Using intervention time series analyses to assess the effects of imperfectly identifiable natural events: a general method and example

Background  

Intervention time series analysis (ITSA) is an important method for analysing the effect of sudden events on time series data. ITSA methods are quasi-experimental in nature and the validity of modelling with these methods depends upon assumptions about the timing of the intervention and the response of the process to it.     

A meta-analysis of the effect of HIV prevention interventions on the sex behaviors of drug users in the United States

We examined the effectiveness of 33 U.S.-based HIV intervention studies in reducing the sexual risk behaviors of drug users by reducing unprotected sex or increasing the use of male condoms. The studies, identified as of June 1998, through the HIV/AIDS Prevention Research Synthesis project, were published in 1988 or later, measured behavioral or biologic outcomes, used experimental designs or certain quasi-experimental designs, and reported sufficient data for calculating an effect size for sexual risk reduction. Of the 33 studies, 94% recruited injection drug users; 21% recruited crack users. The mean age of participants was 36 years. Almost all studies were randomized (94%), provided another HIV intervention to the comparison groups (91%), and evaluated behavioral interventions (91%). On average, interventions were conducted in 5 sessions (total, 10 hours) during 4.5 months. Interventions compared with no interventions were strong and significant (k = 3; odds ratio [OR], 0.60; 95% confidence interval [CI], 0.43-0.85). Interventions compared with other HIV interventions showed a modest additional benefit (k = 30; OR, 0.91; 95% CI, 0.81-1.03). When we extrapolated our result (an OR of 0.60) to a population with a 72% prevalence of risk behavior, the proportion of drug users who reduced their risk behaviors was 12.6% greater in the intervention groups than in the comparison groups. Our meta-analysis shows that interventions can lead to sexual risk reduction among drug users and justifies providing interventions to drug users. Developing interventions with stronger effects to further reduce sexual risk behaviors among drug users must remain a high priority.     

Persistent efficacy of topical eprinomectin against nematode parasites in cattle

Six studies were conducted to evaluate the persistent efficacy of eprinomectin pour-on against experimental challenges with infective nematode larvae in calves. In each study, calves were randomly assigned to one untreated group and up to four test groups, which were treated with eprinomectin at 500 μg/kg body weight at weekly intervals before single bolus challenge. The calves were necropsied approximately 4 weeks after challenge infection for nematode recovery. Eprinomectin pour-on provided ≥90% efficacy against challenge with Haemonchus placei, Trichostrongylus axei and T. colubriformis at 21 days after treatment and against Cooperia oncophora, C. punctata, C. surnabada, Dictyocaulus viviparus, Nematodirus helvetianus, Oesophagostomum radiatum and Ostertagia ostertagi at 28 days after treatment. Received: 14 April 2000 / Accepted: 18 May 2000     

Collaborations between allopathic and complementary and alternative medicine health professionals: four initiatives.

An effort to increase the understanding of complementary and alternative medicine (CAM) by health care professionals requires an interdisciplinary and collaborative approach. Between 2000 and 2002, National Institutes of Health National Center for Complementary and Alternative Medicine funded 15 educational institutions to develop curricular models for educating allopathic medical and nursing learners in CAM literacy. Four of these 15 programs, Tufts University School of Medicine, University of California at San Francisco School of Medicine, Oregon Health & Sciences University School of Medicine, and University of Washington School of Nursing, formed collaborative partnerships with nearby academic institutions that train CAM practitioners.This article focuses on these four examples of institutional collaboration, summarizing the challenges faced and the positive outcomes achieved for learners, faculty, and institutions. As collaborations between such institutions increase, future potential directions for consideration include credentialing of CAM practitioners teaching within allopathic health professional institutions, faculty development within existing allopathic health professional schools on incorporating evidence-based CAM content into their standard allopathic education, and viewing CAM as an aspect of cultural sensitivity.     

Translocation (6;9)(p23;q34) in acute nonlymphocytic leukemia: Three new cases

Several recent reports have described cases of acute nonlymphocytic leukemia with a unique chromosome translocation, t(6;9)(p23;q34). We have studied three additional patients who have acute nonlymphocytic leukemia and t(6;9)(p23;q34). Our findings provide additional support for the suggestion that this translocation is yet another distinct cytogenetic abnormality associated with myeloproliferative disorders.     

Local and systemic consequences of acute,low-dose ultraviolet B radiation are mediated by different immune regulatory mechanisms

Acute, low-dose ultraviolet B (UVB) radiation alters the local skin site such that epicutaneous application of hapten fails to induce contact hypersensitivity (CH), but induces tolerance in UVB-susceptible mice. Although the inability of irradiated skin to support CH induction may be a strictly local effect, there may also be systemic immune consequences of UVB radiation delivered in this manner. To examine this matter, abdominal skin of C57BL/6 mice was exposed to acute, low-dose UVB radiation. Dinitrofluorobenzene was immediately painted directly on the irradiated site, or at a distant (unirradiated) site. In separate experiments, epicutaneous application of the hapten on a distant site was delayed for 1–3 days. The mice were tested for acquisition of CH, and for tolerance, i.e. the capacity to become sensitized when exposed subsequently to hapten via normal body wall skin. It was found that, immediately after completion of the UVB regimen, CH was inducible via unirradiated, but not via irradiated, skin. At 3 days post-UVB exposure, CH was no longer inducible even through unirradiated skin. Mice that first encountered hapten via UVB-exposed skin developed tolerance, as did mice that first encountered hapten via unirradiated skin of UVB-treated mice. Neutralizing anti-tumor necrosis factor-α TNF-α antibodies failed (a) to restore the ability of unirradiated skin to support induction of CH, and (b) to interfere with tolerance induction, whether hapten was first painted on irradiated or unirradiates skin. The data indicate that the acute, low-dose regimen of UVB radiation produces effects on the immune system that are manifest locally as well as systemically. By demonstrating that the disruption of CH induction following UVB radiation is TNF-α dependent, whereas locally and systemically induced tolerance is not, our findings encourage further search for other UVB-related modulators of systemic immunity and tolerance.     

Changes in thymic export of L-selectin+ γδ and αβ T cells during fetal and postnatal development

We have used the technique of in situ intrathymic injection of fluorescein isothiocyanate to examine L-selectin expression on γδ and αβ T cells immediately after emigrating from the thymus of fetal and postnatal animals. We found that the percentage of L-selectin⁺ thymocytes exported per day decreased by half after birth and that the export of T cells from the thymus does not rely on expression of the peripheral lymph node homing receptor, L-selectin. Analysis of L-selectin on emigrant and mature T cell subsets revealed a remarkable heterogeneity of expression, both in terms of the numbers of cells expressing this molecule as well as the level of expression. γδ T cells, reportedly not having a propensity for homing to lymph nodes, not only contained the highest proportion of L-selectin⁺ cells, but also expressed far more of this molecule than either CD4⁺CD8^? or CD4^?CD8⁺ αβ T cells. Furthermore, those emigrant T cells expressing L-selectin are somewhat immature in their expression of this molecule. Subsequent maturation resulted in up-regulation of L-selectin on mature peripheral blood T cells, maturation that was clearly independent of extrinsic antigen. This antigen-independent post-thymic maturation appeared to occur as part of the normal progression from immature thymocyte to mature peripheral T cell in both fetal and postnatal animals.     

A canine model for reaginic hypersensitivity and allergic bronchoconstriction

Immunization of neonatal dogs with a conjugate of 2,4-dinitrobenzene and ovalbumin (DNP₂-OA), using aluminum hydroxide as the adjuvant, elicited long-lasting (over 30 wk) anti-DNP and anti-OA IgE antibody responses of high titers as determined by homologous passive cutaneous anaphylaxis. Low antigen doses of 10 or 50 μg were more effective than the higher doses of 250 or 1,250 μg in inducing high IgE antibody levels. However, this method of immunization failed to elicit any detectable IgE antibody response in adult dogs. Bronchoprovocation with antigen of sensitized animals having IgE antibody titers in excess of 64 resulted in a marked increase in airflow resistance, which could be corrected by the administration of nebulized isoproterenol. On the other hand, sensitized animals with IgE antibody titers in the order of 64 did not manifest significant bronchoconstriction on inhalation challenge but developed anaphylaxis following intravenous injection of the antigen.