Modifiable risk factors associated with later gut decolonization of carbapenem-resistant Gram-negative bacteria in children: a prospective cohort study.

BACKGROUND: Nosocomial infections caused by carbapenem-resistant Gram-negative bacteria (CRGNB) are associated with increased mortality and prolonged hospitalization; thus, later CRGNB decolonization has significant clinical and public health implications. AIM: To investigate modifiable/non-modifiable risk factors for CRGNB later gut decolonization in children. METHODS: CRGNB carriers (aged from one day to 16 years) hospitalized in a tertiary level hospital (2018-2019) were included. Upon CRGNB carriage detection, rectal swab cultures were taken weekly, if patients were hospitalized, and monthly after discharge for 12 months. CRGNB decolonization was defined as three consecutive negative rectal-swab cultures obtained ≥1 week apart. Modifiable (treatment administered/medical devices) and non-modifiable (age/gender/comorbidities) risk factors were recorded. Cox regression for later CRGNB decolonization was performed. FINDINGS: One hundred and thirty CRGNB carriers were recorded. After 12 months, 5.4% remained carriers. Risk factors for later decolonization were immunosuppression (hazard ratio: 0.52; 95% confidence interval: 0.31-0.87), carbapenems (0.52; 0.30-0.91), proton pump inhibitors (PPIs) (0.39; 0.24-0.64) and their duration of use, duration of hospitalization (0.90; 0.81-0.92, per 10 days), number of readmissions (0.90; 0.86-0.96), abdominal surgery (0.33; 0.17-0.65), urinary catheter (0.42; 0.24-0.76), and duration of steroid administration per 10 days (0.86; 0.84-0.88). CONCLUSIONS: Carbapenems, PPIs and their duration of use, duration of steroids use, immunosuppression, urinary catheter, readmissions, duration of hospitalization, and abdominal surgery are associated with later CRGNB decolonization among children. Paediatric patients at risk of later decolonization should be under targeted screening and pre-emptive contact precautions. Known carriers at risk of later CRGNB decolonization should be under meticulously applied contact precautions for longer durations.

Impact of COVID-19 pandemic on medical education in Greece: A cross-sectional study.

BACKGROUND: Medical education was widely affected by the Coronavirus disease 2019 (COVID-19) pandemic. Long-distance learning was implemented over the traditional educational paradigm. Clinical clerkships were canceled, and evaluation methods were altered. This study aims to assess this multifaceted impact on the Greek undergraduate medical community. METHODS: A cross-sectional survey study was conducted. All undergraduate medical students at Greek Universities were addressed using social media. The data were post-stratified according to the population's male-to-female ratio and underwent descriptive and inferential statistical analysis. Associations were determined using chi-square and Fisher's exact test. A linear regression model was developed to investigate the factors that contributed to the overall impact of the pandemic on medical education. RESULTS: A total of 905 responses were analyzed, representing 9.8 % of Greece's medical students. Most reported decreased duration of laboratory (n =711, 78.5 %) and clinical (n =526, 96.7 %) practice. The majority stated that their ability to perform practical skills was affected negatively (n =805, 89.0 %). The impact on student's education was positively associated with their psychological impact. Therefore, a more negative effect on the student's education was observed on those whose psychology was affected more negatively [ß =0.49, 95 % confidence interval (CI): 0.40, 0.58, p <0.001). Additionally, the pandemic's overall impact on medical education was much more unfavorable for the clinical than the pre-clinical students (ß =-0.30, 95 % CI: -0.40, -0.20, p <0.001). CONCLUSIONS: This study's findings agree that the COVID-19 pandemic has severely impacted the education and personal life of medical students, especially in the advanced years. An insight into their specific needs to overcome the impact on their education is provided. The necessity of future mitigating actions is underlined. Emphasis should be given to clinical skills and enhancing the students' adaptive behavior to attenuate the consequences on their psychology, social life, and future healthcare provider careers. HIPPOKRATIA 2022, 26 (2):55-61.

Nosocomial infections caused by Crimean-Congo haemorrhagic fever virus.

Crimean-Congo haemorrhagic fever (CCHF) is an acute febrile illness, often accompanied by haemorrhagic manifestations, with a high case fatality rate (CFR). The causative agent is CCHF virus (CCHFV), and is transmitted to humans mainly through tick bites or exposure to blood or tissues of viraemic patients or livestock. Human-to-human transmission usually occurs in hospital settings, and healthcare workers (HCWs) are mainly affected. A review on nosocomial CCHFV infections was performed to elucidate the routes and circumstances of CCHFV transmission in hospital settings. From 1953 to 2016, 158 published cases of CCHFV nosocomial infection in 20 countries in Africa, Asia and Europe were found. Almost all cases were symptomatic (92.4%), with an overall CFR of 32.4%. The majority of cases occurred in hospital clinics (92.0%) and 10 cases (8.0%) occurred in laboratories. Most cases occurred among HCWs (86.1%), followed by visitors (12.7%) and hospitalized patients (1.3%). Nursing staff (44.9%) and doctors (32.3%) were the most affected HCWs, followed by laboratory staff (6.3%). The primary transmission route was percutaneous contact (34.3%). Cutaneous contact accounted for 22.2% of cases, followed by exposure to aerosols (proximity) (18.2%), indirect contact (17.2%) and exposure to patient environment (8.1%). CCHFV can cause nosocomial infections with a high CFR. During the care and treatment of patients with CCHF, standard contact precautions, barrier precautions and airborne preventive measures should be applied. In order to improve patient safety and reduce healthcare-associated CCHFV exposure, there is a need for guidelines and education for HCWs to ensure that CCHF is appropriately included in differential diagnoses; this will enable early diagnosis and implementation of infection prevention measures.

Characteristics of patients with allergic rhinitis in an outpatient clinic: a retrospective study.

BACKGROUND: Allergic rhinitis affects a significant proportion of the European population. Few surveys have investigated this disorder in Greek adults. Our objective was to describe the characteristics of patients with allergic rhinitis in an adult outpatient clinic in Thessaloniki, Greece. METHODS: We studied the medical records of adult patients referred to a Clinical Immunology outpatient clinic from 2001 to 2007. The diagnostic procedure was not changed during the whole study period, including the same questionnaire used at the time of diagnosis, skin prick tests, and serum specific IgE. RESULTS: A total of 1851 patient files with diagnosed allergies were analysed and allergic rhinitis was confirmed in 711 subjects (38.4%). According to ARIA classification, persistent allergic rhinitis was more prevalent than intermittent (54.9% vs. 45.1%), while 60.8% of subjects suffered from moderate/severe disease. In multivariable analysis, factors associated with allergic rhinitis were age (for every 10 years increase, OR: 0.84, 95% CI: 0.77-0.91; p<0.001); working in school environment (teachers or students) (OR: 1.46, 95% CI: 1.05-2.02; p=0.023); parental history of respiratory allergy (OR: 2.41, 95% CI: 1.69-3.43; p<0.001); smoking (OR: 0.71, 95% CI: 0.55-0.91; p=0.007); presence of allergic conjunctivitis (OR: 6.16, 95% CI: 4.71-8.06; p<0.001); and asthma (OR: 2.17, 95% CI: 1.57-3.01; p<0.001). Analysis after multiple imputation corroborated the complete case analysis results. CONCLUSIONS: Allergic rhinitis was documented in 38.4% of studied patients and was frequently characterised by significant morbidity. Factors associated with allergic rhinitis provide insight into the epidemiology of this disorder in our region. Further studies on the general population would contribute to evaluating allergic rhinitis more comprehensively.

Seroepidemiological study of Crimean-Congo haemorrhagic fever in Greece, 2009-2010.

To estimate endemic areas for Crimean-Congo haemorrhagic fever (CCHF) in Greece, a country-wide seroepidemiological study was conducted, and 1611 human sera were prospectively collected along with data regarding possible risk factors for acquisition of infection, and tested for CCHF virus IgG antibodies by ELISA. The overall seroprevalence was 4.2%, with significant differences among prefectures, ranging from 0 to 27.5%. Multivariate analysis revealed that slaughtering and agricultural activities were significant risk factors for CCHFV seropositivity. The significantly high seroprevalence in specific prefectures, together with the extremely low number of CCHF cases, suggest that this phenomenon might be strain-related.

Twenty-four hour efficacy with the dorzolamide/timolol-fixed combination compared with the brimonidine/timolol-fixed combination in primary open-angle glaucoma.

AIM: The aim of this study is to compare the 24-hour efficacy of dorzolamide/timolol-fixed combination (DTFC) and brimonidine/timolol-fixed combination (BTFC) in primary open-angle glaucoma (POAG). METHODS: One eye each of 77 POAG patients was included in this prospective, observer-masked, crossover comparison. Following a 2-month timolol run-in period, patients had three intraocular pressure (IOP) measurements at 1000, 1200 and 1400 h while on timolol treatment. Patients showing at least a 20% IOP reduction on timolol were randomised to 3 months of therapy with DTFC or BTFC, and then were crossed over to the opposite therapy. RESULTS: Sixty POAG patients completed the study. The mean 24-hour IOP was significantly reduced with both the fixed combinations compared with the timolol-treated diurnal IOP (P < 0.001). When the two fixed combinations were compared directly, DTFC demonstrated a lower mean 24-hour IOP level as compared with BTFC (mean difference: -0.7 mm Hg, 95% confidence interval (CI): (-1.0, -0.3), P < 0.001). At two individual time points, DTFC significantly reduced IOP more than BTFC: at 1800 h (-1.0 mm Hg, 95% CI (-1.6,-0.5), P = 0.001) and at 0200 (-0.9 mm Hg, 95% CI: (-1.4,-0.5), P = 0.001). No significant difference existed for the other time points. CONCLUSION: Both the fixed combinations significantly reduce 24-hour IOP in POAG. DTFC provided significantly better 24-hour efficacy.

24-h Intraocular pressure control with evening-dosed travoprost/timolol, compared with latanoprost/timolol, fixed combinations in exfoliative glaucoma.

PURPOSE: To evaluate 24-h efficacy of travoprost/timolol fixed combination (TTFC) vslatanoprost/timolol fixed combination (LTFC) in exfoliative glaucoma (XFG). DESIGN: A prospective, single-masked, crossover, active-controlled, randomized 24-h comparison. METHODS: After up to a 6-week medicine-free period, XFG patients were randomized to either TTFC or LTFC for 3 months, dosed each evening, and then changed to the opposite treatment for another 3 months. At the end of the washout, and both treatment periods, a 24-h intraocular pressure (IOP) curve was measured. RESULTS: In total, 40 patients completed the study. The TTFC group showed a lower mean absolute 24-h IOP (18.7±2.6 vs 19.6±2.6 mm Hg, P<0.001), maximum IOP (20.5±2.6 vs 21.5±2.6 mm Hg, P<0.001) and 24-h IOP range (3.4±1.3 vs 4.1±1.6 mm Hg, P=0.01). At individual time points, TTFC showed reduced IOPs compared with LTFC, after a Bonferroni correction, at 1000, 1800, and 2200 hours (P≤0.04). No statistical differences existed at hours: 0600, 1400, and 0200 (P≥0.05) and for the minimum IOP (P=0.09). CONCLUSIONS: This study suggests that evening-dosed TTFC may provide greater 24-h IOP reduction, primarily at the 1800 hours time point, compared with LTFC in XFG.

Meta-analysis in medical research.

The objectives of this paper are to provide an introduction to meta-analysis and to discuss the rationale for this type of research and other general considerations. Methods used to produce a rigorous meta-analysis are highlighted and some aspects of presentation and interpretation of meta-analysis are discussed.Meta-analysis is a quantitative, formal, epidemiological study design used to systematically assess previous research studies to derive conclusions about that body of research. Outcomes from a meta-analysis may include a more precise estimate of the effect of treatment or risk factor for disease, or other outcomes, than any individual study contributing to the pooled analysis. The examination of variability or heterogeneity in study results is also a critical outcome. The benefits of meta-analysis include a consolidated and quantitative review of a large, and often complex, sometimes apparently conflicting, body of literature. The specification of the outcome and hypotheses that are tested is critical to the conduct of meta-analyses, as is a sensitive literature search. A failure to identify the majority of existing studies can lead to erroneous conclusions; however, there are methods of examining data to identify the potential for studies to be missing; for example, by the use of funnel plots. Rigorously conducted meta-analyses are useful tools in evidence-based medicine. The need to integrate findings from many studies ensures that meta-analytic research is desirable and the large body of research now generated makes the conduct of this research feasible.

Twenty-four-hour intraocular pressure control with the travoprost/timolol maleate fixed combination compared with travoprost when both are dosed in the evening in primary open-angle glaucoma.

OBJECTIVE: To evaluate the 24 h efficacy and safety of the travoprost/timolol maleate fixed combination (TTFC) versus travoprost when both are dosed in the evening in primary open-angle glaucoma patients. METHODS: Prospective, double-masked, crossover, active-controlled, randomised 24 h comparison. After a 6 week medicine-free period, patients were randomised to either TTFC or travoprost for 8 weeks and were then switched to the opposite treatment for another 8 weeks. At the end of the washout and treatment periods, a 24 h pressure curve was performed. RESULTS: Thirty-two patients completed the study. The TTFC group demonstrated a lower absolute intraocular pressure level (2.4 mm Hg) for the 24 h curve and at all time points, compared with travoprost (p0.05). CONCLUSIONS: This study suggests that when both drugs are dosed in the evening the TTFC provides improved intraocular pressure reduction, compared with travoprost, over the 24 h curve and for each individual time point in primary open-angle glaucoma patients.

Mortality from occupational exposure to relatively pure chrysotile: a 39-year study.

BACKGROUND: Asbestos exposure is related to serious adverse health effects. However, there is disagreement about the relationship between chrysotile exposure and mesothelioma or lung cancer. OBJECTIVES: Our aim was to investigate the mortality rate among workers exposed to relatively pure chrysotile in an asbestos cement factory. PATIENTS AND METHODS: In an asbestos cement plant opened in 1968, we prospectively studied all 317 workers. A quantity of 2,000 tons of chrysotile, with minimal amphibole contamination, was used annually until 1 January 2005. Asbestos fiber concentration was measured regularly. Date and cause of death were recorded among active and retired workers. RESULTS: Asbestos fiber concentration was always below permissible levels. Fifty-two workers died during the study. The cause was cancer in 28 subjects; lung cancer was diagnosed in 16 of them. No case of mesothelioma was reported. Death was attributed to cardiovascular diseases in 23 subjects and to liver cirrhosis in 1. Overall mortality rate was significantly lower than that of the Greek general population, standardized mortality ratio (SMR) was 0.71 (95% CI 0.53-0.93). Mortality due to cancer was increased (SMR 1.15, 95% CI 0.77-1.67), mainly due to lung cancer mortality (SMR 1.71, 95% CI 0.98-2.78), but not significantly. CONCLUSIONS: Occupational exposure to relatively pure chrysotile within permissible levels was not associated with a significant increase in lung cancer or with mesothelioma. Decreased overall mortality of workers indicates a healthy worker effect, which--together with the relatively small cohort size--could have prevented small risks to be detected.

Evaluation of pupil mobility in patients with myasthenia gravis.

The aim of this study is to investigate the effect of Myasthenia Gravis (MG) on the Central Nervous System (CNS) and/or the smooth muscles of the iris through pupillometry. Sixteen recently diagnosed Myasthenic and sixteen non-Myasthenic subjects of matching age and gender underwent a pupillometric study of the effects of single flash stimuli of 24.6 candelas/m2 intensity and 20 msec duration. A significant decrease in Amplitude (p < 0.001), Maximum Constriction Velocity (p < 0.001) and especially Maximum Constriction Acceleration with a perfect discrimination ability (AUC= 1, p < 0.001). was observed in the Myasthenic compared to the non-Myasthenic subjects. In contrast, no significant difference was observed in Baseline Pupil Radius (R1) and 3.5 secs Percentage Recovery-Redilatation (R%) (p = 0.051 and p = 0.517, respectively). Of the parameters that are studied, R1 and R% are governed mainly by the action of the Sympathetic Nervous System (SNS) and the rest by the Parasympathetic Nervous System (ParNS), through Acetylcholine. The analysis of these parameters demonstrates that the SNS remains unaltered while the ParNS may be affected in MG. This post-synaptic cholinergic receptors' deficit may be central, within the CNS, or peripheral, related to the Neuromuscular Junction of the iris' sphincter.

Twenty-four-hour intraocular pressure and blood pressure levels with bimatoprost versus latanoprost in patients with normal-tension glaucoma.

AIM: To evaluate 24 h intraocular pressure (IOP) and blood pressure (BP) with bimatoprost or latanoprost in patients with normal-tension glaucoma. DESIGN: Prospective, randomised, crossover, active-controlled, observer-masked study. METHODS: After a 6-week medicine-free period, we randomised patients to either latanoprost or bimatoprost for 8 weeks and then to the opposite medicine for 8 weeks. At baseline, and at the end of each treatment period, we evaluated IOP and BP at 08:00 and then every 2 h over the 24 h day. Diastolic ocular perfusion pressure (DOPP) was calculated from the above parameters. RESULTS: Forty completed patients had a 24 h untreated baseline IOP of 15.5 (2.3) mm Hg, and a DOPP of 59.2 (6.1) mm Hg. Both treatments lowered IOP at each time point (p<0.006), and over the 24 h curve (p<0.001, both medicines 13.1 mm Hg, 16% decrease). No difference existed between treatments in absolute IOP, at each time point, and over the 24 h curve (p>or=0.26). Additionally, no differences were found between treated 24 h systolic (p>or=0.29) and diastolic BP (p>or=0.12). The mean 24 h DOPP for latanoprost was increased from baseline (3%, p = 0.031) but not for bimatoprost (2%, p = 0.21). However, no difference in DOPP existed between treatments at any time point or over the 24 h curve (p>or=0.17). No difference was observed between treatments for any adverse event (p>0.05). CONCLUSIONS: In patients with normal-tension glaucoma, both bimatoprost and latanoprost reduce the 24 h intraocular pressure from untreated baseline to a similar extent. Latanoprost is associated with slightly improved ocular diastolic perfusion pressure over 24 h but similar absolute perfusion levels to that of bimatoprost.

Reduced intraepidermal nerve fiber density in HIV-associated sensory neuropathy.

OBJECTIVE: To explore the relationship between intraepidermal nerve fiber (IENF) density in HIV-associated sensory neuropathy (HIV-SN) to measurements of neuropathy severity and progression of HIV disease. BACKGROUND: SN affects 30% of individuals with AIDS, and treatment is often ineffective. Recombinant human nerve growth factor (rhNGF) has been proposed as a trophic factor for unmyelinated nerve fibers injured in HIV-SN, and a clinical trial has recently concluded. Skin biopsy with IENF density determination has emerged as a diagnostic test for patients with small-fiber sensory neuropathy. METHODS: Sixty-two of the 270 patients with HIV-SN who participated in the trial of rhNGF were included in a substudy examining epidermal nerve fibers. IENF density was compared with neuropathic pain intensity (measured with the Gracely Pain Scale), patient and physician global pain assessments, quantitative sensory testing, CD4 counts, and plasma HIV RNA levels both at baseline and at conclusion of the placebo-controlled phase. RESULTS: IENF density was inversely correlated with neuropathic pain as measured by patient (p = 0.004) and physician (p = 0.05) global pain assessments, but not using the Gracely Pain Scale. Decreased IENF density at the distal leg was associated with lower CD4 counts and higher plasma HIV RNA levels. IENF density measurements were stable over time. CONCLUSIONS: IENF loss at the distal leg is associated with increased neuropathic pain, lower CD4 counts, and higher plasma viral load in HIV-SN. The robustness of the longitudinal measurement of IENF density supports its use in future longitudinal studies and clinical trials.

Effect of early patient enrollment on the time to completion and publication of randomized controlled trials.

The authors evaluated whether early enrollment affects the significance of the results and the time to completion and publication of randomized controlled trials. Seventy-seven efficacy randomized controlled trials (total enrollment, 28,992 patients) initiated by the Acquired Immunodeficiency Syndrome Clinical Trials Group between 1986 and 1996 were evaluated. After adjustment for target sample size, for each 10-fold increase in the first-month accrual, the odds of a trial reaching statistically significant results increased 2.8-fold (p = 0.040). The relative enrollment during the first month over target sample size (hazard ratio (HR) = 1.40 per 10 percent increase, p = 0.004) and masking (HR = 1.78 for double-blind vs. single or unblinded studies, p = 0.031) were the major predictors of faster completion. Rapid early accrual (HR = 1.09 per 10 additional patients accrued the first month, p = 0.011) and statistical significance in favor of an experimental arm (HR = 2.47, p = 0.004) independently predicted faster publication. Early enrollment is a strong predictor of whether a study will reach formal statistical significance, and it can offer predictive information on the time needed to complete the study and publish its findings. Ongoing unpublished studies and their enrollment rates may need to be considered when interpreting the accumulated evidence.

Comparison of evidence of treatment effects in randomized and nonrandomized studies.

CONTEXT: There is substantial debate about whether the results of nonrandomized studies are consistent with the results of randomized controlled trials on the same topic. OBJECTIVES: To compare results of randomized and nonrandomized studies that evaluated medical interventions and to examine characteristics that may explain discrepancies between randomized and nonrandomized studies. DATA SOURCES: MEDLINE (1966-March 2000), the Cochrane Library (Issue 3, 2000), and major journals were searched. STUDY SELECTION: Forty-five diverse topics were identified for which both randomized trials (n = 240) and nonrandomized studies (n = 168) had been performed and had been considered in meta-analyses of binary outcomes. DATA EXTRACTION: Data on events per patient in each study arm and design and characteristics of each study considered in each meta-analysis were extracted and synthesized separately for randomized and nonrandomized studies. DATA SYNTHESIS: Very good correlation was observed between the summary odds ratios of randomized and nonrandomized studies (r = 0.75; P<.001); however, nonrandomized studies tended to show larger treatment effects (28 vs 11; P =.009). Between-study heterogeneity was frequent among randomized trials alone (23%) and very frequent among nonrandomized studies alone (41%). The summary results of the 2 types of designs differed beyond chance in 7 cases (16%). Discrepancies beyond chance were less common when only prospective studies were considered (8%). Occasional differences in sample size and timing of publication were also noted between discrepant randomized and nonrandomized studies. In 28 cases (62%), the natural logarithm of the odds ratio differed by at least 50%, and in 15 cases (33%), the odds ratio varied at least 2-fold between nonrandomized studies and randomized trials. CONCLUSIONS: Despite good correlation between randomized trials and nonrandomized studies-in particular, prospective studies-discrepancies beyond chance do occur and differences in estimated magnitude of treatment effect are very common.

Patterns of patient enrollment in randomized controlled trials.

We aimed to describe enrollment patterns in a large cohort of randomized controlled trials (RCTs) and evaluate whether early recruitment predicts the ability of RCTs to reach their target enrollment. We considered all 77 efficacy RCTs initiated by the AIDS Clinical Trials Group between 1986 and 1996 (28,992 patients enrolled until November 1999). Thirteen RCTs (17%) failed to reach half their target recruitment. Enrollment trajectories showed that the initial rate of accrual determined the subsequent rates of enrollment. The target sample size was attained by 7/8, 11/14, 15/35 and 4/20 of trials with very rapid, rapid, moderate and slow enrollment during the first 3 months, respectively (P < 0.001). Enrollment during the first month or two strongly correlated with subsequent accrual (P < 0.001). The patient pool, the eligibility criteria, the attractiveness of a trial and adequacy of the network of clinical sites may influence RCT enrollment. Early enrollment offers strong evidence on the feasibility of a trial and is indicative of its future pace of recruitment.

Determinants of patient recruitment in a multicenter clinical trials group: trends, seasonality and the effect of large studies.

BACKGROUND: We examined whether quarterly patient enrollment in a large multicenter clinical trials group could be modeled in terms of predictors including time parameters (such as long-term trends and seasonality), the effect of large trials and the number of new studies launched each quarter. We used the database of all clinical studies launched by the AIDS Clinical Trials Group (ACTG) between October 1986 and November 1999. Analyses were performed in two datasets: one included all studies and substudies (n = 475, total enrollment 69,992 patients) and the other included only main studies (n = 352, total enrollment 57,563 patients). RESULTS: Enrollment differed across different months of the year with peaks in spring and late fall. Enrollment accelerated over time (+27 patients per quarter for all studies and +16 patients per quarter for the main studies, p < 0.001) and was affected by the performance of large studies with target sample size > 1,000 (p < 0.001). These relationships remained significant in multivariate autoregressive modeling. A time series based on enrollment during the first 32 quarters could forecast adequately the remaining 21 quarters. CONCLUSIONS: The fate and popularity of large trials may determine the overall recruitment of multicenter groups. Modeling of enrollment rates may be used to comprehend long-term patterns and to perform future strategic planning.

Reporting of conflicts of interest in guidelines of preventive and therapeutic interventions.

BACKGROUND: Guidelines published in major medical journals are very influential in determining clinical practice. It would be essential to evaluate whether conflicts of interests are disclosed in these publications. We evaluated the reporting of conflicts of interest and the factors that may affect such disclosure in a sample of 191 guidelines on therapeutic and/or preventive measures published in 6 major clinical journals (Annals of Internal Medicine, BMJ, JAMA, Lancet, New England Journal of Medicine, Pediatrics) in 1979, 1984, 1989, 1994 and 1999. RESULTS: Only 7 guidelines (3.7%) mentioned conflicts of interest and all were published in 1999 (17.5% (7/40) of guidelines published in 1999 alone). Reporting of conflicts of interest differed significantly by journal (p=0.026), availability of disclosure policy by the journal (p=0.043), source of funding (p < 0.001) and number of authors (p=0.004). In the entire database of 191 guidelines, a mere 18 authors disclosed a total of 24 potential conflicts of interest and most pertained to minor issues. CONCLUSIONS: Despite some recent improvement, reporting of conflicts of interest in clinical guidelines published in influential journals is largely neglected.