Improvement in secondary hyperparathyroidism due to drug adherence monitoring in dialysis patients.

BACKGROUND: Poor medication adherence is a frequent cause of treatment failure but is difficult to diagnose. In this study we have evaluated the impact of measuring adherence to cinacalcet-HCl and phosphate binders in dialysis patients with uncontrolled secondary hyperparathyroidism. METHODS: 7 chronic dialysis patients with iPTH-levels >= 300 pg/ml despite treatment with >= 60 mg cinacalcet-HCl were included. Medication adherence was measured using the "Medication Events Monitoring System" during 3 months, followed by another 3-month period without monitoring. The adherence results were monthly discussed with the patients, as well as strategies to improve them. RESULTS: During monitoring, the percentage of prescribed doses taken was higher for cinacalcet-HCl (87.4%) and sevelamer (86.3%) than for calcium acetate (76.1%), as was the taking adherence (81.9% vs. 57.3% vs. 49.1%) but not the percentage of drug holidays (12.3% vs. 4.5% vs. 3.6%). Mean PO4 levels (from 2.24 +/- 0.6 mmol/l to 1.73 +/- 0.41 mmol/l; p = 0.14) and Ca++ x PO4 product (4.73 +/- 1.43 to 3.41 +/- 1.04 mmol2/l2; p = 0.12) improved and iPTH-level improved significantly from 916 +/- 618 pg/ml to 442 +/- 326 pg/ml (p = 0.04), without any change in medication. However, as drug monitoring was interrupted, all laboratory parameters worsened again. CONCLUSIONS: Assessment of drug adherence helped to document episodes of non-compliance and helped to avoid seemingly necessary dose increases.

Conceiving Comparative Policy Analysis : Implementing Air Quality Improvement Programs

The comparative analysis of air quality control policies provides an interesting field for studies of comparative policy analysis including program formulation and implementation processes. In European countries, the problem is comparable, whereas implementation structures, programs and policy impacts vary to a considerable extent. Analysis testing possibilities and constraints of air control policies under varying conditions are likely to contribute to a further development of a theory of policy analysis. This paper presents the analytical framework applied in a continuing empirical study explaining program formulation and implementation processes with respect to the different actors involved. Concrete emitter behavior can be explained by interaction processes at the very local level, by program elements of national legislation, and by structural constraints under which such programs are produced.

Angiogenesis inhibition for the improvement of photodynamic therapy: The revival of a promising idea.

Photodynamic therapy (PDT) is a minimally invasive form of treatment, which is clinically approved for the treatment of angiogenic disorders, including certain forms of cancer and neovascular eye diseases. Although the concept of PDT has existed for a long time now, it has never made a solid entrance into the clinical management of cancer. This is likely due to secondary tissue reactions, such as inflammation and neoangiogenesis. The recent development of clinically effective angiogenesis inhibitors has lead to the initiation of research on the combination of PDT with such angiostatic targeted therapies. Preclinical studies in this research field have shown promising results, causing a revival in the field of PDT. This review reports on the current research efforts on PDT and vascular targeted combination therapies. Different combination strategies with angiogenesis inhibition and vascular targeting approaches are discussed. In addition, the concept of increasing PDT selectivity by targeted delivery of photosensitizers is presented. Furthermore, the current insights on sequencing the therapy arms of such combinations will be discussed in light of vascular normalization induced by angiogenesis inhibition.

Transitions in partnership and parental status, gender, and political and civic participation

Participation research has documented the effect of partner and parenthood status, thereby ignoring the dynamic aspect of status changes. Based on theoretical insights on changes in political resources and interest, this study looks at partnership and parenthood as dynamic characteristics. Using data from the Swiss Household Panel (SHP), it examines to what extent important life-cycle transitions in partnership and parental status influence various forms of political and civic participation and whether they affect men and women's participation differently. Our regression analyses reveal that particularly the entry into separation or divorce is a main key point driving change in political and civic participation. Its effect is also highly gendered. Following separation, women participate less in voting, whereas men's participation rates are not affected in a negative way. Separation even increases men's level of anticipated activism. Children entering or leaving the household do not seem to represent key points of change in political and civic participation of the couple. Yet, the transition to having school-aged children significantly increases some types of participation, at least for women.

Image en fluorescence en endoscopie: contribution dans la prise en charge des tumeurs de vessie [Fluorescence guided endoscopy: improvement in the management of bladder cancer].

White-light cystoscopy and cytology are the standard tools to diagnose bladder cancer. White-light cystoscopy is excellent to detect macroscopic exophytic tumors, but its sensitivity is poor for flat tumors such as carcinoma in situ. Use of fluorescence cystoscopy during transurethral bladder resection improve tumor detection, particulary for carcinoma in situ. Fluorescence cystoscopy reduce residual tumor rate, especially for voluminous and multifocal tumors with consecutive lower recurrence. Fluorescence is now recommended to diagnose and treat bladder cancer.

Improvement of saliva production in ENT cancer patients treated by IMRT

Intensity modulated radiotherapy (IMRT) is a conformal radiotherapy that produces concave and irregular target volume dose distributions. IMRT has a potential to reduce the volume of healthy tissue irradiated to a high dose, but this often at the price of an increased volume of normal tissue irradiated to a low dose. Clinical benefits of IMRT are expected to be most pronounced at the body sites where sensitive normal tissues surround or are located next to a target with a complex 3D shape. The irradiation doses needed for tumor control are often markedly higher than the tolerance of the radiation sensitive structures such as the spinal cord, the optic nerves, the eyes, or the salivary glands in the treatment of head and neck cancer. Parotid gland salivary flow is markedly reduced following a cumulative dose of 30 50 Gy given with conventional fractionation and xerostomia may be prevented in most patients using a conformal parotid-sparing radiotherapy technique. However, in cohort studies where IMRT was compared with conventional and conformal radiotherapy techniques in the treatment of laryngeal or oropharyngeal carcinoma, the dosimetric advantage of IMRT translated into a reduction of late salivary toxicity with no apparent adverse impact on the tumor control. IMRT might reduce the radiation dose to the major salivary glands and the risk of permanent xerostomia without compromizing the likelihood for cure. Alternatively, IMRT might allow the target dose escalation at a given level of normal tissue damage. We describe here the clinical results on postirradiation salivary gland function in head and neck cancer patients treated with IMRT, and the technical aspects of IMRT applied. The results suggest that the major salivary gland function can be maintained with IMRT without a need to compromise the clinical target volume dose, or the locoregional control.

ECG interpretation during the acute phase of coronary syndromes: in need of improvement?

QUESTION UNDER STUDY: Emergency room (ER) interpretation of the ECG is critical to assessment of patients with acute coronary syndromes (ACS). Our aim was to assess its reliability in our institution, a tertiary teaching hospital. METHODS: Over a 6-month period all consecutive patients admitted for ACS were included in the study. ECG interpretation by emergency physicians (EPs) was recorded on a preformatted sheet and compared with the interpretation of two specialist physicians (SPs). Discrepancies between the 2 specialists were resolved by an ECG specialist. RESULTS: Over the 6-month period, 692 consecutive patients were admitted with suspected ACS. ECG interpretation was available in 641 cases (93%). Concordance between SPs was 87%. Interpretation of normality or abnormality of the ECG was concordant between EPs and SPs in 475 cases (74%, kappa = 0.51). Interpretation of ischaemic modifications was concordant in 69% of cases, and as many ST segment elevations were unrecognised as overdiagnosed (5% each). The same findings occurred for ST segment depressions and negative T waves (12% each). CONCLUSIONS: Interpretation of the ECG recorded during ACS by 2 SPs was discrepant in 13% of cases. Similarly, EP interpretation was discrepant from SP interpretation in 25% of cases, equally distributed between over- and underdiagnosing of ischaemic changes. The clinical implications and impact of medical education on ECG interpretation require further study.

Rapid Improvement in Health-Related Quality of Life in Gouty Arthritis Patients Treated with Canakinumab (ACZ885) Compared to Triamcinolone Acetonide

Background: Gout patients initiating urate lowering therapy have an increased risk of flares. Inflammation in gouty arthritis is induced by interleukin (IL)-1b. Canakinumab inhibits IL-1b effectively in clinical studies. This study compared different doses of canakinumab vs colchicine in preventing flares in gout patients initiating allopurinol therapy.Methods: In this 24 wk double blind study, gout patients (20-79 years) initiating allopurinol were randomized (1:1:1:1:1:1:2) to canakinumab s.c. single doses of 25, 50, 100, 200, 300 mg, or 150mg divided in doses every 4 wks (50þ50þ25þ25mg [q4wk]) or colchicine 0.5mg p.o. daily for 16 wks. Primary outcome was to determine the canakinumab dose giving comparable efficacy to colchicine with respect to number of flares occurring during first 16 wks. Secondary outcomes included number of patients with flares and C-reactive protein (CRP) levels during the first 16 wks.Results: 432 patients were randomized and 391 (91%) completed the study. All canakinumab doses were better than colchicine in preventing flares and therefore, a canakinumab dose comparable to colchicine couldn't be determined. Based on a negative binomialmodel, all canakinumab groups, except 25 mg, reduced the flare rate ratio per patient significantly compared to colchicine group (rate ratio estimates 25mg 0.60, 50mg 0.34, 100mg 0.28, 200mg 0.37, 300mg 0.29, q4wk 0.38; p_0.05). Percentage of patients with flares was lower for all canakinumab groups (25mg 27.3%, 50mg 16.7%, 100mg 14.8%, 200mg 18.5%, 300mg 15.1%, q4wk 16.7%) compared to colchicine group (44.4%). All patients taking canakinumab were significantly less likely to experience at least one gout flare than patients taking colchicine (odds ratio range [0.22 - 0.47]; p_0.05 for all). Median baseline CRP levels were 2.86 mg/L for 25 mg, 3.42 mg/L for 50 mg, 1.76 mg/L for 100 mg, 3.66 mg/L for 200 mg, 3.21 mg/L for 300 mg, 3.23 mg/L for q4wk canakinumab groups and 2.69 mg/L for colchicine group. In all canakinumab groups with median CRP levels above the normal range at baseline, median levels declined within 15 days of treatment and were maintained at normal levels (ULN¼3 mg/L) throughout the 16 wk period. Adverse events (AEs) occurred in 52.7% (25 mg), 55.6% (50 mg), 51.9% (100 mg), 51.9% (200 mg), 54.7% (300 mg), 58.5% (q4wk) of patients on canakinumab vs 53.7% of patients on colchicine. Serious AEs (SAE) were reported in 2 (3.6%; 25 mg), 2 (3.7%, 50 mg), 3 (5.6%, 100 mg), 3 (5.6%, 200 mg), 3 (5.7%, 300 mg), 1 (1.9%, q4wk) patients on canakinumab and in 5 (4.6%) patients on colchicine. 1 fatal SAE (myocardial infarction, not related to study drug) occurred in colchicine group.Conclusions: In this randomized, double-blind active controlled study of flare prevention in gout patients initiating allopurinol therapy, treatment with canakinumab led to a statistically significant reduction in flares compared with colchicine and was well tolerated.Disclosure statement: U.A., A.B., G.K., D.R. and P.S. are employees of and have stock options or bold holdings with Novartis Pharma AG. E.M. is a principal investigator for Novartis Pharmaceuticals Corporation. E.N. has received consulting fees from Roche. N.S. has received research grants from Novartis Pharmaceuticals Corporation. A.S. has received consultancy fees from Novartis Pharma AG, Abbott, Bristol-Myers Squibb, Essex, Pfizer, MSD, Roche, UCB and Wyeth. All other authors have declared no conflicts of interest.

Improvement of the specificity of cancer detection by autofluorescence imaging in the tracheo-bronchial tree using backscattered violet light.

BACKGROUND: Autofluorescence bronchoscopy (AFB) is a highly sensitive tool for the detection of early bronchial cancers. However, its specificity remains limited due to primarily false positive results induced by hyperplasia, metaplasia and inflammation. We have investigated the potential of blue-violet backscattered light to eliminate false positive results during AFB in a clinical pilot study. METHODS: The diagnostic autofluorescence endoscopy (DAFE) system was equipped with a variable band pass filter in the imaging detection path. The backscattering properties of normal and abnormal bronchial mucosae were assessed by computing the contrast between the two tissue types for blue-violet wavelengths ranging between 410 and 490 nm in 12 patients undergoing routine DAFE examination. In a second study including 6 patients we used a variable long pass (LP) filter to determine the spectral design of the emission filter dedicated to the detection of this blue-violet light with the DAFE system. RESULTS: (Pre-)neoplastic mucosa showed a clear wavelength dependence of the backscattering properties of blue-violet light while the reflectivity of normal, metaplastic and hyperplastic autofluorescence positive mucosa was wavelength independent. CONCLUSIONS: Our results showed that the detection of blue-violet light has the potential to reduce the number of false positive results in AFB. In addition we determined the spectral design of the emission filter dedicated to the detection of this blue-violet light with the DAFE system.

Tetracycline-regulated expression of VEGF-A in beta cells induces angiogenesis: improvement of engraftment following transplantation.

Early revascularization of pancreatic islet cells after transplantation is crucial for engraftment, and it has been suggested that vascular endothelial growth factor-A (VEGF-A) plays a significant role in this process. Although VEGF gene therapy can improve angiogenesis, uncontrolled VEGF secretion can lead to vascular tumor formation. Here we have explored the role of temporal VEGF expression, controlled by a tetracycline (TC)-regulated promoter, on revascularization and engraftment of genetically modified beta cells following transplantation. To this end, we modified the CDM3D beta cell line using a lentiviral vector to promote secretion of VEGF-A either in a TC-regulated (TET cells) or a constitutive (PGK cells) manner. VEGF secretion, angiogenesis, cell proliferation, and stimulated insulin secretion were assessed in vitro. VEGF secretion was increased in TET and PGK cells, and VEGF delivery resulted in angiogenesis, whereas addition of TC inhibited these processes. Insulin secretion by the three cell types was similar. We used a syngeneic mouse model of transplantation to assess the effects of this controlled VEGF expression in vivo. Time to normoglycemia, intraperitoneal glucose tolerance test, graft vascular density, and cellular mass were evaluated. Increased expression of VEGF resulted in significantly better revascularization and engraftment after transplantation when compared to control cells. In vivo, there was a significant increase in vascular density in grafted TET and PGK cells versus control cells. Moreover, the time for diabetic mice to return to normoglycemia and the stimulated plasma glucose clearance were also significantly accelerated in mice transplanted with TET and PGK cells when compared to control cells. VEGF was only needed during the first 2-3 weeks after transplantation; when removed, normoglycemia and graft vascularization were maintained. TC-treated mice grafted with TC-treated cells failed to restore normoglycemia. This approach allowed us to switch off VEGF secretion when the desired effects had been achieved. TC-regulated temporal expression of VEGF using a gene therapy approach presents a novel way to improve early revascularization and engraftment after islet cell transplantation.

Brain dynamics underlying training-induced improvement in suppressing inappropriate action.

Inhibitory control, a core component of executive functions, refers to our ability to suppress intended or ongoing cognitive or motor processes. Mostly based on Go/NoGo paradigms, a considerable amount of literature reports that inhibitory control of responses to "NoGo" stimuli is mediated by top-down mechanisms manifesting ∼200 ms after stimulus onset within frontoparietal networks. However, whether inhibitory functions in humans can be trained and the supporting neurophysiological mechanisms remain unresolved. We addressed these issues by contrasting auditory evoked potentials (AEPs) to left-lateralized "Go" and right NoGo stimuli recorded at the beginning versus the end of 30 min of active auditory spatial Go/NoGo training, as well as during passive listening of the same stimuli before versus after the training session, generating two separate 2 × 2 within-subject designs. Training improved Go/NoGo proficiency. Response times to Go stimuli decreased. During active training, AEPs to NoGo, but not Go, stimuli modulated topographically with training 61-104 ms after stimulus onset, indicative of changes in the underlying brain network. Source estimations revealed that this modulation followed from decreased activity within left parietal cortices, which in turn predicted the extent of behavioral improvement. During passive listening, in contrast, effects were limited to topographic modulations of AEPs in response to Go stimuli over the 31-81 ms interval, mediated by decreased right anterior temporoparietal activity. We discuss our results in terms of the development of an automatic and bottom-up form of inhibitory control with training and a differential effect of Go/NoGo training during active executive control versus passive listening conditions.

Inpatient diabetes care in a Swiss multi-site hospital: is there room for improvement?

Background and objective: Optimal care of diabetic patients (DPs) decreases the risk of complications. Close blood glucose monitoring can improve patient outcomes and shorten hospital stay. The objective of this pilot study was to evaluate the treatment of hospitalized DPs according to the current standards, including their diabetic treatment and drugs to prevent diabetes related complications [=guardian drugs: angiotensin converting enzyme inhibitors (ACEI) or Angiotensin II Receptor Blockers (ARB), antiplatelet drugs, statins]. Guidelines of the American Diabetes Association (ADA) [1] were used as reference as they were the most recent and exhaustive for hospital care. Design: Observational pilot study: analysis of the medical records of all DPs seen by the clinical pharmacists during medical rounds in different hospital units. An assessment was made by assigning points for fulfilling the different criteria according to ADA and then by dividing the total by the maximum achievable points (scale 0-1; 1 = all criteria fulfilled). Setting: Different Internal Medicine and Geriatric Units of the (multi-site) Ho^pital du Valais. Main outcome measures: - Completeness of diabetes-related information: type of diabetes, medical history, weight, albuminuria status, renal function, blood pressure, (recent) lipid profile. - Management of blood glucose: Hb1Ac, glycemic control, plan for treating hyper-/hypoglycaemia. - Presence of guardian drugs if indicated. Results: Medical records of 42 patients in 10 different units were analysed (18 women, 24 men, mean age 75.4 ± 11 years). 41 had type 2 diabetes. - Completeness of diabetes-related information: 0.8 ± 0.1. Information often missing: insulin-dependence (43%) and lipid profile (86%). - Management of blood glucose: 0.5 ± 0.2. 15 patients had suboptimal glycemic balance (target glycaemia 7.2-11.2 mmol/ l, with values[11.2 or\3.8 mmol/l, or Hb1Ac[7%), 10 patients had a deregulated balance (more than 10 values[11.2 mmol/l or \3.8 mmol/l and even values[15 mmol/l). - Presence of guardian drugs if indicated: ACEI/ARB: 19 of 23 patients (82.6%), statin: 16 of 40 patients (40%), antiplatelet drug: 16 of 39 patients (41%). Conclusions: Blood glucose control was insufficient in many DPs and prescription of statins and antiplatelet drugs was often missing. If confirmed by a larger study, these two points need to be optimised. As it is not always possible and appropriate to make those changes during hospital stay, a further project should assess and optimise diabetes care across both inpatient and outpatient settings.

Use of lights and siren: is there room for improvement?

OBJECTIVE: The objective of this study was to analyse the use of lights and siren (L&S) during transport to the hospital by the prehospital severity status of the patient and the time saved by the time of day of the mission. METHODS: We searched the Public Health Services data of a Swiss state from 1 January 2010 to 31 December 2010. All primary patient transports within the state were included (24 718). The data collected were on the use of L&S, patient demographics, the time and duration of transport, the type of mission (trauma vs. nontrauma) and the severity of the condition according to the National Advisory Committee for Aeronautics (NACA) score assigned by the paramedics and/or emergency physician. We excluded 212 transports because of missing data. RESULTS: A total of 24 506 ambulance transports met the inclusion criteria. L&S were used 4066 times, or in 16.6% of all missions. Of these, 40% were graded NACA less than 4. Overall, the mean total transport time to return to the hospital was 11.09 min (confidence interval 10.84-11.34) with L&S and 12.84 min (confidence interval 12.72-12.96) without. The difference was 1.75 min (105 s; P<0.001). For night-time runs alone, the mean time saved using L&S was 0.17 min (10.2 s; P=0.27). CONCLUSION: At present, the use of L&S seems questionable given the severity status or NACA score of transported patients. Our results should prompt the implementation of more specific regulations for L&S use during transport to the hospital, taking into consideration certain physiological criteria of the victim as well as time of day of transport.