Cancer care for Ukrainian refugees: Strategic impact assessments in the early days of the conflict.

BACKGROUND: The invasion of Ukraine by Russia in February 2022 has resulted in destruction of healthcare infrastructure and triggered the largest wave of internally displaced populations and refugees since World War Two. Conflicts in transitioned countries such as Ukraine create new non-communicable disease (NCD) challenges, especially for cancer care for refugees and humanitarian assistance in host countries. In the early days, rapid attempts were made to model possible impacts. METHODS: By evaluating open source intelligence used in the first three months of the conflict through snowball search methods, we aimed to address: (i) burden of cancer in Ukrainian population, specifically considering translating to the refugees population, and its cancer care capacity; ii) baseline capacity/strengths of cancer systems in initial host countries. Moreover, using a baseline scenario based on crude cancer incidence in Ukraine, and considering data from UNHCR, we estimated how cancer cases would be distributed across host countries. Finally, a surveillance assessment instrument was created, intersecting health system's capacity and influx of internally displaced populations and refugees. FINDINGS AND CONCLUSIONS: The total new cancer patients per month in pre-conflict Ukraine was estimated as 13,106, of which < 1 % are paediatric cases. The estimated cancer cases in the refugee population (combining prevalent and incident), assuming 7.5 million refugees by July 2022 and a female:male ratio of 9:1, was 33,121 individuals (Poland: 19284; Hungary: 3484; Moldova: 2651; Slovakia: 2421; Romania: 5281). According to our assessments, Poland is the only neighbouring country classified as green/yellow for cancer capacity, i.e. sufficient ablility to absorb additional burden into national health system; Slovakia we graded as yellow, Hungary and Romania as yellow/red and Moldova as red.

Efficacy of an organically modified bentonite to adsorb 2,4-dichlorophenoxyacetic acid (2,4-D) and prevent its phytotoxicity.

The herbicide 2,4-dichlorophenoxyacetic acid (2,4-D) is widely used due to it selective action, and preferential control of dicotyledonous weeds affecting cereal crops. Physiological responses of sensitive dicotyledonous plants to 2,4-D include growth retardation, senescence, and cell death. Due to soil and water contamination by agricultural practices, 2,4-D constitutes a potential risk to non-target plant species. In this work, the potential advantage of using organic modified bentonite (Bent) to adsorb 2,4-D and therefore mitigate damage produced by this herbicide on sensitive not-target vegetable species was investigated. Dodecylamine (DDA) was used as an organic modifier to change the hydrophilic nature of Bent into an organophilic matrix. The adsorption performances of 2,4-D by Bent-DDA were analyzed. The maximum adsorptions of 2,4-D (22.1 mg/L) from aqueous solution containing 1.0 or 2.5 mg/mL Bent-DDA were 40 and 80 %, respectively. The physical interaction of Bent-DDA with 2,4-D was characterized by Wide Angle X-ray Scattering (WAXS) and thermogravimetric analysis (TGA). The biological functionality of Bent-DDA matrix as 2,4-D adsorbent was tested in a bioassay in the Arabidopsis thaliana plant model system. The primary root growth of Arabidopsis seedlings is strongly inhibited by low concentrations of 2,4-D. Arabidopsis seedlings submitted to Bent-DDA pre-treated herbicide aqueous solution showed similar root growth than 2,4-D non-treated seedlings. Finally, the ability of Bent-DDA to prevent 2,4-D phytotoxicity was exploratory investigated in lettuce plants. Lettuce plants pre-treated with 20 µg/mL Bent-DDA showed reduced sensitivity to 2,4-D including an increment on chlorophyll content and biomass compared with non-treated plants. Our findings revealed a promising scenario for the application of Bent-DDA as an effective adsorbent of 2,4-D at productive scale.

Characterization of minimal lesions related to the presence of visna/maedi virus in the mammary gland and milk of dairy sheep.

BACKGROUND: In order to characterize the complete range of lesions, especially minimal, affecting mammary gland and viral antigen distribution and target cells using immunohistochemistry in naturally Visna/maedi (VM) 84 infected sheep were studied, forty-four from flocks with clinical cases (A) and 35 randomly sampled from two abattoirs (B) together with five negative controls (C). An immunocytochemistry technique was developed and further milk samples (n = 39) were used to study viral excretion, carrier cells and the role of milk and colostrum in the transmission of the disease. RESULTS: All sheep from group C and three sheep from group B were negative to VM in tissue sections by histopathology, immunohistochemistry and PCR, and also in serum using ELISA. Several degrees of CD3 + lymphocytic interstitial mastitis were observed in groups A and B: minimal (+) n = 26 sheep; moderate (++), n = 32 and severe (+++), n = 12. No differences in lesion distribution were observed between groups A and B. Viral presence was confirmed by immunohistochemistry using two different antibodies and/or PCR in every tissue with lesions while serology was negative in six sheep with lesions. Two milk samples taken from milk tanks from two flocks from group A and fourteen milk samples from 29 infected sheep from group B were positive to VM (most of them from animals with moderate and severe lesions). Positivity was only found in macrophages, even in focal and minimal lesions, while no positivity was observed in epithelial or any other cells in either tissue and milk samples. CONCLUSIONS: This new observation of the minimal lesions described in this work increased the prevalence of VM lesions in mammary gland up to 90.9% and VM should be considered as a differential diagnosis when minimal interstitial lesions are detected. A high prevalence of VM was observed in intensive milk-producing sheep, ELISA serology did not detect as positivity all infected animals, while histology, IHC or PCR showed higher sensitivity. The cytological technique developed was very useful in milk-cell studies using hematoxylin and eosin and immunocytochemistry. Viral detection in milk samples (16/39) confirms a potential but limited role of milk/colostrum in viral transmission.

Effects of 3-butenyl isothiocyanate on phenotypically different prostate cancer cells.

Isothiocyanates (ITCs) have gained increasing attention since they have been attributed the merits for the potential beneficial effects of cruciferous vegetable dietary consumption on cancer. The aim of the present study was to determine the cytotoxic effects of 3-butenyl ITC (3-BI) on prostate cancer (PC) cells under in vitro conditions. Two androgen-insensitive human PC cell lines, PC-3 and DU145, were assayed. Cells were cultured in the presence of increasing concentrations of 3-BI (5, 10, 30 and 50 µM) in the absence or presence of the chemotherapeutic drug docetaxel (DOCE) (1 and 2 nM). The cytotoxic effects of these compounds were analyzed using the trypan blue exclusion assay at 24, 48 and 72 h. Apoptosis and migration assays were also performed. The results showed that 3-BI induced a dose-dependent cytotoxic effect on PC-3 cells at 24, 48 and 72 h. These effects were significantly higher than those found with DOCE at 72 h of culture. Moreover, 3-BI also potentiated the effects of DOCE in a dose-dependent manner. Additionally, 3-BI showed inhibition of the migration of PC-3 cells. Nevertheless, 3-BI was not effective in the DU145 PC cell line. These results show a promising role for the 3-BI compound as a co-adjuvant agent in DOCE-based therapy in certain types of PC.

Inflammatory Lesion Patterns in Target Organs of Visna/Maedi in Sheep and their Significance in the Pathogenesis and Diagnosis of the Infection.

Ovine visna/maedi (VM) infection is characterized by the development of chronic inflammatory lesions in different organs, mainly in the lung, mammary gland and central nervous system (CNS), with either histiocytic or lymphocytic pattern predominance being described in the CNS. To help to understand the role of host immune response in the development of these patterns, 50 naturally-infected sheep and eight non-infected sheep from intensive milk-producing flocks were studied. The histological lesion patterns in the three main target organs in each sheep were characterized. Lesion severity was determined, including minimal lesions. A histiocytic pattern was observed in 23 sheep (46%), a lymphocytic inflammatory pattern in 19 sheep (38%) and a mixed inflammatory pattern in eight sheep (16%). Forty animals showed moderate or severe lesions (80%), while 10 had minimal lesions (20%). Moderate or severe lesions affected only one target organ in 20 sheep (50%), two organs in 14 sheep (35%) and all three target organs in six sheep (15%). Infection was confirmed by immunohistochemistry (IHC) using an antibody specific for p28 of VM virus/caprine arthritis and encephalitis virus and by polymerase chain reaction (PCR) in all sheep. Minimal inflammatory lesions associated with positive IHC and PCR were observed. The results suggest that the development of a predominant inflammatory pattern in different organs within the same animal may be related to the host immune response. Minimal and focal lesions, not considered previously, should be taken into account when formulating a differential diagnosis in affected sheep.

Diffuse intrinsic pontine gliomas (DIPG) at recurrence: is there a window to test new therapies in some patients?

Children with diffuse intrinsic pontine glioma (DIPG) need new and more efficient treatments. They can be developed at relapse or at diagnosis, but therefore they must be combined with radiotherapy. Survival of children after recurrence and its predictors were studied to inform the possibility to design early phase clinical trials for DIPG at this stage. Among 142 DIPG patients treated between 1998 and 2014, 114 had biopsy-proven DIPG with histone H3 status available for 83. We defined as long survivors' patients who survived more than 3 months after relapse which corresponds to the minimal life expectancy requested for phase I/II trials. Factors influencing post-relapse survival were accordingly compared between short and long-term survivors after relapse. Fifty-seven percent of patients were considered long survivors and 70% of them had a Lansky Play Scale (LPS) above 50% at relapse. Patients who became steroids-independent after initial treatment for at least 2 months had better survival after relapse (3.7 versus 2.6 months, p = 0.001). LPS above 50% at relapse was correlated with better survival after relapse (3.8 versus 1.8 months, p < 0.001). Patients with H3.1 mutation survived longer after relapse (4.9 versus 2.7 months, p = 0.007). Patients who received a second radiotherapy at the time of relapse had an improved survival (7.5 versus 4 months, p = 0.001). In the two-way ANOVA analysis, steroid-independence and LPS predicted survival best and the type of histone H3 (H3.1 or H3.3) mutated did not improve prediction. Survival of many DIPG patients after relapse over 3 months would make possible to propose specific trials for this condition. Steroid-independence, H3 mutation status and LPS should be considered to predict eligibility.

Burden assessment in caregivers of patients with home artificial nutrition: a need and a challenge.

BACKGROUND/OBJECTIVES: Caregiving can be a stressful task with severe consequences on caregivers' health. Our aim was to evaluate the profile and the burden of caregivers of patients with home artificial nutrition (HAN) in our area. SUBJECTS/METHODS: We conducted a prospective observational study of patients who had started HAN over a period of a year (n=573) and their home caregivers (n=103). Epidemiological characteristics of the patients and the type of HAN were registered. Caregivers' profile data (gender, age and degree of kinship) and Zarit Burden Assessments were recorded. RESULTS: Care recipients had a median age of 79.0 (IQR 87) years, neurological and oncological diseases in 50% and a high rate of mobility limitations (80%). Oral supplements with high-calorie formulas were predominant (60%). The usual caregiver profile was a patient's daughter with a mean age of 53.1 (s.d. 13.4) years acting as the primary caregiver. Burden was absent in 49.5%, light in 18.4% and intense in 32% of caregivers. Intense burden was more frequent in oral over enteral nutrition (42% versus 22.6%; P=0.036). Supplementary nutrition was also associated with higher caregiver burden scores compared with complete diets. In patients with functional limitations, a tendency toward a slightly higher burden was observed. No differences in caregiver burden were detected according to other patient or caregiver characteristics. CONCLUSIONS: HAN type appears to be a factor influencing caregiver burden and therefore, evaluation of caregiver burden should be part of HAN programs.

Understanding the directed ortho lithiation of (R)-Ph2P(=NCO2Me)NHCH(Me)Ph. NMR spectroscopic and computational study of the structure of the N-lithiated species.

A multinuclear magnetic resonance ((1)H, (7)Li, (13)C, (15)N, (31)P) and DFT computational study at the M06-2X(SMD,THF)/6-311+G(d,p)//B3LYP/6-31G(d) level of the structure of a N-lithiated phosphinimidic amide (R)-Ph2P(=NCO2Me)NHCH(Me)Ph 13 has been performed. In THF solution it exists as an equilibrium mixture of monomers and dimers. The monomers consist of a six-membered ring formed by coordination of the lithium atom with the deprotonated nitrogen and the oxygen atom of the carbonyl group. This coordination mode is in contrast to the standard N,N-chelation observed in N-lithiated N,N'-bis(trimethylsilyl)phosphinimidic amides. The calculations showed that the metallacycle adopts a twist-boat conformation and that the lithium atom is in a tetrahedral environment involving O,N-chelation by the ligand and coordination to two/one THF molecules in the monomer/dimer. Dimerization takes place through O-Li bridges. For all species two series of isomers have been identified, which originated by restricted rotation of the methoxy group and ring inversion. The twist-boat conformational interconversion seems to be operating for explaining the pattern of signals observed in the (7)Li and (31)P NMR spectra. The structure found for the most stable dimer is analogous to the molecular structure reported for a related C(α)-lithiated phosphazene 20. The structural study revealed that the chiral side-arm of the N-lithiated species is oriented to the outer face of the pro-S P-phenyl ring, which shows one ortho-proton very close to the nitrogen atom of the carbamate moiety. In this conformation, proton abstraction by a base is highly favoured, in agreement with the experimental results.

Recurrent outbreaks of myelodysplasia in newborn calves.

The present study records recurrent outbreaks of myelodysplasia of unknown origin occurring in a specific geographical location in the north of Spain, and involving up to 30% of the calves born in affected herds. The affected calves were of different breeds and displayed non-progressive signs of spinal cord dysfunction. The disease has occurred annually in February-March over a period of at least 15 years. Only calves born to cattle grazed on mountainside pastures and under high grazing pressure were affected. Seven calves were subjected to necropsy examination. Myelodysplasia was not associated with vertebral defects or arthrogryposis and involved the entire length of the spinal cord. Microscopically, there was abnormal distribution of the grey matter, aberrations of the central canal and failure of formation of the ventral median fissure. Infectious, nutritional and physical disorders were ruled out as possible aetiologies. A critical period of embryonic susceptibility to the causal agent was identified. This was during the time of secondary neurulation when cows in the early stages of gestation were grazed on mountainside pastures. Consequently, the presence of neuroteratogenic plants in these pastures is proposed as a likely cause. Two plants, Carex brevicollis and Erythronium dens-canis, which contain alkaloids, were identified on the mountainsides where affected cattle were grazed and not in other pastures, and are proposed as the possible aetiology of the disease.

[Design of a semantic framework for contextualized retrieval of scientific documents in the health domain]. / Diseño de un marco semántico para la recuperación contextualizada de documentos científicos en el ámbito sanitario.

Personalized healthcare requires recombining heterogeneous publicly available data with a patient's or group of patient's profile. A well-known problem in state-of-the-art information management is the overwhelming amount of information available. Besides, state-of-the-art solutions do not take advantage of modern semantic processing to adequately transform data into knowledge. This issue is especially relevant in the health domain, as key processes depend dramatically on the access to high quality, complete, up-to-date, and relevant content (e.g. diagnostics, risk assessment, public health interventions, etc.). This proposal aims to provide novel information management and retrieval solutions in the domain of health sciences to address the situation discussed above. More specifically, we introduce semantic reasoning to retrieve the most relevant knowledge available according to the health profile of a given person. For this, we developed a semantic model to represent health profiles of people and to characterize existing sources of relevant information in order to crawl them to populate a semantic repository with content references and properties. We outline the tools needed to query the knowledge base using the semantic profiles of individuals to get the most relevant content. The proposed solution, discussed here as a proof-of-concept, aims to contribute to the realm of personal health and evidence-based medicine technologies. The tools developed could also be used to take advantage of existing knowledge to facilitate a systematic review of reports, studies and analysis that may be relevant to the health conditions of single patients or patient profiles.

Parche de lidocaína 5 por ciento en el tratamiento de cicatrices postquirúrgicas dolorosas. A propósito de un caso / No disponible

No disponible

Time course of reendothelialization of stents in a normal coronary swine model: characterization and quantification.

Late thrombosis of coronary drug-eluting stents is an infrequent but serious complication of percutaneous transluminal coronary angioplasty. The best predictor of this event is the lack of endothelialization of stent struts. The objective of this study is to characterize and quantify the time course of endothelialization of different stents implanted in nonatherosclerotic swine coronary arteries. Thirty-three Carbofilm-coated stents were implanted percutaneously in 11 anesthetized domestic, crossbred pigs (weight 25 ± 3 kg, 2 months old). Each animal received 1 stainless steel stent (SS), 1 cobalt-chromium stent (CCS), and 1 tacrolimus-eluting stent (TES) in each coronary artery. Follow-up periods were 1 day (n = 9 stents), 3 days (n = 9 stents), and 7 days (n = 15 stents). Longitudinal sections of the stented vessels were examined using scanning electron microscopy. At 1 day, there was scarce, patchy endothelialization with areas of fibrin; the endothelialization rate was similar for all the stents (SS, 29% ± 23%; CCS, 29% ± 24%; TES, 31% ± 25%; P = .9). At 3 days, there were more endothelial cells but with immature features and giant cells over fibrin; the endothelialization was greater in SS and CCS than in TES (SS, 79% ± 14%; CCS, 81% ± 17%; TES, 46% ± 9%; P = .007). At 7 days, arteries showed better endothelialization with few giant cells; the endothelialization was greater in SS and CCS than in TES (SS, 95% ± 4%; CCS, 98% ± 4%; TES, 79% ± 9%; P = .01). In conclusion, the described model is useful for the analysis of endothelialization of coronary stents and facilitates measurement of its rate of formation and characterization of the involved cell types.

Undifferentiated high-grade pleomorphic sarcoma in a California sea lion (Zalophus californianus).

A tumour located in the pectoral region and the left front flipper was observed in a 29-year-old female California sea lion (Zalophus californianus) that died following signs of respiratory disease and inappetence. Metastases were present in the lung and adrenal gland. The histological pattern of the tumour was variable. In some areas the tumour consisted of pleomorphic fibroblast-like cells arranged in a storiform pattern, while in other areas it comprised oval or polygonal cells with round to oval nuclei and some bizarre cells arranged in an alveolar pattern. Occasionally, multinucleated giant cells were observed. Immunohistochemically, the neoplastic cells only expressed vimentin. On the basis of the microscopical and immunohistochemical features the tumour was diagnosed as an undifferentiated high-grade pleomorphic sarcoma. This type of neoplasm with disseminated involvement of other organs is rare in all species and has never been reported in California sea lions.

Human tuberculosis due to Mycobacterium bovis and M. caprae in Spain, 2004-2007.

OBJECTIVE: To identify the characteristics associated with human tuberculosis (TB) caused by Mycobacterium bovis and M. caprae in Spain. DESIGN: Retrospective study covering all M. bovis and M. caprae isolates identified at the National Mycobacterial Reference Laboratory (NRL) from 2004 to 2007. We studied the microbiological and epidemiological characteristics of patients and performed a genetic analysis of isolates. RESULTS: The study covered 110 isolates (89 M. bovis and 21 M. caprae) that accounted for respectively 1.9% and 0.3% of the M. tuberculosis complex isolates available at the NRL. Data on risk of exposure to M. bovis or to M. caprae were available in 82 (74%) of the 110 cases, with 60 (73%) registering a probable or possible risk of exposure and 22 (27%) registering no risk. Probable exposure mainly included crop and livestock farmers, and possible exposure included patients born in countries with a high prevalence of bovine TB. Spoligotyping of strains yielded 36 different patterns, with SB0121, SB0134 and SB0157 being predominant. CONCLUSIONS: In Spain, cases of human TB due to M. bovis and M. caprae represent a small proportion of all TB cases, and for a high percentage of cases this is linked to occupational exposure and coming from countries endemic for bovine TB.

Effect of different vaccine formulations on the development of Glässer's disease induced in pigs by experimental Haemophilus parasuis infection.

Four groups of pigs immunized with different vaccines and a group of non-vaccinated controls were challenged intratracheally with a lethal dose (5 x 10(9) colony-forming units) of Haemophilus parasuis, the aetiological agent of Glässer's disease. A vaccine containing inactivated whole organisms gave strong protection against clinical signs, death, pathological changes and persistence of organisms in vivo. However, all non-immunized pigs, all pigs given a vaccine consisting of the recombinant transferring-binding protein (Tbp) B, some pigs given an outer membrane protein (OMP) formulation enriched with TbpB and some pigs immunized with a sub-lethal dose of live organisms died at various times after challenge, yielding positive cultures from most organs post mortem and having shown hyperthermia and other clinical signs before death. Animals that died showed fibrinosuppurative polyserositis, exudative pneumonia, and lesions compatible with acute septicaemia, e.g., disseminated intravascular coagulation with multiple fibrinous thrombi in arterioles and capillaries, depletion of splenic white pulp, and acute lymphadenitis. The results suggested that, in addition to the protection given by inactivated whole organisms, partial protection was given by the OMP formulation and by a sub-lethal dose of living organisms; however, the recombinant TbpB preparation gave no protection.

[Prevalence of malnutrition in medical and surgical wards of a university hospital]. / Prevalencia de malnutrición en los servicios médicos y quirúrgicos de un hospital universitario.

INTRODUCTION: Malnutrition is frequently found in hospitals, where is related to poor outcomes. There are contradictory data about if prevalence of malnutrition is greater in surgical or medical patients. The aim of this study is to know the prevalence of malnutrition in both groups of patients. METHODS: The nutritional status of 189 patients from medical and surgical wards was assessed with Subjective Global Assessment, and data about sex, age, length of hospital stay, mortality, diseases, and wards of admission were collected. Qualitative variables were compared with chi-square test, and independent quantitative variables with Student's t test. P < 0.05 was accepted as significative. RESULTS: The prevalence of malnutrition was 40.2%. Malnourished patients have lost 7.3% of their weight, 67.1% referred a diminished oral intake, and 53.9% anorexia. Malnutrition was significatively associated to male sex, greater length of stay, and cancer. Prevalence and severity of malnutrition were similar in medical and surgical wards, and malnourished patients just differed in diseases (chronic diseases in medical; surgical procedures and cancer in surgery). CONCLUSIONS: Malnutrition is equally prevalent in medical and surgical wards, probably due to different but highly frequent risk factors, and is related to a longer hospital stay.

Cutaneous lesions associated to multiple endocrine neoplasia syndrome type 1.

BACKGROUND: Multiple endocrine neoplasia type 1 (MEN1) is a genetic disease that predisposes to endocrine tumour development. Some cutaneous lesions (angiofibromas, collagenomas, melanosis guttaca, lipomas, melanomas, 'cafe au lait macules') have been associated to this syndrome. We compare the prevalence of cutaneous lesion in affected patients with their non-carrier relatives. PATIENTS AND METHOD: We studied 9 patients with MEN1 and 20 non-carrier, first-degree relatives. Genetic screening was realized in all of them. Patients were examined by dermatologist, and biopsy was performed when necessary. RESULTS: Patients with MEN1 presented hyperparathyroidism (100%), neuroendocrine tumours of pancreas (66%) and pituitary adenomas (44%); their relatives were free of endocrine features of MEN1. The studied cutaneous lesions were more prevalent in affected patients than in non-carriers (55.5% vs. 25%; P = 0.029). Odds ratio of developing cutaneous lesions in MEN1 patients was 6.6 (95% confidence interval, 1.09-40.43). The frequency of angiofibromas was lower (22.2%) than the reported in other studies (43-88%), and we did not find any collagenoma. CONCLUSIONS: MEN1 is associated to some cutaneous lesions and could be useful for detecting MEN1 carriers in an affected family. Cutaneous lesions should be assessed in MEN1 patients.

Home artificial nutrition in a sanitary area of Galicia (Spain): descriptive study and proposals for the future.

OBJECTIVES: Home artificial nutrition (HAN) is a technique in increasing use, but the available data about it is limited because record-keeping in most countries is voluntary. Our objective is to describe the characteristics of HAN in our setting and to design a future proposal that improves its coordination. SUBJECTS: Retrospective review of 237 clinical histories of the patients who began with HAN in 2006 in our unit. VARIABLES: epidemiological information, indications, type of HAN, duration, complications and costs. RESULTS: Mean age: 75.4 years. Neurological and neoplasic diseases were the most frequent diagnoses (39.7% and 32.1%, respectively). Main indications were: reduction of ingestion (41.8%) and neurological dysphagia (27.8%). 48.1% presented an important functional impairment and 63.7% needed a caregiver. HAN duration was < 3 months in 43.9% and the principal cause of suspension was the lack of follow-up. Oral nutrition was the preferred route (70.9%), gastrostomy was found in only 3.4%. High-energy formulas were mostly used in patients with supplements (53.3%) and standard formulas in those with complete diets (32.4%). Complications related to this therapy were low, mainly in the oral route. The most frequent were gastrointestinal (19.3%). Mean monthly cost: 159.3 euros/patient and an average travel distance of 26 km to pick up supplies. CONCLUSION: HAN is a safe, short-term therapy, indicated in patients with diminished ingestion due to an acute situation. Our future proposal tries to improve the selection of patients, to facilitate the provision of materials and to customize follow-up to patient needs.

Genotyping of Mycobacterium tuberculosis over two periods: a changing scenario for tuberculosis transmission.

OBJECTIVE: To evaluate changes in the molecular epidemiology of tuberculosis (TB) in Zaragoza, Spain, over a decade that has seen large social and health changes, including the attenuation of the human immunodeficiency virus (HIV) epidemic and increased immigration. DESIGN: A population-based molecular study was conducted using standard restriction fragment length polymorphism IS6110 typing that included all patients with bacteriologically confirmed TB living in the Zaragoza area from 2001 to 2004. The current situation was compared with that described in a previous study from 1993 to 1995. RESULTS: A total of 454 Mycobacterium tuberculosis isolates were genotyped; 239 (52.6%) were grouped in 45 clusters composed of 2 to 85 isolates. Independent risk factors for clustering were identified. The main differences with the previous study were the increase of TB cases among immigrants, a decrease in HIV-TB co-infected patients and the occurrence of a large TB outbreak involving 85 patients (M. tuberculosis Zaragoza [MTZ] strain). CONCLUSION: A change in the epidemiological pattern of TB has been observed in the last years. TB transmission is more common among the Spanish-born population, while foreign birth is significantly less associated with clustering. A single epidemic strain caused 18.7% of all TB cases.