Evidence-based medicine: benefits, inconveniences and risks of a new dogma

Progress in biostatistics and epidemiology during twentieth century contributed to clinical research development. Controversy about the real role of these disciplines in validating clinical activity isn't new: in history of medicine there are evidence since nineteenth century. Evidence-based medicine is a recent methodology to evaluate clinical investigation that begins to be considered gold standard in knowledge and medical practice evaluation. Its method is based mainly in systematized meta-analyses or revisions through which tries to offer answers to concrete clinical questions. These answers are, however, clearly of statistical nature. It is not useful in clinical practice but rather should be focused to teaching-learning process, as well as on the creation of work regulations. Its application implies certain benefits, but also several practical difficulties in cultural, academic and socio-economic fields, due to its use without discriminating. Thus, its correct use is a challenge to contemporary medicine.     

Abortion in democratic Spain: the parliamentary political agenda 1979-2004

Since Spain's transition to democracy, abortion has been a public policy issue both inside and outside parliament. This paper describes the history of abortion law reform in Spain from 1979 to 2004 and analyses the discourse on abortion of members of the Spanish parliament by sex and political allegiance. The analysis is based on a retrospective study of the frequency of legislative initiatives and the prevalence of different arguments and positions in debates on abortion found through a systematic search of the parliamentary database. Little time was given to abortion in the parliamentary agenda compared to other women's issues such as violence against women. There were 229 bills and other parliamentary initiatives in that period, 60% initiated and led by pro-choice women. 143 female and 72 male parliamentarians took part in the debates. The inclusion of socio-economic grounds for legal abortion (64%), and making abortion on request legal in the first 12 weeks of pregnancy (60%) were the most frequent forms of law reform proposed, based most often on pro-women's rights arguments. Male and female members of anti-choice parties and most male members of other parties argued for fetal rights. Pro-choice parties tabled more bills than anti-choice parties but till now all reforms proposed since 1985 have been voted down.     

STUDIES ON TYPHUS FEVER : VII. ACTIVE IMMUNIZATION AGAINST MEXICAN TYPHUS FEVER WITH DEAD VIRUS

Guinea pigs can be immunized against Mexican typhus virus by peritoneal injections of formalinized Rickettsia material, provided sufficient amounts of the organisms are used. Our results in this respect are analogous to those of Spencer and Parker with carbolized virus of Rocky Mountain spotted fever. The Rickettsia suspensions appear to possess considerable toxicity. We do not wish to be misunderstood as implying that the results in guinea pigs offer anything more than a demonstration of the principle of active immunization with killed Rickettsiae. Application to man will have to be worked out, and preliminary to this, we are now attempting to apply the methods to a limited number of monkeys.     

STUDIES ON TYPHUS FEVER : III. STUDIES OF LICE AND BEDBUGS (CIMEX LECTULARIUS) WITH MEXICAN TYPHUS FEVER VIRUS

Our experiments have shown that the Mooser bodies or Rickettsiae derived from guinea pigs with Mexican typhus fever can survive in bedbugs after intra-coelomic injection for 10 days, remaining capable of infection. We have also succeeded in similarly infecting bedbugs by allowing them to feed on benzolized rats in whose blood Rickettsiae had been shown to be present. Injection of the organs of such bedbugs 5 days after the last, 9 days after the first infectious feeding into guinea pigs produced typical Mexican typhus fever. Some of the guinea pigs infected with such bedbug organs and passing through a typical typhus proved to be immune to subsequent inoculation with the European disease. Attempts to infect normal guinea pigs by allowing infected bedbugs to feed on them or by rubbing the feces into the uninjured skin have, so far, been unsuccessful. We have not, therefore, completed the cycle proving that bedbugs can transmit the disease, but we have shown that this is a possibility when dealing with man, obviously more susceptible to the disease than any of our experimental animals. The ease with which the Rickettsiae seem to survive in the bedbugs suggests the desirability of investigating other common insects for a similar capacity of harboring the typhus Rickettsiae-experiments which we have not yet had the time to carry out.     

THE ANTIGENIC RELATIONSHIP BETWEEN PROTEUS X-19 AND TYPHUS RICKETTSIAE : A STUDY OF THE WEIL-FELIX REACTION

1. The absorption of typhus sera (human or antityphus horse serum) with Proteus X-19 removes only the Proteus agglutinins, leaving the Rickettsia agglutinins intact. 2. The absorption of typhus sera with Mexican Rickettsiae removes the agglutinins for both the Rickettsia and Proteus X-19. 3. While normal or formalinized Rickettsiae are not agglutinated by anti-Proteus serum, these organisms—when formalinized and heated at 75°C.—become agglutinable by such serum. 4. The absorption of anti-Proteus serum with Mexican Rickettsiae removes agglutinins for formalinized and heated Rickettsiae but does not affect those for Proteus X-19.     

THE MULTIPLICATION OF THE VIRUS OF MEXICAN TYPHUS FEVER IN FLEAS

The virus of Mexican typhus has been shown to multiply abundantly in the following species of fleas: Xenopsylla cheopis, Ceratophyllus fasciatus, Leptopsylla musculi, Ctenocephalus canis, Ctenocephalus felis. In all fleas, Rickettsia prowazeki was demonstrated within the epithelial cells of the stomach and within the cells of the Malpighian tubules. Whereas in infected lice enormous numbers of these organisms are discharged from the disintegrating cells into the intestinal content, only few Rickettsiae are found in the lumen of the fleas'' intestines. They are held back by the peritrophic membrane, which covers the mucosa of the entire stomach. Rickettsiae seem to enter the lumen of the gut almost exclusively by the route of the Malpighian tubules. Observations were made which seem to indicate that the fleas recover from the infection and that they are able to regenerate the partly destroyed intestinal mucosa. An explanation is given for the relative harmlessness of fleas as vectors of typhus.     

Evaluation of the multimorbidity network and its relationship with clinical phenotypes in chronic obstructive pulmonary disease: The GALAXIA study

BackgroundChronic obstructive pulmonary disease (COPD) is a complex and heterogeneous condition, in which taking into consideration clinical phenotypes and multimorbidity is relevant to disease management. Network analysis, a procedure designed to study complex systems, allows to represent connections between the distinct features found in COPD.MethodsNetwork analysis was applied to a cohort of patients with COPD in order to explore the degree of connectivity between different diseases, taking into account the presence of two phenotypic traits commonly used to categorize patients in clinical practice: chronic bronchitis (CB⁺/CB⁻) and the history of previous severe exacerbations (Ex⁺/Ex⁻). The strength of association between diseases was quantified using the correlation coefficient Phi (ɸ).ResultsA total of 1726 patients were included, and 91 possible links between 14 diseases were established. Although the four phenotypically defined groups presented a similar underlying comorbidity pattern, with special relevance for cardiovascular diseases and/or risk factors, classifying patients according to the presence or absence of CB implied differences between groups in network density (mean ɸ: 0.098 in the CB⁻ group and 0.050 in the CB⁺ group). In contrast, between‐group differences in network density were small and of questionable significance when classifying patients according to prior exacerbation history (mean ɸ: 0.082 among Ex⁻ subjects and 0.072 in the Ex⁺ group). The degree of connectivity of any given disease with the rest of the network also varied depending on the selected phenotypic trait. The classification of patients according to the CB⁻/CB⁺ groups revealed significant differences between groups in the degree of conectivity between comorbidities. On the other side, grouping the patients according to the Ex⁻/Ex⁺ trait did not disclose differences in connectivity between network nodes (diseases).ConclusionsThe multimorbidity network of a patient with COPD differs according to the underlying clinical characteristics, suggesting that the connections linking comorbidities between them vary for different phenotypes and that the clinical heterogeneity of COPD could influence the expression of latent multimorbidity. Network analysis has the potential to delve into the interactions between COPD clinical traits and comorbidities and is a promising tool to investigate possible specific biological pathways that modulate multimorbidity patterns.