On the normativity of evidence - Lessons from philosophy of science and the "VALIDATE" project.

"Evidence" is a key term in medicine and health services research, including Health Technology Assessment (HTA). Randomized clinical trials (RCTs) have undoubtedly dominated the scene of generating evidence for a long period of time, becoming the hallmark of evidence-based medicine (EBM). However, due to a number of misunderstandings, the lay audience and some researchers have sometimes placed too much trust in RCTs compared to other methods of investigation. One of the principal misunderstandings is to consider RCTs findings as isolated and self-apparent pieces of information. In other words, what has been essentially lacking was the awareness of the value-context of the evidence and, in particular, the value- and theory-ladenness (normativity) of scientific knowledge. This paper aims to emphasize the normativity that exists in the production of scientific knowledge, and in particular in the conduct of RCTs as well as in the performance of HTA. The work is based on some lessons learned from Philosophy of Science and the European project "VALIDATE" (VALues In Doing Assessments of healthcare TEchnologies"). VALIDATE was a three-year EU Erasmus+ strategic partnerships project (2018-2021), in which training in the field of HTA was further optimized by using insights from political science and ethics (in accordance with the recent definition of HTA). Our analysis may reveal useful insights for addressing some challenges that HTA is going to face in the future.

DNA fingerprints from Mycobacterium tuberculosis isolates of patients confined for therapy noncompliance show frequent clustering.

STUDY OBJECTIVE: To test the hypothesis that individuals chronically noncompliant with antituberculous chemotherapy are vectors for ongoing transmission of the disease in the community. DESIGN: Cohort study. SETTING: A large public hospital with a tuberculosis detention unit for patients with repeated and prolonged nonadherence to therapy. PATIENTS: Mycobacterium tuberculosis isolates from patients confined on the detention unit were obtained from the hospital's mycobacteriology laboratory. INTERVENTIONS: None. MEASUREMENTS AND RESULTS: A standardized IS6110-based Southern blot hybridization protocol was used to genotype M tuberculosis isolates recovered from patients confined on the detention unit at the hospital. Each DNA fingerprint pattern was compared with the IS6110-fingerprint database at the Public Health Research Institute Tuberculosis Center, which has archived fingerprint patterns from over 2,500 M tuberculosis isolates collected from New York City patients in the past 5 years. Eighty percent of available isolates from detained patients belonged to an identifiable DNA fingerprint cluster, suggesting an epidemiologic link between the detainees and other New York City tuberculosis patients. CONCLUSIONS: Chronic noncompliance with therapy is associated with ongoing spread of tuberculosis in the community. Aggressive measures, including detention, for the small number of recalcitrant, noncompliant patients may interrupt a chain of transmission and contribute to a decline in the spread of tuberculosis in urban areas.

Prerequisites required for the provision and use of web-based communication for psychosocial support in haematologic care.

PURPOSE: The purpose of this study was to describe the prerequisites required for the provision and use of web-based communication for psychosocial support within a haematology clinic, from a patient and family perspective. METHOD: A qualitative design using content analysis was used. A strategically selected sample of patients (n = 11) and family members (n = 6) were offered access to a web-based communication capability with a nurse. After four months, individual interviews were conducted with all participants, in order to identify necessary prerequisites. RESULTS: Preferences and characteristics of the individual patient or family member are crucial as to whether web-based communication for support is perceived as useful. To feel comfortable with writing and to self-identify the need for support are fundamental in getting motivated to use web-based communication. An effective organization around psychosocial support in general is another prerequisite. Goals and responsibilities must be clearly defined for patients and family members to understand their rights and enable the transformation of opportunities into practice. The use of web-based communication must also be a convenient and naturally incorporated part of both individual and organizational use of the web in general. CONCLUSIONS: Prerequisites of taking into account caretakers' different preferences and needs, providing highly structured psychosocial support activities and providing a congruent range of web services, are necessary for successful provision and use of web-based communication for psychosocial support.

Inactivated hepatitis A vaccine: a safety and immunogenicity study in health professionals.

The safety and immunogenicity of an inactivated hepatitis A vaccine (HM175) were evaluated in 151 seronegative health professionals (age range, 21-65 years; mean, 30). A 720-ELISA unit dose was administered to 78 vaccinees at 0, 1, and 6 months and to 73 vaccinees at 0, 1, and 12 months. Seroconversion rates were 90% in both groups 1 month after the first inoculation and 99% and 100%, respectively, 1 month after the second inoculation. Geometric mean antibody titers (GMTs) 1 month after the third inoculation were highest in the group vaccinated at 0, 1, and 12 months. GMTs were higher in women than in men. The vaccine was well tolerated; the most frequent side effect was transient soreness at the site of inoculation. No serious adverse reactions were observed. Thus, HM175 inactivated hepatitis A vaccine is safe and highly immunogenic.

Inactivated hepatitis A vaccine: a safety and immunogenicity study in health professionals.

The safety and immunogenicity of an inactivated hepatitis A vaccine (HM175 strain) were evaluated in 150 seronegative health professionals. The age range was 21-65 years and the mean age was 30 years. The vaccine was administered at a dose of 720 ELISA units (EU) to 73 vaccinees at 0, 1 and 6 months, and to 77 vaccinees at 0, 1 and 12 months. The seroconversion rates were 88 and 90% in the two groups, respectively, one month after the first inoculation and 99 and 100% one month after the second inoculation. The geometric mean antibody titres were similar in both groups, exceeding 3000 mIU/ml one month after the third inoculation. The vaccine was well tolerated. The most frequent side effect was transient soreness at the site of the inoculation. No serious adverse reactions were observed. The study demonstrated that the HM175 inactivated hepatitis A vaccine was safe and highly immunogenic.

Risk factors for rifampin-monoresistant tuberculosis: A case-control study.

Rifampin is the cornerstone of short-course chemotherapy for the treatment of tuberculosis (TB). Rifampin monoresistance (RMR) is less common than resistance to isoniazid alone or in combination with other antituberculous medications. We conducted a retrospective case-control study to identify risk factors for RMR-TB. Complete records for 21 of a total of 26 RMR patients from 1990 to 1997 were available for review, and were compared with those of 48 patients with drug-susceptible TB, controlling for year of diagnosis. Cases more frequently had a history of TB than did controls (61% versus 22%, p < 0.01), and were more often human immunodeficiency virus (HIV) positive (81% versus 46%, p = 0.02). With control for HIV status, cases were more likely to have extrapulmonary involvement (47.6% versus 11.6%, p = 0.05). Four cases (19%) and one control (2. 1%) died (p = 0.02) during hospitalization. Cases more often had a history of incarceration (71.4% versus 37.5%, p = 0.09). Among the 13 cases with a history of TB, five had evidence of malabsorption (vomiting and/or diarrhea), versus none of the 11 controls with prior TB. These data support the hypothesis that RMR is seen primarily in individuals with a history of TB and who are HIV positive. Cases were frequently noncompliant with previous treatment for TB, had a history of incarceration, and had poor outcomes.

Effect of age on the immunogenicity of yeast recombinant hepatitis B vaccines containing surface antigen (S) or PreS2 + S antigens.

A single-blind, multicenter, phase II trial of yeast recombinant hepatitis B virus (HBV) vaccines containing surface antigen (S) alone or with PreS2 (PreS2 + S) was conducted in 282 healthy HBV-seronegative adults aged 20-59 years. Each volunteer was randomly assigned to receive HBV vaccine containing 10 micrograms of S or one of three doses of PreS2 plus S: 2 + 10 micrograms, 4 + 20 micrograms, or 8 + 40 micrograms. The level of antibody to HBV surface antigen reached depended on the dose of S, not PreS2, received. In each vaccine group, volunteers 20-39 years old had higher titers of anti-PreS2 and antibody to S than those 40-59 years old. The age-related effect on immune response to HBV vaccination suggests that adults should be immunized against hepatitis B at as early an age as possible and that older persons may need a higher dose or booster immunizations to achieve durable immunity.