Adherence to anti-hypertensive treatment within a chronic disease management program: A longitudinal, retrospective study

Objective This study assessed pharmacological treatment adherence using the Morisky-Green Test and identified related variables. Method A longitudinal and retrospective study examined 283 patients with hypertension (62.5% women, 73.4 [10.9] years old) who were being monitored by a chronic disease management program for 17 months between 2011 and 2012. Nurses performed all the actions of the program, which consisted of advice via telephone and periodic home visits based on the risk stratification of the patients. Results A significant increase in treatment adherence (25.1% vs. 85.5%) and a decrease in blood pressure were observed (p<0.05). Patients with hypertension and chronic renal failure as well as those treated using angiotensin-converting enzyme inhibitors were the most adherent (p<0.05). Patients with hypertension who received angiotensin receptor blockers were less adherent (p<0.05). Conclusions Strategies such as nurse-performed chronic disease management can increase adherence to anti-hypertensive treatment and therefore contribute to the control of blood pressure, minimizing the morbidity profiles of patients with hypertension.

A non-randomized direct comparison of cognitive-behavioral short- and long-term treatment for binge eating disorder

Background: To compare treatment outcomes of a cognitive-behavioral long-term (CBT-L) and short-term (CBT-S) treatment for binge eating disorder (BED) in a non-randomized comparison and to identify moderators of treatment outcome. Methods: 76 female patients with BED participated in the study: 40 in CBT-L and 36 in CBT-S. Outcome values were compared at the end of the active treatment phase (16 sessions for CBT-L, 8 sessions for CBT-S) and at 12-month follow-up. Results: Both treatments produced significant reductions in binge eating. At the end of active treatment, but not at the end of follow-up, effects of primary outcomes (e.g. remission from binge eating, EDE shape concern) were better for CBT-L than for CBT-S. Dropout rates were significantly higher in CBT-L (35%) than in CBT-S (14%). Moderator analyses revealed that treatment efficacy for rapid responders and individuals exhibiting high scores on the mixed dietary negative affect subtype differed between the CBT-L and CBT-S with respect to objective binges, restraint eating and eating concern. Conclusion: Findings suggest that CBT in general represents an effective treatment for BED, but that subgroups of patients might profit more from a prolonged treatment. Short, lessintensive CBT treatments could nevertheless be a viable option in the treatment of BED.

Home and hospital treatment of acute seizures in children with nasal midazolam.

Rectal diazepam is widely used in the treatment of acute seizures in children but has some disadvantages. Nasal/sublingual midazolam administration has been recently investigated for this purpose but never at home or in a general paediatric hospital. The aim of this open study was to determine the efficacy, the tolerance and the applicability of nasal midazolam during acute seizures in children both in hospital and at home. We included known epileptic children for treatment at home and all children with acute seizures in the hospital. In all, 26 children were enrolled, 11 at home and 17 in the hospital (including two treated in both locations); only one had simple febrile seizure. They had a total of 125 seizures; 122 seizures (98%) stopped within 10 minutes (average 3.6 minutes). Two patients in the hospital did not respond and in three, seizures recurred within 3 hours. None had serious adverse effects. Parents had no difficulties administering the drug at home. Most of those who were using rectal diazepam found that nasal midazolam was easier to use and that postictal recovery was faster. Among 15 children who received the drug under electroencephalogram monitoring (six without clinical seizures), the paroxysmal activity disappeared in ten and decreased in three. Nasal midazolam is efficient in the treatment of acute seizures. It appears to be safe and most useful outside the hospital in severe epilepsies, particularly in older children because it is easy for parents to use. These data should be confirmed in a larger sample of children. Its usefulness in febrile convulsions also remains to be evaluated.

LIF and sIL-2R plasma concentrations in IVF patients on the day of embryo transfer: predictive markers of IVF outcome.

Successful implantation is still the limiting step in IVF. We hypothesized that maternal plasma concentrations of certain cytokines at the time of embryo transfer could predict the likelihood of successful implantation and pregnancy. sIL-2R, IL-6, LIF, and MMP2 concentrations were measured in plasma from 160 IVF patients (natural and stimulated IVF cycles) on the morning of the embryo transfer (ET0) and 14days later (ET+14). Patients were ultimately subdivided into four groups depending on the IVF treatment outcome (pregnancy failure, biochemical pregnancy, first-trimester miscarriage and normal term delivery). In natural and stimulated IVF cycles at ET0, sIL-2R concentrations were threefold higher in biochemical pregnancies than in pregnancy failures (P=0.020), and in natural cycles only, 2.5-fold higher in normal term deliveries than in pregnancy failures (P=0.023). Conversely, in natural and stimulated IVF cycles at ET0, LIF concentrations were one third lower in biochemical pregnancies/first-trimester miscarriages compared with pregnancy failures (P=0.042). We suggest that high sIL-2R and low LIF concentrations in maternal plasma on the morning of the embryo transfer might be associated with increased risks of early pregnancy loss, while a basal level of sIL-2R is necessary for normal term delivery outcome. Both cytokine measurements might therefore be useful in the management of IVF patients, and modulation of their concentrations could be investigated as a therapeutic alternative for women with abnormal concentrations at the time of embryo transfer.

Leadership in cardiac surgery.

Despite the efficacy of cardiac surgery, less invasive interventions with more uncertain long-term outcomes are increasingly challenging surgery as first-line treatment for several congenital, degenerative and ischemic cardiac diseases. The specialty must evolve if it is to ensure its future relevance. More importantly, it must evolve to ensure that future patients have access to treatments with proven long-term effectiveness. This cannot be achieved without dynamic leadership; however, our contention is that this is not enough. The demands of a modern surgical career and the importance of the task at hand are such that the serendipitous emergence of traditional charismatic leadership cannot be relied upon to deliver necessary change. We advocate systematic analysis and strategic leadership at a local, national and international level in four key areas: Clinical Care, Research, Education and Training, and Stakeholder Engagement. While we anticipate that exceptional individuals will continue to shape the future of our specialty, the creation of robust structures to deliver collective leadership in these key areas is of paramount importance.

Introducing systematic dispatcher-assisted cardiopulmonary resuscitation (telephone-CPR) in a non-Advanced Medical Priority Dispatch System (AMPDS): implementation process and costs.

OBJECTIVE: In order to improve the quality of our Emergency Medical Services (EMS), to raise bystander cardiopulmonary resuscitation rates and thereby meet what is becoming a universal standard in terms of quality of emergency services, we decided to implement systematic dispatcher-assisted or telephone-CPR (T-CPR) in our medical dispatch center, a non-Advanced Medical Priority Dispatch System. The aim of this article is to describe the implementation process, costs and results following the introduction of this new "quality" procedure. METHODS: This was a prospective study. Over an 8-week period, our EMS dispatchers were given new procedures to provide T-CPR. We then collected data on all non-traumatic cardiac arrests within our state (Vaud, Switzerland) for the following 12months. For each event, the dispatchers had to record in writing the reason they either ruled out cardiac arrest (CA) or did not propose T-CPR in the event they did suspect CA. All emergency call recordings were reviewed by the medical director of the EMS. The analysis of the recordings and the dispatchers' written explanations were then compared. RESULTS: During the 12-month study period, a total of 497 patients (both adults and children) were identified as having a non-traumatic cardiac arrest. Out of this total, 203 cases were excluded and 294 cases were eligible for T-CPR. Out of these eligible cases, dispatchers proposed T-CPR on 202 occasions (or 69% of eligible cases). They also erroneously proposed T-CPR on 17 occasions when a CA was wrongly identified (false positive). This represents 7.8% of all T-CPR. No costs were incurred to implement our study protocol and procedures. CONCLUSIONS: This study demonstrates it is possible, using a brief campaign of sensitization but without any specific training, to implement systematic dispatcher-assisted cardiopulmonary resuscitation in a non-Advanced Medical Priority Dispatch System such as our EMS that had no prior experience with systematic T-CPR. The results in terms of T-CPR delivery rate and false positive are similar to those found in previous studies. We found our results satisfying the given short time frame of this study. Our results demonstrate that it is possible to improve the quality of emergency services at moderate or even no additional costs and this should be of interest to all EMS that do not presently benefit from using T-CPR procedures. EMS that currently do not offer T-CPR should consider implementing this technique as soon as possible, and we expect our experience may provide answers to those planning to incorporate T-CPR in their daily practice.

MGMT promoter methylation is prognostic but not predictive for outcome to adjuvant PCV chemotherapy in anaplastic oligodendroglial tumors: a report from EORTC Brain Tumor Group Study 26951.

PURPOSE: O6-methylguanine-methyltransferase (MGMT) promoter methylation has been shown to predict survival of patients with glioblastomas if temozolomide is added to radiotherapy (RT). It is unknown if MGMT promoter methylation is also predictive to outcome to RT followed by adjuvant procarbazine, lomustine, and vincristine (PCV) chemotherapy in patients with anaplastic oligodendroglial tumors (AOT). PATIENTS AND METHODS: In the European Organisation for the Research and Treatment of Cancer study 26951, 368 patients with AOT were randomly assigned to either RT alone or to RT followed by adjuvant PCV. From 165 patients of this study, formalin-fixed, paraffin-embedded tumor tissue was available for MGMT promoter methylation analysis. This was investigated with methylation specific multiplex ligation-dependent probe amplification. RESULTS: In 152 cases, an MGMT result was obtained, in 121 (80%) cases MGMT promoter methylation was observed. Methylation strongly correlated with combined loss of chromosome 1p and 19q loss (P = .00043). In multivariate analysis, MGMT promoter methylation, 1p/19q codeletion, tumor necrosis, and extent of resection were independent prognostic factors. The prognostic significance of MGMT promoter methylation was equally strong in the RT arm and the RT/PCV arm for both progression-free survival and overall survival. In tumors diagnosed at central pathology review as glioblastoma, no prognostic effect of MGMT promoter methylation was observed. CONCLUSION: In this study, on patients with AOT MGMT promoter methylation was of prognostic significance and did not have predictive significance for outcome to adjuvant PCV chemotherapy. The biologic effect of MGMT promoter methylation or pathogenetic features associated with MGMT promoter methylation may be different for AOT compared with glioblastoma.

Transapical aortic 'valve-in-valve' procedure for degenerated stented bioprosthesis.

Standard surgical aortic valve replacement with a biological prosthesis remains the treatment of choice for low- and mid-risk elderly patients (traditionally >65 years of age) suffering from severe symptomatic aortic valve stenosis or insufficiency, and for young patients with formal contraindications to long-lasting anticoagulation. Unfortunately, despite the fact that several technical improvements have noticeably improved the resistance of pericardial and bovine bioprostheses to leaflet calcifications and ruptures, the risk of early valve failure with rapid degeneration still exists, especially for patients under haemodialysis and for patients <60 years of age at the time of surgery. Until now, redo open heart surgery under cardiopulmonary bypass and on cardioplegic arrest was the only available therapeutic option in case of bioprosthesis degeneration, but it carried a higher surgical risk when elderly patients with severe concomitant comorbidities were concerned. Since a few years, the advent of new transcatheter aortic valve procedures has opened new horizons in cardiac surgery and, in particular, the possibility of implanting stented valves within the degenerated stented bioprosthesis, the so-called 'valve-in-valve' (VinV) concept, has become a clinical practice in experienced cardiac centres. The VinV procedure represents a minimally invasive approach dedicated to high-risk redo patients, and published preliminary reports have shown a success rate of 100% with absence of significant valvular leaks, acceptable transvalvular gradients and low complication rate. However, this procedure is not riskless and the most important concerns are about the size mismatch and the right positioning within the degenerated bioprosthesis. In this article, we review the limited available literature about VinV procedures, underline important technical details for the positioning and provide guidelines to prevent valve-prosthesis mismatch comparing the three sizes of the only commercially available transapical device, the Edwards Sapien, with the inner diameter of three of the most commonly used stented bioprostheses.

Phase II study of imatinib in patients with recurrent gliomas of various histologies: a European Organisation for Research and Treatment of Cancer Brain Tumor Group Study.

PURPOSE: To evaluate the safety and the efficacy of imatinib in recurrent malignant gliomas. PATIENTS: AND METHODS: This was a single-arm, phase II study. Eligible patients had recurrent glioma after prior radiotherapy with an enhancing lesion on magnetic resonance imaging. Three different histologic groups were studied: glioblastomas (GBM), pure/mixed (anaplastic) oligodendrogliomas (OD), and low-grade or anaplastic astrocytomas (A). Imatinib was started at a dose of 600 mg/d with dose escalation to 800 mg in case of no toxicity; during the trial this dose was increased to 800 mg/d with escalation to 1,000 mg/d. Trial design was one-stage Fleming; both an objective response and 6 months of progression-free survival (PFS) were considered a successful outcome to treatment. RESULTS: A total of 112 patients (51 patients with GBM, 25 patients with A, and 36 patients with OD) were enrolled. Imatinib was in general well tolerated. The median number of cycles was 2.0 (range, 1 to 43 cycles). Five patients had an objective partial response, including three patients with GBM; all had 6 months of PFS. The 6-month PFS rate was 16% (95% CI, 8.0% to 34.0%) in GBM, 4.0% (95% CI, 0.3% to 15.0%) in OD, and 9% (95% CI, 2.0% to 25.0%) in A. The exposure to imatinib was significantly lower in patients using enzyme-inducing antiepileptic drugs. The presence of ABCG2 point mutations were not correlated with pharmacokinetic findings. No somatic activating mutations of KIT or platelet-derived growth factor receptor-A or -B were found. CONCLUSION: In the dose range of 600 to 1,000 mg/d, single-agent imatinib is well tolerated but has limited antitumor activity in patients with recurrent gliomas.

Swiss consensus statement: Recommendations for optimising re-treatment with MabThera (rituximab) in rheumatoid arthritis.

Rituximab is an effective treatment of rheumatoid arthritis (RA), which has been approved for the treatment of moderate to severe disease in patients with an inadequate response to anti-TNF therapies. Rituximab differs from other available biological agents for RA by way of its unique mode of action and unrivalled long dosing interval. The efficacy of rituximab subsides progressively over time and re-therapy is generally required to maintain long term disease control. The timing of re-treatment is currently not well established and varies widely in clinical practice. The present document is a concise recommendation regarding re-treatment with rituximab, based on validated outcomes such as the DAS28 and the EULAR response criteria. The recommendation was established through consensus between practitioners familiar with rituximab therapy in RA. Optimisation of the rituximab re-treatment schedule may improve patient outcomes and balance risks and benefits for the individual patient.

Application of the 2008 definitions for invasive fungal diseases to the trial comparing voriconazole versus amphotericin B for therapy of invasive aspergillosis: a collaborative study of the Mycoses Study Group (MSG 05) and the European Organization for Research and Treatment of Cancer Infectious Diseases Group.

BACKGROUND: Strict definition of invasive aspergillosis (IA) cases is required to allow precise conclusions about the efficacy of antifungal therapy. The Global Comparative Aspergillus Study (GCAS) compared voriconazole to amphotericin B (AmB) deoxycholate for the primary therapy of IA. Because predefined definitions used for this trial were substantially different from the consensus definitions proposed by the European Organization for Research and Treatment of Cancer/Mycoses Study Group in 2008, we recategorized the 379 episodes of the GCAS according to the later definitions. METHODS: The objectives were to assess the impact of the current definitions on the classification of the episodes and to provide comparative efficacy for probable/proven and possible IA in patients treated with either voriconazole or AmB. In addition to original data, we integrated the results of baseline galactomannan serum levels obtained from 249 (65.7%) frozen samples. The original response assessment was accepted unchanged. RESULTS: Recategorization allowed 59 proven, 178 probable, and 106 possible IA cases to be identified. A higher favorable 12-week response rate was obtained with voriconazole (54.7%) than with AmB (29.9%) (P < .0001). Survival was higher for voriconazole for mycologically documented (probable/proven) IA (70.2%) than with AmB (54.9%) (P = .010). Higher response rates were obtained in possible IA treated with voriconazole vs AmB with the same magnitude of difference (26.2%; 95% confidence interval [CI], 7.2%-45.3%) as in mycologically documented episodes (24.3%; 95% CI, 11.9%-36.7%), suggesting that possible cases are true IA. CONCLUSIONS: Recategorization resulted in a better identification of the episodes and confirmed the higher efficacy of voriconazole over AmB deoxycholate in mycologically documented IA.

Predictors and Moderators of Clinical Outcomes in Adolescents with Severe Mental Disorders After an Assertive Community Treatment.

Previous studies have shown that stressful life events (SLEs), gender, social functioning and pretreatment severity are some of the predictors and/or moderators of treatment outcome in psychiatric care. The current study explored the effect of these predictors and moderators on the treatment outcome related to assertive community treatment (ACT) proposed to young people with severe mental disorders. 98 patients were assessed for externalizing and emotional difficulties, at admission and then at discharge of an ACT. Analyses revealed significant improvements in terms of symptomatology. In particular, regression analyses showed that pretreatment severity is a significant predictor of the outcome on emotional symptoms and is moderated by SLE on the outcome on externalizing symptoms. Furthermore, higher social functioning proved to predict better outcome on externalizing symptoms. Our results further evidence that these factors can explain inter-individual differences in outcome related to ACT. The theoretical and clinical implications of these results are discussed.

Adverse events to antiretrovirals in the Swiss HIV Cohort Study: effect on mortality and treatment modification.

BACKGROUND: Antiretroviral therapy (ART) decreases morbidity and mortality in HIV-infected patients but is associated with considerable adverse events (AEs). METHODS: We examined the effect of AEs to ART on mortality, treatment modifications and drop-out in the Swiss HIV Cohort Study. A cross-sectional evaluation of prevalence of 13 clinical and 11 laboratory parameters was performed in 1999 in 1,078 patients on ART. AEs were defined as abnormalities probably or certainly related to ART. A score including the number and severity of AEs was defined. The subsequent progression to death, drop-out and treatment modification due to intolerance were evaluated according to the baseline AE score and characteristics of individual AEs. RESULTS: Of the 1,078 patients, laboratory AEs were reported in 23% and clinical AEs in 45%. During a median follow up of 5.9 years, laboratory AEs were associated with higher mortality with an adjusted hazard ratio (HR) of 1.3 (95% confidence interval [CI] 1.2-1.5; P < 0.001) per score point. For clinical AEs no significant association with increased mortality was found. In contrast, an increasing score for clinical AEs (HR 1.11,95% CI 1.04-1.18; P = 0.002), but not for laboratory AEs (HR 1.07, 95% CI 0.97-1.17; P = 0.17), was associated with antiretroviral treatment modification. AEs were not associated with a higher drop-out rate. CONCLUSIONS: The burden of laboratory AEs to antiretroviral drugs is associated with a higher mortality. Physicians seem to change treatments to relieve clinical symptoms, while accepting laboratory AEs. Minimizing laboratory drug toxicity seems warranted and its influence on survival should be further evaluated.

Outcome and patterns of failure in testicular lymphoma: a multicenter Rare Cancer Network study.

PURPOSE: To assess the outcome and patterns of failure in patients with testicular lymphoma treated by chemotherapy (CT) and/or radiation therapy (RT). METHODS AND MATERIALS: Data from a series of 36 adult patients with Ann Arbor Stage I (n = 21), II (n = 9), III (n = 3), or IV (n = 3) primary testicular lymphoma, consecutively treated between 1980 and 1999, were collected in a retrospective multicenter study by the Rare Cancer Network. Median age was 64 years (range: 21-91 years). Full staging workup (chest X-ray, testicular ultrasound, abdominal ultrasound, and/or thoracoabdominal computer tomography, bone marrow assessment, full blood count, lactate dehydrogenase, and cerebrospinal fluid evaluation) was completed in 18 (50%) patients. All but one patient underwent orchidectomy, and spermatic cord infiltration was found in 9 patients. Most patients (n = 29) had CT, consisting in most cases of cyclophosphamide, doxorubicin, vincristine, and prednisolone (CHOP) with (n = 17) or without intrathecal CT. External RT was delivered to scrotum alone (n = 12) or testicular, iliac, and para-aortic regions (n = 8). The median RT dose was 31 Gy (range: 20-44 Gy) in a median of 17 fractions (10-24), using a median of 1.8 Gy (range: 1.5-2.5 Gy) per fraction. The median follow-up period was 42 months (range: 6-138 months). RESULTS: After a median period of 11 months (range: 1-76 months), 14 patients presented lymphoma progression, mostly in the central nervous system (CNS) (n = 8). Among the 17 patients who received intrathecal CT, 4 had a CNS relapse (p = NS). No testicular, iliac, or para-aortic relapse was observed in patients receiving RT to these regions. The 5-year overall, lymphoma-specific, and disease-free survival was 47%, 66%, and 43%, respectively. In univariate analyses, statistically significant factors favorably influencing the outcome were early-stage and combined modality treatment. Neither RT technique nor total dose influenced the outcome. Multivariate analysis revealed that the most favorable independent factors predicting the outcome were younger age, early-stage disease, and combined modality treatment. CONCLUSIONS: In this multicenter retrospective study, CNS was found to be the principal site of relapse, and no extra-CNS lymphoma progression was observed in the irradiated volumes. More effective CNS prophylaxis, including combined modalities, should be prospectively explored in this uncommon site of extranodal lymphoma.