Comparative Analysis of Mortality From Coronavirus Disease 2019 Across the European Union Countries and the Effects of Vaccine Coverage.

BACKGROUND: Mortality is a critical measure of disease impact. The European Union (EU) countries share the same regulatory framework but different implementation policies. METHODS: We extracted cumulative COVID-19 mortality data across the EU countries. We evaluated the 27 member states using the location quotient (LQ) to adjust for the expected mortality in the whole EU region, where an LQ <1 signifies a more and an LQ >1 a less favorable outcome. We categorized EU members into 3 distinct profiles based on their LQ estimates: favorable profile, LQ ≤0.9; unfavorable profile, LQ >1.10; and average profile, LQ between 0.9 and 1.10. We compared LQ estimates and profiles with the prevaccination era that ended in December 2020 with the COVID-19 vaccine rollout. RESULTS: Twelve member states had a favorable profile, 4 had an average profile, and 11 had an unfavorable profile. In quantitative analysis, an improvement (negative LQ difference) was noted across countries with higher vaccination coverage (median, 71% fully vaccinated vs 57% for countries with positive LQ differences). There was a significant negative association between the share of fully vaccinated and LQ changes (ρ = -0.62, P < .001) and a significant 4-month lag effect. After COVID-19 vaccines became available, 4 countries improved their profile and 5 moved to a worse profile. CONCLUSIONS: There is significant variability in mortality and impact of COVID-19 between countries, even if they share the same regulatory framework. Extending immunization coverage may lead the transition to a more favorable profile, and alter the trajectory of COVID-19 mortality.

Automated monitoring compared to standard care for the early detection of sepsis in critically ill patients.

BACKGROUND: Sepsis is a life-threatening condition that is usually diagnosed when a patient has a suspected or documented infection, and meets two or more criteria for systemic inflammatory response syndrome (SIRS). The incidence of sepsis is higher among people admitted to critical care settings such as the intensive care unit (ICU) than among people in other settings. If left untreated sepsis can quickly worsen; severe sepsis has a mortality rate of 40% or higher, depending on definition. Recognition of sepsis can be challenging as it usually requires patient data to be combined from multiple unconnected sources, and interpreted correctly, which can be complex and time consuming to do. Electronic systems that are designed to connect information sources together, and automatically collate, analyse, and continuously monitor the information, as well as alerting healthcare staff when pre-determined diagnostic thresholds are met, may offer benefits by facilitating earlier recognition of sepsis and faster initiation of treatment, such as antimicrobial therapy, fluid resuscitation, inotropes, and vasopressors if appropriate. However, there is the possibility that electronic, automated systems do not offer benefits, or even cause harm. This might happen if the systems are unable to correctly detect sepsis (meaning that treatment is not started when it should be, or it is started when it shouldn't be), or healthcare staff may not respond to alerts quickly enough, or get 'alarm fatigue' especially if the alarms go off frequently or give too many false alarms. OBJECTIVES: To evaluate whether automated systems for the early detection of sepsis can reduce the time to appropriate treatment (such as initiation of antibiotics, fluids, inotropes, and vasopressors) and improve clinical outcomes in critically ill patients in the ICU. SEARCH METHODS: We searched CENTRAL; MEDLINE; Embase; CINAHL; ISI Web of science; and LILACS, clinicaltrials.gov, and the World Health Organization trials portal. We searched all databases from their date of inception to 18 September 2017, with no restriction on country or language of publication. SELECTION CRITERIA: We included randomized controlled trials (RCTs) that compared automated sepsis-monitoring systems to standard care (such as paper-based systems) in participants of any age admitted to intensive or critical care units for critical illness. We defined an automated system as any process capable of screening patient records or data (one or more systems) automatically at intervals for markers or characteristics that are indicative of sepsis. We defined critical illness as including, but not limited to postsurgery, trauma, stroke, myocardial infarction, arrhythmia, burns, and hypovolaemic or haemorrhagic shock. We excluded non-randomized studies, quasi-randomized studies, and cross-over studies . We also excluded studies including people already diagnosed with sepsis. DATA COLLECTION AND ANALYSIS: We used the standard methodological procedures expected by Cochrane. Our primary outcomes were: time to initiation of antimicrobial therapy; time to initiation of fluid resuscitation; and 30-day mortality. Secondary outcomes included: length of stay in ICU; failed detection of sepsis; and quality of life. We used GRADE to assess the quality of evidence for each outcome. MAIN RESULTS: We included three RCTs in this review. It was unclear if the RCTs were three separate studies involving 1199 participants in total, or if they were reports from the same study involving fewer participants. We decided to treat the studies separately, as we were unable to make contact with the study authors to clarify.All three RCTs are of very low study quality because of issues with unclear randomization methods, allocation concealment and uncertainty of effect size. Some of the studies were reported as abstracts only and contained limited data, which prevented meaningful analysis and assessment of potential biases.The studies included participants who all received automated electronic monitoring during their hospital stay. Participants were randomized to an intervention group (automated alerts sent from the system) or to usual care (no automated alerts sent from the system).Evidence from all three studies reported 'Time to initiation of antimicrobial therapy'. We were unable to pool the data, but the largest study involving 680 participants reported median time to initiation of antimicrobial therapy in the intervention group of 5.6 hours (interquartile range (IQR) 2.3 to 19.7) in the intervention group (n = not stated) and 7.8 hours (IQR 2.5 to 33.1) in the control group (n = not stated).No studies reported 'Time to initiation of fluid resuscitation' or the adverse event 'Mortality at 30 days'. However very low-quality evidence was available where mortality was reported at other time points. One study involving 77 participants reported 14-day mortality of 20% in the intervention group and 21% in the control group (numerator and denominator not stated). One study involving 442 participants reported mortality at 28 days, or discharge was 14% in the intervention group and 10% in the control group (numerator and denominator not reported). Sample sizes were not reported adequately for these outcomes and so we could not estimate confidence intervals.Very low-quality evidence from one study involving 442 participants reported 'Length of stay in ICU'. Median length of stay was 3.0 days in the intervention group (IQR = 2.0 to 5.0), and 3.0 days (IQR 2.0 to 4.0 in the control).Very low-quality evidence from one study involving at least 442 participants reported the adverse effect 'Failed detection of sepsis'. Data were only reported for failed detection of sepsis in two participants and it wasn't clear which group(s) this outcome occurred in.No studies reported 'Quality of life'. AUTHORS' CONCLUSIONS: It is unclear what effect automated systems for monitoring sepsis have on any of the outcomes included in this review. Very low-quality evidence is only available on automated alerts, which is only one component of automated monitoring systems. It is uncertain whether such systems can replace regular, careful review of the patient's condition by experienced healthcare staff.

Medicare part D prescribing for direct oral anticoagulants in the United States: Cost, use and the "rubber effect".

INTRODUCTION: Direct oral anticoagulants (DOAC) have gained an increased share over warfarin for prevention and treatment of thromboembolic disease. We studied DOAC adoption across providers and medical specialties. METHODS: Retrospective, cross-sectional analysis of Medicare Part D public use files (PUF), 2013 to 2015. We summarized prescription data for claims and drug payment, stratified by drug class, specialty and calendar year. We treated DOAC claims as a count outcome and explored patterns of expansion across prescribers via a truncated negative binomial regression. We described dispersion and spread in DOAC prescribing, across hospital referral regions (HRRs), including the p90/p10 ratios, and the median absolute deviation from the median. RESULTS: In 2015 part D PUF, oral anticoagulant claims have climbed to approximately 24.4 million with a payment cost of approximately $3.3 billion. DOAC claims comprised 31.0% of oral anticoagulant claims, showing a relative increase of approximately 127% compared to 2013. The upper decile of prescribers accounted for half of the oral anticoagulant prescriptions and the resulting cost. The median cost per DOAC claim in 2015 was $367.4 (interquartile range 323.9 to 445.9), as opposed to $12.3 (interquartile range 9.2 to 16.5) for warfarin. The median cost per standardized (30-day supply) prescription was $317.0 (interquartile range 303.8 to 324.3) and $8.0 (6.7 to 9.8) for DOACs and warfarin, respectively. DOAC adoption differs by specialty. Cardiologists, cardiac electrophysiologists and orthopedics had the highest predicted DOAC share per 100 claims (53.8, 72.9 and 71.5, respectively in 2015); nephrologists, family practitioners and geriatricians the lowest (22.3, 21.5 and 20.7, respectively in 2015). The p90/p10 ratio and the median absolute deviation from the median varied across HRRs and correlated positively with the prevalence of stroke and atrial fibrillation in the Medicare population. CONCLUSIONS: DOACs have been increasing their share year-over-year, but adoption varies across specialties. In prevalent areas for stroke and atrial fibrillation, prescription dispersion magnifies, and this may signify a rapid adoption by top providers.

Bosentan for patients with echocardiographic evidence of pulmonary hypertension due to long-standing rheumatic mitral stenosis.

INTRODUCTION: Vasoconstrictive endothelin signaling is not limited to idiopathic pulmonary arterial hypertension, but has also been implicated in pulmonary hypertension due to valvular heart disease. The efficacy and safety of endothelin receptor antagonists in these patients is unknown. We investigated the effects of bosentan in patients with transthoracic echocardiographic (TTE) evidence of pulmonary hypertension due to mitral stenosis associated with rheumatic fever. METHODS: This was a prospective, single-center, open-label, uncontrolled study of bosentan in outpatients with uncorrected mitral stenosis due to rheumatic fever. The primary endpoint was exercise capacity at six months, as determined by six-minute walking distance (6MWD) and maximal oxygen uptake (VO2max). Secondary endpoints were the BORG dyspnea index (BDI), echocardiographic left ventricular ejection fraction (LVEF) and pulmonary arterial pressure (PAP), serum pro-brain natriuretic peptide (proBNP), and adverse events at six months. RESULTS: Ten patients (eight females; mean age 75 years) were enrolled. Bosentan was well tolerated by nine, whereas one withdrew from treatment. By intention-to-treat analysis, bosentan resulted in a marked increase in 6MWD (+32 m, p=0.015), but a significant reduction in VO2max (-0.45 mL/min/kg, p=0.011). Peak PAP did not change significantly, but mean PAP dropped by 16% (p=0.03) and LVEF increased by 6.5% (p=0.003). Profound reductions were observed in BDI and serum proBNP (-67% and -37%, p=0.002 and p=0.011, respectively). Adverse events included minor reductions in body mass and hematocrit. CONCLUSION: The results of this pilot study suggest that endothelin receptor antagonism improves the functional status of patients with TTE evidence of pulmonary hypertension due to valvular heart disease. Randomized controlled trials are needed to confirm the results.

Infections in patients undergoing craniotomy: risk factors associated with post-craniotomy meningitis.

OBJECT The authors performed a prospective study to define the prevalence and microbiological characteristics of infections in patients undergoing craniotomy and to clarify the risk factors for post-craniotomy meningitis. METHODS Patients older than 18 years who underwent nonstereotactic craniotomies between January 2006 and December 2008 were included. Demographic, clinical, laboratory, and microbiological data were systemically recorded. Patient characteristics, craniotomy type, and pre- and postoperative variables were evaluated as risk factors for meningitis RESULTS Three hundred thirty-four procedures were analyzed (65.6% involving male patients). Traumatic brain injury was the most common reason for craniotomy. Almost 40% of the patients developed at least 1 infection. Ventilator-associated pneumonia (VAP) was the most common infection recorded (22.5%) and Acinetobacter spp. were isolated in 44% of the cases. Meningitis was encountered in 16 procedures (4.8%), and CSF cultures were positive for microbial growth in 100% of these cases. Gram-negative pathogens (Acinetobacter spp., Klebsiella spp., Pseudomonas aeruginosa, Enterobacter cloaceae, Proteus mirabilis) represented 88% of the pathogens. Acinetobacter and Klebsiella spp. demonstrated a high percentage of resistance in several antibiotic classes. In multivariate analysis, the risk for meningitis was independently associated with perioperative steroid use (OR 11.55, p = 0.005), CSF leak (OR 48.03, p < 0.001), and ventricular drainage (OR 70.52, p < 0.001). CONCLUSIONS Device-related postoperative communication between the CSF and the environment, CSF leak, and perioperative steroid use were defined as risk factors for meningitis in this study. Ventilator-associated pneumonia was the most common infection overall. The offending pathogens presented a high level of resistance to several antibiotics.

Biologic therapies in rheumatoid arthritis and the risk of opportunistic infections: a meta-analysis.

OBJECTIVE: Biologic agents are increasingly used to treat patients with rheumatoid arthritis (RA). We aimed to review their association with opportunistic infections (OIs), including fungal, viral (with a focus on herpesvirus-related infections), tuberculosis and other mycobacterial infections. METHODS: We searched PubMed and EMBASE through June 24, 2013, and complemented the search with the reference lists of eligible articles. The analysis included randomized trials on RA that compared any approved biologic agent with controls and reported the risk of OIs. RESULTS: A total of 70 trials that included 32 504 patients (21 916 patients receiving biologic agents and 10 588 receiving placebo) were deemed eligible. Biologic agents increased the risk of OIs (pooled Peto odds ratio [OR], 1.79; 95% confidence interval [CI], 1.17-2.74; I(2) = 3%), resulting in 1.7 excess infections per 1000 patients treated (number needed to harm, 582). A significant risk was noted for mycobacterial (OR, 3.73; 95% CI, 1.72-8.13; I(2) = 0), and viral (OR, 1.91; 95% CI, 1.02-3.58; I(2) = 0) infections. Interestingly, no significant differences were found for invasive and superficial fungal infections (1.31; 95% CI, .46-3.72), invasive fungal infections (2.85; .68-11.91), P. jirovecii pneumonia (1.77; .42-7.47), varicella-zoster virus (1.51; .71-3.22), as well as overall mortality attributed to OIs (1.91; .29-12.64). CONCLUSIONS: Among patients with RA, biologic agents are associated with a small but significant risk of specific OIs. This increase is associated with mycobacterial diseases and does not seem to affect overall mortality. Because OIs are a relatively rare complication of biologic agents, large registries are needed to identify the exact effect in different OIs and to compare the different biologic agents.

Systemic antifungal prophylaxis after hematopoietic stem cell transplantation: a meta-analysis.

BACKGROUND: Hematopoietic stem transplant recipients are subject to increased risk for invasive fungal infections. OBJECTIVE: This meta-analysis was undertaken to explore the comparative effectiveness of systemic antifungal prophylaxis in hematopoietic stem cell transplant recipients. METHODS: We searched PubMed and The Cochrane Register of Randomized Controlled Trials up to March 2013 for randomized studies on systemic antifungal prophylaxis after hematopoietic stem cell transplantation. We performed a meta-analysis on the relative effectiveness of systemic antifungal prophylaxis on proven or probable invasive fungal infections using direct and indirect effects. Relative effectiveness was reported as odds ratio (OR) for invasive fungal infections, causative agent, empirical antifungal therapy, and withdrawals due to drug adverse events. RESULTS: Twenty evaluable studies provided data on 4823 patients. The risk for invasive fungal infections while on prophylaxis was 5.1% (95% CI, 3.6-6.8%). In patients receiving fluconazole, risks of proven or probable invasive fungal infections (OR = 0.24; 95% CI, 0.11-0.50; number needed to treat [NNT] = 8), systemic candidiasis (OR = 0.11; 95% CI, 0.05-0.24; NNT = 7), and overall need for empiric antifungal treatment (OR = 0.60; 95% CI, 0.44-0.82; NNT = 8) were reduced compared with patients receiving placebo. Itraconazole was more effective than fluconazole for the prevention of aspergillosis (OR = 0.40; 95% CI, 0.19-0.83; NNT = 23) at the expense of more frequent withdrawals (OR = 3.01; 95% CI, 1.77-5.13; number needed to harm = 6). Micafungin was marginally more effective than fluconazole for the prevention of all mold infections (OR = 0.35; 95% CI, 0.10-1.18; NNT = 79) and invasive aspergillosis (OR = 0.19; 95% CI, 0.03-1.11; NNT = 78) and reducing the need for empiric antifungal treatment (OR = 0.40; 95% CI, 0.13-1.21; NNT = 8). There was a relative lack of comparisons between different antifungal prophylactic strategies, including the newer azoles, voriconazole and posaconazole, in this population. Direct effects derived from single studies showed marginally significant effects for voriconazole compared with fluconazole regarding invasive aspergillosis (OR = 0.50; 95% CI, 0.20-1.20; NNT = 35) and the need for empiric treatment (OR = 0.72; 95% CI, 0.50-1.06; NNT = 15). Voriconazole compared with itraconazole (OR = 0.59; 95% CI, 0.40-0.88; NNT = 8) and posaconazole compared with amphotericin B (OR = 0.28; 95% CI, 0.06-1.24, marginal significance; NNT = 3) were better regarding empirical antifungal treatment. CONCLUSIONS: Even when on antifungal therapy, invasive fungal infection will develop in 1 of 20 patients undergoing hematopoietic stem cell transplantation. There is evidence for the comparable effectiveness of different antifungal drugs used for prophylaxis. Fluconazole is the most widely studied agent, but micafungin might prove to be more effective. There is a relative paucity of studies for the newer azoles, although both voriconazole and posaconazole give proof of their comparative or higher effectiveness to fluconazole in single randomized studies.

Fungal central nervous system infections: prevalence and diagnosis.

Fungal infections of the central nervous system (CNS) are rare but they pose a significant challenge. Their prevalence spans a wide array of hosts including immunosuppressed and immunocompetent individuals, patients undergoing neurosurgical procedures and those carrying implantable CNS devices. Cryptococcus neoformans and Aspergillus spp. remain the most common pathogens. Magnetic resonance imaging can help localize the lesions, but diagnosis is challenging since invasive procedures may be needed for the retrieval of tissue, especially in cases of fungal abscesses. Antigen and antibody tests are available and approved for use in the cerebrospinal fluid (CSF). PCR-based techniques are promising but they are not validated for use in the CSF. This review provides an overview on the differential diagnosis of the fungal CNS disease based on the host and the clinical syndrome and suggests the optimal use of diagnostic techniques. It also summarizes the emergence of Cryptococcus gatti and an unanticipated outbreak caused by Exserohilum rostratum.

Pegfilgrastim vs. filgrastim for supportive care after autologous stem cell transplantation: can we decide?

Granulocyte-colony-stimulating factors are helpful for the support of patients receiving autologous hematopoietic stem cell transplantation, resulting in faster neutrophil recovery and lower incidence of febrile neutropenia (FN). Our aim was to evaluate the use of pegfilgrastim vs. filgrastim with regard to absolute neutrophil count (ANC) recovery, risk, and duration of FN and length of hospital stay. Mean difference was the summary effect for continuous data, and odds ratio for binary data, using random-effects modeling. MEDLINE, EMBASE, and the Cochrane Registry of Randomized Controlled Trials were included in the search. Randomized controlled trials (RCTs), case-control studies, and studies with historical control group for filgrastim were eligible. Of the initial 114 studies screened, 12 studies were analyzed (four were RCTs, including one phase III trial). The use of pegfilgrastim resulted in a one d gain in ANC recovery (mean difference -0.82, 95% CI -1.07 to -0.57, p < 0.001) and duration of FN (-0.67, 95% CI -1.28 to -0.06, p < 0.001) but had no effect on the risk of FN or length of stay. Pegfilgrastim was more expensive (baseline marginal cost €116.97, p < 0.001), which was largely determined by the treatment duration and pegfilgrastim cost. Non-randomized setting attenuated the effect on duration of FN whereas delayed onset of filgrastim injections (to pegfilgrastim) overestimated the protective effect on the risk of FN. Both drugs are at least equally effective, though methodology and disease stratification in published trials warrant further improvement.

Infections in patients with traumatic brain injury who undergo neurosurgery.

OBJECTIVE: Several factors place victims with traumatic brain injury (TBI) at increased risk for infection. The purpose of this study was to delineate the frequency, types and risk factors for infection in patients with TBI who undergo neurosurgery. MATERIALS AND METHODS: Retrospective surveillance of infections in patients with TBI, aged  ≥18 years who underwent neurosurgery in University of Crete between 1999 and 2005. RESULTS: Two hundred fifty-eight patients (76.7% men) who underwent 342 procedures were included. One hundred forty-two infections occurred, mainly lower respiratory tract infections (44.4% of the number of infections) and surgical site infections (SSIs) (25.4%). In multivariate analysis, SSIs were independently associated with the length of stay (p < 0.001), history of malignancy (p = 0.008), CSF leak (p = 0.012), any concomitant infection (p = 0.010), particularly urinary tract infections (p = 0.001) and the use of lumbar and/or ventricular drains (p = 0.005). Meningitis was independently associated with the total length of stay (p < 0.001), the need for intubation and mechanical ventilation beyond surgery (p = 0.028) and the presence of a lumbar and/or ventricular drain (p < 0.001). CONCLUSIONS: Respiratory tract infections were common in patients with TBI who underwent surgery with Acinetobacter spp. being the emerging offending pathogens. Device-related postoperative communication of the CSF and the environment was a significant risk factor for SSI development and meningitis in particular. Malignancy was an independent risk factor for SSIs. The prevalence of the offending pathogens must be determined institution by institution for the establishment of proper antibiotic treatment on suspicion.

Impact of prolonged treatment with high-dose ciprofloxacin on human gut flora: a case report.

INTRODUCTION: Ciprofloxacin is a commonly marketed fluoroquinolone. It is not effective against obligate anaerobes, hence it is considered unlikely to have an impact on colonic microflora. We report the case of a patient who received prolonged treatment with high-dose ciprofloxacin for extensive pelvic osteomyelitis. We also report on the medication's effects on his bowel flora. To the best of our knowledge, this is the first report discussing the effects of prolonged administration of a quinolone on microbial flora. CASE PRESENTATION: A 62-year-old Caucasian man with diabetes presented with low back pain of four months' duration. A magnetic resonance imaging of his pelvis revealed sacroiliitis and extensive pelvic osteomyelitis. Pseudomonas aeruginosa, which is susceptible to ciprofloxacin, was noted as the offending pathogen. After seven weeks of intravenous treatment, he was prescribed with high-dose oral ciprofloxacin that he continued to take for the next 20 months. Quantitative stool cultures of our patient were obtained a month later as well as at the end of his treatment to record his corresponding sensitivities to the medication. The Gram-negative population of his bowel flora was restored fully upon the discontinuation of this medication. The Gram-negative population was shown to be fully sensitive to ciprofloxacin. His yeast levels were also found to be slightly increased, and no growth of resistant enterococci was noted. CONCLUSION: The findings of this case report suggest that long term and high dose ciprofloxacin administration might be safe in preventing the risk of colonization with resistant Gram negative pathogens, overgrowth of anaerobes and the development of resistant enterococci.

Effectiveness of systemic antifungal prophylaxis in patients with neutropenia after chemotherapy: a meta-analysis of randomized controlled trials.

BACKGROUND: Invasive fungal infections are responsible for substantial morbidity and mortality among patients with neutropenia after chemotherapy. OBJECTIVE: This meta-analysis was conducted to estimate the effect of systemic antifungal prophylaxis on the frequency of invasive fungal infections in patients with neutropenia and the mortality associated with these infections. METHODS: MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials were searched through September 15, 2010, for English-language publications of randomized controlled trials that compared systemic antifungal prophylaxis with placebo or no treatment in patients with neutropenia. Studies involving nonsystemic antifungal agents, direct comparisons of antifungal agents, and empirical, preemptive, or salvage treatment were excluded. Data were extracted according to European Organization for Research and Treatment of Cancer definitions of proven, possible, or probable fungal infections. Effect measures were reported as odds ratios (ORs) for fungal infection and mortality. Outcomes were pooled using random-effects meta-analysis. Study quality was assessed based on the study setting (single center or multicenter), institutional review board approval/informed consent, randomization, description of allocation concealment, double blinding, and reporting of dropouts. RESULTS: Twenty-six trials including a total of 3979 patients were included in the meta-analysis. Antifungal prophylaxis was associated with significant reductions in proven fungal infections (OR = 0.43; 95% CI, 0.31-0.60; number needed to treat [NNT] = 20) and mortality attributed to fungal infections (OR = 0.49; 95% CI, 0.30-0.80; NNT = 53). Overall mortality was not affected by antifungal prophylaxis (OR = 0.92; 95% CI, 0.74-1.14). Antifungal prophylaxis was associated with a reduction in risk for proven Candida infections (OR = 0.28; 95% CI, 0.20-0.38), but not for aspergillosis or zygomycosis. Antifungal prophylaxis was also associated with a decreased need for antifungal therapy (OR = 0.64; 95% CI, 0.48-0.86). In an explanatory subgroup analysis of major outcomes, only recipients of a hematopoietic stem cell transplant (HSCT) had a significant likelihood of benefiting from antifungal prophylaxis in terms of reductions in risk for proven infections (OR = 0.27; 95% CI, 0.16-0.44) and mortality attributed to infections (OR = 0.41; 95% CI, 0.21-0.81). A metaregression analysis indicated that a multicenter (vs single-center) design and a double-blind (vs unblinded) design were significant moderators of the effect of antifungal prophylaxis on overall mortality and proven systemic fungal infections, respectively. CONCLUSIONS: Systemic antifungal prophylaxis was associated with a reduction in proven fungal infections and mortality attributed to these infections in patients with neutropenia after chemotherapy. In the setting of HSCT, antifungal prophylaxis was associated with reductions in both proven infections and mortality attributed to infections. There was no significant association between antifungal prophylaxis and overall mortality.

Spinal infections: evolving concepts.

PURPOSE OF REVIEW: Although rare, spinal infections are characterized by an indolent clinical course and delay in diagnosis. Physicians should be aware of current diagnostic and therapeutic developments. RECENT FINDINGS: The range of the pathogens causing spinal infections has expanded as a result of the increasing number of individuals at risk and enhanced diagnostics. The role of newer biological therapies in producing spinal infections has not been elucidated yet. Pyogenic bacteria still account for most of the cases; however, tuberculosis and brucellosis remain major causes in endemic countries and susceptible patients. Endoscopic techniques assist in sampling suspicious lesions and molecular microbiology has revolutionized diagnosis. Magnetic resonance imaging techniques remain the gold standard for diagnostic imaging; their role in follow-up is a matter of debate. Long-term antimicrobial treatment is currently the standard of care. The identification of individuals most likely to benefit from surgical intervention is crucial. Surgery may be required early to address any neurological deficits and later to treat infection refractory to conservative treatment. SUMMARY: Prompt diagnosis is essential in spinal infections. Early surgical intervention is required in patients with neurological deficits. Further research should clarify the appropriate duration of antimicrobial treatment and the overall role of surgery.

Mycobacterial species diversity at a general hospital on the island of Crete: first detection of Mycobacterium lentiflavum in Greece.

The objective of the present study was to investigate the diversity of mycobacterial isolates in a general hospital in Crete, Greece. 48 positive Lowenstein-Jensen cultures over a 3-y period were analysed by means of AccuProbe and GenoType assays. Non-tuberculous mycobacteria (NTM) comprised the majority of the isolates (56.3%, 27/48) vs 33.3% (16/48) of M. tuberculosis; 10.4% of the isolates could not be classified. Among NTM, M. lentiflavum was the predominant species isolated (9/27) followed by M. kansasii, M. gordonae and M. peregrinum, whereas no M. avium complex isolates were detected. This is the first detection of M. lentiflavum in Greece. The susceptibilities of the M. lentiflavum isolates to an extended panel of antibiotics were determined by the proportions method and the medical files of the 9 patients were reviewed. Three isolates were from urine, which is an unusual site. All strains exhibited multidrug resistance. The patients were adults with immunosuppression or predisposing conditions for NTM infection. Diagnosis of true infection was either not pursued or the patients died shortly after isolation.

Risk factors associated with postcraniotomy meningitis.

OBJECTIVE: The authors conducted a retrospective cohort study to determine the incidence, bacteriological features, and risk factors for postcraniotomy meningitis. METHODS: Patients older than 18 years who underwent nonstereotactic craniotomies between January 1996 and March 2000 and who survived for more than 7 days were included. Operations for placement of burr holes and shunts were excluded. Records of the first 30 postoperative days were abstracted. Host factors, types of craniotomy, and pre- and postoperative variables were evaluated as risk factors for meningitis RESULTS: Among 453 patients, there were 25 cases of meningitis. Eight out of 12 culture-positive cases were the result of gram-positive cocci. Four hundred twenty (92%) patients received antibiotic prophylaxis, most commonly a first-generation cephalosporin. In multivariate analysis, the risk of meningitis was increased by surgery that entered a sinus (odds ratio [OR], 4.49; P = 0.018), an increase in the American Society of Anesthesiologists score (OR, 1.72; P = 0.023), and increases in the number of days of external ventricular drainage (OR, 1.21; P = 0.049) and intracranial pressure monitoring (OR, 1.24; P = 0.002). CONCLUSION: Access of upper airway bacteria to the surgical wound, host factors as expressed by the American Society of Anesthesiologists score, and duration of device-related postoperative communication of the cerebrospinal fluid and the environment are major risk factors for postoperative meningitis after craniotomy.

Mycobacterium tuberculosis malate synthase- and MPT51-based serodiagnostic assay as an adjunct to rapid identification of pulmonary tuberculosis.

The 81-kDa malate synthase (MS; Rv 1837c) and the 27-kDa MPT51 (Rv 3803c) of Mycobacterium tuberculosis are immunodominant antigens recognized by serum antibodies from approximately 80% of human immunodeficiency virus-negative smear-positive tuberculosis patients from India. We now provide evidence that the use of the MS/MPT51-based serodiagnostic assay can serve as an adjunct to sputum microscopy in the rapid diagnosis of pulmonary tuberculosis.

Biological therapies of autoimmune diseases.

The advances in the understanding of the pathogenesis of the autoimmune diseases have led to new treatment targets. Biological agents enhance or replace conventional immunosuppressive therapies in the treatment of autoimmune diseases. TNF-alpha has been validated as a good treatment target but the potential modalities also include the inhibition of the interaction between LFA-3 (lymphocyte function-associated antigen 3) and CD2, the blockade of the IL-1 receptors, the antibodies against the alpha4 integrins, the antibodies against B-cell CD20 and the inhibition of the activation of T-cells. The new treatments have had a major impact on inflammatory symptoms, the radiological damage and the anemia of chronic disease in rheumatoid arthritis and have substantially controlled the signs and symptoms in the spondylarthropathies group and plaque-type psoriasis. The efficacy of the biologic agents in systemic lupus erythematosus warrants further investigation but there have been some promising results in proliferative lupus nephritis. Several small studies have explored their use in the treatment of Sjogren's syndrome, adult onset Still's disease and several vasculitides but the results are still preliminary and warrant confirmation. The efficacy of the biological agents has been impressive. Susceptibility to infections has always been a major concern; a high level of suspicion is necessary and strategies should be implemented for the prevention, the rapid identification and pre-emptive therapy of such infections.