Beliefs about medicines and self-reported adherence among pharmacy clients

OBJECTIVES: To analyse any association between general beliefs about medicines and self-reported adherence among pharmacy clients. Further, to examine general beliefs about medicines by background variables. METHODS: The data were collected by questionnaires including the general section of the Beliefs about Medicines Questionnaire (BMQ), the self-reporting Medication Adherence Report Scale (MARS) and the following background variables: gender, age, education, country of birth and medicine use. The General BMQ measures beliefs about medicines as something harmful (General-Harm), beneficial (General-Benefit) and beliefs about how doctors prescribe medicines (General-Overuse). RESULTS: Of the 324 participating pharmacy clients, 54% were considered non-adherent. An association was found between General-Harm and adherence. Adherent behaviour and higher level of education were associated respectively with more beneficial and less harmful beliefs about medicines. Those born in the Nordic countries regarded medicines as more beneficial. Current users of herbal medicines and non-users of medicines were more likely to believe that doctors overprescribed medicines. CONCLUSIONS: General-Harm was associated with adherence to medication among Swedish pharmacy clients. Country of birth, education and medicine use influenced beliefs about medicines. PRACTICE IMPLICATIONS: Increased awareness of the patient's beliefs about medicines is needed among healthcare providers. We should encourage patients to express their views about medicines in order to optimize and personalize the information process. This can stimulate concordance and adherence to medication.     

Interleukin-17A during Local and Systemic Staphylococcus aureus-Induced Arthritis in Mice

Staphylococcus aureus is one of the dominant pathogens that induce septic arthritis in immunocompromised hosts, e.g., patients suffering from rheumatoid arthritis treated with immunosuppressive drugs. S. aureus-induced arthritis leads to severe joint destruction and high mortality despite antibiotic treatment. Recently, interleukin-17A (IL-17A) has been discovered to be an important mediator of aseptic arthritis both in mice and humans, but its function in S. aureus-induced arthritis is largely unknown. Here, we investigated the role of IL-17A in host defense against arthritis following systemic and local S. aureus infection in vivo. IL-17A knockout mice and wild-type mice were inoculated systemically (intravenously) or locally (intra-articularly) with S. aureus. During systemic infection, IL-17A knockout mice lost significantly more weight than the wild-type mice did, but no differences were found in the mortality rate. The absence of IL-17A had no impact on clinical arthritis development but led to increased histopathological erosivity late during systemic S. aureus infection. Bacterial clearance in kidneys was increased in IL-17A knockout mice compared to the level in wild-type mice only 1 day after bacterial inoculation. During systemic S. aureus infection, serum IL-17F protein levels and mRNA levels in the lymph nodes were elevated in the IL-17A knockout mice compared to the level in wild-type mice. In contrast to systemic infection, the IL-17A knockout mice had increased synovitis and erosions and locally decreased clearance of bacteria 3 days after local bacterial inoculation. On the basis of these findings, we suggest that IL-17A is more important in local host defense than in systemic host defense against S. aureus-induced arthritis.Patients with rheumatoid arthritis (RA) are susceptible to bacterial joint infections as a result of immunosuppressive treatments and the disease per se (24). The most common agent causing joint infections is Staphylococcus aureus, a microbe that can also cause sepsis. S. aureus-induced arthritis is a severe problem with a mortality rate of 5 to 20%, and 25 to 70% of affected patients develop permanent joint damage despite treatment (24). Although substantial efforts have been made to understand the immunological mechanisms that lead to S. aureus-induced joint destruction, it remains difficult to treat the infection (by maintaining the host''s ability to clear bacteria) while simultaneously limiting the joint destruction (by suppressing the immunological response). Thus, there is a need to identify new ways to treat RA that do not increase the severity of S. aureus-induced arthritis following infection.Recent evidence from humans and mice suggesting that the proinflammatory cytokine interleukin-17A (IL-17A) is an important player in RA (3, 19, 21) prompted an ongoing clinical trial of IL-17A-blocking antibodies to treat RA (6). Interleukin-17A was first described in 1993, but it was not until 2005, when Harrington et al. (8) described the unique Th17 subset, that the relevance of this cytokine was widely recognized among immunologists (5, 13, 15). Interleukin-17A appears to play a key role in host defense against local Gram-negative extracellular bacterial infections (4, 7, 9, 10, 17, 22, 29, 30) and local S. aureus infections (18) by inducing the production of neutrophil-mobilizing chemokines and growth factors and the subsequent mobilization of neutrophils (5, 13, 15, 16). Importantly, Ishigame et al. have recently shown that genetical knockout of IL-17A plus IL-17F (double knockout) in mice has very little impact on the general outcome of systemic S. aureus infection, measured as mortality and bacterial clearance at a single time point after bacterial inoculation compared with wild-type mice (11). However, in that study, the respective roles of IL-17A and -17F in S. aureus-induced arthritis were not specifically addressed (11), and this aspect is the main focus of this study. S. aureus-induced arthritis is a great concern in RA (24), and the first phase I study using IL-17A-blocking antibodies as a treatment in RA has recently been published (6). Thus, it is clinically important to determine whether reduced IL-17A levels in RA patients would have a detrimental effect on S. aureus-induced arthritis.It is well-known that, within the IL-17 family, IL-17F is the cytokine that shares the greatest structural and functional homology with IL-17A (5, 15). Both IL-17A and IL-17F exist as homodimers or as IL-17A-IL-17F heterodimers and bind to the IL-17 receptor A (IL-17RA)-IL-17RC receptor complex (28). Furthermore, these three IL-17 cytokines may exert similar biological effects, in particular with reference to the local mobilization of neutrophils (23). Studies of healthy mice have also shown that IL-17A is capable of inhibiting the production of IL-17F under certain conditions, through a IL-17RA-dependent mechanism (27). Thus, IL-17A and IL-17F seem to be functionally linked.In the present study, we characterized the kinetics of systemic and local S. aureus infections in the presence and absence of IL-17A in mice. For this purpose, we used IL-17A knockout mice (21) and wild-type control mice in our well-established mouse models of systemic and local S. aureus-induced arthritis (1) and assessed specific aspects of arthritis and more-general clinical outcomes. Using this approach, we obtained evidence that bacterial clearance, cytokine pattern, and degree of arthritis vary over time during systemic S. aureus infection and that IL-17A plays a more important role in local host defense than in systemic host defense against S. aureus-induced arthritis.