Estimating the Total Mortality Among Problem Drug Users

This paper's objective is to develop a method to estimate the total mortality among problem drug users. The total mortality is given by a base rate of mortality not related to drugs and the deaths that are directly and indirectly related to drugs. A fatal poisoning by drugs (overdose) is directly related to drugs, whereas a casualty due to a drug-related disease or a drug-related accident is indirectly related to drugs. As an example of a method to estimate the total mortality, the results from a cohort study among methadone patients in Amsterdam were projected on the whole population of problem drug users in The Netherlands. Due to differences between the problem drug users in Amsterdam and the rest of the country, adjustments were required. It was found that an initial estimation did not require adjustment for injection behavior and gender but did require adjustment for age and the percentage of HIV infection. In a first unadjusted estimation, the total number of deaths among problem drug users in The Netherlands in 2001 was estimated at 606 deaths. After adjustment for age, the estimated mortality decreased to 573 deaths, and after adjustment for HIV infection, this estimation again decreased to 479 deaths. From the ultimately estimated mortality, 11% was considered to be not related to drugs, 23% was attributed directly to drugs, and 66% was attributed indirectly to drugs. The number of direct deaths, as estimated by this method, falls in the same order of magnitude as the number extracted from the Causes of Death Statistics, when selecting cases according to the Drug-Related Deaths Standard as established by the European Monitoring Centre for Drugs and Drug Addiction (EMCDDA). Further cross-validation with other measures will be needed to assess the accuracy of the method, the limitations of which are discussed with respect to stipulating directions for future research.     

Maximal external electrical stimulation for treatment of neurogenic or non-neurogenic urgency and/or urge incontinence

Maximal electrical stimulation by intravaginal or intra-anal electrodes was used for treatment of 75 patients with complaints of urgency and/or urge incontinence. The patient group consisted of 51 women and 24 men. A neurogenic background was present in 30 of the women who had a diagnosis of multiple sclerosis, in the other 45 patients the pathology was idiopathic in nature. After 3 weeks of maximal electrical stimulation treatment, composed of 15 sessions of 20 minutes duration, 59% of the patients had urodynamic and subjective improvement and an additional 40% only subjective improvement. One patient found no benefit after this treatment. The effect lasted for at least 2 years in 64% of the idiopathic group. In the multiple sclerosis group relapse occurred within about 2 months. Re-treatment of the failures was successful again immediately; the multiple sclerosis patients do need daily home stimulation treatments. © 1996 Wiley-Liss, Inc.     

Elevated blood pressure and self-reported symptom complaints, daily hassles, and defensiveness

The association between elevated blood pressure and low rates of self-reported problems has been hypothesized to be mediated by defensiveness. In a population screening study in which 1,120 women and 903 men between 20 and 55 years of age participated, multiple resting home blood pressure measurements were performed and questionnaires were administered measuring symptom complaints, daily hassles, and defensiveness. In women, after control for potential confounders, a low number of self-reported symptoms was associated with elevated blood pressure. However, this effect was not mediated by defensiveness, although repressive defensiveness predicted independently elevated blood pressure in women. In men, no significant associations were obtained. Furthermore, no relations emerged between daily hassles and elevated blood pressure. In conclusion, although defensiveness was more prevalent among women with elevated blood pressure, it does not provide a good explanation for the low rates of self-reported symptoms found in these women.     

Marker chromosome identification by micro-FISH

Micro-FISH was used to elucidate the chromosomal origin of marker chromosomes in three patients. Ten copies of marker chromosomes were collected with microneedles from GTG banded metaphases, transferred to a collecting drop and amplified by means of DOP-PCR. The PCR products were labeled with biotin-14-dATP and used as FISH probes for hybridization to normal metaphase chromosomes and to metaphase chromosomes of the patients (reverse painting). With the generation of chromosome region-specific painting probes by PCR amplification of microdissected DNA and subsequent FISH it was possible to identify the marker chromosomes in all patients. One marker appeared to be derived from the centromere region of the X-chromosome and the proximal third of the long arm, one from the centromere region of chromosome 17 and one marker chromosome was identified as an isochromosome 18p.     

Oral bioavailability of phenobarbital: a comparison of a solution in myvacet 9‐08, a suspension, and a tablet

Purpose: A threeway crossover study with seven healthy male volunteers was conducted to determine the relative bioavailability of phenobarbital after single dose administration of 100 mg of phenobarbital as oral solution in Myvacet 908, and as a suspension, compared with a 100 mg phenobarbital tablet. Materials and methods: At 4week intervals each subject received the solution in Myvacet 908, the suspension and the tablet in randomized order. Blood samples were collected for 48 h after each dose for analysis of phenobarbital. From the individual serum concentrationversustime curves C _maxand T _max were determined and AUC₀₄₈ was calculated. Results: All three oral dosage forms of phenobarbital are bioequivalent. No significant diffences in T _maxwere observed. Conclusion: The oral solution in Myvacet 908, and the suspension of phenobarbital proved to be bioequivalent to a tablet.     

Herd immunity to Newcastle disease virus in poultry by vaccination.

Newcastle disease is an economically important disease of poultry for which vaccination is applied as a preventive measure in many countries. Nevertheless, outbreaks have been reported in vaccinated populations. This suggests that either the vaccination coverage level is too low or that vaccination does not provide perfect immunity, allowing the virus to spread in partially vaccinated populations. Here we study the requirements of an epidemiologically effective vaccination program against Newcastle disease in poultry, based on data from experimental transmission studies. The transmission studies indicate that vaccinated birds with low or undetectable antibody titres may be protected against disease and mortality but that infection and transmission may still occur. In fact, our quantitative analyses show that Newcastle disease virus is highly transmissible in poultry with low antibody titres. As a consequence, herd immunity can only be achieved if a high proportion of birds (>85%) have a high antibody titre (log(2) haemagglutination inhibition titre > or =3) after vaccination. We discuss the implications for the control of Newcastle disease in poultry by vaccination.     

Prognosis of Limitations in Activities in Osteoarthritis of the Hip or Knee: A 3-Year Cohort Study

van Dijk GM, Veenhof C, Spreeuwenberg P, Coene N, Burger BJ, van Schaardenburg D, van den Ende CH, Lankhorst GJ, Dekker J, on behalf of the CARPA Study Group. Prognosis of limitations in activities in osteoarthritis of the hip or knee: a 3-year cohort study.

Objective

To describe the course of limitations in activities in elderly patients with osteoarthritis (OA) of the hip or knee over a follow-up period of 3 years, and to identify prognostic factors of the course of limitations in activities, focusing on body functions, comorbidity, and cognitive functioning.

Design

A longitudinal cohort study with 3 years of follow-up. Measurements were conducted annually. Statistical analyses included t tests, univariate regression analyses, and multivariate regression analyses.

Setting

Rehabilitation centers and hospitals (Departments of Orthopedics, Rheumatology, and Rehabilitation) in The Netherlands.

Participants

Patients (N=237) with hip or knee OA.

Interventions

Not applicable.

Main Outcome Measures

Patient-perceived change, self-reported limitations in activities measured by the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), and observed limitations in activities (timed walking test). Prognostic factors: demographic data, clinical data, body function (pain, muscle strength, range of motion [ROM]), comorbidity, and cognitive functioning (cognitive decline, memory, attention).

Results

Self-reported limitations in activities measured by the WOMAC improved slightly after 3-year follow-up. In knee OA, reduced ROM at 1-year follow-up (β=.120), increased pain at 1-year follow-up (β=−.177), and higher morbidity count (β=−.180) predicted worsening of self-reported limitations in activities. In hip OA, reduced ROM at 1-year follow-up (β=.201 for hip external rotation and β=.144 for knee extension), increased pain at 1-year follow-up (β=−.134), higher morbidity count (β=−.220), or the presence of moderate to severe cardiac disease (β=−.214) and poorer cognitive functioning (β=.181) predicted worsening of self-reported limitations in activities. Performance-based limitations in activities measured by the timed walking test did not change after 3 years of follow-up. In knee OA, decreased muscle strength at 1-year follow-up (β=−.272) and higher morbidity count (β=.199) predicted worsening of performance-based limitations in activities. In hip OA, better ROM (β=.182), higher morbidity count (β=.232), or the presence of moderate to severe cardiac and eye-ear-nose-throat disease (β=.210 and β=.188, respectively) and older age (β=.355) predicted worsening of performance-based limitations in activities.

Conclusions

Overall, at the group level, limitations in activities of patients with OA of the hip or knee recruited from hospitals and rehabilitation centers seem fairly stable during the first 3 years of follow-up. However, at the level of individual patients, considerable variation occurs. Prognostic factors for worsening of limitations in activities include increased pain, reduced ROM, and decreased muscle strength at 1-year follow-up; higher morbidity count; and to a lesser extent poor cognitive functioning.     

Predictors of depressive symptoms 12 months after surgical treatment of early‐stage breast cancer

Objective: Nearly half of the women with breast cancer (BC) show depressive symptoms in the first year after diagnosis. This has a major impact on patients' lives. Therefore, the aim of this study was to identify predictors of depressive symptoms 12 months after surgical treatment. Furthermore, the stability of depressive symptoms across 12 months was investigated for persons scoring high versus low/moderately on agreeableness, trait anxiety, and neuroticism. Methods: From the 609 women with an abnormality in the breast, 223 appeared to have early‐stage BC. A depressive symptoms questionnaire (Center for Epidemiological Studies—Depression Scale) was completed before diagnosis and 1, 3, 6, and 12 months after surgical treatment. In addition, patients completed questionnaires on personality (State Trait Anxiety Inventory, Neuroticism‐Extraversion‐Openness‐Five Factor Inventory), fatigue (Fatigue Assessment Scale), and aspects of quality of life (World Health Organization Quality of Life assessment instrument—100). Results: Before diagnosis and 1 year later, 40.9% and 27.8% of the women, respectively, scored above the established cut‐off score for depressive symptoms. Depressive symptoms significantly improved in this period. Patients reported higher scores, when they had a breast‐conserving therapy (BCT), scored low on agreeableness, scored high on neuroticism, or reported higher scores on depressive symptoms or fatigue before diagnosis. Other clinical and socio‐demographic factors did not predict depressive symptoms. Conclusions: Besides BCT, fatigue, and depressive symptoms, personality, especially neuroticism and agreeableness, predicted depressive symptoms 1 year after surgical treatment. Therefore, it is important to screen patients on these characteristics in order to prevent long‐term depressive symptoms. Copyright © 2009 John Wiley & Sons, Ltd.     

Dendritic cells are crucial for maintenance of tertiary lymphoid structures in the lung of influenza virus–infected mice

Tertiary lymphoid organs (TLOs) are organized aggregates of B and T cells formed in postembryonic life in response to chronic immune responses to infectious agents or self-antigens. Although CD11c⁺ dendritic cells (DCs) are consistently found in regions of TLO, their contribution to TLO organization has not been studied in detail. We found that CD11c^hi DCs are essential for the maintenance of inducible bronchus-associated lymphoid tissue (iBALT), a form of TLO induced in the lungs after influenza virus infection. Elimination of DCs after the virus had been cleared from the lung resulted in iBALT disintegration and reduction in germinal center (GC) reactions, which led to significantly reduced numbers of class-switched plasma cells in the lung and bone marrow and reduction in protective antiviral serum immunoglobulins. Mechanistically, DCs isolated from the lungs of mice with iBALT no longer presented viral antigens to T cells but were a source of lymphotoxin (LT) β and homeostatic chemokines (CXCL-12 and -13 and CCL-19 and -21) known to contribute to TLO organization. Like depletion of DCs, blockade of LTβ receptor signaling after virus clearance led to disintegration of iBALT and GC reactions. Together, our data reveal a previously unappreciated function of lung DCs in iBALT homeostasis and humoral immunity to influenza virus.The organized accumulation of lymphocytes in lymphoid organs serves to optimize both homeostatic immune surveillance and chronic responses to pathogenic stimuli (Cupedo and Mebius, 2005). During embryonic development, circulating hemopoietic cells gather at predestined sites throughout the body, where they are subsequently arranged in T and B cell–specific areas, which is characteristic of secondary lymphoid organs (SLOs). In contrast, the body seems to harbor a limited second set of selected sites that support neoformation of organized lymphoid aggregates in adult life. However, these are only revealed at times of local chronic inflammation when so-called tertiary lymphoid organs (TLOs) appear. As such, TLO was found in the pancreas of autoimmune diabetic mice (Kendall et al., 2007), around blood vessels in chronic allograft rejection (Nasr et al., 2007) and atherosclerosis (Gräbner et al., 2009), and in the brain in experimental allergic encephalitis (Magliozzi et al., 2004). In humans, TLO has been observed in the joint and lung of rheumatoid arthritis (Rangel-Moreno et al., 2006), around the airways of COPD patients (Hogg et al., 2004), and in the thyroid (Marinkovic et al., 2006). Certain infectious diseases are also accompanied by formation of TLO. Influenza virus infection of the respiratory tract leads to formation of inducible bronchus-associated lymphoid tissue (iBALT) that supports T and B cell proliferation and productive immunoglobulin class switching in germinal centers (GCs; Moyron-Quiroz et al., 2004, 2006).Although the embryonic development of SLO requires CD3⁻CD4⁺ lymphoid tissue–inducer cells, these are not a prerequisite for TLO induction (Marinkovic et al., 2006; Rangel-Moreno et al., 2007). Like SLOs, TLOs are formed in a highly regulated manner via production of homeostatic chemokines (CXCL13 and CCL19/CCL21), partially in response to signaling from the heterotrimer lymphotoxin (LT) α₁β₂ acting on the LTβ receptor on stromal lymphoid tissue organizer cells (Drayton et al., 2006). The instruction of stromal cells leads to formation of specialized high endothelial venules, and the organized production of chemokines leads to cellular organization of T cells and B cells in discrete areas. In all instances where TLOs have been described, antigen-presenting DCs have been found interspersed with T and B cell area, just as they are in SLO (Kratz et al., 1996; Cupedo et al., 2004; Moyron-Quiroz et al., 2004; Marinkovic et al., 2006; Tsuji et al., 2008). So far, the precise role of DCs in the functional organization of TLO has not been studied in great detail. Although DCs are mainly known for their function as antigen-presenting cells (Banchereau and Steinman, 1998), they are also a prominent source of homeostatic and inflammatory chemokines that can attract T and B cells and, thus, may contribute to TLO homeostasis (Beaty et al., 2007; GeurtsvanKessel and Lambrecht, 2008). In this paper, we have studied the precise contribution of DCs in the functional organization of iBALT, a specific form of TLO found in the lung after influenza virus infection (Moyron-Quiroz et al., 2004; Kocks et al., 2007).