Acrodermatitis chronica atrophicans: clinical and microbiological characteristics of a cohort of 693 Slovenian patients.

BACKGROUND: Information on large groups of patients with acrodermatitis chronica atrophicans (ACA) is limited. METHODS: We assessed clinical and microbiological characteristics of patients with ACA diagnosed at a single medical centre and compared findings in periods 1991-2004 vs. 2005-2018. The cohort is representative of Slovenian ACA patients. RESULTS: We assessed 693 patients: 461 females and 232 males, with median age of 64 years. Median duration of ACA before diagnosis was 12 months. In all but 2 patients, the skin lesions were located on extremities, more often on the lower (70.0%) than the upper (45.2%), bilaterally in 42.4%. Reddish-blue discoloration, swelling, thinning and wrinkling of skin were present in 95.2%, 28.1%, 46.4% and 20.5% of patients, respectively. Overall, 64.4% of patients reported constitutional symptoms, 23.1% had local symptoms, and 20.8% had symptoms/signs of peripheral neuropathy. Nodules, arthritis, joint deformity, muscle atrophy and paresis were rare (<3%). Borreliae were isolated from 200/664 (30.1%) skin samples; 92.8% were Borrelia afzelii. B. garinii and B. burgdorferi s.s. were more often isolated from the skin of male patients (OR = 4.17) and from those with arthropathy (OR = 11.74). Patients included in the more recent period were older, complained less often of constitutional symptoms but more often of local symptoms, and more often had local swelling but less often skin atrophy and bilateral involvement, probably as a consequence of earlier diagnosis. CONCLUSIONS: ACA, typically caused by B. afzelii, usually affects older women. Clinical presentation depends on the duration of illness and probably on the Borrelia species causing the disease.

Tick-borne encephalitis in patients vaccinated against this disease.

BACKGROUND: Information on tick-borne encephalitis (TBE) in patients already vaccinated against the disease is limited. OBJECTIVES: To compare the course and outcome in patients with vaccination breakthrough TBE with findings in patients who developed TBE without previous vaccination. METHODS: All adult patients diagnosed with TBE at a single medical centre during a 16-year period and who had received at least two doses of TBE vaccine before the onset of illness qualified for the study. For each patient with breakthrough TBE, two unvaccinated sex- and age-matched patients, diagnosed with TBE in the same year, were included for comparison. RESULTS: Amongst 2332 patients diagnosed with TBE in the period 2000-2015, 39 (1.7%) had been vaccinated against the disease. Their median age was 59 (20-83) years; 22 of 39 (56.4%) were male. In comparison with unvaccinated patients with TBE, those with breakthrough disease more often experienced a monophasic course of illness (P = 0.006), had a higher CSF leucocyte count (P = 0.005), more often had urine retention (P = 0.012), more often needed ICU treatment (P = 0.009), were hospitalized for longer (P = 0.002) and had more severe acute illness (P = 0.004 for simple clinical assessment, P = 0.001 for severity score). CONCLUSION: In addition to several findings corroborating previous results in patients with vaccination breakthrough TBE, such as older age and the presence of a particular specific serum antibody pattern indicating anamnestic response, findings in this study indicate that the acute illness in patients with breakthrough TBE is more severe than in unvaccinated sex- and age-matched patients who develop the disease.

Clinical-pharmacogenetic predictive models for MTX discontinuation due to adverse events in rheumatoid arthritis.

We describe a novel approach to investigate and evaluate combined effect of a large number of clinical and pharmacogenetic factors on treatment outcome. We have used this approach to investigate predictors of methotrexate (MTX)-induced adverse events (AEs) leading to treatment discontinuation in rheumatoid arthritis (RA) patients. In total, 333 RA patients were genotyped for 34 polymorphisms in MTX transporters, folate and adenosine pathways. The effect of clinical and pharmacogenetic factors was assessed with penalized regression in the cause-specific Cox proportional hazards model. The predictive capacity was evaluated with the area under time-dependent receiver operating characteristic curve where cross-validation was applied. SLC19A1, ABCG2, ADORA3 and TYMS were associated with discontinuation because of AEs in clinical-pharmacogenetic model. Cross-validation showed that both clinical-pharmacogenetic model and nongenetic model had worthless predictive ability for MTX discontinuation because of AEs. These models could be further improved, either with additional polymorphisms or with epigenetic predictors.

Oseltamivir prophylaxis in controlling influenza outbreak in nursing homes: a comparison between three different approaches.

PURPOSE: To assess influenza outbreaks in nursing homes (NHs) using different pharmacological preventive measures. METHODS: We compared characteristics of influenza A outbreaks that occurred during 2011/2012 influenza season in three NHs of similar size (208, 167, and 164 residents in NH1, NH2, and NH3, respectively) implementing comparable treatment approaches and non-pharmacological outbreak control measures but different prophylactic pharmacological interventions including oseltamivir 75 mg o.d. for 10 days for all residents (NH1), for directly exposed residents (NH2), and no prophylaxis (NH3). RESULTS: The proportions of residents who developed acute respiratory infection (ARI) in the course of influenza outbreak were 55/208 (26.4 %) in NH1, 64/167 (38.3 %) in NH2, and 31/164 (18.9 %) in NH3; hospital admission was required in 2/55 (3.6 %), 5/64 (7.8 %), and 5/31 (16.1 %) residents of NH1, NH2, and NH3, respectively, while 1/55 (1.8 %), 1/64 (1.6 %), and 3/31 (9.7 %) residents of the corresponding NHs died during influenza outbreak. The duration of the outbreak was shorter in the NH1 where oseltamivir prophylaxis was instituted for all residents (8 days), than in NHs where selective prophylaxis with oseltamivir and no prophylaxis were used (14 and 12 days, respectively). The calculated vaccine effectiveness in residents was 48, 71, and 44 % in NH1, NH2, and NH3, respectively. Staff members had similar ARI attack rate but in comparison to residents were less often vaccinated against influenza and demonstrated higher influenza vaccine effectiveness. CONCLUSIONS: Comparison of influenza outbreaks in three NHs revealed that the duration of the outbreak was the shortest in the NH where prophylaxis with oseltamivir was given to all residents.

Bacterial infection in elderly nursing home and community-based patients: a prospective cohort study.

PURPOSE: The aim of the study was to assess differences between elderly nursing home (NH) residents and elderly patients living in the community admitted to hospital for bacterial infection. METHODS: We conducted a prospective cohort study with manual data collection. Patients aged 65 years and older from NHs and from the community admitted to hospital for bacterial infection were included in the study. Patient characteristics, site of infection, microorganism profile, and final outcome were assessed and compared between these two subgroups of patients. RESULTS: Two hundred and sixty-two patients were from NHs and 707 were from the community. Patients from NHs were older, had more underlying chronic illnesses, and more often showed characteristics indicating advanced debility. In both groups, the most common site of infection was the respiratory tract. In comparison to the community group, patients from NHs had a higher fatality rate (23.3 vs. 10.9%) and more often experienced functional decline at discharge (27.5 vs. 16.8%). After adjustment for age, sex, presence of comorbidity, and debility, NH residence remained associated with increased in-hospital mortality but not with functional decline. CONCLUSIONS: Elderly patients from NHs admitted to hospital for bacterial infection are older and more debilitated than their counterparts from the community. Microorganisms found in the NH residents are somewhat different from those in the community dwellers. The community dwellers had a better survival rate than those admitted from the NHs after adjusting for age, sex, presence of any comorbidity, and debility.

Respiratory viruses in patients and employees in an intensive care unit.

PURPOSE: To evaluate the frequency of respiratory viruses in a nonselected population of intensive care unit patients and employees and to investigate the clinical as well as the epidemiological association with virological findings. METHODS: Between 12 January and 5 March 2009, nasopharyngeal swabs were collected from 55 intensive care unit (ICU) patients and 41 medical personnel at 16 different time-points and tested for 11 respiratory viruses by single real-time PCR using TaqMan or MGB probes. RESULTS: Among the 55 ICU patients tested, there were 30 virus-positive respiratory specimens (30/173, 17.3%) and 23 patients who tested positive at least once for respiratory viruses (23/55, 41.8%). Only the time from admission to the ICU was associated with the probability of testing positive, with the probability of testing positive decreasing with increasing length of stay (P < 0.001). Of the 418 respiratory specimens collected from the healthcare personnel, 27 (6.5%) tested positive. Seventeen employees tested positive at least once for respiratory viruses (17/41, 41.5%). Among the employees, calendar time (P = 0.03) and having sick contacts at home (P = 0.006) were significantly associated with swab positivity. Among the study population, patients had a significantly higher probability of having a positive swab result than employees. The distribution of viruses differed between the two groups. CONCLUSIONS: Our results suggest that when hygiene precautions are adopted, the possibility of transmitting selected respiratory viruses between patients and personnel is limited. They also point to a greater importance of the community over the hospital environment for acquisition of viral respiratory infections by ICU patients and employees.

Quantitative and qualitative characterization of plasma DNA identifies primary and recurrent colorectal cancer.

Because plasma DNA may be a useful tool for cancer detection, we screened primary tumors and related multiple plasma samples at the time of surgery and during the follow-up period for plasma DNA level as well as for K-Ras mutations and p16INK4a promoter hypermethylation in colorectal cancer patients. At the time of surgery, DNA levels were higher in tumor patients than in healthy donors, and K-Ras and p16INK4a alterations were detected in 7 and 11 cancers respectively, and in all related plasma samples. During the follow-up, plasma DNA levels decrease progressively but rapidly increased when a relapse occurred, whereas K-Ras and p16INK4a alterations were detected only in relapsed patients. Therefore, combined quantitative and qualitative analyses of plasma DNA confirm the presence of colorectal cancer, define disease-free status and indicate the presence of relapse.

Questioning the utility of pooling samples in microarray experiments with cell lines.

We describe a microarray experiment using the MCF-7 breast cancer cell line in two different experimental conditions for which the same number of independent pools as the number of individual samples was hybridized on Affymetrix GeneChips. Unexpectedly, when using individual samples, the number of probe sets found to be differentially expressed between treated and untreated cells was about three times greater than that found using pools. These findings indicate that pooling samples in microarray experiments where the biological variability is expected to be small might not be helpful and could even decrease one's ability to identify differentially expressed genes.