Oral antigen uptake can induce systemic immune responses ranging from tolerance to immunity. However, the underlying mechanisms are poorly understood, especially in humans. Here, keyhole limpet hemocyanin (KLH), a neoantigen which has been used in earlier studies of oral tolerance, was fed in a repeated low-dose and a single high-dose protocol to healthy volunteers. KLH-specific CD4 1 T-cell proliferation and cytokine production, as well as KLH-specific serum Ab and the effects of oral KLH on a subsequent parenterally induced systemic immune response, were analyzed. Repeated low-dose oral KLH alone induced antigen-specific CD4 1 T cells positive predominantly for the gut-homing receptor integrin b7 and the cytokines IL-2 and TNF-a; some CD4 1 T cells also produced IL-4.Oral feeding of KLH accelerated a subsequent parenterally induced systemic CD4 1 T-cell response. The cytokine pattern of KLH-specific CD4 1 T cells shifted toward more IL-4-and IL-10-and less IFN-c-, IL-2-and TNF-a-producing cells. The parenterally induced systemic KLH-specific B-cell response was accelerated and amplified by oral KLH. The impact of single high-dose oral KLH on antigen-specific immune responses was less pronounced compared with repeated low-dose oral KLH. These findings suggest that oral antigen can effectively modulate subsequently induced systemic antigen-specific immune responses. Immunomodulation by oral antigen may offer new therapeutic strategies for Th type1-mediated inflammatory diseases and for the development of vaccination strategies. [1,[4][5][6][7]. Systemic tolerance in these models may result from a variety of effects including clonal anergy, clonal deletion and active regulation [2]. Understanding the mechanisms leading to such diverse outcomes after mucosal antigen uptake is not only important for mucosal vaccination [3,7], but may also offer new options for immunomodulation or the treatment of autoimmune diseases [8][9][10]. Unfortunately, responses to oral antigen differ significantly between species [8,11], and human studies are rare.Similar to mouse models, systemic immune responses can be induced in humans by oral uptake of pathogens which invade the mucosa, e.g. Salmonella typhi Ty21a [12,13], or of toxins which can bind to mucosal epithelial cells and compromise the mucosal barrier, e.g. cholera toxin [14,15].The induction of human oral tolerance has been described [16][17][18] after feeding keyhole limpet hemocyanin (KLH), a neoantigen which is safe to use in humans. Compared with rodent studies, the antigen doses used were much lower and effects observed were not as uniform: reduced delayed-type hypersensitivity (DTH) [17,18] and antigen-specific proliferation of PBMC [16][17][18] have been reported after feeding KLH, although KLH-specific B-cell responses were unaffected [16] or even amplified [17,18].Functional Th-cell subsets are believed to determine the type of immune responses, but have not been examined after oral antigen challenge in humans. The frequencies of human antigenspecific Th cells or e...

Aim: To measure the extent of polypharmacy, multimorbidity and potential medication-related problems in elderly patients with chronic pain receiving home care.Methods: Data of 355 patients aged ≥65 years affected by chronic pain in home care who were enrolled in the ACHE study in Berlin, Germany, were analyzed. History of chronic diseases, diagnoses, medications including self-medication were collected for all patients. Multimorbidity was defined as the presence of ≥2 chronic conditions and levels were classified by the Charlson-Comorbidity-Index. Polypharmacy was defined as the concomitant intake of ≥5 medications. Potentially clinically relevant drug interactions were identified and evaluated; underuse of potentially useful medications as well as overprescription were also assessed.Results: More than half of the patients (55.4%) had moderate to severe comorbidity levels. The median number of prescribed drugs was 9 (range 0–25) and polypharmacy was detected in 89.5% of the patients. Almost half of them (49.3%) were affected by excessive polypharmacy (≥10 prescribed drugs). Polypharmacy and excessive polypharmacy occurred at all levels of comorbidity. We detected 184 potentially relevant drug interactions in 120/353 (34.0%) patients and rated 57 (31.0%) of them as severe. Underprescription of oral anticoagulants was detected in 32.3% of patients with atrial fibrillation whereas potential overprescription of loop diuretics was observed in 15.5% of patients.Conclusion: Multimorbidity and polypharmacy are highly prevalent in elderly outpatients with chronic pain receiving home care. Medication-related problems that could impair safety of drug treatment in this population are resulting from potentially relevant drug interactions, overprescribing as well as underuse.

Objective To analyze the pattern and appropriateness of pain medications in older adults receiving home care. Methods We performed a prospective cross-sectional study in patients �65 years old having chronic pain and receiving home care in Berlin, Germany. Data on prescribed pain medications were collected using self-reported information, nursing documents, and medication plans during interviews at home. Pain intensity was determined with the numeric rating scale (NRS) and the Pain Assessment In Advanced dementia (PAINAD) scale. The Pain Medication Appropriateness Scale score (S PMAS) was applied to evaluate inappropriateness (i.e. a score �67) of pain medication. Results Overall 322 patients with a mean age of 82.1 ± 7.4 years (71.4% females) were evaluated. The average pain intensity scores during the last 24 hours were 5.3 ± 2.1 and 2.3 ± 2.3 on NRS and PAINAD scale (range 0-10, respectively). Sixty (18.6%) patients did not receive any pain medication. Among the treated patients, dipyrone was the most frequently prescribed analgesic (71.4%), while 50.8% and 19.1% received systemic treatment with opioids and non-steroidal anti-inflammatory drugs, respectively. The observed median S PMAS was 47.6 (range 0-100) with 58 (18.0%) of patients achieving appropriate values. Half of the patients were treated with scheduled, while 29.9% were only treated with on-demand medications. Cognitive status had no effect on appropriateness of pain treatment.