and closure time with the use of strips could not be synthesized; however, regarding the latter 2 outcomes, application of strips seemed favorable. There was significant heterogeneity among the studies. Conclusions. The findings suggest that adhesive strips may be an efficient closure material for certain small-length incisions. Further research is warranted on outcomes such as dehiscence and the need for resuturing.