Use of thyroid hormones in hypothyroid and euthyroid patients: A 2020 THESIS questionnaire survey of members of the Danish Endocrine Society.

PURPOSE: The standard treatment of hypothyroidism is levothyroxine (LT4), which is available as tablets or soft-gel capsules in Denmark. This study aimed to investigate Danish endocrinologists' use of thyroid hormones in hypothyroid and euthyroid patients. METHODS: An e-mail with an invitation to participate in an online survey investigating practices about substitution with thyroid hormones was sent to all members of the Danish Endocrine Society (DES). RESULTS: Out of 488 eligible DES members, a total of 152 (31.2%) respondents were included in the analysis. The majority (94.1%) of responding DES members use LT4 as the treatment of choice. Other treatment options for hypothyroidism are also used, as 58.6% prescribe combination therapy with liothyronine (LT3) + LT4 in their clinical practice. LT4 + LT3 combination is preferred in patients with persistent symptoms of hypothyroidism despite biochemical euthyroidism on LT4 treatment. Over half of the respondents answered that thyroid hormone therapy is never indicated for euthyroid patients, but 42.1% will consider it for euthyroid infertile women with high antibody levels. In various conditions that could interfere with the absorption of LT4, most responding Danish endocrinologists prefer tablets and do not expect a significant difference when switching from one type of tablet formulation to another. CONCLUSION: The treatment of choice for hypothyroidism is LT4. Combination therapy with LT4 + LT3 is considered for patients with persistent symptoms. Even in the presence of conditions affecting bioavailability, responding Danish endocrinologists prefer LT4 tablets rather than newer LT4 formulations, such as soft-gel capsules.

[Features of the use of synthetic analogues of thyroid hormones: а 2020 THESIS* questionnaire survey of members of the Belarusian Public Medical Association of Endocrinology and Metabolism].

BACKGROUND: The standard treatment for hypothyroidism is levothyroxine (LT4), which in the Republic of Belarus is available in tablet form whereas liothyronine (LT3) is not registered, but patients can purchase them on their own abroad. AIM: This study aimed to investigate Belarusian endocrinologists' attitude of thyroid hormones in hypothyroid and euthyroid patients. MATERIALS AND METHODS: An online survey was conducted, for which members of the Belarusian Medical Association of Endocrinology and Metabolism were invited by posting information in the group chat and by e-mail. The research period was from October 1 to December 26, 2020. 210 questionnaires were received, 146 of which were used. RESULTS: The majority of participants, 145 (99.3%), indicated that they were using LT4 as the first-choice drug for the treatment hypothyroidism. Sixty-one (41.8%) doctors answered that LT3 + LT4 combination likely can be used in patients with long-term untreated hypothyroidism and 15 (10.3%) - in patients with persistent symptoms of hypothyroidism, despite biochemical euthyroidism on therapy LT4. Over half of the respondents 84 (57.5%) answered that thyroid hormone therapy was never indicated for euthyroid patients, but 50 (34.2%) would consider it for female infertility with high level of thyroid antibodies and 36 (24.7%) for simple goiter growing over time. In various conditions that could interfere with absorption of LT4, most responding Belarusian endocrinologists do not expect a significant difference with different formulations (tablets+"I do not expect major changes in different forms" vs. "soft gel capsules"+"liquid solution"; p <0.001). Persistent symptoms of hypothyroidism on the background of LT4 replacement therapy with the achievement of the target TSH can mainly be caused by psychosocial factors, concomitant diseases, unrealistic patient expectations, chronic fatigue syndrome, and the burden of chronic disease. CONCLUSION: The method of choice of Belarusian endocrinologists in the treatment of hypothyroidism is LT4 replacement therapy, but the appointment of LT4 + LT3 combination therapy can be considered in certain clinical situations. As a rule, endocrinologists do not prescribe LT4 in patients with euthyroidism and do not expect a significant difference when using other forms of levothyroxine.

Use of Thyroid Hormones in Hypothyroid and Euthyroid Patients: A Thesis* Questionnaire Survey of Romanian Physicians *Thesis: Treatment of Hypothyroidism in Europe by Specialists: an International Survey.

OBJECTIVE: Romania has no national guidelines for hypothyroidism treatment, nor are there any recommendations from national societies to adhere to international guidelines. Our aim was to identify the attitudes of Romanian physicians relating to hypothyroidism treatment focusing on available formulations of levothyroxine (LT4). METHODS: All 748 members of the Romanian Society of Endocrinology were invited to participate in a web-based survey. A total of 316 (42.24%) members responded, of whom 222 (70.2%) completed all questions. RESULTS: Half of the respondents recommended LT4 treatment in euthyroid patients, from 3.6% in euthyroid patients with obesity to 36.4% in euthyroid females with infertility associated with high levels of thyroid antibodies. LT4 was considered the preferred treatment for hypothyroidism (compared to combination treatment of LT4 with LT3 or LT3 alone) by 98.6% of respondents. LT4 in liquid solution was preferred over tablets if malabsorption is suspected (56.5% vs. 27.3%), for patients with unexplained poor biochemical control (52.5% vs. 22.9%) and for patients not able to adhere to ingesting LT4 fasted (74.0% vs. 9.8%). The most and least probable explanations for persistent symptoms in patients with hypothyroidism who achieve a normal TSH under medication were "psychosocial factors" and "burden of having to take medication", respectively. CONCLUSION: A significant proportion of Romanian physicians would use LT4 in some groups of euthyroid patients, contrary to current evidence. The preferred treatment for hypothyroidism was LT4. Alternative LT4 formulations (liquid solution) are considered in specific clinical conditions. Diversification of available thyroid hormone formulations was readily incorporated into everyday practice.

Epidemiological and virological findings during an outbreak of equine influenza in Uruguay in 2018.

Equine influenza is one of the major respiratory infectious diseases in horses. In 2018, equine influenza virus (EIV) was confirmed as the cause of outbreaks of respiratory disease in horses in Chile and Argentina. In the same year, for the first time in Uruguay, EIV infection was confirmed by isolation and molecular analysis to be the cause of respiratory disease among hundreds of clinically affected thoroughbred horses in training and racing facilities. The virus was detected in nasopharyngeal swabs by a pan-reactive influenza type A realtime reverse transcription polymerase chain reaction (rRT-PCR). The partial nucleotide sequence of the haemagglutinin 1 (HA1 ) gene (994 base pairs) was determined and analysed phylogenetically using MEGA X software. Amino acid sequence alignments were constructed, and serum samples were tested by haemagglutination inhibition and single radial haemolysis. The diagnosis of EIV was confirmed by rRT-PCR, virus isolation and serological testing. The phylogenetic analysis of the partial HA1 gene sequence of the isolated virus indicated that it belongs to clade 1 of the Florida sub-lineage of the American lineage and is closely related to viruses isolated in the recent past. Study of the HA1 region (331 amino acids) of the virus identified in horses in racing facilities in Uruguay displayed the highest amino acid sequence identity with viruses detected in Argentina, Chile and the United Kingdom in 2018. The surveillance data reported illustrate the international spread of EIVs and support the recommendation of the World Organisation for Animal Health (OIE) Expert Surveillance Panel to include viruses of the Florida sub-lineage in vaccines.

La grippe équine est l'une des principales maladies respiratoires infectieuses affectant les équidés. En 2018, il a été confirmé que des foyers de maladie respiratoire enregistrés chez des chevaux au Chili et en Argentine étaient dus au virus de la grippe équine. Cette même année en Uruguay, pour la première fois dans ce pays, il a été établi par isolement viral et par des méthodes moléculaires que le virus de la grippe équine était l'agent causal d'une maladie respiratoire affectant cliniquement des centaines de chevaux pur-sang dans des centres d'entraînement et des hippodromes. La détection du virus s'est faite à partir d'écouvillons prélevés par voie naso-pharyngée en appliquant une technique d'amplification en chaîne par polymérase couplée à une transcription inverse en temps réel (rRT­PCR) à large spectre pour les virus influenza de type A. Une séquence nucléotidique partielle correspondant au gène de l'hémagglutinine 1 (HA1) (994 paires de bases) a fait l'objet d'une analyse phylogénétique au moyen du programme informatique MEGA X. Il a été procédé à la construction d'une matrice d'alignements de ces séquences d'acides aminés. D'autre part, des prélèvements de sérum issus de chevaux atteints ont été soumis à l'épreuve d'inhibition de l'hémagglutination et à une hémolyse radiale unique. Aussi bien la rRT­PCR que l'isolement viral et l'analyse sérologique ont confirmé le diagnostic de l'infection par le virus de la grippe équine. Il ressort de l'analyse phylogénétique du fragment de séquence du gène HA1 du virus isolé que ce dernier appartient au clade 1 de la sous-lignée Florida de la lignée américaine et qu'il est étroitement apparenté à des virus isolés au cours des dernières années. L'étude de la région HA1 (331 acides aminés) du virus détecté chez des chevaux de course en Uruguay a montré que les virus qui présentaient la plus grande similitude avec cette séquence d'acides aminés étaient ceux détectés en Argentine, au Chili et au Royaume-Uni en 2018. Les données de surveillance rapportées illustrent la propagation à l'échelle internationale des virus de la grippe équine et renforcent la recommandation émise par le Groupe d'experts de l'Organisation mondiale de la santé animale (OIE) chargé de la surveillance de la composition des vaccins contre la grippe équine d'inclure les virus de la sous-lignée Florida dans la composition de ces vaccins.

La gripe equina es una de las principales infecciones respiratorias que afectan al caballo. En 2018 se confirmó que el virus de la gripe equina era la causa de diversos brotes de afección respiratoria que habían afectado a caballos de Chile y Argentina. Ese mismo año, por primera vez en el Uruguay, se confirmó por aislamiento y análisis molecular que el virus de la gripe equina era la causa de una infección respiratoria que, acompañada de manifestaciones clínicas, afectó a cientos de caballos purasangre de hipódromos y centros de adiestramiento. El virus fue detectado en muestras de frotis nasales mediante una técnica de reacción en cadena de la polimerasa acoplada a transcripción inversa en tiempo real (rRT­PCR, por sus siglas en inglés) que reacciona ante todos los virus gripales de tipo A. Tras secuenciar parcialmente el gen de la hemaglutinina 1 (HA1 ) (994 pares de bases), se procedió a su análisis filogenético empleando el programa informático MEGA X. Además de crear una matriz de alineamiento de secuencias de aminoácidos, se sometieron muestras de suero a pruebas de inhibición de la hemaglutinación y hemólisis radial simple. Así, el diagnóstico que apuntaba al virus de la gripe equina fue confirmado por rRT­PCR, aislamiento vírico y análisis serológico. El análisis filogenético de la secuencia parcial del gen HA1 del virus aislado puso de manifiesto que pertenece al clado 1 del sublinaje Florida del linaje americano y guarda estrecho parentesco con otros virus aislados en fechas recientes. El estudio de la región HA1 (331 aminoácidos) del virus detectado en caballos de hipódromos uruguayos reveló que el mayor nivel de concordancia de su secuencia de aminoácidos se daba con virus detectados en Argentina, Chile y el Reino Unido en 2018. Los datos de vigilancia comunicados dan fe de la propagación internacional de los virus de la gripe equina y avalan la recomendación formulada por el Panel de expertos en vigilancia de la composición de las vacunas contra la gripe equina de la Organización Mundial de Sanidad Animal (OIE), que aboga por incluir virus del sublinaje Florida en las vacunas.

Cost of influenza and influenza-like syndromes (I-LSs) in Italy: Results of a cross-sectional telephone survey on a representative sample of general population.

OBJECTIVES: Influenza and Influenza-like syndromes (I-LSs) are very common events in general practice, and their relevance is frequently underestimated. Aim of the study was to assess the economic impact of influenza and Influenza-like syndromes (I-LSs) in the Italian general population by using real-world data from a retrospective database. METHODS: A cross-sectional survey via Computer Assisted Telephone Interview (CATI) was carried out by using a specific questionnaire which is able to assess the rate of infectious episodes, together with subject's behavior in case of influenza or I-LSs, and prescribed therapy. Collected data were statistically analyzed to calculate the economic impact of influenza and I-LSs episodes according to both the National Health System Perspective (NHS-P) and the Italian Families Perspective (S-P). The components of cost were: influenza vaccination, used drugs, General Practitioner (GP) visits, Emergency Room (ER) visits, hospitalizations, and productivity loss. RESULTS: According to the NHS-P, the annual cost for managing influenza or I-LSs amounted to € 60.24, corresponding to € 38.71 per episode. About 72% of the cost was due to GP/ER visits and hospitalization; 22% to drugs, and 6% to vaccination. In the IF-P, the annual cost increased to € 249.70 (€ 140.33 per episode) and almost 90% of the cost was related to workdays lost, while only 11% and 1.3% were due to drugs and vaccination, respectively. Annual cost was highly related to the mean duration of influenza or I-LSs episodes in both perspectives (€ 111─388 in IF-P and € 56─68 in NHS-P). Furthermore, the number of workdays lost due to these episodes showed a significant impact on the overall cost (€ 195─304) only in the NHS-P. CONCLUSIONS: Influenza and I-LSs have a not negligible economic impact, both for the NHS and for the society. Resource consumption is considerable in the NHS-P, while the productivity loss due to people absenteeism causes the most relevant impact in the IF-P.

Patient Related Outcomes-BODE (PRO-BODE): A composite index incorporating health utilization resources predicts mortality and economic cost of COPD in real life.

Multidimensional scores were proposed for defining COPD outcomes, but without any incorporation of the economic COPD cost to clinical indices. AIM: using mortality as an outcome, the hypothesis that adding total health care cost to the BODE index would better predict mortality in COPD was investigated. METHODS: 275 COPD patients were surveyed. Anthropometrics, lung function, the BODE and the Charlson Comorbidity Index were determined. History of exacerbations, ER visits, hospitalizations and mortality were also determined over the next three years, being their rates graded and added to the BODE index according to a simple algorithm. The novel PRO-BODE index ranged 0-10 points; its relationship to annual total COPD cost and survival was assessed by linear regression analysis. RESULTS: total COD cost showed the highest relationship with survival (r = -0.58), even higher than that of age and of BODE index (r = -0.28 and r = -0.21, respectively). The integrated Pro-BODE score proved proportional to the cost of care and inversely proportional to the length of survival. CONCLUSIONS: Pro-BODE is a novel composite index which helps in predicting in real life the impact of COPD over three years, both in terms of patients' survival and of COPD economic burden.

Prevalence of different comorbidities in COPD patients by gender and GOLD stage.

BACKGROUND: Several comorbidities frequently affect COPD progression. Aim of the study was to assess the prevalence of main comorbidities by gender and disease severity in a cohort of COPD patients referring for the first time to a specialist institution. METHODS: The study was a non-interventional, cross-sectional investigation carried out via automatic and anonymous selection from the institutional data base over the period 2012-2015. Inclusion criteria were: subjects of both sex aged ≥40 years; diagnosis of COPD according to GOLD guidelines 2014; the availability of a complete clinical record file. Variables collected were: lung function; smoking history; BMI; the Charlson Comorbidity Index (CCI); number and kind of comorbidities for each patient. RESULTS: At least one comorbidity of clinical relevance was found in 78.6 % of patients, but at least two in 68.8 %, and three or more were found in 47.9 % of subjects. Mean CCI was 3.4 ± 1.6sd. The overall prevalence was 2.6 comorbidities per patient, but 2.5 in males, and 3.0 in females, respectively (p < 0.05). Cardio-vascular disorders were the most frequent, but significantly more frequent in males (44.7 vs 30.7 %, respectively), while the metabolic, the digestive and the osteo-articular disorders were prevailing in females (12.4 vs 9.2; 14.2 vs 4.8, and 6.0 vs 3.8, respectively). In particular, chronic cor pumonale and arrhythmias mainly prevailed in men and congestive heart failure in females, while arterial hypertension resulted equally distributed. As concerning respiratory disorders, pneumonia, pleural effusions and chronic respiratory failure were more frequently found in men, while bronchiectasis and asthma-COPD overlap syndrome (ACOS) in females. Anaemia, gall bladder stones, osteoporosis and spontaneous fractures mostly prevailed in females, while gastric disorders of inflammatory origin and arthrosis were more frequent in males. Cognition disorders, dementia and signs of degenerative brain disorders were more frequently found in men, while depression in females. Finally, lung cancer was at the first place in men, but at the second in females. CONCLUSIONS: All comorbidities increased their prevalence progressively up to the last stage of COPD severity, except the cardio-vascular and the metabolic ones which dropped in the IV GOLD stage, presumably due to the high mortality rate in this severe COPD stage. The gender-dependency of comorbidities was confirmed in general terms, even if lung cancer proved a dramatic increase almost independently of sex.

Efficacy of erdosteine 900 versus 600 mg/day in reducing oxidative stress in patients with COPD exacerbations: Results of a double blind, placebo-controlled trial.

BACKGROUND: Acute exacerbations of chronic obstructive pulmonary disease (AECOPD) are associated with increased airway and systemic inflammation. There is evidence that erdosteine accelerates recovery from AECOPD by reducing airway inflammation. AIM: To investigate the dose-dependent antioxidant/anti-inflammatory activity of erdosteine in COPD patients. METHODS: In this single-centre, double blind, double dummy study, patients with mild-to-moderate COPD (GOLD stage II-III), were randomised to receive either placebo or two dosages of oral erdosteine (300 mg tid or 300 mg bid + 1 capsule of indistinguishable placebo) for 28 days in addition to their standard treatment. Primary variables were plasma reactive oxygen species (ROS) and 8-isoprostane levels, while secondary variable was lung function (FEV1; FEV1/FVC; FEV1 short-term reversibility), all assessed in baseline; every two weeks during the study, and one week after the end of the study. RESULTS: Baseline demographic characteristics, plasma ROS and 8-isoprostane levels and lung function were not significantly different in the 24 eligible patients (14 males, aged 38-75 years). At 2 weeks, there was a dose-dependent decrease in ROS in the erdosteine groups. By week 4 there were significant differences in ROS levels compared to baseline between patients receiving 900 mg/day (p < 0.003) and those receiving 600 mg/day (p < 0.04). This effect continued in the follow-up week (p < 0.021). Erdosteine also lowered 8-isoprostane plasma levels after 4 weeks (p < 0.01), and this effect lasted over the post-treatment week. Moreover, % FEV1 reversibility after salbutamol 400 mcg obtained after a 4 -week treatment of erdosteine 900 mg/day was significantly higher than that obtained after 600 mg/day (p < 0.01). Erdosteine was well tolerated and no treatment-related adverse event was reported. CONCLUSIONS: Results confirm the antioxidant dose- and time-dependent activity of erdosteine, and support the utility of including erdosteine it in the therapeutic strategy for the prevention and treatment of oxidative stress-induced inflammation, which frequently leads to AECOPD occurrence.

Essential amino acid supplementation in patients with severe COPD: a step towards home rehabilitation.

BACKGROUND: Pulmonary Rehabilitation ("Rehabilitation") can improve both lung function and quality of life in patients suffering from chronic obstructive pulmonary disease (COPD) even if only a very small proportion of patients have access to Rehabilitation. Supplementation of Essential Amino Acids (EAAs) might allow COPD patients to achieve some typical Rehabilitation outcomes such as a better physical performance and an improved health status. METHODS: 88 COPD out-patients (GOLD class 3-4) with a body mass index (BMI) < 23 Kg/m2 were randomised to receive EAAs (n = 44) or placebo (n = 44) for twelve weeks. Primary outcome measures were changes in both physical activities in daily life (measured by Sense Wear Armband in terms of mean steps walked in one week) and in quality of life (measured by the St George's Respiratory Questionnaire, SGRQ). RESULTS: After 12 weeks, the physical performance was significantly increased vs baseline only in patients who received EAAs (1140.33 +/- 524.69 and 638.68 +/- 662.1 steps/day, respectively; p = 0.02), being also the comparison vs the placebo group highly significant (p = 0.003). Similarly, the SGRQ score improved significantly only in EAA patients (69.35 +/- 9.51 vs baseline 72.04 +/- 8.62; p < 0.01), and changes were significantly different from those measured in the placebo group (p < 0.001). Furthermore, when compared to those who received placebo, EAAs patients significantly increased their fat-free mass (p = 0.04), muscle strength (p < 0.01), saturation of oxygen (p = 0.05), serum albumin (p < 0.001), and also ameliorated their original cognitive dysfunction (p = 0.02). CONCLUSIONS: Oral supplementation with EAAs contribute to improve the daily-life performance in domiciliary severe COPD patients who can not enter any Rehabilitation programme, together with their quality of life; nutritional and cognitive status, and muscle strength.

Omalizumab modulates bronchial reticular basement membrane thickness and eosinophil infiltration in severe persistent allergic asthma patients.

Severe persistent asthma causes a substantial morbidity and mortality burden and is frequently not well controlled, despite intensive guideline-based therapy. The unique monoclonal antibody approved for patients with severe allergic asthma is omalizumab: a recombinant humanised murine against IgE antibodies. The aim of the present study is to investigate the effect of long-term anti-IgE on the thickening of the reticular basement membrane (RBM) and eosinophil infiltration in bronchial biopsies from patients with severe persistent allergic asthma. Biopsies were obtained from 11 patients with severe persistent allergic asthma before and after (12 months) treatment with omalizumab. RBM thickness and eosinophils were measured by using light microscope image analysis. A significant mean reduction in RBM thickness and eosinophil infiltration were measured after one-year omalizumab treatment. No correlation between eosinophil reduction and RBM thickness reduction was found. No correlation between each of the previous two parameters and clinical parameters was detected. In conclusion, our study showed that a substantial proportion of severe asthmatics reduced the original bronchial RBM thickness and eosinophil infiltration after one-year treatment with anti-IgE, thus emphasizing the possible role of omalizumab in affecting airway remodeling in severe persistent allergic asthma.

Pattern of airway inflammation and remodelling in mild persistent atopic asthma and in mild persistent asthma related to gastroesophageal reflux.

BACKGROUND: The increase of basement membrane thickness (BMAT) represents a structural feature described as commonly characterizing airway remodelling in asthma, even if the non-atopic condition had been investigated only episodically from this point of view. Gastrooesophageal-reflux is a pathological condition which can frequently cause and/or sustain asthma in non-atopic individuals. OBJECTIVES: The aim of the study was to measure BMT; some inflammatory mediators in BAL; cys-leucotrienes (LTE4) in urine; e-NO, and BHR to Methacholine (MCh) in mild atopic and in mild non-atopic, GER-related asthma. METHODS: After their informed consent, 25 mild atopic (40.9 years +/- 13.1 sd, FEV1 = 95.9% pred. +/- 12.9 sd) and 39 non-atopic, GER-related asthmatics (57.3 years +/- 14.2 ds, FEVY1 = 101.3% pred. +/- 12.2 sd), nonsmoker and of a comparable asthma duration, underwent measurements of basal lung function and bronchial response to MCh (PD20 FEV1); endobronchial biopsies and BAL (in the right middle lobe), and a 24-h gastroesophageal pHmetry. RESULTS: Atopic GER-related asthma showed two distinct patterns of airway inflammation. The eosinophilic contribution to airway inflammation was systematically prevailing in the former group, such as: EOS = 10.7% +/- 13.4 sd vs 2.0% +/- 2.8 sd, p = 0.001; ECP = 344.9 mcg/l +/- 635.9 sd vs 59.2 mcg/l +/- 75.1 sd, p = 0.001. CONCLUSIONS: Data from the present study are suggesting that persistent mild atopic and mild GER-related asthma seem to represent two distinct phenotypes of asthma in terms of airway remodelling, and in particular of BMT involvement.

Cost-utility of add-on omalizumab in difficult-to-treat allergic asthma in Italy.

OBJECTIVE: Omalizumab (OM), an innovative biological treatment for difficult asthma with perennial sensitisations, is an humanized monoclonal anti-IgE antibody that binds free circulating IgE; inhibits mast cell and basophil activation by combining free IgE, leads to IgE receptor down-regulation, thus blocking the inflammatory cascade. AIM OF THE STUDY: To assess real-world cost-utility ofadd-on OM in Italy. METHODS: changes in clinical and economical outcomes, and in quality of life (QoL) associated with add-on OM in adults (n=23) with severe dfficult asthma were compared with those recorded before OM in the same subjects. Variables were: lung function; IgE levels; health status; ACT score; QoL (SGRQ); n. GP and specialist visits; emergency visits; hospitalizations, and concomitant pharmacological treatments. Further indices were: changes in Health-related QoL; total health-care costs, and incremental cost/utility. Data were statistically compared (Student's T test), and p < 0.01 was accepted for statistical significance. RESULTS: asthma clinical outcomes and patients' health-related quality of life improved significantly by adding OM, and both costs for drugs and hospital care dropped significantly (p < 0.01). The net economic effect was a 350 Euro increase in overall monthly costs; when related to health benefits, it corresponded to an incremental cost/utility ratio ofabout 26,000 Euro/QALY, which represents a quite favourable figure in terms of willingness to pay for health benefits in industrialised countries. CONCLUSIONS: Omalizumab added to an optimised therapy significantly improves clinical outcomes in difficult-to-treat, persistent allergic asthma. Costs also increased, but proved justified by health benefits achieved.

Properties of the COPD assessment test in a cross-sectional European study.

A short, easy-to-use health status questionnaire is needed in the multidimensional assessment of chronic obstructive pulmonary disease (COPD) in routine practice. The performance of the eight-item COPD assessment test (CAT) was analysed in 1,817 patients from primary care in seven European countries. The CAT has a scoring range of 0-40 (high score representing poor health status). Mean CAT scores indicated significant health status impairment that was related to severity of airway obstruction, but within each Global Initiative for Obstructive Lung Disease stage (I to IV) there was a wide range of scores (I: 16.2 ± 8.8; II: 16.3 ± 7.9; III: 19.3 ± 8.2; and IV: 22.3 ± 8.7; I versus II, p = 0.88; II versus III, p<0.0001; III versus IV, p = 0.0001). CAT scores showed relatively little variability across countries (within ± 12% of the mean across all countries). Scores were significantly better in patients who were stable (17.2 ± 8.3) versus those suffering an exacerbation (21.3 ± 8.4) (p<0.0001); and in patients with no (17.3 ± 8.1) or one or two (16.6 ± 8.2) versus three or more (19.7 ± 8.5) comorbidities (p<0.0001 for both). The CAT distinguished between classes of other impairment measures and was strongly correlated with the St George's Respiratory Questionnaire (r = 0.8, p<0.0001). The CAT is a simple and easy-to-use questionnaire that distinguishes between patients of different degrees of COPD severity and appears to behave the same way across countries.

Thyroid autoimmunity and pre-term delivery: brief review and meta-analysis.

BACKGROUND: About 10% of women in childbearing age are positive for thyroid antibodies. The presence of such antibodies has been associated with adverse obstetrical outcomes, in particular miscarriage and pre-term delivery, even though the strength of these associations varies widely from one study to another. AIM: To evaluate from the available data of the literature, the association between thyroid autoimmunity and pre-term delivery. MATERIALS AND METHODS: MEDLINE, EMBASE, Cochrane Library search from 1990 to 2010. A combination of key words was used to generate 2 subset of citations, one indexing thyroid antibodies and the other indexing pre-term delivery as adverse outcome. RESULTS: Seven studies, collecting about 23,000 patients were selected. Meta-analysis of the studies showed an association between thyroid autoimmunity and pre-term delivery [odds ratio =1.67 (confidence interval: 1.44- 1.94; p<0.001)]. CONCLUSIONS: The results of the meta-analysis confirmed the association between thyroid autoimmunity and pre-term delivery. A cause-effect relationship has to be still clarified and interventional studies are required.

Changes of clinical outcomes and health care resources in moderate and in severe COPD treated uniquely with tiotropium 18 mcg od for twenty-four months.

UNLABELLED: Chronic obstructive pulmonary disease (COPD) is a complex and progressive respiratory disease characterized by incompletely reversible bronchial obstruction. The effects of current therapeutic options in early stages of COPD have been poorly investigated in the past, being this specific topic revamped by the results of recent secondary analyses from large international trials. AIM: To measure and monitor in real life the changes in main clinical outcomes and health care resources in patients suffering from mild-to-moderate and severe COPD treated with only tiotropium br. for twenty-four months. METHODS: The population sample of the present observational retrospective study consists of 319 COPD subjects (214 males; average age 71.7 years ± 06 se) automatically extracted from the DataBase of the Health Care Institution. Inclusion criteria were: age ≥ 40 y; basal FEV1 < 80% predicted and FEV1/FVC < 70%; regular treatment with only 18 mcg tiotropium br. for the following two years. All subjects were divided into two subsets according to their FEV1 basal value: (Group A ≤ 50%, and Group B >50% predicted). Lung function; n. exacerbations; n. hospitalizations; absenteeism; n. GP's visits, and use of systemic steroids or antibiotics were checked during the observational period and mean values compared in both subsets with those of the twelve months preceding tiotropium br. (such as during other therapeutic strategies). T test was used for checking the comparability of groups, while ANOVA--Duncan test was used to compare the trends of all variables over time; p < 0.05 was accepted. RESULTS: Group A, 154 individuals (104 males; mean age 72.1 years ± 0.51 se) had a mean FEV1 value of 45.4% pred. ± 0.61 se, while the remaining 165, Group B (111 males; mean age 71.4 years ± 0.60 se) had a mean FEV1 value of 65.5% pred. ± 5.7 se (p < 0,01). The two subsets were well matched for gender, age, and previous use of systemic steroids, but significantly different in terms of basal lung function, COPD morbidity, and antibiotic use. Basically, the impact of COPD confirmed higher in severe patients even if it was unexpectedly remarkable in mild-to-moderate individuals in terms of consumption of health care resources. The overall reduction in COPD morbidity was significant in both groups, but the improvement in FEV1 and in other main long-term outcomes observed in subjects with mild-to-moderate COPD was particularly significant and substantial (p < 0.001), these subjects confirming to be worth of earlier therapeutic attention. CONCLUSIONS: 18 mcg tiotropium br. monotherapy for twenty-four months on a regular daily basis enables a significant minimization of COPD impact, and consents the progressive lung function recovery also in mild-to-moderate individuals, thus suggesting a possible role of tiotropium br. in affecting the natural history of COPD.

Reference urinary LTE4 levels in normal individuals: a pilot study.

UNLABELLED: The definition of reference normal values for urinary LTE4 still represents an open question. AIM: to assess the influence of gender and age on urinary LTE4 levels in normal individuals. METHODS: after their informed consent, urinary LTE4 was measured in 124 well matched, non smoker, non atopic subjects (mean age 49.5 y +/- 20.1 sd; range 4-85 y, 57 m;) without any clinically evident disease and not taking any drug for several months. In all subjects, urine were collected in the morning, and processed by an immunoenzimatic method (Cayman Chem, Mi, USA) via the Triturus system (Grifols, Spain). STATISTICS: t test, anova, linear regression, assuming p < 0.05. RESULTS: mean urinary LTE4 were 57.3 pg/ml in males (mean age 51.2 y +/- 21.3 sd) and 57.0 pg/ml in females (mean age 48.1 y + 19.1 sd), p = ns. Linear regression showed no relationship between urinary LTE4 levels and subjects' age in the whole sample of subjects. When subjects were divided according to 4 different classes of age (0-14; 15-40; 41-60; > 60), anova proved that mean urinary LTE4 levels were significantly different in the different classes of age, being higher in younger subjects (67.1 pg/ml +/- 33.4 sd; 69.8 pg/ml +/- 27.5 sd; 57.1 pg/ml +/- 25.4 sd, and 45.1 pg/ml +/- 24.9, respectively) (anova p < .002; Welch test p < .005). CONCLUSIONS: 1) gender does not affect urinary LTE4 levels in normals; 2) mean urinary LTE4 concentrations tend to a slight, but significant, decrease with the increase of the subjects' age, and this is clear in those over-60; 3) reference values for younger and older normal subjects (such as, under- and over-60 years) should be assumed accordingly.