Determinants of between-hospital variations in outcomes for patients admitted with COPD exacerbations: findings from a nationwide clinical audit (AUDIPOC) in Spain.

BACKGROUND: Previous studies have demonstrated significant variability in the processes of care and outcomes of chronic obstructive pulmonary disease (COPD) exacerbations. The AUDIPOC is a Spanish nationwide clinical audit that identified large between-hospital variations in care and clinical outcomes. Here, we test the hypothesis that these variations can be attributed to either patient characteristics, hospital characteristics and/or the so-called hospital-clustering effect, which indicates that patients with similar characteristics may experience different processes of care and outcomes depending on the hospital to which they are admitted. METHODS: A clinical audit of 5178 COPD patients consecutively admitted to 129 Spanish public hospitals was performed, with a 90-day follow-up. Multilevel regression analysis was conducted to model the probability of patients experiencing adverse outcomes. For each outcome, an empty model (with no independent variables) was fitted to assess the clustering effect, followed by a model adjusted for the patient- and hospital-level covariables. The hospital-clustering effect was estimated using the intracluster correlation coefficient (ICC); the cluster heterogeneity was estimated with the median odds ratio (MOR), and the coefficients of predictors were estimated with the odds ratio (OR). RESULTS: In the empty models, the ICC (MOR) for inpatient mortality and the follow-up mortality and readmission were 0.10 (1.80), 0.08 (1.65) and 0.01 (1.24), respectively. In the adjusted models, the variables that most represented the patients' clinical conditions and interventions were identified as outcome predictors and further reduced the hospital variations. By contrast, the resource factors were primarily unrelated with outcomes. CONCLUSIONS: This study demonstrates a noteworthy reduction in the observed crude between-hospital variation in outcomes after accounting for the hospital-cluster effect and the variables representing patient's clinical conditions. This emphasises the predictor importance of the patients' clinical conditions and interventions, and understates the impacts of hospital resources and organisational factors.

[Critical reading of systematic reviews and meta-analyses about diagnostic imaging]. / Lectura crítica de revisiones sistemáticas y metanálisis en el diagnóstico por imagen.

Systematic reviews of diagnostic validity have been proposed as the best methodological tool to integrate all the available evidence and to help physicians decide whether to use a given diagnostic test. These studies aim to synthesize the results obtained in different primary studies into a couple of indices, generally sensitivity and specificity, or into a summary receiver operating characteristic (ROC) curve. Although there is a certain parallelism with reviews about the efficacy of therapeutic interventions, reviews of diagnostic validity have certain peculiarities that add complexity to the analysis and interpretation of the results. This article emphasizes the methodological aspects that make it possible to critically assess the extent to which the results of a review of the validity of diagnostic tests are valid and provides rudimentary knowledge of the statistics necessary to understand the results.

Visual analogue scales for grading faecal incontinence and quality of life: their relationship with the Jorge-Wexner score and Rockwood scale.

BACKGROUND: The purpose of this study was to determine the probability of substituting two validated methods frequently used for scoring severity and quality of life of faecal incontinence (FI) by a single score represented in a visual analogue scale (VAS). METHODS: One hundred and three consecutive unselected patients affected by FI of different aetiologies were prospectively included in the study. Evaluation of the continence status and quality of life referred to the last month was scored by (1) Jorge-Wexner score, (2) Rockwood FIQL scale, (3) Visual Analogue Scale for Faecal Incontinence (VASFI), and (4) Visual Analogue Scale for Quality of Life (VASQL). Patients unable to respond accurately to one or more of the questionnaires were excluded. The Bland and Altman method was applied to evaluate the agreement between Jorge-Wexner and VASFI. Correlation between both the analogue scales (VASFI and VASQL) and each one with each of the four FIQL scale scores was first determined by an analysis of simple correlation with each subscale and thereafter by multiple regression analysis following the backward strategy. RESULTS: Comparison of VASFI with the Jorge-Wexner score shows that the two methods are neither concordant nor interchangeable, and in a given patient, the differences between both may fluctuate between 5.4 and -10.6 (95 % confidence interval). Correlation of VASFI and VASQL shows that the correlation between both the analogue scales is middling (r (2) = 0.543, ß coefficient -0.538). Correlation of VASFI and FIQL subscales shows that in simple regression analysis, VASFI correlates with lifestyle, coping/behaviour, and embarrassment, but after multiple regression analysis, VASFI correlates significantly only with embarrassment. Correlation of VASQL and FIQL subscales shows that in simple regression analysis, VASQL correlates with lifestyle, coping/behaviour, and embarrassment, but after multiple regression analysis, VASQL only correlates significantly with coping/behaviour. CONCLUSIONS: This study shows that a VAS for FI cannot replace the Jorge-Wexner score and a VAS for quality of life cannot substitute all the four subscales of FIQL. Severity of FI and its impact on quality of life expressed in a VAS only have a fair correlation, showing that they do not assess the same issues, which is also supported by the finding that VASFI correlates significantly only with the embarrassment subscale of FIQL.

Utility of diagnostic tests in the follow-up of egg-allergic children.

BACKGROUND: Better knowledge of the accuracy of a skin prick test (SPT) and specific IgE (sIgE) levels to egg allergens would help to identify persistent egg-allergic children, avoiding unnecessary risky challenges. This study was designed to assess the accuracy of a SPT and sIgE levels to egg allergens in order to determine persistent egg allergy in IgE-mediated allergic children after an egg-free diet. METHODS: Children below 16 years were prospectively and consecutively recruited. Inclusion criteria were: allergy to egg proteins (children with a positive clinical case of IgE-mediated egg allergy and a positive SPT to egg allergens and/or positive sIgE levels), and strict egg avoidance diet followed for at least 6 months. Clinical histories were recorded and all patients underwent SPTs, sIgE levels to egg allergens and the gold standard -a double-blind placebo-controlled egg challenge (DBPCFG). DBPCFG was interpreted without knowledge of the results of the other tests and vice-versa. A SPT and sIgE levels' ROC curves analysis was performed to compare the diagnostic performance of the different tests. RESULTS: Finally, 157 children were included in the study. One hundred out of these 157 children (63.7%) had a positive oral challenge. Ninety-six were male (61%), and the median age was 2.5 years. One hundred and three (66.9%) had atopic dermatitis. A 7 mm egg white prick test had a positive likelihood ratio (+LR) of 6.7, and a level of 1.3 KU/L egg white-sIgE had a +LR of 5.1. A 7 mm egg white SPT had a positive predictive value of 92.3% (95% CI 85.1-99.5), and for a 9 mm egg white SPT this value was 95.6% (95% CI 87.3-100.0). For egg white-sIgE, 1.5 KU/L had a positive predictive value of 90.4% (95% CI 82.4-98.4) and for 25 KU/L it was 100.0% (95% CI 100.0-100.0). SPTs with ovotransferrin and lysozyme showed the lowest accuracy, followed by yolk and ovalbumin SPTs. CONCLUSION: This study is the first to evaluate both tests (SPT and sIgE levels) and all egg allergens to determine the persistence of egg allergy in IgE-mediated allergic children. Measuring the SPT and sIgE levels is useful to predict persistent allergy in these children, especially with the egg white complete extract. An oral challenge should not be performed in egg allergic paediatric patients with either an egg white prick test above 7 mm or a white egg-sIgE determination above 1.3 KU/L, because there is a 90% probability of remaining allergic.

Agreement in the interpretation of magnetic resonance images of the lumbar spine.

BACKGROUND: Correlation between clinical features and magnetic resonance imaging (MRI) findings is essential in low-back-pain patients. Most previous studies have analyzed concordance in the interpretation of lumbar MRI among a few radiologists who worked together. This may have overestimated concordance. PURPOSE: To evaluate intra- and interobserver agreement in the interpretation of lumbar MRI performed in an open 0.2 T system. MATERIAL AND METHODS: Seven radiologists from two different geographic settings in Spain interpreted the lumbar MRIs of 50 subjects representative of the general Danish population aged 40 years. The radiologists interpreted the images in routine clinical practice, having no knowledge of the clinical and demographic characteristics of the subjects and blinded to their colleagues' assessments. Six of the radiologists evaluated the same MRIs 14 days later, having no knowledge of the previous results. Data on the existence of disc degeneration, high-intensity zones, disc contour, Schmorl nodes, Modic changes, osteophytes, spondylolisthesis, and spinal stenosis were collected in the Nordic Modic Consensus Group Classification form. Intra- and interobserver agreement was analyzed for variables with a prevalence >or=10% and

The association between sleep quality, low back pain and disability: A prospective study in routine practice.

BACKGROUND: The objective of this study was to estimate the association between sleep quality (SQ) and improvements in low back pain (LBP) and disability, among patients treated for LBP in routine practice. METHODS: This prospective cohort study included 461 subacute and chronic LBP patients treated in 11 specialized centres, 14 primary care centres and eight physical therapy practices across 12 Spanish regions. LBP, leg pain, disability, catastrophizing, depression and SQ were assessed through validated questionnaires upon recruitment and 3 months later. Logistic regression models were developed to assess: (1) the association between the baseline score for SQ and improvements in LBP and disability at 3 months, and (2) the association between improvement in SQ and improvements in LBP and disability during the follow-up period. RESULTS: Seventy-three per cent of patients were subacute. Median scores at baseline were four points for both pain and disability, as assessed with a visual analog scale and the Roland-Morris Questionnaire, respectively. Regression models showed (OR [95% CI]) that baseline SQ was not associated with improvements in LBP (0.99 [0.94; 1.06]) or in disability (0.99 [0.93; 1.05]), although associations existed between 'improvement in SQ' and 'improvement in LBP' (4.34 [2.21; 8.51]), and 'improvement in SQ' and 'improvement in disability' (4.60 [2.29; 9.27]). CONCLUSIONS: Improvement in SQ is associated with improvements in LBP and in disability at 3-month follow-up, suggesting that they may reflect or be influenced by common factors. However, baseline SQ does not predict improvements in pain or disability. SIGNIFICANCE: In clinical practice, sleep quality, low back pain and disability are associated. However, sleep quality at baseline does not predict improvement in pain and disability.

Phacoemulsification in previously vitrectomized patients: an analysis of the surgical results in 100 eyes as well as the factors contributing to the cataract formation.

PURPOSE: To evaluate the safety and effectiveness of phacoemulsification with clear corneal incision in previously vitrectomized patients as well as factors affecting the development time and type of cataract occurring after pars plana vitrectomy (PPV). METHODS: The authors conducted a prospective study of 100 consecutive eyes of patients who developed a cataract after PPV. Three groups were established based on the underlying vitreoretinal pathology. The main outcome measurements were intraoperative and postoperative complications and changes in best-corrected visual acuity (BCVA). RESULTS: The median interval between PPV and phacoemulsification was 11.5 months. Patients with proliferative diabetic retinopathy required phacoemulsification earlier (p=0.018). Posterior subcapsular cataracts developed more frequently in patients <50 years (73.7%, p=0.000) and affected those who underwent vitrectomy primarily for complicated retinal detachment (48.8%, p=0.046). Intraoperative complications included posterior capsular tears (4%), luxated nucleus into vitreous (2%), and zonular dialysis (5%). Postoperative complications were vitreous hemorrhage (6%), retinal redetachment (4%), pupillary synechiae (6%), ocular hypertension (4%), and Seidel phenomenon (3%). Posterior Nd:YAG laser capsulotomy was required in 44% of eyes. BCVA was improved in 85% of cases at the end of follow-up (median, 15.5 months). Twenty-one patients with one functioning eye (61.9%) demonstrated visual improvement compared with 79 patients with bilateral vision (91.1%; p=0.003). CONCLUSIONS: The technique allows stable improvement in BCVA through long follow-ups. It is more risky than in nonvitrectomized eyes. The visual results after phacoemulsification in vitrectomized eyes seem to be limited by retinal comorbidity and surgical complications.

Assessment of the reproducibility of oligoclonal IgM band detection for its application in daily clinical practice.

BACKGROUND: The presence of oligoclonal IgM bands (OCMB) in cerebrospinal fluid (CSF) is an unfavourable prognostic marker in multiple sclerosis. There is no commercial test to investigate OCMB status. However, a sensitive and specific isoelectrofocusing (IEF) and western blot method was described. We aimed to study the inter-centre reproducibility of this technique, a necessary condition for a reliable test to be incorporated into clinical practice. METHODS: The presence of OCMB was analysed by IEF and western blot with prior reduction of pentameric IgM. We assayed the reproducibility of this test in a blinded multicentre study performed in 13 university hospitals. Paired-CSF and serum samples from 52 neurological patients were assayed at every centre. RESULTS: Global analysis rendered a concordance of 89.8% with a kappa value of 0.71. CONCLUSION: These data indicate that OCMB detection by means of IEF and western blot with IgM reduction shows a good interlaboratory reproducibility and thus can be used in daily clinical setting.

Is clinical expressiveness of Paget's disease of bone decreasing?

Recent data have suggested secular changes implying a current trend toward decreased clinical severity of Paget's disease of bone (PD). To test this hypothesis, we conducted a study comparing the characteristics of two groups of PD patients, as disclosed from a sample assessed systematically. The investigation was a hospital-based study of all cases followed up at our unit since 1980. Throughout the follow-up period, diagnosis was based on standard X-ray criteria and the same clinical assessment was applied. Group I (n = 124) represented patients born before 1926, whereas group II (n = 109) included those born after that year. A bone scan performed with 99mTc-EHDP was available for all patients. X-rays of the pelvis and spine, and views of any hot spot observed on the scintigraphy scans were reviewed. The skeletal extent of PD, based on bone scan uptake, was determined by using the index proposed by Coutris. Alkaline phosphatase and hydroxyproline excretion levels were determined in blood and urine, respectively. Baseline characteristics were recorded on a purpose-designed computerized database. The proportion of males (47% in group I vs. 65% in group II; p = 0.007) and the mean (+/-SD) age at diagnosis (69.0 +/- 8.15 vs. 54.3 +/-9.14; p < 0.001) differed significantly between groups. The year of birth showed a strong negative correlation with age at diagnosis (r = -0.83, p < 0.0001) and a weak, but significant, negative correlation with extent of bone lesion (r = -0.20; p = 0.002). Likewise, subjects born prior to 1926 showed a greater percentage of affected skeleton cases (9.6 plus minus 8.01 vs. 7.06 +/- 5.79; p = 0.001). Group I individuals who had pelvic and/or femoral bone lesions were more prone to suffer "pagetic coxopathy" (65% vs. 40%; p = 0.003) with "protrusio acetabuli" (32% vs. 17%; p = 0.01), and the percentage of patients showing radiographic Monckeberg-type vascular calcifications (36% vs. 14%; p = 0.0006) was higher than in those born after 1926. No other epidemiologically clinically, or biochemically relevant differences were seen in the crude analysis. Multivariate analysis identified extent of skeletal lesions (OR = 0.76; p = 0.01), age at diagnosis (OR = 0.79; p = 0.008), number of bones involved (OR = 1.53; p = 0.03), and occupation (p < 0.0001) as the predictive variables linked to year of birth. Our data are consistent with a temporal tendency toward a smaller number of bone lesions and a decreased percentage of instances of affected skeleton. An earlier age at recent diagnosis times and absence of any relevant clinical or biochemical differences seems more likely linked to recent changes in referral and sociological patterns.

Autoperception and satisfaction with health: two medical care markers in elderly hospitalized patients. Quality of life as an outcome estimate of clinical practice.

This paper reports a prospective study, carried out in elderly patients hospitalized for acute illness, designed to evaluate the effectiveness of medical treatment from the point of view of quality of life (QoL). Patient's autoperception and satisfaction with health, the most relevant subjective estimates of QoL, were assessed on admission to hospital and at check-up after discharge. A comprehensive functional evaluation of the patients was made. The results indicated an improvement in health autoperception coherent with the professional view. However, health satisfaction was not modified in any way after medical treatment. This dissonance could be explained because the predictors of satisfaction, age, sex, functional status and comorbidity, are the factors least modified by treatment. Satisfaction with ones own health could be a crucial marker of QoL especially for chronic diseases, but not appropriate for monitoring treatment effectiveness of acute illness. Health autoperception seems to be more desirable as an outcome estimate for this purpose.

Whooping cough and Parkinson's disease. The Europarkinson Preparatory Activity Research Group.

BACKGROUND: We reported high levodopa use and prevalences of Parkinson's Disease (PD) in periodically, time-clustered, icelandic cohorts born after major whooping cough epidemics (MWCE). METHODS: In order to quantify a possible relationship between age at first post-birth MWCE and risk of PD we: 1) calculated cumulative incidences of PD during the period 1954-1963 in one-year Icelandic cohorts born between 1869 and 1927, using raw material from a reported survey; 2) identified MWCE from 1869 onwards in Iceland; 3) estimated cohort ages at onset of incidence period and at first MWCE; and 4) combined the above-mentioned information using log-linear models. In addition, we studied the prevalence of levodopa users in Icelandic birth cohorts during a recent period. RESULTS: The curves of the above-mentioned incidences and prevalences in one-year birth-cohorts showed: 1) a similar, age-related, inverted V profile; and 2) a systematic notchy pattern, with peak values for one or both measurements for cohorts born during or after each of nine MWCE identified during the period 1869-1927. When 13 cohorts born in years with MWCE were excluded from the analysis, the risk of PD rose with age at first defined MWCE, with the linear increase being 8.4% per year (95% CI: -0.1-18.3%). CONCLUSIONS: These results are consistent with reported effects of age at exposure in animal models of toxic parkinsonism, age-related changes in the dopamine receptor-GPT-binding protein-adenylatecyclase system observed in rats treated with pertussis toxin, and some PD epidemiological features. They suggest that pertussis neurotoxicity could be casually treated to PD worldwide.

In vivo determination of extracellular concentration of amino acids in the rat hippocampus. A method based on brain dialysis and computerized analysis.

Extracellular (EC) concentrations of amino acids were determined in the rat dentate gyrus by means of non-linear regression analysis of 'in vivo' brain dialysis data, considering a simple model of diffusion through a dialysis membrane. The apparent diffusion constants (K) of several amino acids were also calculated in the 'in vivo' situation. While putative amino acid neurotransmitters (glutamate, aspartate and gamma-aminobutyric acid (GABA) were present in the EC fluid at the low micromolar range (0.8-2.9 microM), glutamine was by far the most prominent (193.4 microM). The values of intra/extracellular concentration ratios formed 3 groups: high (greater than 2000) for putative neurotransmitters; low (less than 100) for serine, glutamine, arginine and alpha-alanine; and intermediate (about 400) for taurine. The 'in vivo' calculated K values proved useful for estimation of both basal and changing EC concentrations of amino acids in relatively brief perfusions. These data were evaluated in terms of the functional significance of absolute EC concentrations and tissue-EC fluid ratios. Present findings indicate the simultaneous existence of both an inhibitory and an excitatory tonus as well as the utility of high intra/extracellular concentration ratios in determination of the possible neurotransmitter role of specific amino acids.

Evaluation of the international index in the prognosis of high grade gastric malt lymphoma.

The International Prognostic Index identifies four risk groups with different survival rates in aggressive non-Hodgkin's lymphoma. We have studied whether a slight modification of this index has prognostic significance in high grade gastric B-cell MALT lymphoma. In 53 patients with high grade gastric B-cell MALT lymphoma the following survival factors were investigated: age over or under 60 years, sex, B symptoms, more than one extranodal site of involvement other than the stomach, serum LDH levels, performance status, stage I/IIE1/IIE2 v.s. stage III/IV, treatment with surgery, chemotherapy or both modalities together and the four risk groups as defined by the Modified International Prognostic Index (MIPI). A multivariate Cox's test was used to evaluate the independent prognostic significance on survival of all the above variables. Advanced stage (III/IV) and involvement of more than one extranodal site not including stomach were the only variables influencing survival. The MIPI was not sufficient to separate groups with significant differences in survival or to stratify prognostic groups. In this series, the MIPI did not show prognostic significance in high grade gastric B-cell MALT lymphoma.

Epstein-Barr virus-latent membrane protein 1 expression has a favorable influence in the outcome of patients with Hodgkin's Disease treated with chemotherapy.

The effect of molecular factors in the outcome of Hodgkin's Disease (HD) is being currently studied. In a previous series of HD, including patients treated only with radiotherapy and patients treated with chemotherapy (with or without radiotherapy), we found that a high proliferation index had an adverse influence in overall survival (OS) and in the achievement of a complete remission (CR). Loss of Rb expression also had an adverse prognostic influence in achievement of CR. On the other hand LMP1-EBV expression had a favorable influence for OS. The expression of other molecular factors, p53, bcl2 and CD15 did not show prognostic influence. In the present paper we have studied the effect of these molecular variables in 110 patients, of the previous series who had been treated with chemotherapy. A retrospective study was performed in these 110 patients with HD treated with chemotherapy (ABVD or variants, 62%, or regimes not containing adriamycin, 38%) with or without adjutant radiotherapy, collected at the 11 centers belonging to the Spanish Collaborative Group for the Study of Hodgkin's Disease. The prognostic value of clinical variables and the expression of p53, bcl2, CD15, Rb, LMP 1-EBV and proliferative fraction demonstrated with sensitive immunohistochemical methods were studied. Cox's multivariate analysis was performed to assess their influence in failure-free survival (FFS) and OS. A multivariate logistic regression analysis was performed for studying the effect of the variables in the achievement of a CR. Of the clinical variables, only advanced stage (III/IV) had a significant independent adverse influence in FFS, in OS and in the achievement of CR and advanced age in OS. Of the molecular variables, LMP1-EBV had an independent and strong favorable influence in FFS, in OS and in the achievement of CR. Rb expression had a modest favorable influence in CR. The rest of the molecular variables had no independent influence on the outcome of the disease. In conclusion these results confirm the favorable prognostic value of LMP1-EBV expression in the subset of patients with HD treated with chemotherapy.

Other cancers in patients with gastric MALT lymphoma.

Patients with Hodgkin's disease and nodal non-Hodgkin's lymphomas seem to have an excess risk for other cancers. A high incidence of other cancers has also been found in some series of patients with gastric MALT lymphomas. In a series of 136 patients with gastric MALT lymphomas the occurrence and features of other cancers have been described. In order to evaluate their occurrence statistically (excluding skin cancers) standard incidence ratios (SRI) have been calculated, using the incidence rates of a Cancer Registry in Spain as a reference. A Cox's multivariate proportional hazard model was fitted in order to evaluate the influence of age, sex, histological grade and treatment with chemotherapy or chemotherapy plus radiotherapy in the development of other non-skin cancers occurring after the diagnosis of MALT lymphoma. Other cancers were detected in 16 of the 136 patients (11.7%); the other cancer was detected prior to MALT gastric lymphoma in 6 patients (4.41%), concomitantly in 4 (2.9%) and after diagnosis of the lymphoma in 6 (4.41%). Other cancers occurred in 14.4% of the male and in 8.3% of the female patients; in 12% of the patients with low grade and in 11% of the patients with high grade lymphomas. Of the 6 cancers that occurred after diagnosis of the gastric lymphoma, 3 did in the 80 patients (3.7%) that had been treated with chemotherapy, 1 in the 3 cases (33%) treated with chemotherapy and radiotherapy and 2 in the 53 patients (3.7%) who had not received chemotherapy or radiotherapy. The most frequent other cancers were lymphoid neoplasms and gastric carcinoma. There was not an excess of other cancers in the whole cohort or in the sex or histological grade strata. There was an excess close to significance (SIR =2.59; 95% CI:0.98-6.88) in the patients under 50 years of age. In the Cox's analysis, age, sex, histological grade and treatment did not influence the occurrence of other cancers after the diagnosis of lymphoma. In conclusion, in patients with gastric MALT lymphoma other cancers also occur. An excess incidence was not demonstrated, although it may exist in patients under 50 years. Of special importance is the occurrence of gastric cancer that appears concomitantly or after gastric lymphoma.

Hippocampal EEG theta power density is similar during slow-wave sleep and paradoxical sleep. A long-term study in rats.

Rat hippocampal EEG and motor activity were studied during 15 days in relation to the vigilance state and to the light-dark cycle with a computerized system. During slow-wave sleep (SS) the hippocampal EEG has an outstanding mean power density in the theta band, similar to the large values present during paradoxical sleep. A circadian modulation was found for motor activity in SS and wakefulness (i.e. day-sleep is more restless, day-wakefulness is more quiet than night), and for EEG mean theta power in SS (i.e. less during day-sleep than night-sleep). These data underline the importance of analyzing the dark period when studying nocturnal animals.

Identification of possible areas of high prevalence of Paget's disease of bone in Spain.

OBJECTIVE: In view of the fact that Paget's disease of bone (PD) tends to appear in so-called 'foci', a case-control study was undertaken with the dual aim of: 1) identifying areas having a higher likelihood of constituting PD 'foci'; and 2) detecting the geographic origin of 'PD-carrier' families. METHODS: Two data sets were analysed, one covering the place of birth of 231 cases and 436 controls, and the other covering the place of birth of cases, controls and their parents. Analysis was restricted to six Autonomous Regions accounting for 60% of Spain's towns and cities. To identify geographical areas of high prevalence we used the scan statistic. RESULTS: In the first analysis, 6 possible clusters were detected, corresponding to the districts of Avila (Avila), Lozoya-Somosierra (Madrid), Tierra de Campos(Palencia), the Guadalajara Range, South-west Madrid and Cuenca Hills. The second analysis confirmed the 6 groupings identified by the above procedure and, in addition, detected a further 8 possible clusters. Geographical proximity suggests that in some cases, rather than individual groupings, these may instead constitute larger foci. CONCLUSION: The results point to the possible existence of different PD foci, some coinciding with clusters that have already been reported, and others indicating familial origin in areas that had never previously received PD-specific attention.

Assessment of cardiac function by echocardiography in Paget's disease of bone.

OBJECTIVE: To identify the mechanisms which influence the development of cardiac insufficiency in Paget's disease of bone (PD). METHODS: In this hospital-based case-control study 23 consecutive, recently diagnosed and untreated PD patients were compared against 23 controls frequency-matched by sex, age and body index. All subjects underwent non-invasive assessment of cardiac function by two-dimensional Doppler echocardiography. Calcium, phosphate, and creatinine were determined in the serum and urine, along with alkaline phosphatase and hydroxyproline excretion, two biochemical parameters of PD activity. RESULTS: Peripheral vascular resistance proved lower (1604.9 +/- 390.1 vs 1801.2 +/- 421.0) and the stroke volume higher in PD patients (67.2 +/- 14.4 vs 56.0 +/- 8.6; p = 0.07) compared with controls. These differences were greater (1504.7 +/- 289.9 and 71.0 +/- 6.2) and attained statistical significance (p = 0.008) when the subgroup with more extensive skeletal disease only was considered. A moderate correlation was observed between hydroxyproline excretion and the E/A ratio (r = 0.45; p = 0.03), peripheral vascular resistance (r = -0.42; p = 0.04), and diastolic arterial pressure (r = -0.42; p = 0.04). The final model obtained via multivariate analysis identified both urinary hydroxyproline and age as predictive variables linked to peripheral vascular resistance. CONCLUSION: In the early phases of PD there is a trend towards a reduction in peripheral vascular resistance. If this persists, it may lead progressively to increased cardiac output, which is mainly influenced by the degree of turnover impairment and the age of the individual.

Basal and stimulated gastrin and pepsinogen levels after eradication of Helicobacter pylori: a 1-year follow-up study.

AIM: A decrease in gastrin and pepsinogen (PG) levels 1 month after Helicobacter pylori eradication has been described repeatedly, but the long-term progression of such a decrease has been scarcely studied. We therefore studied the effect of H. pylori eradication on basal and stimulated gastrin and PG levels for 1 year. Initially, the usefulness of measuring these parameters for the noninvasive diagnosis of H. pylori eradication was validated. Furthermore, an assessment was made of the association between H. pylori reinfection and a re-increase in gastrin and PG values. Finally, an evaluation was made of the variables influencing gastrin and PG concentration, with particular attention to H. pylori infection and histological lesions of gastric mucosa. METHODS: Two-hundred and twenty-two patients with duodenal ulcer were studied prospectively. Exclusion criteria were the administration of antibiotics, H2 antagonists, omeprazole or bismuth prior to endoscopy. In all patients serum basal levels of gastrin, PGI, and PGII were measured before and 1 month after completing eradication therapy. In the successfully eradicated patients, gastrin, PGI, and PGII were also measured at 6 and 12 months. In 80 patients stimulated measurements of gastrin (after ingestion of two beef cubes) and PGI (after injection of pentagastrin) were also performed. H. pylori-negative patients after therapy underwent a urea breath test at 6 and 12 months, and patients who had stimulated gastrin and PG concentration measured had also an endoscopy performed at 6 months. RESULTS: H. pylori was eradicated in 73% of patients. A histological improvement was observed 1 month after completing H. pylori eradication therapy, both at gastric antrum and body (P < 0.001), while a further improvement at antrum was demonstrated at 6 months (P < 0.01). With regard to the different cut-off points for decreased basal and stimulated measurements for diagnosing H. pylori eradication, the best results were obtained, respectively, with PGII (sensitivity of 90% and specificity of 76%) and PGI 30 min after stimulation (sensitivity and specificity of 82%), with an area under the ROC curve of 0.87 in both cases. In the multiple regressions analysis H. pylori status correlated with gastrin, PGI and PGII after therapy (P < 0.001), while histological lesions correlated only with gastrin levels (P < 0.05). A decrease in basal and stimulated serum parameters was demonstrated immediately after eradication (Wilcoxon test, P < 0.001), and an additional decrease (at 6 months) was observed just in PGI (Friedman test, P < 0.01). However, gastrin and PGII values remained unchanged after the first month post-eradication. Seven patients were reinfected with H. pylori during follow-up. Quantitation of basal and stimulated gastrin and PGI levels was not reliable as a reinfection marker. Regarding basal PGII, the parallelism was strong at 6 months (re-increase in all four reinfected patients), although only in one out of three with reinfection at 1 year did PGII rise at that stage. CONCLUSIONS: (1) Measurement of gastrin and PG levels (especially basal PGII values) is a useful non-invasive method to confirm H. pylori eradication after therapy. (2) H. pylori eradication is associated with a significant decrease in basal and stimulated gastrin levels and in basal PGII levels that is detected immediately (1 month) after finishing treatment, and remains unchanged for 1 year. However, the decrease in basal and stimulated PGI levels occurs progressively for 6 months, although such levels remain also unchanged afterwards. (3) Measurement of gastrin and PGI concentrations has a limited usefulness in the diagnosis of H. pylori reinfections after successful eradication, although PGII determination could be more useful in this situation.

Local and remote sustained trigger point therapy for exacerbations of chronic low back pain. A randomized, double-blind, controlled, multicenter trial.

STUDY DESIGN: A randomized, double-blind, controlled, multicenter trial was conducted. OBJECTIVES: To assess the efficacy of neuroreflexotherapy in the management of low back pain. SUMMARY AND BACKGROUND DATA: Neuroreflexotherapy consists of temporary implantation of epidermal devices in trigger points in the back and referred tender points in the ear. METHODS: The rheumatology and rehabilitation departments of three teaching hospitals in Madrid recruited 78 patients with chronic low back pain. These patients were randomly assigned to the control group (37 patients) or to the treatment group (41 patients). Patients in the treatment group underwent one neuroreflexotherapeutic intervention. The control group received sham treatment consisting of placement of the same number of epidermal devices within a 5-cm radius of the target zones. Patients from both groups were allowed to continue drug treatment as previously prescribed. The use of medications during the trial was recorded. RESULTS: Patients underwent clinical evaluations on three occasions: within 5 minutes before intervention, within 5 minutes after intervention, and 45 days later. The preintervention assessment was carried out by the physician from each hospital department who included the patient in the study. Each of the two follow-up assessments were carried out independently by two of three physicians who had no connection with the research team. Patients in the treatment group showed immediate lessening of pain compared with the results in patients in the control group. The pain relief was clinically relevant and statistically significant, and it persisted up to the end of the trial. CONCLUSIONS: Neuroreflexotherapy intervention seems to be a simple and effective treatment for rapid amelioration of pain episodes in patients with chronic low back pain. At this time, the duration of pain relief beyond 45 days has not been evaluated.