Mobile applications for diabetics: a systematic review and expert-based usability evaluation considering the special requirements of diabetes patients age 50 years or older.

BACKGROUND: A multitude of mhealth (mobile health) apps have been developed in recent years to support effective self-management of patients with diabetes mellitus type 1 or 2. OBJECTIVE: We carried out a systematic review of all currently available diabetes apps for the operating systems iOS and Android. We considered the number of newly released diabetes apps, range of functions, target user groups, languages, acquisition costs, user ratings, available interfaces, and the connection between acquisition costs and user ratings. Additionally, we examined whether the available applications serve the special needs of diabetes patients aged 50 or older by performing an expert-based usability evaluation. METHODS: We identified relevant keywords, comparative categories, and their specifications. Subsequently, we performed the app review based on the information given in the Google Play Store, the Apple App Store, and the apps themselves. In addition, we carried out an expert-based usability evaluation based on a representative 10% sample of diabetes apps. RESULTS: In total, we analyzed 656 apps finding that 355 (54.1%) offered just one function and 348 (53.0%) provided a documentation function. The dominating app language was English (85.4%, 560/656), patients represented the main user group (96.0%, 630/656), and the analysis of the costs revealed a trend toward free apps (53.7%, 352/656). The median price of paid apps was €1.90. The average user rating was 3.6 stars (maximum 5). Our analyses indicated no clear differences in the user rating between free and paid apps. Only 30 (4.6%) of the 656 available diabetes apps offered an interface to a measurement device. We evaluated 66 apps within the usability evaluation. On average, apps were rated best regarding the criterion "comprehensibility" (4.0 out of 5.0), while showing a lack of "fault tolerance" (2.8 out of 5.0). Of the 66 apps, 48 (72.7%) offered the ability to read the screen content aloud. The number of functions was significantly negative correlated with usability. The presence of documentation and analysis functions reduced the usability score significantly by 0.36 and 0.21 points. CONCLUSIONS: A vast number of diabetes apps already exist, but the majority offer similar functionalities and combine only one to two functions in one app. Patients and physicians alike should be involved in the app development process to a greater extent. We expect that the data transmission of health parameters to physicians will gain more importance in future applications. The usability of diabetes apps for patients aged 50 or older was moderate to good. But this result applied mainly to apps offering a small range of functions. Multifunctional apps performed considerably worse in terms of usability. Moreover, the presence of a documentation or analysis function resulted in significantly lower usability scores. The operability of accessibility features for diabetes apps was quite limited, except for the feature "screen reader".

Treatment of neurological autoimmune diseases with immunoglobulins: first insights from the prospective SIGNS registry.

PURPOSE: Several immunoglobulin (IG) preparations have been approved for the immunomodulatory treatment of the neurological autoimmune diseases (AID) Guillain-Barré syndrome (GBS), chronic inflammatory demyelinating polyneuropathy (CIDP), and multifocal motor neuropathy (MMN). Although efficacy has been proven in randomised clinical trials, long-term outcome data on drug utilization, effectiveness, tolerability, health related quality of life, and economic variables are lacking. METHODS: In the prospective, observational internet-based SIGNS registry, patients of all age groups are eligible if they have received or are scheduled for IG therapy for neurological AID or primary or severe secondary immunodeficiency. RESULTS: Of the 306 patients currently included in the database (1 November 2011), 51 have neurological AID (27 males; mean age 56 ± 15 years): 21 CIDP, 7 MMN, 11 multiple sclerosis (MS), 6 myasthenia gravis, 2 myositis, 4 others (no cases of GBS). Mean duration of disease since first symptoms was 7.8 years, and disease duration since diagnosis was 5.9 years. Eight different IG preparations have been reported as current therapy. According to SF-36, patients' quality of life is substantially impaired. CONCLUSIONS: Present data indicate some off-label use of IG (e.g. in MS) in patients with neurological AID. Quality of life in these patients is substantially compromised. Increasing patient numbers and extended follow-up periods will provide data on treatment concepts and disease development in AID patients.

Evaluation of a program of integrated care to reduce recurrent osteoporotic fractures.

PURPOSE: To evaluate the outcomes of patients participating in a program of integrated care for osteoporosis in terms of medication supply, fracture incidence and expenses. METHODS: Outcomes were assessed from secondary data provided by the AOK PLUS health insurance for 2455 participants of the program and the same number of matched controls who were also diagnosed with osteoporosis but did not participate in the program. Supply with Calcium and Vitamin D, antiresorptive agents and analgesics was assessed by defined daily doses. Osteoporotic fractures were identified by hospitalization data. Costs for fracture treatment, medication supply and additional expenses of the program were also included in the dataset. RESULTS: Patients enrolled in the program of integrated care received significantly more medication to treat osteoporosis than controls. There was no significant reduction in fracture incidence among participants of integrated care, but a reduced need of analgesics was noted. Additional costs for patients enrolled in the program were caused by a higher number of drug prescriptions, higher costs for stationary treatment and additional expenses for program related care and diagnostics. CONCLUSIONS: The program of integrated care was not found to be effective in reducing recurrent fractures. Cost effectiveness defined as a reduced rate of fractures in integrated care patients could not be shown by the assessed outcome measures. This missing reduction in fracture incidence may be explained by a non-sufficient improvement - compared to a placebo-controlled clinical trial - in medication supply and non-comparability of our real-world patient population with highly controlled clinical trial participants.

Managing hypertension among nursing-home residents and community-dwelling elderly in Germany: a comparative pharmacoepidemiological study.

PURPOSE: The purpose of this study was to investigate the adequacy of hypertension management in hypertensive elderly living in long-term-care facilities compared with home-living elderly. METHODS: This retrospective, cross-sectional, pharmacoepidemiological study compared data from a community-dwelling population (CD) and from four nursing homes (NH) in Dresden, Germany. Individuals aged ≥ 65 with the diagnosis of arterial hypertension were included. Demographical, medical, and drug prescription data as well as blood pressure (BP) values were analyzed and compared descriptively after matching the populations by age and gender. RESULTS: Each population comprised 209 patients (mean age 80.4 years [± 6], 70.3% women). NH showed a higher number of diseases [7 (5-9) vs. 5 (3-7); p < 0.001]. BP (<140/90 mmHg) was better controlled in NH (61.0% vs. 48.1%; p = 0.015). The median number of BP-lowering drugs was three (2-4; CD) and two (1-3; NH) (range: 0-9). Most frequently used antihypertensives were diuretics and beta-blockers. Among renin-angiotensin system (RAS) blockers, angiotensin-receptor blockers (ARBs) were preferred in CD and angiotensin-converting enzyme (ACE) inhibitors in NH. Drug treatment for secondary prevention of myocardial infarction or stroke [acetylsalicylic acid (ASA) 100, RAS-blocker, beta-blocker, statin] was low among both groups (CD 21.3%; NH 1.6%; p = 0.01). NH received more inappropriate drugs, especially tranquillizers (31.2% vs. 21.0%; p < 0.05) [according to the PRISCUS (Latin for "old and venerable") list for potentially inappropriate medications in the elderly (PIM)]. CONCLUSIONS: NH residents showed better BP control than CD elderly while receiving less antihypertensive drugs. The prescription of antihypertensives was assumed to be more cost effective in NH. Nevertheless, inappropriate drug use is still high (NH > CD), and there is an extended need for professional medication assessment in both groups of elderly.

Potentially inappropriate prescribing for elderly outpatients in Germany: a retrospective claims data analysis.

OBJECTIVE: To quantify the frequency of potentially inappropriate medication (PIM) prescribing for outpatients aged 65 years and older using claims data of a German statutory health insurance. METHODS: Based on the 2002 Beers criteria for PIM use, a retrospective evaluation of drug prescription data in outpatient care was conducted for the years 2003 and 2004 using data from a German statutory health insurance (AOK) in the area of Saxony. The study was limited to those drugs classified as being potentially inappropriate according to the criteria independent of existing medical conditions and without any restrictions concerning dosage or duration of use, because this information was not available from the data. RESULTS: In 2003, 3.3% (408,375) of all 12,513,584 drug prescriptions for patients 65 years and older which were analyzed included a PIM from the Beers list. In 2004, it was 2.9% (297,524) of 10,126,809 (p < 0.001). The most frequently prescribed PIMs were short-acting nifedipine (13.4%), indomethacin (12.3%) and diazepam (11.8%) in 2003, and diazepam (14.6%) followed by indomethacin (13.7%) and doxazosin (10.9%) in 2004. 21.7% (119,482) and 18.2% (98,465) of patients 65 years or older received at least one prescription of a PIM in 2003 and 2004, respectively (p < 0.001). In a multivariate logistic regression model female gender and a higher number of prescribed drugs were significantly associated with an increased frequency of receiving a PIM in both years. CONCLUSIONS: In our study, approximately every 5th older patient was prescribed at least one PIM. For the future an ongoing update of the Beers criteria to further include newer agents and an adaptation to the different situation in European countries is desirable.

Pharmaco-economic impact of demographic change on pharmaceutical expenses in Germany and France.

BACKGROUND: Most European health care systems are suffering from the impact of demographic change. In short, aging of society is leading to higher costs of treatment per capita, while reproduction rates below 2.1 children per woman lead to a reduced number of younger people to provide for the necessary contributions into the health insurance system.This research paper addresses the questions what impact the demographic development will have on one particular spending area, what are pharmaceutical expenditure in two of Europe's largest health care systems, Germany and France, and what the implications are for pharmaceutical companies. METHODS: The research is based on publicly available data from German and French health ministries, the OECD, and institutes which focus on projection of demographic development in those countries. In a first step, data was clustered into age groups, and average spending on pharmaceuticals was allocated to that. In the second step, these figures were extrapolated, based on the projected change in the demographic structure of the countries from 2004 until 2050. This leads to a deeper understanding of demand for pharmaceutical products in the future due to the demographic development as a single driving factor. RESULTS: - Pharmaceutical expenses per head (patient) will grow only slightly until 2050 (0.5% p.a. in both countries). - Demographic change alone only provides for a slowly growing market for pharmaceutical companies both in Germany and in France, but for a relevant change in the consumption mix of pharmaceutical products, based on a shift of relevance of different age groups. CONCLUSIONS: Despite demographic changes pharmaceutical expenses per head (patient) and the overall pharmaceutical markets will grow only slightly until 2050 in Germany as well as in France. Nevertheless, the aging of society implies different challenges for pharmaceutical companies and also for the health care system. Companies have to cope with the shift of relevance of different age groups and within the health care system new options for financing the slowly growing expenses have to be found.

Performance of different data sources in identifying adverse drug events in hospitalized patients.

PURPOSE: The incidence of adverse drug events (ADE) is an important parameter in determining the quality of medical care. We identified the probability that a specific data source would identify ADEs in patients on the oncology ward, that could be assigned to one substance. METHODS: We captured all medical adverse events (AE) from five different data sources. Each AE was determined to be drug-related according to the WHO criteria and classified according to the severity, category, and causality of the ADE. RESULTS: The study recorded 129 patients with 252 hospitalizations over a 5-month period. A total of 3,341 medical events were captured and resulted in 1,121 ADEs. In 122 patients, at least one ADE (95%) was observed. Only 39 hospitalizations were believed not to have an ADE (15%). No ADE was captured by all data sources. The patient record captured 550, the nursing record 569, the laboratory tests 387, the questionnaire 63, and the event monitoring during grand rounds 141 ADEs. Only the nursing record and the laboratory tests had a significantly different probability of observing indicative ADEs. CONCLUSION: For all AEs reported in the data sources, physicians and nurses were the best source for ADEs. Data sources differed in identifying indicative ADEs and were influenced by specific patient parameters.

Oral health-related quality of life and oral status in a German working population.

The study aim was to identify predictors of impaired oral health-related quality of life (OHRQoL). Employees of five companies were offered a clinical full-mouth examination. Oral health-related quality of life was measured with the German version of the Oral Health Impact Profile (OHIP) and summarized as additive scores (OHIP-ADD) and as prevalence of negative impacts (OHIP-SC). Two logistic regression models were developed for the odds of increased scores of the target variables OHIP-ADD and OHIP-SC. The target variables were dichotomized, and for the OHIP-ADD, the cut-off point for having impaired OHRQoL was heuristically defined as OHIP-ADD > 34. For the OHIP-SC, the corresponding threshold was OHIP-SC > 0. In the model for the OHIP-ADD, female gender, impaired aesthetics, few posterior occluding pairs, and painful masticatory muscles proved to be significant independent variables. For the OHIP-SC, female gender, impaired aesthetics, painful masticatory muscles, joint sounds, missing mandibular teeth, and carious teeth were significant. This cross-sectional study showed that within the models for both OHIP-ADD and OHIP-SC the high-risk person for impaired OHRQoL is a woman with impaired aesthetics and painful masticatory muscles.

Early exposure to antibiotics and infections and the incidence of atopic eczema: a population-based cohort study.

It has been suggested that infants exposed to antibiotics are at increased risk for atopic eczema (AE), whereas the early exposure to infections might be protective. This study describes the complex relationship between early exposure to infections, anti-infectious treatment with antibiotics, and incident AE. Using a German population-based administrative health-care and prescription database, we established a cohort of 370 children not diagnosed as having AE during their first year of life. For each individual child we identified all infections and prescriptions of antibiotics within the first year as well as incident AE within the second year of life. Crude analyses suggested that early infections and exposure to antibiotics are risk factors for AE. However, stratified analyses indicated that early infections were only associated with a higher rate of AE when treated with broad-spectrum antibiotics such as cephalosporines or macrolides. The risk ratio (RR) of children with early respiratory tract infections not treated with antibiotics was 0.69 [95% confidence interval (95% CI) 0.39 to 1.24], whereas respiratory tract infections treated with macrolides (RR: 2.15, 95% CI: 1.18-3.91) or cephalosporines (RR: 1.93, 95% CI: 1.07-3.49) significantly increased the risk for AE. The results for other common childhood infections tended to be similar. Antibiotic treatment appears to modify the association between early infections and subsequent AE. We found no evidence that infections per se significantly alter the likelihood for subsequent AE.

Drug information for patients--an update of long-term results: type of enquiries and patient characteristics.

PURPOSE: To analyse the type of enquiries to a drug information service in Germany, available exclusively for patients. METHODS: Sociodemographic characteristics of the patients who used the service, number and kind of drugs taken, existing diseases, reasons for enquiry as well as type of answers provided were recorded. For the present evaluation we analysed all enquiries to the service from August 2001 to January 2007. RESULTS: A total of 5587 enquiries were received. 5013 enquiries from 4091 patients were available for further analysis in detail. The patient group using the service most frequently were women between 61 and 70 years (23.3%). 1457 enquiries (29.1%) were made by patients who had contacted the information service once or several times before. The group of drugs most often asked about were cardiovascular drugs (33.4%), followed by drugs for the nervous system (16.2%) and for the alimentary tract and metabolism (12.4%). On average, each patient had questions about 2.6 (median 1; 1-22) drugs simultaneously. Common reasons for contacting the service were adverse drug reactions (22.1%), the need for general information about the drug (19.9%), information about therapy (12.4%) and drug interactions (10.2%). CONCLUSIONS: A lot of patients need additional information about their medication, especially concerning drug groups that are frequently prescribed. The presented drug information service can be one helpful tool to counteract these information deficits and to increase patients' knowledge about their drugs.

Simultaneous determination of three anticonvulsants using hydrophilic interaction LC-MS.

A specific and automated method was developed to quantify the anticonvulsants gabapentin, pregabalin and vigabatrin simultaneously in human serum. Samples were prepared with a protein precipitation. The hydrophilic interaction chromatography (HILIC) with a mobile phase gradient was used to divide off ions of the matrix and for separation of the analytes. Four different HILIC-columns and two different column temperatures were tested. The Tosoh-Amid column gave the best results: single small peaks. The anticonvulsants were detected in the multiple reaction monitoring mode (MRM) with ESI-MS-MS. Using a volume of 100 microL biological sample the lowest point of the standard curve, i.e. the lower LOQs were 312 ng/mL. The described HILIC-MS-MS method is suitable for therapeutic drug monitoring and for clinical and pharmcokinetical investigations of the anticonvulsives.

Characteristics, management and attainment of lipid target levels in diabetic and cardiac patients enrolled in Disease Management Program versus those in routine care: LUTZ registry.

BACKGROUND: Since 2002 the sick funds in Germany have widely implemented disease management programs (DMPs) for patients with type 2 diabetes mellitus (DM) and coronary heart disease (CHD). Little is known about the characteristics, treatment and target attainment lipid levels of these patients enrolled in DMPs compared to patients in routine care (non-DMP). METHODS: In an open, non-interventional registry (LUTZ) in Germany, 6551 physicians documented 15,211 patients with DM (10,110 in DMP, 5101 in routine care) and 14,222 (6259 in DMP, 7963 in routine care) over a follow-up period of 4 months. They received the NCEP ATP III guidelines as a reminder on lipid level targets. RESULTS: While demographic characteristics of DMP patients were similar to routine care patients, the former had higher rates of almost all cardiovascular comorbidities. Patients in DMPs received pharmacological treatment (in almost all drug classes) more often than non-DMP patients (e.g. antiplatelets: in DM 27.0% vs 23.8%; in CHD 63.0% vs. 53.6%). The same applied for educational measures (on life style changes and diet etc.). The rate of target level attainment for low density lipoprotein cholesterol (LDL-C) < 100 mg/dl was somewhat higher in DMP patients at inclusion compared to non-DMP patients (DM: 23.9% vs. 21.3%; CHD: 30.6% vs. 23.8%) and increased after 4 months (DM: 38.3% vs. 36.9%; CHD: 49.8% vs. 43.3%). Individual LDL-C target level attainment rates as assessed by the treating physicians were higher (at 4 months in DM: 59.6% vs. 56.5%; CHD: 49.8% vs 43.3%). Mean blood pressure (BP) and HbA1c values were slightly lowered during follow-up, without substantial differences between DMP and non-DMP patients. CONCLUSION: Patients with DM, and (to a greater extent) with CHD in DMPs compared to non-DMP patients in routine care have a higher burden of comorbidities, but also receive more intensive pharmacological treatment and educational measures. The present data support that the substantial additional efforts in DMPs aimed at improving outcomes resulted in quality gains for achieving target LDL-C levels, but not for BP or HbA1c. Longer-term follow-up is needed to substantiate these results.

Inhibition of endothelin receptors in the treatment of pulmonary arterial hypertension: does selectivity matter?

Treatment options for pulmonary arterial hypertension (PAH) have considerably improved in the past few years. Endothelin (ET)-receptor antagonism has been established as a first-line option for the majority of PAH patients. Endothelin-receptor antagonists (ETRAs) comprise sulfonamide and non-sulfonamide agents with different affinities for ET-receptor subtypes (ET(A) and ET(B)), and the focus of development has shifted from drugs with less selectivity to those with high selectivity. There is ongoing debate as to whether selective or non-selective ET-receptor antagonism is more beneficial in the treatment of PAH. This paper reviews the current evidence from experimental and clinical studies obtained from a thorough literature search focusing on the three marketed drugs bosentan, sitaxentan, and ambrisentan. A clinically meaningful difference among the three approved ETRAs with respect to their ET-receptor selectivity could not be demonstrated to date. Therefore, in clinical practice, other features are likely to be of greater relevance when considering treatment, such as the potential for serious drug-drug interactions, convenience of dosing schedule, or rates of limiting side effects. These characteristics bear more relation to the chemical or pharmacological properties of the drugs than to receptor selectivity itself.

Effects of the introduction of the German "Praxisgebühr" on outpatient care and treatment of patients with atopic eczema.

BACKGROUND: The introduction of a co-payment of 10 Euros per quarter and physician for adults (the so called "Praxisgebühr") as of January 01, 2004 was a significant health policy measure with unknown effects on medical care of patients with atopic eczema (AE). METHODS: Analysis of an administrative healthcare database from Saxony, Germany. Comparison of outpatient care and treatment of 11,036 patients with AE (6,696 adults) in the year before (2003) and after (2004) the introduction of the co-payment using descriptive statistics and logistic regression modeling. RESULTS: The proportion of adults with AE treated by dermatologists decreased from 52.8 % in 2003 to 42.3 % in the year after the co-payment was introduced. Consultations of general practitioners by adults and health services utilization by children/adolescents did not change. Treatment with topical calcineurin inhibitors in 2003 was an independent predictor for re-consultation in 2004 (p < 0.001). The proportion of adults receiving systemic steroids for AE significantly increased in 2004 (males: 2003: 5.9 %, 2004: 10.3 %, p < 0.001; females: 2003: 5.7 %, 2004: 8.2 %, p < 0.001). The risk for treatment with systemic steroids increased with the decrease in consulting frequency due to AE relative to 2003 (p = 0.006). CONCLUSIONS: After the introduction of the German "Praxisgebühr" fewer patients with AE received dermatological treatment. Simultaneously, an unexpectedly significant increase in the (non evidence-based) treatment of AE with systemic steroids was observed, of which patients with relatively lower consultation frequency after the introduction of the co-payment were particularly affected.

Outpatient care and medical treatment of children and adults with atopic eczema.

BACKGROUND: Despite the high prevalence, morbidity and economic burden of atopic eczema (AE), data on outpatient care of affected patients are missing. METHODS: Utilizing a population-based administrative health care database from Saxony, Germany, this study describes outpatient care and medical treatment of AE by different medical disciplines in 2003 and 2004 by means of a representative sample of 11,555 patients with AE. RESULTS: About 60% of all patients with AE seeking outpatient care were adults. Of the adults 66% and among children 51% consulted a dermatologist at least once within the study period. More than 50% of patients in all age groups received potent topical steroids. Of all patients 8% and 3% received topical pimecrolimus and topical tacrolimus, respectively. More than 10% of patients received systemic steroids, while less than 0.1% was given cyclosporine. The mean annual amount of topical anti-inflammatory treatment per patient was about 40 grams. CONCLUSIONS: Unexpectedly high proportions of patients with AE received potent topical and systemic steroids. The average total amount of prescribed medications was low. This study suggests insufficient care and medical treatment of patients with AE in routine practice.

Pharmacokinetic/pharmacodynamic modelling of venlafaxine: pupillary light reflex as a test system for noradrenergic effects.

BACKGROUND AND OBJECTIVE: Venlafaxine and its major active metabolite O-desmethylvenlafaxine selectively inhibit serotonin and norepinephrine reuptake from the synaptic gap. The inhibition of norepinephrine uptake is assumed to enhance antidepressant efficacy when venlafaxine is given at higher therapeutic doses. Thus investigation of the concentration-response relationship of noradrenergic effects is of clinical interest. We used pupillography as a test system for the pharmacodynamic response to venlafaxine, since it had been shown to be useful for assessment of noradrenergic effects on the autonomous nervous system. The aim of the study was to develop a pharmacokinetic/pharmacodynamic model by means of nonlinear mixed-effects modelling in order to describe the time course of the noradrenergic response to venlafaxine. SUBJECTS AND METHODS: Twelve healthy male subjects received venlafaxine 37.5 mg or placebo orally twice daily for 7 days and subsequently 75 mg or placebo twice daily for another 7 days. After a 14-day washout phase, the two groups were crossed over. After the last dose of venlafaxine or placebo on day 14, blood samples were drawn to determine venlafaxine and O-desmethylvenlafaxine concentrations and the amplitude and recovery time of the pupillary light reflex were measured. A pharmacokinetic/pharmacodynamic model was developed to describe the data using nonlinear mixed-effects modelling. RESULTS: The pharmacokinetic part of the model could be simultaneously fitted to both venlafaxine and O-desmethylvenlafaxine data, yielding precise parameter estimates that were similar to published data. The model detected high variability of the intrinsic clearance of venlafaxine (94.8%), most likely due to cytochrome P450 2D6 polymorphism. Rapid development of tolerance of the pupillary light reflex parameters was seen and could be successfully accounted for in the pharmacodynamic part of the model. The half-life of development and regression of tolerance was estimated to be 30 minutes for the amplitude and 40 minutes for the recovery time. CONCLUSION: The time course of the effect and the concentration-response relationship were successfully described by a pharmacokinetic/pharmacodynamic model that takes into account the rapid development of tolerance of pupillary light reflex parameters. This provides a basis for further investigations of the applicability of pupillography as a surrogate measurement of the effectivity of antidepressant drugs with norepinephrine reuptake-inhibiting properties.

Prospective cohort comparison of flavonoid treatment in patients with resected colorectal cancer to prevent recurrence.

AIM: To investigate biological prevention with flavonoids the recurrence risk of neoplasia was studied in patients with resected colorectal cancer and after adenoma polypectomy. METHODS: Eighty-seven patients, 36 patients with resected colon cancer and 51 patients after polypectomy, were divided into 2 groups: one group was treated with a flavonoid mixture (daily standard dose 20 mg apigenin and 20 mg epigallocathechin-gallat, n = 31) and compared with a matched control group (n = 56). Both groups were observed for 3-4 years by surveillance colonoscopy and by questionnaire. RESULTS: Of 87 patients enrolled in this study, 36 had resected colon cancer and 29 of these patients had surveillance colonoscopy. Among the flavonoid-treated patients with resected colon cancer (n = 14), there was no cancer recurrence and one adenoma developed. In contrast the cancer recurrence rate of the 15 matched untreated controls was 20% (3 of 15) and adenomas evolved in 4 of those patients (27%). The combined recurrence rate for neoplasia was 7% (1 of 14) in the treated patients and 47% (7 of 15) in the controls (P = 0.027). CONCLUSION: Sustained long-term treatment with a flavonoid mixture could reduce the recurrence rate of colon neoplasia in patients with resected colon cancer.

[Cost-effectiveness evaluation of drugs: multidisciplinary collaboration and transparency are key]. / Kosten-Nutzen-Bewertung von Arzneimitteln: Fachübergreifende Zusammenarbeit und Transparenz sind entscheidend.

BACKGROUND: A new German law introduced the cost-effectiveness evaluation of drugs. In Germany, the Institute for Quality and Efficiency in Health Care (IQWiG) is responsible for such evaluations. Currently, however, there is a heavy and controversial debate about the correct method to be applied. A recent proposal of IQWiG on the method to be used for cost-effectiveness evaluations has been dismissed by an expert panel. Moreover, previous IQWiG assessments are criticized and the institute is accused of providing insufficient transparency of its evaluation procedures. The head organizations of the compulsory health insurances focus on their own method to analyze and judge new drugs (EVITA), which is claimed to provide the desired results faster than IQWiG. In Germany, the current situation appears obscure and there is the threat of confusing and contradictory methods for cost-effectiveness evaluations yielding inconsistent assessments. PURPOSE: This paper aims at outlining the current situation in Germany and providing potential solutions. CONCLUSION: It requires an early and multidisciplinary collaboration to achieve the goal of a valid and fully transparent cost-effectiveness evaluation.

Comparison of inhibitory effects of irbesartan and atorvastatin treatment on the renin angiotensin system (RAS) in veins: a randomized double-blind crossover trial in healthy subjects.

Experimental studies point to an interplay between hypercholesterolemia and hypertension, acting through the renin angiotensin system. In a crossover study design with 8 healthy subjects, the authors tested the hypothesis that statin treatment exerts renin angiotensin system-modulating effects in veins by down-regulation of AT1-receptors, resulting in reduced Angiotensin II (Ang II)-induced venoconstriction and by increasing the pleiotropic Ang II-metabolite Ang-(1-7). Irbesartan was used as positive control. Ang II-induced venoconstriction was 49% +/- 9% before and 64% +/- 10% after 30 days of atorvastatin treatment compared to 50% +/- 8% before and 15% +/- 9% after irbesartan (P = .004). Plasma angiotensin levels significantly increased only after irbesartan treatment (Ang II: 35 +/- 4 vs 329 +/- 101 pg/mL [P = .02]; Ang-(1-7): 10 +/- 3 vs 35 +/- 6 pg/mL [P = .01]) compared to atorvastatin treatment (Ang II: 26 +/- 5 vs 31 +/- 4 pg/mL [P = ns]; Ang-(1-7): 9 +/- 2 vs 11 +/- 3 pg/mL [P = ns]). The data indicate that atorvastatin does not inhibit Ang II-induced venoconstriction in vivo and point toward a supportive role of Ang-(1-7) in contributing to the antihypertensive and beneficial vascular effects of irbesartan.

Asymptomatic statin-induced rhabdomyolysis after long-term therapy with the hydrophilic drug pravastatin.

CASE SUMMARY: A male patient aged 73 years, 165 cm in height, and weighing 78 kg presented to the emergency department with dsypnea. He had undergone heart transplantation 7 years earlier and been receiving daily pravastatin therapy for >3 years without complaining of any symptoms. A physical examination of the patient at admission was unremarkable, except for dyspnea. However, laboratory testing revealed that his serum creative kinase (CK) concentration was substantially above the reference range. Pravastatin was immediately discontinued, and the patient was admitted to the intensive care unit for treatment. CK values declined after 3 days, and they returned to within reference range after 3 weeks. The patient was diagnosed with acute rhabdomyolysis; a score of 6 on the Naranjo adverse drug reaction probability scale indicated that pravastatin was the probable cause. DISCUSSION: The hydrophilic statin pravastatin is frequently recommended for patients who have undergone heart transplantation due to its favorable tolerability profile. Unlike lipophilic statins, hydrophilic statins such as pravastatin are not metabolized in the liver via the cytochrome P450 system and have little potential for adverse events through interaction with drugs metabolized via this pathway. Based on a search of relevant literature, this report appears to be the first to describe a case of asymptomatic rhabdomyolysis occurring in a patient receiving long-term daily therapy with pravastatin after undergoing heart transplantation and who had no muscular symptoms or history of intense physical exertion. The occurrence of acute statin-induced rhabdomyolysis in this case suggests that even hydrophilic statins may have the potential to damage myocytes. CONCLUSIONS: The hydrophilic statin pravastatin appears to have caused asymptomatic rhabdomyolysis, in the absence of physical exertion, in a patient who had undergone heart transplantation and had been receiving the drug for >3 years. Statin therapy should be initiated at the lowest effective dose, especially in patients who have undergone heart transplantation, and should be followed by close monitoring.