Search

Objective: The aim was to retrieve and analyse the serious adverse events of venous occlusion systems used in cyanoacrylate adhesive closure (CAC) submitted to regulatory agencies. Methods: The Total Product Life Cycle (TPLC) database of the US Food and Drug Administration (FDA), the Database of Adverse Event Notifications (DAEN) of the Australian Therapeutic Goods Administration (TGA), and the Yellow Card database of the UK Medicines and Healthcare Products Regulatory Agency (MHRA) were reviewed. Three Freedom of Information (FOI) requests had to be submitted to the MHRA to obtain data. Results: The TPLC contained 899 reports which included 13 cases of death, 7 strokes, 211 thromboembolic events, and 482 immune reactions. The DAEN recorded three reportable adverse events, and the MHRA recorded seven adverse incidents including one death. Conclusion: CAC is associated with serious adverse events including death. These events are under-reported in the medical literature and only sub-optimally reported to the regulatory agencies. [ABSTRACT FROM AUTHOR]

Background: Radiolabeled antibody fragments present a promising opportunity as theranostic agents, offering distinct advantages over whole antibodies. In this study, the authors investigate the potential of [177Lu]Lu-DTPA-F(ab′)2-pertuzumab as a theranostic agent for precise targeting of human epidermal growth factor receptor 2 (HER2)-positive cancers. Additionally, the authors aim to quantitatively assess the binding synergism in the presence of cold trastuzumab. Materials and Methods: F(ab′)2-pertuzumab was prepared by pepsin digestion and conjugated with a bifunctional chelator. The immunoconjugate was radiolabeled with 177Lu and characterized by chromatography techniques. Binding parameters (affinity, specificity, and immunoreactivity) and cellular binding enhancement studies were evaluated in HER2-overexpressing and triple-negative cell lines. The in vivo enhancement in tumor uptake of the radiolabeled immunoformulation was assessed in severe combined immunodeficient (SCID) mice bearing tumors, both in the presence and absence of unlabeled trastuzumab. Results: The formulation of [177Lu]Lu-DTPA-F(ab′)2-pertuzumab could be prepared in high yields and with consistent radiochemical purity, ensuring reproducibility. Comprehensive in vitro and in vivo evaluation studies confirmed high specificity and immunoreactivity of the formulation toward HER2 receptors. Binding synergism of radiolabeled pertuzumab fragments in the presence of trastuzumab to HER2 receptors was observed. Conclusions: The radioformulation of [177Lu]Lu-DTPA-F(ab′)2-pertuzumab holds great promise as a targeted approach for addressing HER2-positive cancers. A potentially effective strategy to amplify therapeutic efficacy involves dual epitope targeting by combining radiolabeled pertuzumab with cold trastuzumab. [ABSTRACT FROM AUTHOR]

Immune-checkpoint inhibitors (ICIs) are the most effective treatments nowadays. Nivolumab was the second ICI used for treating solid tumors with amazing results. Patients treated with Nivolumab may react differently to this treatment. Some people tolerate this treatment very well without experiencing any adverse reactions, whilst some may have mild symptoms and a part of them can present severe reactions. In our research, we sought to identify the answers to four questions: 1. what type of cancer has more severe hypersensitivity reactions to Nivolumab, 2. what is the time frame for developing these severe reactions to Nivolumab, 3. whether it is best to continue or stop the treatment after a severe hypersensitivity reaction to Nivolumab and 4. what severe hypersensitivity reactions are the most frequent reported along Nivolumab treatment. This review also highlights another problem with regard to the usage of concomitant and prior medications or other methods of treatment (e.g., radiation therapy), which can also lead to severe reactions. Treatment with Nivolumab is very well tolerated, but patients should also be warned of the possibility of severe hypersensitivity reactions for which they should urgently see a doctor for a personalized evaluation. There are some options for individuals with severe hypersensitivity reactions, for eg. switching the medication or applying a desensitization protocol. [ABSTRACT FROM AUTHOR]

Adherence to allergen immunotherapy (AIT) is crucial for its efficacy. Subcutaneous AIT requires monthly visits (or more extended in the case of venom immunotherapy), while sublingual AIT is performed with a daily intake of allergen drops. Non-adherence to an AIT schedule and premature discontinuation are common problems. Various studies have shown controversial results on the rate of AIT adherence. The aim of this review is to describe the problem of non-adherence and to offer some evidence-based advice to allergologists on how to increase it. Better patient education at the beginning of treatment, sharing with patients the decision on which type of immunotherapy to select and showing sincere interest in their treatment concerns are some tips that can help to increase adherence. A well organized allergologist time schedule not only increases safety but also offers the possibility of close follow-up and an increase in patient loyalty. [ABSTRACT FROM AUTHOR]

Background: To investigate the associations between the perceived barriers and benefits of using HIV pre-exposure prophylaxis medication, including worries about the side effects, disliking taking drugs, perceived burden of taking medication, positive expectations as to the efficacy of the drugs, favourable doctor-patient relationships, and medication adherence among men who have sex with men (MSM) to provide a target for improving medication adherence and reducing HIV infection among MSM.Methods: MSM were recruited in western China from April 2013 to October 2014, administered oral tenofovir (TDF) daily and followed up every 12 weeks for 2 years. At each follow-up, the medication rate was calculated based on the self-reported number of missed doses over 2 weeks, and then, the medication adherence was evaluated. The barriers and benefits perceived during medication were obtained by a self-administered questionnaire, and their effects on medication adherence were analysed by linear mixed models.Results: A total of 411 participants were enrolled in this study, and 1561 follow-up observation points were obtained. The average medication rate was 0.62 ± 0.37, and the medication rate increased with longer follow-up (P < 0.05). The medication rate was higher among MSM who were divorced (compared to those who were unmarried, P < 0.0001). MSM with more positive expectations as to the efficacy of the drugs showed higher rates of medication (P < 0.0001), while those who were more worried about side effects had a lower medication rate (P = 0.0208). In contrast, the dislike of taking the drugs and the burden perceived during medication had no effects on the actual medication rate of taking TDF (P > 0.05).Conclusion: How to obtain and maintain high medication adherence among MSM is the key to the PrEP intervention strategy for effective reduction of HIV infection. For MSM in China, we should deepen their understanding of the effectiveness and safety of PrEP and increase their confidence in PrEP, thereby improving their medication adherence.Trial Registration: ChiCTR-TRC-13003849 . Registered on 24/06/2013. [ABSTRACT FROM AUTHOR]

Millions of Americans are living with at least one chronic disease, and while the majority has been prescribed medication to control symptoms-medication adherence is a widespread problem. Medication nonadherence varies by chronic disease, patient characteristics, and insurance coverage, and previous research has identified non-financial barriers including disease-related knowledge, health literacy and polypharmacy. However, given the increasing popularity of online health communities, little research examines the influence of user-generated content on health behaviors. Many patients use the internet to seek and share information related to prescription medications. The current study examines patients' attitudes and behavioral intentions formed (in part) by the user-generated content exchanged within online health communities. Specifically, the Health Belief Model's perceived barriers and perceived benefits are explored here. Twenty members from online health communities related to arthritis are interviewed to understand how peer-to-peer communication is used in regards to medication adherence. Three themes emerged from the data, including striving for pain relief, negotiating potential side effects, and finding the new normal. Theoretical and practical implications are discussed. [ABSTRACT FROM AUTHOR]

Background Co-administration of vaccines in adolescents may improve coverage. We assessed co-administration of quadrivalent meningococcal serogroups A, C, W and Y tetanus toxoid-conjugate vaccine (MenACWY-TT), human papillomavirus 16/18 AS04-adjuvanted vaccine (AS04-HPV16/18) and tetanus-diphtheria-acellular pertussis vaccine (Tdap) in girls and young women. Methods In this phase IIIb study (NCT01755689), 1300 healthy 9–25-year-old females were randomized (1:1:1:1:1) to receive: MenACWY-TT at month (M) 0 and AS04-HPV16/18 at M1, M2, M7; MenACWY-TT and AS04-HPV16/18 at M0 and AS04-HPV16/18 at M1, M6; AS04-HPV16/18 at M0, M1, M6; MenACWY-TT, Tdap and AS04-HPV16/18 at M0 and AS04-HPV16/18 at M1, M6; Tdap and AS04-HPV16/18 at M0 and AS04-HPV16/18 at M1, M6. Immunogenicity, safety and reactogenicity were evaluated. Results Immunogenicity of MenACWY-TT and AS04-HPV16/18 when co-administered was non-inferior to that of the 2 vaccines given separately. Co-administration of MenACWY-TT, AS04-HPV16/18 and Tdap was non-inferior to MenACWY-TT administered alone or to Tdap co-administered with AS04-HPV16/18 in terms of immunogenicity for all vaccine components, except pertussis antigens. Post-vaccination, ≥89.5% of participants reached antibody levels above the pre-specified threshold for all antigens. No safety concerns were identified. Conclusion Our data support co-administration of MenACWY-TT with Tdap and AS04-HPV16/18 vaccines in adolescents. [ABSTRACT FROM AUTHOR]

Rapid elimination of microbes from the bloodstream, along with the ability to mount an adaptive immune response, are essential for optimal host-defense. Kupffer cells are strategically positioned in the liver sinusoids and efficiently capture circulating microbes from the hepatic artery and portal vein, thus preventing bacterial dissemination. In vivo and in vitro studies have probed how complement receptor of the immuno g lobulin superfamily (CRIg), also referred to as Z39Ig and V-set and Ig domain-containing 4 (VSIG4), acts as a critical player in pathogen recognition and clearance. While recent data suggested that CRIg may bind bacterial cell wall components directly, the single transmembrane receptor is best known for its interaction with complement C3 opsonization products on the microbial surface. On Kupffer cells, CRIg must capture opsonized microbes against the shear forces of the blood flow. In vivo work reveals how immune adherence (IA), a process in which blood platelets or erythrocytes associate with circulating bacteria, plays a critical role in regulating pathogen capture by CRIg under flow conditions. In addition to its typical innate immune functions, CRIg was shown to directly and indirectly influence adaptive immune responses. Here, we review our current understanding of the diverse roles of CRIg in pathogen elimination, anti-microbial immunity and autoimmunity. In particular, we will explore how, through selective capturing by CRIg, an important balance is achieved between the immunological and clearance functions of liver and spleen. [ABSTRACT FROM AUTHOR]

Background: Inadequate description of non-pharmacological complex interventions in trial publications means that they cannot be replicated or assessed for generalisability. There are published guidelines on how to describe an intervention, such as those from the CONSORT Group. However, there have been few evaluations of whether intervention reporting is improving.Methods: We aimed to assess whether descriptions of multicomponent, non-pharmacological interventions evaluated in randomised trials are improving. To do so, we chose trials of educational and psychotherapeutic interventions to promote adherence to therapy, and compared those published between 2002 and 2007 (Time-1) with those between 2010 and 2015 (Time-2). These time periods were chosen to concord with the publication in 2008 of the CONSORT extension statement of reporting guidelines for non-pharmacological treatment which included items on intervention description. We assessed 19 items, based on the CONSORT Statement and the more recent Template for Intervention Description and Replication Checklist (TIDieR). Two reviewers independently extracted data. We created a quality score of the eight items we considered key information for replication and assessment of generalisability (setting, provider, recipient, comparator, intervention intensity, how it was conducted, existence of a manual or protocol, and detail of whether there was an assessment of fidelity). Score per item was '1' if reported adequately and '0' if not.Results: Of the eligible trials, 42 were published in Time-1 and 134 published in Time-2. The trials included were published in 112 peer-reviewed journals, 52 of these journals currently require authors to follow the CONSORT Statements, while only one recommended adherence to the TIDieR. Most items of CONSORT and TIDieR were reported by more than half of the trials at both time points. Few trials reported fidelity. A large proportion of the trials did not report the existence of a manual or protocol, or what the comparator group received. We found no statistically significant improvement in the eight-item quality score (Time-1: mean 5.71 (standard deviation (SD) 1.09), Time-2: 5.87 (SD 1.28), p = 0.49).Conclusions: We found no overall evidence that reporting the specifics of multicomponent, non-pharmacological interventions is improving. Details to replicate interventions remain lacking, impairing best implementation or meaningful further research. Editorial endorsement of reporting checklists needs to be more extensive. [ABSTRACT FROM AUTHOR]

The aim of the study was to determine the prevalence of virulence genes responsible for the adhesion ( flaA , cadF and racR ) and invasion ( virB11 , iam and pldA ) in Campylobacter isolates from cattle and swine and determine their adherence and invasion abilities. The studies conducted revealed high prevalence rate of adherence and invasion associated genes irrespective of the isolates origin. All Campylobacter strains of swine and cattle origin adhered to HeLa cells at mean level 0.1099% ± SD 0.1341% and 0.0845% ± SD 0.1304% of starting viable inoculum, respectively. However swine isolates exhibited higher invasion abilities (0.0012% ± SD 0.0011%) compared to bovine isolates (0.00038% ± SD 0.00055%). The results obtained revealed significantly positive correlation between invasion and adherence abilities of swine origin isolates (R = 0.4867 in regard to C. jejuni and R = 0.4507 in regard to C. coli ) and bovine origin isolates (R = 0.726 in regard to C. jejuni ). Bacterial virulence is multifactorial and it is affected by the expression of virulence genes. Moreover the presence of virulence genes determines the ability of Campylobacter isolates to adhere and invade the cells. [ABSTRACT FROM AUTHOR]

Background Participants' experience with a screening test can influence adherence, and therefore the efficacy of screening programs. We compared screening with unsedated flexible sigmoidoscopy and fecal immunochemical testing (FIT) for participants' satisfaction with the decision and for willingness to repeat colorectal cancer screening. Methods In a prospective, randomized trial 3257 individuals (50 - 74 years) were invited to either flexible sigmoidoscopy or FIT (1:1), of whom 1650 took up the offer (52.6 %). In total, 1497 screening participants completed at least one questionnaire, either before screening, and/or at three time points in the following year, that measured willingness to repeat screening, willingness to recommend screening, and satisfaction with decision to attend. There were 769 and 728 responders in the flexible sigmoidoscopy and FIT group, respectively. Additionally, 581 flexible sigmoidoscopy participants also completed a pain questionnaire. Results 1 year later, 10 % of the flexible sigmoidoscopy participants were not willing to repeat screening, compared to 5 % of FIT participants. A higher percentage of women compared to men would not repeat flexible sigmoidoscopy screening (adjusted odds ratio [OR] 2.52, 95 % confidence interval [95 %CI] 1.48 to 4.28). Notably, 22 % of women reported pain during flexible sigmoidoscopy compared to 5 % of men. When we added pain to the statistical model, pain was significantly associated with unwillingness to repeat flexible sigmoidoscopy (OR 3.15, 95 %CI 1.68 to 5.87), while gender was no longer associated (OR 1.53, 95 %CI 0.82 to 2.88). Conclusion Acceptability for flexible sigmoidoscopy and for FIT was high among Norwegian screening participants, though FIT participants were more willing to repeat screening. Women were less willing to repeat screening with flexible sigmoidoscopy compared to men. This gender difference seemed partly due to pain, and therefore preventable.This study is registered at ClinicalTrials.gov: NCT01538550. [ABSTRACT FROM AUTHOR]

Objective: Non-adherence to tamoxifen is common in breast cancer survivors and is associated with poor clinical outcomes. This study aimed to understand womens' experiences of taking tamoxifen and to identify factors which may be associated with non-adherence.Design: A qualitative study using semi-structured interviews.Methods: Thirty-two breast cancer survivors who had been prescribed tamoxifen took part in interviews conducted face to face or over the telephone. They were transcribed verbatim and analysed using inductive thematic analysis with elements of grounded theory.Results: A key theme identified in the data was weighing up costs and benefits of treatment, which resulted in women falling into three groups; tamoxifen is keeping me alive, tamoxifen is not worth the reduced risk of recurrence, or conflicting beliefs about the harms and benefits of treatment. Additional themes were living with risk of recurrence and information & support.Conclusions: Women who believed that the necessity of tamoxifen outweighed its costs were more likely to be adherent, whereas women who thought that the benefits did not outweigh the side effects were more likely to have discontinued. A third more ambivalent group believed strongly in the importance of treatment, but were struggling with side effects and were often non-adherent. Patients sometimes felt unsupported and discussed a need for more comprehensive information. To increase adherence, future research needs to explore ways to increase beliefs around tamoxifen necessity and how to help women cope with side effects. Statement of contribution What is already known on this subject? Non-adherence to tamoxifen is associated with increased risk of recurrence and mortality. Up to 50% of patients are non-adherent to tamoxifen by the fifth year of treatment Few consistent predictors of tamoxifen non-adherence have been identified. What does this study add? Many women report not knowing how to manage their side effects. Non-adherence is related to how women weigh up their side effects against their medication beliefs. Interventions aiming to increase necessity beliefs and improve symptom management may be effective. [ABSTRACT FROM AUTHOR]

Background: Guidelines for the treatment of nonmetastatic inflammatory breast cancer (IBC) using trimodality therapy (TT) (chemotherapy, surgery, and radiotherapy) have remained largely unchanged since 2000. However, many patients with nonmetastatic IBC do not receive TT. It is unknown how patient-level (PL) and facility-level (FL) factors contribute to TT use.Methods: Using the National Cancer Data Base, patients with nonmetastatic IBC who underwent locoregional treatment from 2003 through 2011 were identified. The authors correlated PL factors, including demographic and tumor characteristics, with TT use. An observed-to-expected ratio for the number of patients treated with TT was calculated for each hospital by adjusting for significant PL factors. Hierarchical mixed effects models were used to assess the percentage of variation in TT use attributable to PL and FL factors, respectively.Results: Of the 542 hospitals examined, 55 (10.1%) and 24 (4.4%), respectively, were identified as significantly low and high outliers for TT use (P<.05). The percentage of the total variance in the use of TT attributable to the facility (11%) was nearly triple the variance attributable to the measured PL factors (3.4%). The nomogram generated from multivariate logistic regression of PL factors only allows a facility to assess TT use given their PL data.Conclusions: FL factors rather than PL factors appear to contribute disproportionately to the underuse of TT in patients with nonmetastatic IBC. To improve treatment guideline adherence for patients with nonmetastatic IBC, it is critical to identify the specific FL factors associated with TT underuse. More organized FL intervention is required to train physicians and to build multidisciplinary teams. Cancer 2017;123:2618-25. © 2017 American Cancer Society. [ABSTRACT FROM AUTHOR]

Introduction: Successful population-level antiretroviral therapy (ART) adherence will be necessary to realize both the clinical and prevention benefits of antiretroviral scale-up and, ultimately, the end of AIDS. Although many people living with HIV are adhering well, others struggle and most are likely to experience challenges in adherence that may threaten virologic suppression at some point during lifelong therapy. Despite the importance of ART adherence, supportive interventions have generally not been implemented at scale. The objective of this review is to summarize the recommendations of clinical, research, and public health experts for scalable ART adherence interventions in resource-limited settings. Methods: In July 2015, the Bill and Melinda Gates Foundation convened a meeting to discuss the most promising ART adherence interventions for use at scale in resource-limited settings. This article summarizes that discussion with recent updates. It is not a systematic review, but rather provides practical considerations for programme implementation based on evidence from individual studies, systematic reviews, meta-analyses, and the World Health Organization Consolidated Guidelines for HIV, which include evidence from randomized controlled trials in low- and middle-income countries. Interventions are categorized broadly as education and counselling; information and communication technology-enhanced solutions; healthcare delivery restructuring; and economic incentives and social protection interventions. Each category is discussed, including descriptions of interventions, current evidence for effectiveness, and what appears promising for the near future. Approaches to intervention implementation and impact assessment are then described. Results and discussion: The evidence base is promising for currently available, effective, and scalable ART adherence interventions for resource-limited settings. Numerous interventions build on existing health care infrastructure and leverage available resources. Those most widely studied and implemented to date involve peer counselling, adherence clubs, and short message service (SMS). Many additional interventions could have an important impact on ART adherence with further development, including standardized counselling through multi-media technology, electronic dose monitoring, decentralized and differentiated models of care, and livelihood interventions. Optimal targeting and tailoring of interventions will require improved adherence measurement. Conclusions: The opportunity exists today to address and resolve many of the challenges to effective ART adherence, so that they do not limit the potential of ART to help bring about the end of AIDS. [ABSTRACT FROM AUTHOR]

Objective: This study examined statin adherence amongst Kuwaiti hypercholesterolemic patients in order to identify factors associated with poor adherence and to determine whether or not an association exists between statin adherence and the risk profile of coronary heart disease (CHD).Subjects and Methods: Two hundred hypercholesterolemic patients (30-69 years of age) were recruited from Kuwaiti primary healthcare clinics and interviewed about demographic characteristics, pre-existing self-reported medical conditions and prescribed medications. The Morisky Medication Adherence Scale was used to assess statin adherence (a self-reported, medication-adherence questionnaire divided into 3 levels, with a score of 8 denoting high adherence, 6 to <8 denoting medium adherence and <6 denoting low adherence). Data regarding anthropometric, psychological and serum risk factors were collected using 2 additional questionnaires, laboratory tests and bioelectrical impedance scales. Binary logistic regression was used to determine predictors of adherence and general linear modelling was used to test relationships between continuous outcomes and statin adherence.Results: Of the 200 participants, 117 (58.5%) reported low adherence, 83 (41.5%) reported medium adherence and no patients (0%) scored high adherence. Younger patients (aged 30-50 years) had lower adherence than older patients (>50 years) [odds ratio (OR) 1.05; 95% confidence interval (CI) 1.01-1.09] for every extra year; p < 0.01). Those without diabetes, i.e. 113 (56.5%), were less likely to report medium adherence than those with diabetes (OR 0.42; 95% CI 0.23-0.75; p < 0.01). Low statin adherence was associated with higher levels of plasma cholesterol (p < 0.001) and low-density lipoprotein (p < 0.01).Conclusion: In this study, there was a high prevalence of low statin adherence, especially among younger patients with fewer concomitant diseases. The results indicated an inverse relationship between statin adherence and CHD risk profile. [ABSTRACT FROM AUTHOR]

Objective: To examine medication adherence and associated factors among adolescents with bipolar disorder (BP) using both objective and subjective methods.Method: Participants were 21 adolescents with a primary BP diagnosis recruited from a pediatric specialty clinic. All participants were prescribed at least one psychotropic medication. Self- and parent-reported adherence were assessed monthly over 6 months. Objective data on medication adherence were gathered through an electronic weekly pillbox. Demographic and clinical factors were assessed through self, parent, and physician ratings at baseline, 3, and 6 months.Results: Objective data indicate 41.5% of doses (58.6% of days) were not taken as prescribed over a mean of 3 months of follow-up. Subjective reports (patient, parent, and physician) significantly overestimated adherence as compared with objective data. Factors from multiple domains were associated with poorer adherence, including more daily doses, higher weight, dose timing (poorer on mornings/afternoons and weekends), less temporal proximity to medication management appointment, greater self-reported cognitive difficulties with adhering to treatment; the most potent predictor of missed doses was greater overall illness severity.Conclusions: Findings provide further evidence of poor medication adherence among youth with BP, and highlight the limits of subjective report of adherence. Providers should give careful attention to adherence when making decisions regarding treatment response and changes to medication regimen when working with youth with BP. [ABSTRACT FROM AUTHOR]

The activation of the complement system by canonical and non-canonical mechanisms results in the generation of multiple C3 and C5 cleavage fragments including anaphylatoxins C3a and C5a as well as opsonizing C3b/iC3b. It is now well appreciated that anaphylatoxins not only act as pro-inflammatory mediators but as immunoregulatory molecules that control the activation status of cells and tissue at several levels. Likewise, C3b/iC3b is more than the opsonizing fragment that facilitates engulfment and destruction of targets by phagocytes. In the circulation, it also facilitates the transport and delivery of bacteria and immune complexes to phagocytes, through a process known as immune adherence, with consequences for adaptive immunity. Here, we will discuss non-classical immunoregulatory properties of C3 and C5 cleavage fragments. We highlight the influence of anaphylatoxins on Th2 and Th17 cell development during allergic asthma with a particular emphasis on their role in the modulation of CD11b+ conventional dendritic cells and monocyte-derived dendritic cells. Furthermore, we discuss the control of anaphylatoxin-mediated activation of dendritic cells and allergic effector cells by adaptive immune mechanisms that involve allergen-specific IgG1 antibodies and plasma or regulatory T cell-derived IL-10 production. Finally, we take a fresh look at immune adherence with a particular focus on the development of antibacterial cytotoxic T-cell responses. [ABSTRACT FROM AUTHOR]

The article presents a study which focuses on the role of the respiratory epithelium in defending against microbial pathogens and in facilitating synergistic pathogenic interactions. The topics discussed include role of the respiratory epithelium in innate and adaptive immunity, the mechanism that drives the increase of bacterial adherence and colonization of viral infection and the skew of direction of immune status of the respiratory tract to predispose to secondary bacterial infection.

Background: There is evidence for a relevant role of inflammation in the pathogenesis of Parkinson's disease (PD). Mutations in the LRRK2 gene represent the most frequent genetic cause for autosomal dominant PD. LRRK2 is highly expressed in macrophages and microglia suggesting an involvement in inflammatory pathways. The objectives are to test (1) whether idiopathic PD and LRRK2-associated PD share common inflammatory pathways or present distinct profiles and (2) whether non-manifesting LRRK2 mutation carriers present with similar aspects of inflammatory profiles as seen in PD-affected patients.Methods: We assessed serum profiles of 23 immune-associated markers and the brain-derived neurotrophic factor in 534 individuals from the MJFF LRRK2 consortium.Results: A large proportion of inflammatory markers were gender-dependent. Both PD-affected cohorts showed increased levels of the pro-inflammatory marker fatty-acid-binding protein. Additionally, idiopathic PD but not LRRK2-associated PD patients showed increased levels of the pro-inflammatory marker interleukin-12-p40 as well as the anti-inflammatory species interleukin-10, brain-derived neurotrophic factor, and stem cell factor. Non-manifesting LRRK2 mutation carriers including those with prodromal characteristics of PD presented with control-like inflammatory profiles.Conclusions: Concomitant inflammation seems to be associated with idiopathic and LRRK2-associated PD. Identifying PD patients in whom inflammatory processes play a major role in their pathophysiology might offer a new therapeutic window at least for a subgroup of patients. Since non-manifesting LRRK2 mutation carriers with symptoms of the prodromal phase of PD did not show inflammatory profiles, activation of the immune system seems not an early event in the disease cascade. [ABSTRACT FROM AUTHOR]

Background and aims:Treatment adherence is one of the most important factors that may determine treatment response in patients with bipolar disorders (BD). Many factors have been described to be associated with treatment adherence in BD. Temperament that can influence the course of BD will have an impact on treatment adherence. The aim of this study is to investigate temperament effect on treatment adherence in euthymic patients with BD-I.Methods:Eighty patients with BD-I participated in the study. A psychiatrist used the Structured Clinical Interview for DSM-IV Axis-I Disorders to determine the diagnosis and co-morbidities. Hamilton Depression and Young Mania Rating Scale were used to detect the remission. We used the Temperament Evaluation of Memphis, Pisa, Paris, San Diego Autoquestionnaire and the 4-item Morisky Medication Adherence Scale to evaluate temperament and treatment adherence, respectively. The study group was divided into two groups as “treatment adherent” and “treatment non-adherent”.Results:The cyclothymic and anxious temperament scores of the treatment non-adherent patients with BD-I were significantly higher than those of the treatment adherent group (p < 0.001, p = 0.006, respectively). Multiple linear regression analysis determined that cyclothymic temperament predicted treatment non-adherence (p = 0.009).Conclusion:It should be kept in mind that BD-I patients with cyclothymic temperament may be treatment non-adherent and future studies should explore whether temperament characteristics deteriorate BD-I course by disrupting treatment adherence. [ABSTRACT FROM PUBLISHER]

Neutralizing antibodies induced by vaccination or natural infection play a critically important role in protection against the viral diseases. In general, neutralization of the viral infection occurs via two major pathways: pre- and post-attachment modes, the first being the most important for such infections as influenza and polio, the latter being significant for filoviruses. Neutralizing capacity of antibodies is typically evaluated by virus neutralization assays that assess reduction of viral infectivity to the target cells in the presence of functional antibodies. Plaque reduction neutralization test, microneutralization and immunofluorescent assays are often used as gold standard virus neutralization assays. However, these methods are associated with several important prerequisites such as use of live virus requiring safety precautions, tedious evaluation procedure and long assessment time. Hence, there is a need for a robust, inexpensive high throughput functional assay that can be performed rapidly using inactivated virus, without extensive safety precautions. Herein, we report a novel high throughput Fluorescence Adherence Inhibition assay (fADI) using inactivated virus labeled with fluorescent secondary antibodies virus and Vero cells or erythrocytes as targets. It requires only few hours to assess pre-attachment neutralizing capacity of donor sera. fADI assay was tested successfully on donors immunized with polio, yellow fever and influenza vaccines. To further simplify and improve the throughput of the assay, we have developed a mathematical approach for calculating the 50% titers from a single sample dilution, without the need to analyze multi-point titration curves. Assessment of pre- and post-vaccination human sera from subjects immunized with IPOL®, YF-VAX® and 2013–2014 Fluzone® vaccines demonstrated high efficiency of the assay. The results correlated very well with microneutralization assay performed independently by the FDA Center of Biologics Evaluation and Research, with plaque reduction neutralization test performed by Focus Diagnostics, and with hemaglutination inhibition assay performed in-house at Sanofi Pasteur. Taken together, fADI assay appears to be a useful high throughput functional immunoassay for assessment of antibody-related neutralization of the viral infections for which pre-attachment neutralization pathway is predominant, such as polio, influenza, yellow fever and dengue. [ABSTRACT FROM AUTHOR]

Background: In Africa, fewer than half of patients receiving therapy for multidrug-resistant TB (MDR TB) are successfully treated, with poor outcomes reported for HIV-coinfected patients.Methods: A standardised second-line drug (SLD) regimen was used in a non-governmental organisation-Ministry of Health (NGO-MOH) collaborative community and hospital-based programme in Ethiopia that included intensive side effect monitoring, adherence strategies and nutritional supplementation. Clinical outcomes for patients with at least 24 months of follow-up were reviewed and predictors of treatment failure or death were evaluated by Cox proportional hazards models.Results: From February 2009 to December 2014, 1044 patients were initiated on SLD. 612 patients with confirmed or presumed MDR TB had ≥ 24 months of follow-up, 551 (90.0%) were confirmed and 61 (10.0%) were suspected MDR TB cases. 603 (98.5%) had prior TB treatment, 133 (21.7%) were HIV coinfected and median body mass index (BMI) was 16.6. Composite treatment success was 78.6% with 396 (64.7%) cured, 85 (13.9%) who completed treatment, 10 (1.6%) who failed, 85 (13.9%) who died and 36 (5.9%) who were lost to follow-up. HIV coinfection (adjusted HR (AHR): 2.60, p<0.001), BMI (AHR 0.88/kg/m(2), p=0.006) and cor pulmonale (AHR 3.61, p=0.003) and confirmed MDR TB (AHR 0.50, p=0.026) were predictive of treatment failure or death.Conclusions: We report from Ethiopia the highest MDR TB treatment success outcomes so far achieved in Africa, in a setting with severe resource constraints and patients with advanced disease. Intensive treatment of adverse effects, nutritional supplementation, adherence interventions and NGO-MOH collaboration were key strategies contributing to success. We argue these approaches should be routinely incorporated into programmes. [ABSTRACT FROM AUTHOR]

Objective. To find a convenient and efficient way to isolate MSCs from human menstrual blood and to investigate their biological characteristics, proliferative capacity, and secretion levels. Methods. MSCs were isolated from menstrual blood of 3 healthy women using adherence. Cell immunological phenotype was examined by flow cytometry; the adipogenic, osteogenic, and chondrogenic differentiation of MSCs was examined by Oil-Red-O staining, ALP staining, and Alcian Blue staining, respectively; and the secretion of cytokines, including vascular endothelial growth factor (VEGF), hepatocyte growth factor (HGF), and insulin-like growth factor-1 (IGF-1), was detected using enzyme-linked immunosorbent assay. Results. MB-MSCs were successfully isolated from human menstrual blood using adherence. They were positive for CD73, CD105, CD29, and CD44, but negative for CD31 and CD45. The differentiated MB-MSCs were positive for ALP staining, Oil-Red-O staining, and Alcian Blue staining. In addition, they could secrete antiapoptotic cytokines, such as VEGF, IGF-1, and HGF. Conclusion. It is feasible to isolate MSCs from human menstrual blood, thus avoiding invasive procedures and ethical controversies. Adherence could be a promising alternative to the density gradient centrifugation for the isolation of MSCs from menstrual blood. [ABSTRACT FROM AUTHOR]

The neonatal FcR (FcRn) belongs to the extensive and functionally divergent family of MHC molecules. Contrary to classical MF1C family members, FcRn possesses little diversity and is unable to present Ags. Instead, through its capacity to bind IgG and albumin with high affinity at low pfl, it regulates the serum half-lives of both of these proteins. In addition, FcRn plays an important role in immunity at mucosal and systemic sites through its ability to affect the lifespan of IgG, as well as its participation in innate and adaptive immune responses. Although the details of its biology are still emerging, the ability of FcRn to rescue albumin and IgG from early degradation represents an attractive approach to alter the plasma half-life of pharmaceuticals. We review some of the most novel aspects of FcRn biology, immune as well as nonimmune, and provide some examples of FcRn-based therapies. [ABSTRACT FROM AUTHOR]

Background The use of potent immunosuppressive drugs and increased travel by renal transplant recipients ( RTR) has augmented the risk for infectious complications. Immunizations and changes in lifestyle are protective. The Kidney Disease: Improving Global Outcomes ( KDIGO) Transplant Work Group has developed guidelines on vaccination following solid organ transplantation. The degree of adherence to these guidelines is unknown, as is which barriers must be overcome to improve adherence. Methods We performed a cross-sectional national survey among Dutch nephrologists to assess vaccination policy and adherence to the KDIGO guidelines. In addition, to investigate awareness and attitude of RTR regarding their risk of infection, we performed a cross-sectional survey of RTR in our outpatient clinic. Results A total of 132 (63%) nephrologists completed the survey. Reported immunization rates were 90.8% for influenza and 27.3% for hepatitis B. However, pneumococcal, tetanus toxoid, and meningococcal immunization rates were low. Twenty-seven percent of respondents were familiar with the guideline contents. The most frequent perceived barrier to guideline adherence was expectation of low effectiveness. A total of 403 RTR (62%) completed the survey. Sixty-eight percent perceived more risk for complicated infection. A significant correlation was found between education level and variables concerning awareness and attitude toward risk of infection. Conclusions Our results show that nephrologists' knowledge of and adherence to the recommendations regarding immunization after renal transplantation is suboptimal. Most Dutch RTR are aware of their increased risk and the possible seriousness of infectious complications. However, their behavior does not match their awareness. This disparity points to an important role for nephrologists in providing adequate counseling. [ABSTRACT FROM AUTHOR]

BACKGROUND: Medication non-adherence is a major impediment to the management of cardiovascular disease risk factors. A better understanding of the modifying factors underlying medication non-adherence among individuals with known cardiovascular disease may inform approaches for addressing non-adherence. OBJECTIVE: The purpose of this study was to identify demographic and patient characteristics, medical comorbidities, psychosocial factors, and health belief-related factors associated with medication non-adherence among patients with known cardiovascular disease. DESIGN: We performed secondary analysis of baseline data from a randomized trial. PATIENTS: The study included 405 patients with a diagnosis of hypertension and history of acute myocardial infarction that was diagnosed within a three-year period prior to enrollment. MAIN MEASURES: Baseline demographics and patient characteristics, medical comorbidities, psychosocial factors, health belief-related factors, and patient-reported medication non-adherence were analyzed. KEY RESULTS: Of 405 patients, 173 (42.7 %) reported medication non-adherence. Factors associated with non-adherence in bivariate analysis included younger age, non-white race, having less than 12 years of education, smoking, financial insecurity, identifying as nervous or tense, higher life chaos score, greater worry about having a myocardial infarction, and greater worry about having a stroke. Using multivariable modeling, we determined that age (OR 0.97 per additional year, 95 % CI, 0.95-0.99), life chaos (OR 1.06 per additional point, 95 % CI, 1.00-1.11), and worry about stroke (OR 1.12 per additional point, 95 % CI, 1.01-1.25) remained significantly associated with self-reported medication non-adherence. CONCLUSIONS: We found that worry about having a stroke, higher life chaos, and younger age were all significantly associated with self-reported medication non-adherence in patients with cardiovascular disease and a history of myocardial infarction. Further research exploring these factors as targets for intervention is needed, as is additional research examining modifiable causes of medication non-adherence among patients with cardiovascular disease. [ABSTRACT FROM AUTHOR]

The importance and utility of treatment manuals is controversial, especially with respect to how rigidly they should be implemented. This study examined therapist adherence across the course of CBT and how several patient characteristics influence the association between adherence and outcome. Patients diagnosed with panic disorder with agoraphobia (n = 220, 72.7% female, average age of 34.9 years) were treated in one of two CBT variations: with (T+) and without (T-) explicit therapist-guided exposure. Although adherence did not crucially influence outcome at a global level, results suggest that symptom severity and patients' motivation to continue treatment interacted with adherence to predict outcome. Importantly, these effects differed across timing and treatment conditions. Our findings showed the benefits of individualising the implementation of the treatment manual. [ABSTRACT FROM AUTHOR]

OBJECTIVE Suboptimal adherence to diabetes medications is prevalent and associated with unfavorable health outcomes, but it remains unclear what intervention content is necessary to effectively promote medication adherence in diabetes. In other disease contexts, the Information-Motivation-Behavioral skills (IMB) model has effectively explained and promoted medication adherence and thus may have utility in explaining and promoting adherence to diabetes medications. We tested the IMB model's hypotheses in a sample of adults with type 2 diabetes. RESEARCH DESIGN AND METHODS Participants (N = 314) completed an interviewer-administered survey and A1C test. Structural equation models tested the effects of diabetes medication adherence-related information, motivation, and behavioral skills on medication adherence and the effect of medication adherence on A1C. RESULTS The IMB elements explained 41% of the variance in adherence, and adherence explained 9% of the variance in A1C. As predicted, behavioral skills had a direct effect on adherence (β = 0.59; P < 0.001) and mediated the effects of information (indirect effect 0.08 [0.01-0.15]) and motivation (indirect effect 0.12 [0.05-0.20]) on adherence. Medication adherence significantly predicted glycemic control (β = -0.30; P < 0.001). Neither insulin status nor regimen complexity was associated with adherence, and neither moderated associations between the IMB constructs and adherence. CONCLUSIONS The results support the IMB model's predictions and identify modifiable and intervenable determinants of diabetes medication adherence. Medication adherence promotion interventions may benefit from content targeting patients' medication adherence-related information, motivation, and behavioral skills and assessing the degree to which change in these determinants leads to changes in medication adherence behavior. [ABSTRACT FROM AUTHOR]

The article focuses on a study on the comparison of adherence and persistence associated with the use of nebivolol and hydrochlorothiazide (HCTZ) in the treatment of hypertension. Topics include the meta-analysis of adherence and persistence of diuretics, b-blockers and calcium channel blockers, use of the Truven Health MarketScan Commercial and Medicare Supplemental Research Databases in the study and the use of Charlson Comorbidity Index score (CCI) for the comparison.

Objective: The progression of HIV infection depends not only on the combination of drugs and adherence to the Anti Retroviral therapy (ART), but also on various other factors. The survival of an HIV patient depends on interaction of these factors with the therapy. Material and Methods: The parametric approach with and without covariates have been used to analyze the survival data of HIV/AIDS patients. When covariates are not considered, survival distributions are fitted and best one chosen. The inclusion of covariates is analyzed using Censored Generalized Poisson Regression Model (CGPR). Results: For a retrospective right censored data of 1689 HIV/AIDS patients undergoing ART at the Ram Manohar Lohia Hospital, New Delhi, India, appropriate survival distributions in the absence of covariates are fitted. Using the Akaike Information Criterion, Gamma distribution is found to be the distribution of best fit. Assuming Gamma survival distribution with right censored survival time data, the mean survival time of AIDS patients using the method of maximum likelihood is found to be 11.14 years. Also, CGPR model for estimating the survival time while accounting for the impact of cofactors is used for the first time on the AIDS dataset. Conclusion: The advantage of using a CGPR model over the gamma right censored distribution is that the mean survival time of the AIDS patient undergoing ART can be estimated in the presence of significant prognostic factors. Using this model, age, gender, smoking status, alcoholism, WHO staging, improvement in CD4 count, opportunistic infections, number of visits and weight at initiation of ART are identified as significant prognostic factors effecting the survival time. On averaging the predicted survival times based on CGPR model, the mean survival time of AIDS patients on ART is found to be 12.12 years. [ABSTRACT FROM AUTHOR]

Background. High rates of second-line antiretroviral treatment (ART) failure are reported. The association with resistance and nonadherence on switching to second-line ART requires clarification.Methods. Using prospectively collected data from patients in South Africa, we constructed a cohort of patients switched to second-line ART (1 January 2003 through 31 December 2008). Genotyping and drug concentrations (lamivudine, nevirapine, and efavirenz) were measured on stored samples preswitch. Their association with viral load (VL) <400 copies/mL by 15 months was assessed using modified Poisson regression.Results. One hundred twenty-two of 417 patients (49% male; median age, 36 years) had genotyping (n = 115) and/or drug concentrations (n = 80) measured. Median CD4 count and VL at switch were 177 cells/µL (interquartile range [IQR], 77–263) and 4.3 log10 copies/mL (IQR, 3.8–4.7), respectively. Fifty-five percent (n = 44/80) had subtherapeutic drug concentrations preswitch. More patients with therapeutic vs subtherapeutic ART had resistance (n = 73): no major mutations (3% vs 51%), nonnucleoside reverse transcriptase inhibitor (94% vs 44%), M184V/I (94% vs 26%), and ≥1 thymidine analogue mutations (47% vs 18%), all P = .01; and nucleoside reverse transcriptase inhibitor (NRTI) cross-resistance mutations (26% vs 13%, P = .23). Following switch, 68% (n = 83/122) achieved VL <400 copies/mL. Absence of NRTI mutations and subtherapeutic ART preswitch were associated with failure to achieve VL <400 copies/mL.Conclusions. Nonadherence, suggested by subtherapeutic ART with/without major resistance mutations, significantly contributed to failure when switching regimen. Unresolved nonadherence, not NRTI resistance, drives early second-line failure. [ABSTRACT FROM AUTHOR]

Objective To study the immunologic effects of mannatide as the adjuvant of H1N1 split vaccine and explore mannatide's potential as a mucosal immune adjuvant. Methods H1N1 split vaccine was inoculated intramuscularly or intranasally to Balb/c mice in combination of mannatide. ELISA assay was employed to test the serum specific IgG level and the sIgA antibody level in nasal and bronchoalveolar lavages. MTT assay was used to perform the lymphocyte proliferation test. Results In the dose-effect test, the serum IgG antibodies and the sIgA levels in the nasal and bronchoalveolar lavages of mannatide adjuvant H1N1 vaccine groups were significantly higher than those of H1N1 vaccine group, either intramuscularly or intranasally. Stimulation of T lymphocytes after adjuvant immunization was stronger; the proliferation was significantly enhanced after stimulation with ConA in vitro. In the time-effect tests, the IgG and sIgA levels of adjuvant vaccine group remained higher than those of vaccine group for 12 weeks. Conclusion The results of our research suggest that mannatide put in intramuscular inoculation is a potential adjuvant which can promote both humoral and cellular immune responses. Mannatide put in intranasal inoculation can enhance the immunologic effect of H1N1 split vaccine. Therefore, mannatide has the potential of being a mucosal immune adjuvant. [ABSTRACT FROM AUTHOR]

A substantial proportion of the broadly neutralizing antibodies (bnAbs) identified in certain HIV-infected donors recognize glycan-dependent epitopes on HIV-1 gp120. Here we elucidate how the bnAb PGT 135 binds its Asn332 glycan-dependent epitope from its 3.1-Å crystal structure with gp120, CD4 and Fab 17b. PGT 135 interacts with glycans at Asn332, Asn392 and Asn386, using long CDR loops H1 and H3 to penetrate the glycan shield and access the gp120 protein surface. EM reveals that PGT 135 can accommodate the conformational and chemical diversity of gp120 glycans by altering its angle of engagement. Combined structural studies of PGT 135, PGT 128 and 2G12 show that this Asn332-dependent antigenic region is highly accessible and much more extensive than initially appreciated, which allows for multiple binding modes and varied angles of approach; thereby it represents a supersite of vulnerability for antibody neutralization. [ABSTRACT FROM AUTHOR]

Background: To identify factors and problems influencing treatment adherence in patients undergoing anti-VEGF therapy for neovascular age-related macular degeneration (AMD) under real-life conditions. Methods: Cross-sectional study was conducted of 95 patients receiving ranibizumab therapy on a pro re nata (PRN) regimen with monthly controls in a tertiary health care clinic. Monthly controls included best corrected visual acuity, slit-lamp examination and spectral-domain optical coherence tomography. Adherence was measured using Kaplan-Meier time-to-discontinuation analysis. Patients were asked to respond to a 16-item questionnaire covering items such as anxiety, subjective benefit, and financial issues of therapy. Results: Forty-two men and 53 women were included. After a mean follow-up time of 675 days (range 63-1008), adherence was 81.1 % (77/95). The mean number of follow-up visits was 19 (3-30), the mean number of intravitreal injections was ten (3-23). Seven patients withdrew from treatment due to subjective dissatisfaction with benefit. Other reasons for loss to follow-up were death in one case, serious general disease in three patients, and treatment options closer to home in five cases. Two patients cancelled further follow-up after treatment cessation due to terminal fibrosis. 62.1 % of patients were afraid of a negative examination result, whereas 19.0 % were afraid of intravitreal injections. A major problem was travel to and from the hospital (46.3 %), with 61.5 % of patients requiring escort. Conclusion: Despite necessary monthly visits, patients showed a high adherence to therapy. The major problem was travel to and from the hospital. From the patients' point of view, anxiety of a negative examination result was more pronounced than fear of intraocular injections, which would be an argument for continuous injections rather than for a PRN regimen. [ABSTRACT FROM AUTHOR]

Background Both atopic diseases and sleep disturbances have increased during recent decades, especially in children. Sleep is important for many aspects of immune regulation relevant in allergic diseases, and sleep disturbances are common in patients with such diseases. A connection between sleep disturbances and fatigue, and atopic disease is well established. However, the time course and putative causal relationships between these factors are obscure. Objective We aimed at investigating the developmental relationships between subjectively reported sleep disturbances and symptoms of atopic disease, from childhood to adolescence. Methods This longitudinal study used parent-report questionnaire data on symptoms of atopic disease, and sleep disturbances, from the Twin Study of Child and Adolescent Development ( TCHAD). Overall, 1480 twin pairs born in Sweden were approached first when children were 8-9 years old, and again later at 13-14 years old. Response rates were 75% and 72%. Data from the TCHAD questionnaires were linked to the Swedish Medical Birth Register based on personal identification numbers. Results Being overtired at age 8 increased the risk [ OR; 95% CI (2.59; 1.31-5.11)] to develop rhinitis symptoms at age 13, even when controlling for gender, previous rhinitis, Socio-economic status, birth weight and other sleep disturbances at age 8. Likewise, symptoms of asthma at age 8 was an independent risk factor for being overtired at age 13 [ OR; 95% CI (2.64; 1.44-4.84)], controlling for similar confounders. Conclusion & Clinical Relevance The findings from this study are consonant with the proposition that atopic disease and disturbed sleep are more than passively interrelated. Future research needs to delineate whether causal relationships between these problems are at hand and, if so, at what periods in development this applies. These results point to a need for clinicians to investigate sleep difficulties and treat impaired sleep in paediatric patients with atopic disease. [ABSTRACT FROM AUTHOR]

Background:: Nonadherence to treatment regimens for immunosuppressive agents is one of the major risk factors for allograft failure in kidney transplant recipients. The aim of this study was to estimate the relative effect of daily dosing on treatment adherence, not to identify how patients are non-adherent, in long-term kidney transplant recipients. Methods:: In January 2009, a cross-sectional, anonymous, and voluntary questionnaire survey was given to kidney transplant recipients who regularly visited Inoue Hospital. A self-reporting questionnaire underestimates nonadherence, but we reasoned that the effect of the dosing regimen should be estimated with relative accuracy by using the generalized ordered logit/partial proportional hazard odds model given that the distribution patterns in the degree of nonadherence have been shown to be similar with other measures. Results:: Of 336 eligible patients, 312 (92.9 %) participated in this study. Two hundred seventy-four patients (87.8 %) were more than 3 years post-transplant. Univariate analysis revealed that a single daily dose was significantly associated with better adherence. After controlling for age, sex, time since transplantation, and the number of prescribed drugs, the effect of a single daily dose still remained significant [odds ratio, 0.40 (95 % confidence interval, 0.19-0.81); p = 0.011]. Several sensitivity analyses yielded similar results. Conclusions:: To our knowledge, this is the first report that, in long-term kidney transplant recipients, a single daily regimen-one of few modifiable factors-might improve treatment adherence and allograft survival. [ABSTRACT FROM AUTHOR]

Despite the widespread prescription of highly effective lipid-lowering medications, such as the HMG-CoA reductase inhibitors (statins), a large portion of the population has lipid levels higher than the recommended goals. Treatment failures have been attributed to a variety of causes but the most important is likely to be poor adherence to therapy in the form of irregular or interrupted intake and the high frequency of discontinuation or lack of persistence. Adherence is a multidimensional phenomenon determined by the interplay of patient factors, physician factors, and health care system factors. Patients' knowledge and beliefs about their illness, motivation to manage it, confidence in their ability to engage in illness-management behaviors, and expectations regarding the outcome of treatment and the consequences of poor adherence interact to influence adherence behavior. Patient-related factors account for the largest incremental explanatory power in predicting adherence. This article provides an overview of this critical issue, focusing on patient role in determining adherence level to lipid-lowering therapy. [ABSTRACT FROM AUTHOR]

The immune adherence (IA) between the porcine erythrocytes and the opsonized Escherichia coli carried green fluorescent protein gene (GFP- E.coli) were detected by the fluorescence microscopy, scanning electron microscopy (SEM) and transmission electron microscopy (TEM) with an attempt to verify the existence of IA between the porcine erythrocytes and complemented-opsonized microbes. Under fluorescence microscopy, GFP- E.coli opsonized by fresh rabbit serum complement adhered to the erythrocytes and could not be detached by PBS washing, and no IA was observed between the erythrocytes and nonopsonized GFP- E.coli after co-incubation. SEM and TEM also revealed the existence of IA between the serum complement-opsonized GFP- E.coli membrane and the erythrocyte membrane. The partial complement receptor type 1 (CR1)-like gene from porcine was generated by RT-PCR and rapid amplification of cDNA 3' end (3' RACE) (157bp and 578bp), both of which have high similarity with published mammal's CR1 gene. The sequences were spliced based on homology comparison and submitted to GenBank (GenBank Accession No. JX033989). These results indicated that the porcine erythrocytes were able to bind to the opsonized microorganisms. Furthermore, the sequencing results confirmed that the CR1-like gene exists in porcine. [ABSTRACT FROM AUTHOR]

Introduction: The low adherence to pharmacologic treatment comprises one of the greatest threats to the effectiveness of treatment of patients with HIV. The success of this therapy depends on the high degree of adherence to treatment. Objectives: To determine the degree adherence to pharmacotherapeutic treatment of HIV carriers in Alfenas- MG and to evaluate the predictor factors of adherence. Methodology: This is a quantitative research, exploratory, descriptive and analytical. The survey was conducted in the Dispensing Antiretroviral Medicines Unit (DAMU) and the Counseling and Testing Center (CTC) of the city of Alfenas, where 129 users of antiretroviral drugs were interviewed. It was applied the adherence test CEAT-HIV. For the analysis of results, were done the chi-square and Fisher's exact test, to 5% of significance level. Results: There was a predominance of male patients (57.4%), 39% were aged between 39 to 48 years, mostly single (37.2%), 23% had not completed elementary school and 42% had family incomes up to the minimum wage. Most patients acquired the disease through unprotected sex (77%); they were diagnosed for more than 5 years (33.3%), that don't drink or smoke (58% and 63% respectively). Regarding adherence, only 37.2% had strict adherence, 30.2% good adherence and 32.6% low adherence. The variables that were shown dependent on adherence were gender (pvalor = 0.02) and viral load (pvalor = 0.01). Conclusion: Although the patient is often the focus of interventions to improve adherence to treatment, it is necessary that health care professionals and health services assume co-responsibility in this process. [ABSTRACT FROM AUTHOR]

Background Treatment adherence has been recognized as an important issue in the management of chronic diseases such as psoriasis. Objective The aim of this work was to analyse data about topical treatment adherence in psoriasis. Methods Systematic literature review (62 references) between 1980 and 2011 (database: PubMed, Embase and Cochrane; Mesh keywords: Patient Compliance [Mesh] OR Medication Adherence [Mesh] AND Psoriasis [Mesh]; limits: date of publication >1980, humans subjects, written in French or English, aged ≥19 years). Two parameters were evaluated: (i) the ratio of number of product applications performed vs. number of applications expected according to physician recommendations, (ii) the ratio of amount of product used vs. amount of product prescribed. Results A total of 22 studies were selected. Nine studies reported on the frequency of topical treatment application in a real world setting. Five studies showed a frequency of applications varying between 50% and 60% of those expected. Because of the high variability in medication adherence assessment methods, the data could not be combined. Twelve articles reported on the frequency of topical treatment application in randomized controlled trials with adherence varying between 55% and 100%. Concerning the amount of product use, four studies showed patients applied between 35% and 72% of the recommended dose during a treatment period of 14 days to 8 weeks. The most frequently mentioned reasons for non-adherence to topical treatment were low efficacy, time consumption and poor cosmetic characteristics of topical agents. Patients experiencing adherence issues were significant younger, were men, had younger age at onset of psoriasis and had a higher self-assessed severity. To improve adherence, the following strategies were suggested: to give patients information about psoriasis, to recognize social impact, to give written instructions for use such as a care plan, to explain side effects of topical therapies, to choose treatment and its cosmetic properties in agreement with the patient. Conclusions Literature data about topical treatment adherence are heterogeneous and scarce. They confirm the limited topical treatment adherence in psoriasis in real life, much lower than what is reported in randomized controlled trials. Therapeutic education and clear instructions on the use of topical agents are necessary to improve adherence. Studies are needed to identify predictors of limited adherence and to identify interventions improving adherence to topical medications in psoriasis. [ABSTRACT FROM AUTHOR]

Background: Safe drinking water is critical for health. Household water treatment (HWT) has been recommended for improving access to potable water where existing sources are unsafe. Reports of low adherence to HWT may limit the usefulness of this approach, however. Methods and Findings: We constructed a quantitative microbial risk model to predict gains in health attributable to water quality interventions based on a range of assumptions about pre-treatment water quality; treatment effectiveness in reducing bacteria, viruses, and protozoan parasites; adherence to treatment interventions; volume of water consumed per person per day; and other variables. According to mean estimates, greater than 500 DALYs may be averted per 100,000 person-years with increased access to safe water, assuming moderately poor pre-treatment water quality that is a source of risk and high treatment adherence (>90% of water consumed is treated). A decline in adherence from 100% to 90% reduces predicted health gains by up to 96%, with sharpest declines when pre-treatment water quality is of higher risk. Conclusions: Results suggest that high adherence is essential in order to realize potential health gains from HWT. [ABSTRACT FROM AUTHOR]

Abstract: We evaluated the role of vaccine candidate surface proteins, PhtD and PhtE as antigens with functional importance for Streptococcus pneumoniae (pneumococci) in adherence to nasopharyngeal (D562) and lung (A549) epithelial cell lines. Comparing TIGR4 to PhtD and PhtE- isogenic mutants, a 40% (p =0.001) and 42% (p =0.002) drop in the number of epithelial cells with adherent pneumococci was observed to both cells lines with the mutants, as quantitated using flow cytometry. We expressed PhtD and PhtE on the surface of Escherichia coli and demonstrated that when PhtD and PhtE were surface expressed on E. coli, adherence increased to D562 and A549 cells, compared with the E. coli parent strain (p =0.005, 0.013 for D562 and p =0.034, p =0.035 for A549). Using flow cytometry and confocal microscopy we found that pneumococci aggregated in the presence of human serum IgG, leading to a non-specific drop in adherence. Therefore IgG Fab fragments were prepared to study the functional role of PhtD and PhtE-specific Fabs in blocking adherence. The addition of 1μg of IgG Fab from adult sera led to a 34% reduction (p =0.002) and from children a 20% (p =0.023) reduction in D562 epithelial cells with adherent pneumococci. In purified IgG from adult sera, the depletion of PhtD and PhtE specific Fab from total IgG Fab resulted in a significant increase in the number of D562 epithelial cells with adherent pneumococci (p =0.005 for PhtD and p =0.024 for PhtE). We conclude that antibody directed to PhtD and PhtE adhesins of pneumococci, if raised by vaccination, may function to prevent pneumococcal adherence to human airway epithelial cells. [Copyright &y& Elsevier]

The immune adherence (IA) between the porcine erythrocytes and the opsonized Escherichia coli carried green fluorescent protein gene (GFP-E.coli) were detected by the fluorescence microscopy, scanning electron microscopy (SEM) and transmission electron microscopy (TEM) with an attempt to verify the existence of IA between the porcine erythrocytes and complemented- opsonized microbes. Under fluorescence microscopy, GFP-E.coli opsonized by fresh rabbit serum complement adhered to the erythrocytes and could not be detached by PBS washing, and no IA was observed between the erythrocytes and nonopsonized GFP-E.coli after co-incubation. SEM and TEM also revealed the existence of IA between the serum complement-opsonized GFP-E.coli membrane and the erythrocyte membrane. The partial complement receptor type I (CR 1)-like gene from porcine was generated by RT-PCR and rapid amplification of cDNA 3' end (3' RACE) (I 57bp and 578bp), both of which have high similarity with published mammal's CR1 gene. The sequences were spliced based on homology comparison and submitted to GenBank (GenBank Accession No. JX033989). These results indicated that the porcine erythrocytes were able to bind to the opsonized microorganisms. Furthermore, the sequencing results confirmed that the CR1-like gene exists in porcine. [ABSTRACT FROM AUTHOR]

OBJECTIVES:Nonadherence is an issue in the management of inflammatory bowel disease (IBD), and no validated screening tool is available. We aimed to determine whether scores from a self-reported adherence survey correlated with pharmacy refill data as a reliable measure of medication adherence.METHODS:We used the eight item, self-reported Morisky Medication Adherence Scale. Each question is worth a point, with a maximum score of 8. Pharmacies were contacted for refill information for the previous 3 months, then 3 and 6 months from enrollment. Refill data were recorded for each time interval as the medication possession ratio (MPR); adherence was defined as >80%. Analysis of variance was used to determine the relationship between survey scores and MPR by drug class.RESULTS:One hundred fifty outpatients were enrolled, of whom 94 had Crohn's disease and 56 had ulcerative colitis; 89 were female. At baseline, 47% of patients were on 5-aminosalicylic acid (5-ASA), 54% an immunomodulator, 15% infliximab, 8% an injectable biologic, and 6% budesonide. The median adherence score was 7. Fifty-two percent stated they 'rarely' missed a dose of medication. The median adherence score, as defined by refill data, ranged from 0% (injectable biologic) to 75% (infliximab) by drug class. Only those on an immunomodulator had a survey score that positively correlated with adherence.CONCLUSIONS:Only those on a thiopurine were likely to have a score predicting adherence behavior. Adherence to therapy for IBD is complex and cannot be predicted reliably by a self-reported survey tool validated for other chronic conditions. [ABSTRACT FROM AUTHOR]

The article presents the findings of a research on adherence rates to subsidized, over-the-counter artemisinin combination therapy (ACT) in rural Uganda. It discusses the methodology of the research. It concludes that adherence to subsidized ACT purchased over-the-counter was found to be moderate.

Type I interferon (IFN) induction is a crucial anti-pathogen response mediated by innate immune stimulation. Although it has been appreciated for some time that the presence of pathogen DNA within a cell leads to a type I IFN response, it is only in the past few years that some of the key signalling proteins and DNA sensors that regulate this response have been uncovered. Here, we review the nature of these DNA sensors, which include a new family of pattern recognition receptors termed the AIM2-like receptors, and consider the implications of their discovery for understanding emerging principles of innate immune DNA sensing. Furthermore, we discuss how their discovery provides a rationale as to why accumulation of self-DNA mediates IFN-dependent autoimmunity. [ABSTRACT FROM AUTHOR]

Abstract: An indigenous calcifying bacterial strain CR1, identified as Kocuria flava, was isolated from soil of a mining area, Urumqi, China. An extensive copper bioremediation capacity of this isolate was studied based on microbially induced calcite precipitation (MICP). K. flava CR1 removed 97% of copper when initial Cu concentration was 1000mgL−1. The isolate produced significant amount of urease (472UmL−1), an enzyme that leads to calcite precipitation. The isolate removed 95% of copper from contaminated soil. The MICP process in bioremediation was further confirmed by FTIR and XRD analyses. FTIR analysis showed two different forms of calcium carbonate, i.e., calcite and aragonite, and the results were well supported by XRD. For the first time, the ability of K. flava has been documented in the bioremediation of polluted soil. This study showed that MICP-based bioremediation by K. flava is a viable, environmental friendly technology for cleaning-up the copper-contaminated site. [Copyright &y& Elsevier]

Effective blood pressure therapy is a central health goal, although several studies worldwide show inacceptable control rates. Lack of patient compliance is a major factor responsible for the differences between clinical triáls results and real effectiveness in daily medical practice, contributing to an insufficient control of the cardiovascular risk. Non-adherence is probably an important source of preventable cardiovascular morbidity and mortality and the efforts should be addressed to improve and increase the adherence y persistence of the patients to the antihypertensive treatment. [ABSTRACT FROM AUTHOR]

Abstract: Phagocytes play a central role in immune defense. Their dysfunction predisposes to infections. This study determined the expression level of nine receptors involved in Aspergillus immune response as well as the values of phagocytosis and production of radical oxygen species after Aspergillus stimulation, in a healthy adult population. The expression values of the CD11b, CD11c, CD14, CD18, CD35, CD181, CD182, CD282 and CD284 receptors on peripheral human monocytes and granulocytes was established. A heterogenous expression of the CD282 on granulocytes was observed as CD181, CD182 and CD284 on monocytes. Similarly, we observed considerable variation in the expression of these receptors over time. Only CD282 on granulocytes varied with sex. No variation with age was observed. Adherence of Aspergillus conidia to phagocytes was dependent of individual, sex, age and time. A better characterization of these innate immunity parameters is necessary to develop in the future an immunologic surveillance strategy for transplant recipients. [Copyright &y& Elsevier]

The extracellular adherence protein (Eap) from Staphylococcus aureus has been suggested as a vaccine candidate and for therapeutic use due to its immunomodulating and antiangiogenic properties; however, little is known about anti-Eap antibodies in humans. We determined anti-Eap antibody titers by enzyme-linked immunosorbent assay and Western blot and measured serum samples from 92 patients with proven S. aureus infections and 93 healthy controls. The functionality of antibodies was assessed by a phagocytosis assay using Eap-coated fluorescent microspheres. Antibodies were detected in all human samples, but not in mice. Patients showed significantly higher titers than controls [immunoglobulin M (IgM), P=0.007; IgG, P<0.0001]. Patients with deep or severe infections showed higher titers than those with superficial or mild disease. Eap alone was sufficient to promote phagocytosis by peripheral blood mononuclear cell and granulocytes that was moderately enhanced in the presence of human serum, but no correlation was found with the levels of anti-Eap antibodies. Anti-Eap antibodies are prevalent in all tested humans and correlate with the severity of S. aureus infection; however, they do not seem to provide protection against invasive infections. Before considering Eap for therapy or as a vaccine candidate, further studies are warranted to assess the impact of the interference between Eap and its specific antibodies. [ABSTRACT FROM AUTHOR]