Epidemiological Interactions between Urogenital and Intestinal Human Schistosomiasis in the Context of Praziquantel Treatment across Three West African Countries

© 2015 Knowles et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. The attached file is the published version of the article

Treatment of refractory epilepsy with natalizumab in a patient with multiple sclerosis. Case report

Background. Multiple sclerosis (MS) is considered an autoimmune disease of the central nervous system and therapeutic inhibition of leukocyte migration with natalizumab, an anti-alpha4 integrin antibody, is highly effective in patients with MS. Recent studies performed in experimental animal models with relevance to human disease suggested a key role for blood-brain barrier damage and leukocyte trafficking mechanisms also in the pathogenesis of epilepsy. In addition, vascular alterations and increased leukocyte accumulation into the brain were recently documented in patients with refractory epilepsy independently on the disease etiology. Case report. Here we describe the clinical course of a 24-year-old patient with MS in whom abrupt tonic-clonic generalized seizures manifested at disease onset. Although MS had a more favorable course, treatment with glatiramer acetate and antiepileptic drugs for 7 years had no control on seizure generation and the patient developed severe refractory epilepsy. Interestingly, generalized seizures preceded new MS relapses suggesting that seizure activity may contribute to MS worsening creating a positive feedback loop between the two disease conditions. Notably, treatment with natalizumab for 12 months improved MS condition and led to a dramatic reduction of seizures. Conclusion. Our case report suggests that inhibition of leukocyte adhesion may represent a new potential therapeutic approach in epilepsy and complement the traditional therapy with anti-epileptic drugs

Mechanism of Humoral and Cellular Immune Modulation Provided by Porcine Sertoli Cells

The understanding of main mechanisms that determine the ability of immune privilege related to Sertoli cells (SCs) will provide clues for promoting a local tolerogenic environment. In this study, we evaluated the property of humoral and cellular immune response modulation provided by porcine SCs. Porcine SCs were resistant to human antibody and complement-mediated formation of the membrane attack complex (38.41±2.77% vs. 55.02±5.44%, p=0.027) and cell lysis (42.95±1.75% vs. 87.99±2.25%, p<0.001) compared to immortalized aortic endothelial cells, suggesting that porcine SCs are able to escape cellular lysis associated with complement activation by producing one or more immunoprotective factors that may be capable of inhibiting membrane attack complex formation. On the other hand, porcine SCs and their culture supernatant suppressed the up-regulation of CD40 expression (p<0.05) on DCs in the presence of LPS stimulation. These novel findings, as we know, suggest that immune modulatory effects of porcine SCs in the presence of other antigen can be obtained from the first step of antigen presentation. These might open optimistic perspectives for the use of porcine SCs in tolerance induction eliminating the need for chronic immunosuppressive drugs

Physician Perception of Blood Pressure Control and Treatment Behavior in High-Risk Hypertensive Patients: A Cross-Sectional Study

Objective: We examined physician perception of blood pressure control and treatment behavior in patients with previous cardiovascular disease and uncontrolled hypertension as defined by European Guidelines. Methods: A cross-sectional study was conducted in which 321 primary care physicians throughout Spain consecutively studied 1,614 patients aged ≥18 years who had been diagnosed and treated for hypertension (blood pressure ≥140/90 mmHg), and had suffered a documented cardiovascular event. The mean value of three blood pressure measurements taken using standardized procedures was used for statistical analysis. Results: Mean blood pressure was 143.4/84.9 mmHg, and only 11.6% of these cardiovascular patients were controlled according to 2007 European Guidelines for Hypertension Management target of <130/80 mmHg. In 702 (49.2%) of the 1426 uncontrolled patients, antihypertensive medication was not changed, and in 480 (68.4%) of these cases this was due to the physicianś judgment that blood pressure was adequately controlled. In 320 (66.7%) of the latter patients, blood pressure was 130-139/80-89 mmHg. Blood pressure level was the main factor associated (inversely) with no change in treatment due to physician perception of adequate control, irrespective of sociodemographic and clinical factors. Conclusions: Physicians do not change antihypertensive treatment in many uncontrolled cardiovascular patients because they considered it unnecessary, especially when the BP values are only slightly above the guideline target. It is possible that the guidelines may be correct, but there is also the possibility that the care by the physicians is appropriate since BP <130/80 mmHg is hard to achieve, and recent reviews suggest there is insufficient evidence to support such a low BP targetFunding for this study was obtained from RECORDATI ESPAÑA, S.L through an unrestricted grant. Krista Lundelin has a ‘‘Rio Hortega’’ research training contract (Expediente CM10/00327) from the Ministry of Science and Innovation (Instituto de Salud Carlos III), Spain Governmen

Resident physician and hospital pharmacist familiarity with patient discharge medication costs

Objective Cost-related medication non-adherence is associated with increased health-care resource utilization and poor patient outcomes. Physicians-in-training generally receive little education regarding costs of prescribed therapy and may rely on hospital pharmacists for this information. However, little is documented regarding either of these health care providers’ familiarity with out-of pocket medication expenses borne by patients in the community. The purpose of this study was to evaluate and compare resident physician and hospital pharmacist familiarity with what patients pay for medications prescribed once discharged. Setting A major tertiary patient care and medical teaching centre in Canada. Method Internal medicine residents and hospital pharmacists within a specific health care organization were invited to participate in an online survey. Eight patient case scenarios and associated discharge therapeutic regimens were outlined and respondents asked to identify the costs patients would incur when having the prescription filled once discharged. Main Outcome Measure Total number and proportion of estimates above and below actual cost were calculated and compared between the groups using χ2 tests. Responses ±10% of the true cost were considered correct. Mean absolute values and standard deviation estimated costs, as well as cost increments above and below 10%, were calculated to assess the magnitude of the discrepancy between the respondent estimates and the actual total cost. Results Forty-four percent of physician residents and 26% of hospital pharmacists accessed the survey. Overall 39% and 47% of medication costs were under-estimated, 32% and 33% were overestimated, and 29% and 21% were correctly estimated by residents and pharmacists, respectively (P = NS). Incorrect estimates were evident across all therapeutic classes and medical indications presented in the survey. The greatest absolute cost discrepancy for both groups was under-estimation of linezolid ($800 and$400) and over-estimation of clopidogrel ($80) and bisoprolol therapy ($22) by residents and pharmacists, respectively. Conclusion Resident physicians and hospital pharmacists are unfamiliar with what patients must pay for drug therapy once discharged

Therapeutic Targeting of STAT3 (Signal Transducers and Activators of Transcription 3) Pathway Inhibits Experimental Autoimmune Uveitis

Mice with targeted deletion of STAT3 in CD4+ T-cells do not develop experimental autoimmune uveitis (EAU) or experimental autoimmune encephalomyelitis (EAE), in part, because they cannot generate pathogenic Th17 cells. In this study, we have used ORLL-NIH001, a small synthetic compound that inhibits transcriptional activity of STAT3, to ameliorate EAU, an animal model of human posterior uveitis. We show that by attenuating inflammatory properties of uveitogenic lymphocytes, ORLL-NIH001 inhibited the recruitment of inflammatory cells into the retina during EAU and prevented the massive destruction of the neuroretina caused by pro-inflammatory cytokines produced by the autoreactive lymphocytes. Decrease in disease severity observed in ORLL-NIH001-treated mice, correlated with the down-regulation of α4β1 and α4β7 integrin activation and marked reduction of CCR6 and CXCR3 expression, providing a mechanism by which ORLL-NIH001 mitigated EAU. Furthermore, we show that ORLL-NIH001 inhibited the expansion of human Th17 cells, underscoring its potential as a drug for the treatment of human uveitis. Two synthetic molecules that target the Th17 lineage transcription factors, RORγt and RORα, have recently been suggested as potential drugs for inhibiting Th17 development and treating CNS inflammatory diseases. However, inhibiting STAT3 pathways completely blocks Th17 development, as well as, prevents trafficking of inflammatory cells into CNS tissues, making STAT3 a more attractive therapeutic target. Thus, use of ORLL-NIH001 to target the STAT3 transcription factor, thereby antagonizing Th17 expansion and expression of proteins that mediate T cell chemotaxis, provides an attractive new therapeutic approach for treatment of posterior uveitis and other CNS autoimmune diseases mediated by Th17 cells

Interplay between CD8α+ Dendritic Cells and Monocytes in Response to Listeria monocytogenes Infection Attenuates T Cell Responses

During the course of a microbial infection, different antigen presenting cells (APCs) are exposed and contribute to the ensuing immune response. CD8α+ dendritic cells (DCs) are an important coordinator of early immune responses to the intracellular bacteria Listeria monocytogenes (Lm) and are crucial for CD8+ T cell immunity. In this study, we examine the contribution of different primary APCs to inducing immune responses against Lm. We find that CD8α+ DCs are the most susceptible to infection while plasmacytoid DCs are not infected. Moreover, CD8α+ DCs are the only DC subset capable of priming an immune response to Lm in vitro and are also the only APC studied that do so when transferred into β2 microglobulin deficient mice which lack endogenous cross-presentation. Upon infection, CD11b+ DCs primarily secrete low levels of TNFα while CD8α+ DCs secrete IL-12 p70. Infected monocytes secrete high levels of TNFα and IL-12p70, cytokines associated with activated inflammatory macrophages. Furthermore, co-culture of infected CD8α+ DCs and CD11b+ DCs with monocytes enhances production of IL-12 p70 and TNFα. However, the presence of monocytes in DC/T cell co-cultures attenuates T cell priming against Lm-derived antigens in vitro and in vivo. This suppressive activity of spleen-derived monocytes is mediated in part by both TNFα and inducible nitric oxide synthase (iNOS). Thus these monocytes enhance IL-12 production to Lm infection, but concurrently abrogate DC-mediated T cell priming

Variation in antibiotic treatment for diabetic patients with serious foot infections: A retrospective observational study

<p>Abstract</p> <p>Background</p> <p>Diabetic foot infections are common, serious, and diverse. There is uncertainty about optimal antibiotic treatment, and probably substantial variation in practice. Our aim was to document whether this is the case: A finding that would raise questions about the comparative cost-effectiveness of different regimens and also open the possibility of examining costs and outcomes to determine which should be preferred.</p> <p>Methods</p> <p>We used the Veterans Health Administration (VA) Diabetes Epidemiology Cohorts (DEpiC) database to conduct a retrospective observational study of hospitalized patients with diabetic foot infections. DEpiC contains computerized VA and Medicare patient-level data for VA patients with diabetes since 1998, including demographics, ICD-9-CM diagnostic codes, antibiotics prescribed, and VA facility. We identified all patients with ICD-9-CM codes for cellulitis/abscess of the foot and then sub-grouped them according to whether they had cellulitis/abscess plus codes for gangrene, osteomyelitis, skin ulcer, or none of these. For each facility, we determined: 1) The proportion of patients treated with an antibiotic and the initial route of administration; 2) The first antibiotic regimen prescribed for each patient, defined as treatment with the same antibiotic, or combination of antibiotics, for at least 5 continuous days; and 3) The antibacterial spectrum of the first regimen.</p> <p>Results</p> <p>We identified 3,792 patients with cellulitis/abscess of the foot either alone (16.4%), or with ulcer (32.6%), osteomyelitis (19.0%) or gangrene (32.0%). Antibiotics were prescribed for 98.9%. At least 5 continuous days of treatment with an unchanged regimen of one or more antibiotics was prescribed for 59.3%. The means and (ranges) across facilities of the three most common regimens were: 16.4%, (22.8%); 15.7%, (36.1%); and 10.8%, (50.5%). The range of variation across facilities proved substantially greater than that across the different categories of foot infection. We found similar variation in the spectrum of the antibiotic regimen.</p> <p>Conclusions</p> <p>The large variations in regimen appear to reflect differences in facility practice styles rather than case mix. It is unlikely that all regimens are equally cost-effective. Our methods make possible evaluation of many regimens across many facilities, and can be applied in further studies to determine which antibiotic regimens should be preferred.</p

A community-integrated home based depression intervention for older African Americans: descripton of the Beat the Blues randomized trial and intervention costs

ABSTRACT: BACKGROUND: Primary care is the principle setting for depression treatment; yet many older African Americans in the United States fail to report depressive symptoms or receive the recommended standard of care. Older African Americans are at high risk for depression due to elevated rates of chronic illness, disability and socioeconomic distress. There is an urgent need to develop and test new depression treatments that resonate with minority populations that are hard-to-reach and underserved and to evaluate their cost and cost-effectiveness. METHODS/DESIGN: Beat the Blues (BTB) is a single-blind parallel randomized trial to assess efficacy of a non-pharmacological intervention to reduce depressive symptoms and improve quality of life in 208 African Americans 55+ years old. It involves a collaboration with a senior center whose care management staff screen for depressive symptoms (telephone or in-person) using the Patient Health Questionnaire (PHQ-9). Individuals screened positive (PHQ-9 ≥ 5) on two separate occasions over 2 weeks are referred to local mental health resources and BTB. Interested and eligible participants who consent receive a baseline home interview and then are randomly assigned to receive BTB immediately or 4 months later (wait-list control). All participants are interviewed at 4 (main study endpoint) and 8 months at home by assessors masked to study assignment. Licensed senior center social workers trained in BTB meet with participants at home for up to 10 sessions over 4 months to assess care needs, make referrals/linkages, provide depression education, instruct in stress reduction techniques, and use behavioral activation to identify goals and steps to achieve them. Key outcomes include reduced depressive symptoms (primary), reduced anxiety and functional disability, improved quality of life, and enhanced depression knowledge and behavioral activation (secondary). Fidelity is enhanced through procedure manuals and staff training and monitored by face-to-face supervision and review of taped sessions. Cost and cost effectiveness is being evaluated. DISCUSSION: BTB is designed to bridge gaps in mental health service access and treatments for older African Americans. Treatment components are tailored to specific care needs, depression knowledge, preference for stress reduction techniques, and personal activity goals. Total costs are $584.64/4 months; or$146.16 per participant/per month. TRIAL REGISTRATION: ClinicalTrials.gov #NCT00511680