Distribución de la duración de la incapacidad temporal por contingencia común por diagnóstico médico (Cataluña, 2006-2008)

We present a simple and practical tool that allows the usual distribution of the duration of non-occupational sick leave to be determined by medical diagnosis. A total of 2,646,352 episodes of medically certified sick leave, registered by the Catalan Institute of Medical Evaluations for the period 2006-2008, were followed to closure and were entered into a spreadsheet. Given its asymmetric distribution, the median duration of sick leave was 9 days. Musculoskeletal disorders were the most frequent diagnostic group (22.5%), while neoplasms had the longest median duration (56 days). The most common specific diagnoses were diarrhea-gastroenteritis (8.2%; median: 3 days) and acute rhinopharyngitis (5.2%; median: 4 days). The distribution of the duration of sick leave in a population varies by diagnosis and is asymmetric, with most episodes being much shorter than the mean duration. This finding is important for better clinical and administrative management of sick leave episodes.     

Cultural adaptation of the Latin American version of the World Health Organization Composite International Diagnostic Interview (WHO-CIDI) (v 3.0) for use in Spain

Objective

To develop a Spanish version of the WHO-Composite International Diagnostic Interview (WHO-CIDI) applicable to Spain, through cultural adaptation of its most recent Latin American (LA v 20.0) version.

Methods

A 1-week training course on the WHO-CIDI was provided by certified trainers. An expert panel reviewed the LA version, identified words or expressions that needed to be adapted to the cultural or linguistic norms for Spain, and proposed alternative expressions that were agreed on through consensus. The entire process was supervised and approved by a member of the WHO-CIDI Editorial Committee. The changes were incorporated into a Computer Assisted Personal Interview (CAPI) format and the feasibility and administration time were pilot tested in a convenience sample of 32 volunteers.

Results

A total of 372 questions were slightly modified (almost 7% of approximately 5000 questions in the survey) and incorporated into the CAPI version of the WHO-CIDI. Most of the changes were minor — but important — linguistic adaptations, and others were related to specific Spanish institutions and currency. In the pilot study, the instrument's mean completion administration time was 2 h and 10 min, with an interquartile range from 1.5 to nearly 3 h. All the changes made were tested and officially approved.

Conclusions

The Latin American version of the WHO-CIDI was successfully adapted and pilot-tested in its computerized format and is now ready for use in Spain.     

The use of household cleaning products during pregnancy and lower respiratory tract infections and wheezing during early life

Objective

To evaluate the effects of household use of cleaning products during pregnancy on infant wheezing and lower respiratory tract infections (LRTI).

Methods

In four prospective Spanish birth cohorts (n = 2,292), pregnant women reported the use of household cleaning products. When infants were 12–18 months old, current cleaning product use and infant’s wheezing and LRTI were reported. Cohort-specific associations between the use of specific products and respiratory outcomes were evaluated using multivariable regression analyses and estimates were combined using random-effects meta-analyses.

Results

The period prevalence of LRTI was higher when sprays (combined odds ratio (OR) = 1.29; 95 % confidence interval (CI) 1.04–1.59) or air fresheners (OR = 1.29; CI 1.03–1.63) were used during pregnancy. The odds of wheezing increased with spray (OR = 1.37; CI 1.10–1.69) and solvent (OR = 1.30; CI 1.03–1.62) use. The associations between spray and air freshener use during pregnancy and both outcomes remained apparent when these products were not used after pregnancy. Nevertheless, the estimates were higher when post-natal exposure was included.

Conclusion

The use of cleaning sprays, air fresheners and solvents during pregnancy may increase the risk of wheezing and infections in the offspring.     

Hepatitis A virus cellular receptor 1/kidney injury molecule-1 is a susceptibility gene for clear cell renal cell carcinoma and hepatitis A virus cellular receptor/kidney injury molecule-1 ectodomain shedding a predictive biomarker of tumour progression

Aim of the studyTo correlate hepatitis A virus cellular receptor (HAVCR)/kidney injury molecule-1 (KIM-1) expression in clear cell renal cell carcinoma (ccRCC) tumours with patient outcome and study the consequences of HAVCR/KIM-1 ectodomain shedding.MethodsHAVCR/KIM-1 expression in ccRCC, oncocytomes, papillary carcinomas and unaffected tissue counterparts was evaluated. Minimal change disease and pre-clamping normal and ccRCC tissue biopsies were included. Tissue microarrays from 98 ccRCC tumours were analysed. Tumour registry data and patient outcome were retrospectivelly collected. Deletions in HAVCR/KIM-1 ectodomain and lentiviral infection of 786-O cells with HAVCR/KIM-1 mutated constructs to determine their subcellular distribution and invasive capacity were performed.ResultsHAVCR/KIM-1 was expressed in ccRCC, papillary tumours and in tubule cells of adjacent and distal unaffected counterparts of ccRCC tumours. The latest was not related to ischemic or tumour-related paracrine effects since pre-clamping normal biopsies were positive for HAVCR/KIM-1 and unaffected counterparts of papillary tumours were negative. HAVCR/KIM-1 analyses in patients and the invasive capacity of HAVCR/KIM-1 shedding mutants in cell lines demonstrated that: (i) relative low HAVCR/KIM-1 membrane levels correlate with activated shedding in ccRCC patients and mutant cell lines; (ii) augmented shedding directly correlates with higher invasiveness and tumour malignancy.Concluding statementsConstitutive expression of HAVCR/KIM-1 in kidney might constitute a susceptibility trait for ccRCC tumour development. Enhanced HAVCR/KIM-1 ectodomain shedding promotes invasive phenotype in vitro and more aggressive tumours in vivo.     

Real-time multi-modality imaging of glioblastoma tumor resection and recurrence

The lack of relevant pre-clinical animal models incorporating the clinical scenario of Glioblastoma multiforme (GBM) resection and recurrence has contributed significantly to the inability to successfully treat GBM. A multi-modality imaging approach that allows real-time assessment of tumor resection during surgery and non-invasive detection of post-operative tumor volumes is urgently needed. In this study, we report the development and implementation of an optical imaging and magnetic resonance imaging (MRI) approach to guide GBM resection during surgery and track tumor recurrence at multiple resolutions in mice. Intra-operative fluorescence-guided surgery allowed real-time monitoring of intracranial tumor removal and led to greater than 90 % removal of established intracranial human GBM. The fluorescent signal clearly delineated tumor margins, residual tumor, and correlated closely with the clinically utilized fluorescence surgical marker 5-aminolevulinic acid/porphyrin. Post-operative non-invasive optical imaging and MRI confirmed near-complete tumor removal, which was further validated by immunohistochemistry (IHC). Longitudinal non-invasive imaging and IHC showed rapid recurrence of multi-focal tumors that exhibited a faster growth rate and altered blood-vessel density compared to non-resected tumors. Surgical tumor resection significantly extended long-term survival, however mice ultimately succumbed to the recurrent GBM. This multi-modality imaging approach to GBM resection and recurrence in mice should provide an important platform for investigating multiple aspects of GBM and ultimately evaluating novel therapeutics.     

EGFR mutation analysis in sputum of lung cancer patients: A multitechnique study

Objectives

Epidermal growth factor receptor (EGFR) mutations have been identified in lung adenocarcinomas and are associated with high response chance to EGFR tyrosine kinase inhibitors. EGFR mutations can be detected in tumour tissue, cytology specimens and blood from lung cancer patients. Thus far, EGFR mutation analysis has not been systematically demonstrated for sputum samples. The aim of the present study was to determine whether EGFR mutation analysis is attainable on sputum samples, employing different assays in a multicenter study.

Materials and methods

Sputum DNA from 10 lung cancer patients with confirmed EGFR mutation in their tumour tissue, 10 lung cancer patients without evidence of an EGFR mutation, and 10 patients with chronic obstructive pulmonary disease (COPD) was used for mutation analysis by Cycleave PCR, COLD-PCR, PangaeaBiotech SL Technology (PST), and High Resolution Melting, respectively. Targeted resequencing (TruSeq Amplicon Cancer Panel) and droplet digital PCR were additionally performed on the 10 samples with EGFR mutation.

Results

Dependent on the assay, EGFR mutations could be detected in 30–50% of the sputum samples of patients with EGFR mutations. The different techniques revealed consistent results, with slightly higher sensitivity for PST. Neither the lung cancer patients without EGFR mutation nor the COPD controls tested positive for EGFR mutations in their sputum samples, indicating high clinical specificity of all assays.

Conclusion

EGFR mutations can be detected in sputum samples from patients with EGFR-mutated non-small cell lung cancer, which may replace biopsy procedure for some patients.     

Roughness and bonding strength of bioactive apatite layer on dental implants

This study examined the roughness and bonding strength of the chemical-made apatite layer in comparison with the titanium surface and the plasma-sprayed apatite. Commercially pure titanium plates were heated and chemically treated to deposit crystalline apatite on their surface. The roughness of the titanium surface of the original samples and the apatite surface was analyzed by a roughness surface tester. A scratch test was used to compare the adhesion of the chemical apatite layer to the titanium with the adhesion of a plasma-sprayed layer. A dense bone-like apatite layer was formed on the surface of the titanium by a simple chemical method. The surface roughness test showed that the chemical apatite coating increased the roughness of the samples. The scratch test showed that the bonding strength of the chemical-made apatite coatings to the titanium substrate was higher than the plasma-sprayed apatite coatings. The apatite layer produced by chemical treatment did not show a lower roughness than the titanium substrate. This chemical apatite layer also bonded tighter to the titanium than the plasma-sprayed apatite. This chemically made apatite coating is expected to provide a long-term implant-bone fixation.     

Prognostic impact of chromosomal translocations in myelodysplastic syndromes and chronic myelomonocytic leukemia patients. A study by the spanish group of myelodysplastic syndromes

Chromosomal translocations are rare in the myelodysplastic syndromes (MDS) and chronic myelomonocytic leukemia (CMML). With the exception of t(3q), translocations are not explicitly considered in the cytogenetic classification of the IPSS‐R and their impact on disease progression and patient survival is unknown. The present study was aimed at determining the prognostic impact of translocations in the context of the cytogenetic classification of the IPSS‐R. We evaluated 1,653 patients from the Spanish Registry of MDS diagnosed with MDS or CMML and an abnormal karyotype by conventional cytogenetic analysis. Translocations were identified in 168 patients (T group). Compared with the 1,485 patients with abnormal karyotype without translocations (non‐T group), the T group had a larger proportion of patients with refractory anemia with excess of blasts and higher scores in both the cytogenetic and global IPSS‐R. Translocations were associated with a significantly shorter survival and higher incidence of transformation into AML at univariate analysis but both features disapeared after multivariate adjustment for the IPSS‐R cytogenetic category. Patients with single or double translocations other than t(3q) had an outcome similar to those in the non‐T group in the intermediate cytogenetic risk category of the IPSS‐R. In conclusion, the presence of translocations identifies a subgroup of MDS/CMML patients with a more aggressive clinical presentation that can be explained by a higher incidence of complex karyotypes. Single or double translocations other than t(3q) should be explicitly considered into the intermediate risk category of cytogenetic IPSS‐R classification. © 2015 Wiley Periodicals, Inc.     

What if there were no new antibiotics? A look at alternatives

Introduction: Bacterial resistance to antibiotics is increasing worldwide, due to the emergence of multidrug-resistant strains. With this panorama, there is a serious danger that we may be entering the ‘post-antibiotic era’.

Areas covered: We assess why so few new classes of antibiotics have been developed in the past years and discuss a variety of treatments that may be able to replace antimicrobials: monoclonal antibodies, bacteriophages, stem cells and anti-virulence agents such as liposomes.

Expert commentary: There are a series of economic, scientific-research and regulatory reasons for the scarcity of new antimicrobials. New approaches are needed to combat infections. Innovative strategies like Eco-Evo drugs and innovative delivery methods such as aerosol or nanoparticle administration require a new management paradigm, in combination with rapid molecular diagnostic tests. Biopharma, clinical researchers, regulatory agencies, governments and investors must work together in the attempts to achieve effective treatment for infections caused by MDR organisms.