Self-reported nonadherence to antiretroviral therapy as a predictor of viral failure and mortality.

OBJECTIVE To determine the effect of nonadherence to antiretroviral therapy (ART) on virologic failure and mortality in naive individuals starting ART. DESIGN Prospective observational cohort study. METHODS Eligible individuals enrolled in the Swiss HIV Cohort Study, started ART between 2003 and 2012, and provided adherence data on at least one biannual clinical visit. Adherence was defined as missed doses (none, one, two, or more than two) and percentage adherence (>95, 90-95, and <90) in the previous 4 weeks. Inverse probability weighting of marginal structural models was used to estimate the effect of nonadherence on viral failure (HIV-1 viral load >500 copies/ml) and mortality. RESULTS Of 3150 individuals followed for a median 4.7 years, 480 (15.2%) experienced viral failure and 104 (3.3%) died, 1155 (36.6%) reported missing one dose, 414 (13.1%) two doses and, 333 (10.6%) more than two doses of ART. The risk of viral failure increased with each missed dose (one dose: hazard ratio [HR] 1.15, 95% confidence interval 0.79-1.67; two doses: 2.15, 1.31-3.53; more than two doses: 5.21, 2.96-9.18). The risk of death increased with more than two missed doses (HR 4.87, 2.21-10.73). Missing one to two doses of ART increased the risk of viral failure in those starting once-daily (HR 1.67, 1.11-2.50) compared with those starting twice-daily regimens (HR 0.99, 0.64-1.54, interaction P = 0.09). Consistent results were found for percentage adherence. CONCLUSION Self-report of two or more missed doses of ART is associated with an increased risk of both viral failure and death. A simple adherence question helps identify patients at risk for negative clinical outcomes and offers opportunities for intervention.

Mortality associated with discordant responses to antiretroviral therapy in resource-constrained settings

Objectives: We assessed mortality associated with immunologic and virologic patterns of response at 6 months of highly active antiretroviral therapy (HAART) in HIV-infected individuals from resource-limited countries in Africa and South America. Methods: Patients who initiated HAART between 1996 and 2007, aged 16 years or older, and had at least 1 measurement (HIV-1 RNA plasma viral load or CD4 cell count) at 6 months of therapy (3-9 month window) were included. Therapy response was categorized as complete, discordant (virologic only or immunologic only), and absent. Associations between 6-month response to therapy and all-cause mortality were assessed by Cox proportional hazards regression. Robust standard errors were calculated to account for intrasite correlation. Results: A total of 7160 patients, corresponding to 15,107 person-years, were analyzed. In multivariable analysis adjusted for age at HAART initiation, baseline clinical stage and CD4 cell count, year of HAART initiation, clinic, occurrence of an AIDS-defining condition within the first 6 months of treatment, and discordant and absent responses were associated with increased risk of death. Conclusions: Similar to reports from high-income countries, discordant immunologic and virologic responses were associated with intermediate risk of death compared with complete and no response in this large cohort of HIV-1 patients from resource-limited countries. Our results support a recommendation for wider availability of plasma viral load testing to monitor antiretroviral therapy in these settings.

Adherence to the medical regime in patients with heart failure

To assess adherence to medical treatment in patients with heart failure (HF) using a specific questionnaire and measurement of the serum concentration of digoxin.

Effects of adherence to guidelines for the control of major cardiovascular risk factors on outcomes in the REduction of Atherothrombosis for Continued Health (REACH) Registry Europe

To examine the impact of cardiovascular risk factor control on 3-year cardiovascular event rates in patients with stable symptomatic atherothrombotic disease in Europe.

Adherence to ESMO clinial recommendations for prophylaxis of chemotherapy-induced nausea and vomiting

We assessed adherence to the European Society of Medical Oncology (ESMO)/Multinational Association of Supportive Care in Cancer recommendations for prophylaxis of chemotherapy-induced nausea and vomiting (CINV) at our institution.

Atopic dermatitis - from new pathophysiologic insights to individualized therapy

Recently, important novel insights into the complex pathophysiology of atopic dermatitis (AD) have been gained. However, in most cases the therapy of AD is limited to base line therapy with emollients combined with symptomatic, rather general immunosuppressive treatment approaches of the flare-ups. Latest research findings together with experiences from daily clinical practice, which support the concept that a combination of general disease features together with specific trigger factors in the individual patients drive the disease, might be helpful for a subclassification of patients with AD based on the most relevant pathophysiologic modifications. Subclassification of patients with AD seems indispensable to introduce rationale-based, individualized treatment approaches of AD, which target specific modified pathways. In this review, we provide an overview about a selection of pathophysiologic pathways, which hold promise to represent targets of such therapeutic approaches in the near future.

Peri-implantitis susceptibility as it relates to periodontal therapy and supportive care

To assess the long-term survival of implants inserted in periodontally susceptible patients and to investigate the influence of residual pockets on the incidence of peri-implantitis and implant loss.

Completeness of reporting in randomized controlled trials of 3 vaccines: a review of adherence to the CONSORT checklist

Clear reporting of randomized controlled trials (RCTs) of vaccines is important for understanding results and assessing their validity. The CONsolidated Standards of Reporting Trials (CONSORT) statement provides guidance to help authors reporting RCTs. The objective was to assess the completeness of reporting of RCTs of vaccines based on the CONSORT 2010 checklist.

Fertility preservation methods in young women with systemic lupus erythematosus prior to cytotoxic therapy: experiences from the FertiPROTEKT network

Despite new treatment options, some patients with systemic lupus erythematosus (SLE) need to be treated with the cytotoxic agent cyclophosphamide (CYC). Unlike malignant disease, there are no recommendations for ovarian protection in SLE. The clinical experience of the FertiPROTEKT network as well as recommendations after literature review will be presented in this paper.

Hemophilia A pseudoaneurysm in a patient with high responding inhibitors complicating total knee arthroplasty: embolization: a cost-reducing alternative to medical therapy

Joint hemorrhages are very common in patients with severe hemophilia. Inhibitors in patients with hemophilia are allo-antibodies that neutralize the activity of the clotting factor. After total knee replacement, rare intra-articular bleeding complications might occur that do not respond to clotting factor replacement. We report a 40-year-old male with severe hemophilia A and high responding inhibitors presenting with recurrent knee joint hemorrhage after bilateral knee prosthetic surgery despite adequate clotting factor treatment. There were two episodes of marked postoperative hemarthrosis requiring extensive use of substitution therapy. Eleven days postoperatively, there was further hemorrhage into the right knee. Digital subtraction angiography diagnosed a complicating pseudoaneurysm of the inferior lateral geniculate artery and embolization was successfully performed. Because clotting factor replacement therapy has proved to be excessively expensive and prolonged, especially in patients with inhibitors, we recommend the use of cost-effective early angiographic embolization.

Objective response to radiation therapy and long-term survival of patients with WHO grade II astrocytic gliomas with known LOH 1p/19q status

BACKGROUND: WHO grade II gliomas are often approached by radiation therapy (RT). However, little is known about tumor response and its potential impact on long-term survival. PATIENTS AND METHODS: Patients subjected to RT were selected from the own database of WHO grade II gliomas diagnosed between 1991 and 2000. The volumetric tumor response after RT was assessed based on magnetic resonance imaging and graded according to standard criteria as complete, partial (PR, >or= 50%), or minor (MR, 25% to <50%). RESULTS: There were 24 astrocytomas and three oligoastrocytomas. 21 patients (78%) were dead at follow-up (mean survival 74 months). None of the patients had chemotherapy. Objective response occurred in 14 patients (52%, five PR and nine MR) but was not associated with overall survival. The vast majority of the tumors had no loss of heterozygosity (LOH) 1p and/or 19q (86%). CONCLUSION: Approximately 50% of patients with astrocytic WHO grade II gliomas respond to RT despite the absence of LOH for 1p/19q. The potential predictive factors for response and the impact of response on overall survival remain unclear.

Psychobiological responses to drug cues before and after methadone intake in heroin-dependent patients: A pilot study

Craving and stress frequently drive compulsive heroin use. Although methadone attenuates craving, drug-conditioned stimuli can trigger craving and possibly stress arousal in heroin-dependent patients receiving methadone maintenance. This study investigated drug cue-related craving, affectivity, and cortisol reactivity in 16 methadone-maintained patients before and after daily methadone. Unexpectedly, drug cues significantly increased craving after (t[15]=-4.27, p=0.001), but not before methadone intake. Patients displayed blunted cortisol response after post-methadone drug cues (t[15]=3.05, p=0.008) suggesting dissociated craving and cortisol reactivity after methadone intake of possible clinical relevance.

Monotoring adherence to prescribed medication in type 2 diabetic patients treated with sulfonylureas

Data on adherence to prescribed medication amongst diabetics are scarce. The purpose of this study was to collect information about the dynamics and patterns of compliance of elderly patients with type 2 diabetes mellitus on oral treatment by using different assessment techniques.

Cryopreservation and autotransplantation of human ovarian tissue prior to cytotoxic therapy--a technique in its infancy but already successful in fertility preservation

Increasing survival rates in young cancer patients, new reproductive techniques and the growing interest in quality of life after gonadotoxic cancer therapies have placed fertility preservation as an important issue to oncologists, fertility specialists and patients. Several techniques are now available for fertility preservation in these patients. A new promising method is cryopreservation and transplantation of ovarian cortex. Ovarian tissue can be extracted by laparoscopy without any significant delay of gonadotoxic therapy. The tissue can be cryopreserved by specialised centres of reproductive medicine and transplanted in case the women experience premature ovarian failure (POF). This review summarises the European expertise on cryopreservation and transplantation of ovarian tissue, following around 30 reported transplantations globally, resulting in six live births and several ongoing pregnancies. It emphasises that fertility preservation by the cryopreservation of ovarian tissue is a new but already a successful clinical option, which can be considered for selected cancer patients.