[Monitoring of blood parameters under course-modified MS therapy : Substance-specific relevance and current recommendations for action]. / Monitoring von Blutparametern unter verlaufsmodifizierender MS-Therapie : Substanzspezifische Relevanz und aktuelle Handlungsempfehlungen.

With the approval of various substances for the immunotherapy of multiple sclerosis (MS), treatment possibilities have improved significantly over the last few years. Indeed, the choice of individually tailored preparations and treatment monitoring for the treating doctor is becoming increasingly more complex. This is particularly applicable for monitoring for a treatment-induced compromise of the immune system. The following article by members of the German Multiple Sclerosis Skills Network (KKNMS) and the task force "Provision Structures and Therapeutics" summarizes the practical recommendations for approved immunotherapy for mild to moderate and for (highly) active courses of MS. The focus is on elucidating the substance-specific relevance of particular laboratory parameters with regard to the mechanism of action and the side effects profile. To enable appropriate action to be taken in clinical practice, any blood work changes that can be expected, in addition to any undesirable laboratory findings and their causes and relevance, should be elucidated.

[Current aspects of therapy conversion for multiple sclerosis]. / Aktuelles zur Therapieumstellung bei Multipler Sklerose.

In recent years the approval of new substances has led to a substantial increase in the number of course-modifying immunotherapies available for multiple sclerosis. Therapy conversion therefore represents an increasing challenge. The treatment options sometimes show complex adverse effect profiles and necessitate a long-term and comprehensive monitoring. This article presents an overview of therapy conversion of immunotherapies for multiple sclerosis in accordance with the recommendations of the Disease-Related Competence Network for Multiple Sclerosis and the German Multiple Sclerosis Society as well as the guidelines on diagnostics and therapy for multiple sclerosis of the German Society of Neurology and the latest research results. At the present point in time it should be noted that no studies have been carried out for most of the approaches for therapy conversion given here; however, the recommendations are based on theoretical considerations and therefore correspond to recommendations at the level of expert consensus, which is currently essential for the clinical daily routine.

Effects of inhibitors of the renin-angiotensin system on the efficacy of interferon beta-1b: a post hoc analysis of the BEYOND study.

BACKGROUND: In experimental autoimmune encephalomyelitis, inhibition of the renin-angiotensin system with angiotensin receptor blockers (ARBs) or angiotensin-converting enzyme (ACE) inhibitors resulted in a significantly ameliorated disease course. We evaluated the effects of ARBs and ACE inhibitors on the efficacy of interferon beta-1b in patients with relapsing-remitting multiple sclerosis (RRMS). METHODS: In this post hoc analysis of the BEYOND (Betaferon Efficacy Yielding Outcomes of a New Dose) study, clinical and MRI end points were compared between patients treated with interferon beta-1b 250 or 500 µg and concomitant ARBs or ACE inhibitors and patients treated with interferon beta-1b 250 or 500 µg only (reference group). RESULTS: Patients in the ARB group (n = 22) tended to have a higher relapse rate (0.48 vs. 0.23, p = 0.051) and a higher number of new gadolinium-enhancing lesions (0.6 vs. 0.3, p = 0.057) than patients in the reference group. Patients in the ACE inhibitor group (n = 49) also tended to have a higher relapse rate (0.29 vs. 0.22, p = 0.357). No differences were observed for the other end points. CONCLUSION: In the BEYOND study cohort, a concomitant medication with ARBs or ACE inhibitors did not have a beneficial effect in patients with RRMS treated with interferon beta-1b. As patients appeared to have a higher relapse rate, our results warrant further investigation.

[The transient ischemic attack (TIA)--a valid instrument for intern process analyses in neurological departments]. / Die transient ischämische Attacke (TIA)--ein valides Instrument zur internen Prozessanalyse in neurologischen Abteilungen.

BACKGROUND: The aim of this study was to develop a valid tool for internal process analysis of stroke management in order to identify possible improvements. METHOD: 939 stroke patients were classified into DRG diagnoses. Specific parameters known to influence the length of stay were analysed. Subgroup analyses were carried out in patients with TIA regarding a) differences between the neurological sections/ wards, and b) length of stay in correlation with resident level of training and the physician staffing in the particular department/ ward over the year. RESULTS: A difference in the length of stay of 1-2 days was revealed between the neurological departments/wards. Transfer to rehabilitation centres increased the length of stay by 5 days. Length of stay correlated with the training level of residents and staffing in the department/ward. Capacity overload due to reduced staffing or high fluctuation of staff increased the length of stay significantly. CONCLUSION: TIA patients were shown to be a homogeneous subtype of stroke patients, who can be used as a valid tool to analyse internal processes. This analysis revealed that length of stay depends on resident level of training and workload.

Weekly IM interferon beta-1a in multiple sclerosis patients over 50 years of age.

BACKGROUND: Efficacy and safety data have not previously been compiled for intramuscular interferon beta-1a (IM IFNß-1a) in patients with multiple sclerosis (MS) ≥ 50 years of age. We investigated the efficacy and safety of IM IFNß-1a in patients segregated by 50 and 40 years of age in separate meta-analyses. METHODS: The MS Clinical Research Group Study, the Controlled High-Risk Subjects AVONEX(®) (IM IFNß-1a) MS Prevention Study, the IFNß-1a European Dose-Comparison Study, and a multicenter, open-label antigenicity and safety study of human serum albumin-free IM IFNß-1a were analyzed. RESULTS: Overall, 906 patients (68 aged ≥ 50 years and 838 aged <50 years, or 323 aged ≥ 40 years and 583 aged <40 years) received IM IFNß-1a for ≥ 24 months. At baseline, patients ≥ 50 years had significantly higher Expanded Disability Status Scale scores than patients <50 years (3.4 vs. 2.8; P < 0.001), but fewer relapses in the three preceding years (2.6 vs. 3.4; P < 0.001); patients ≥ 40 years and <40 years exhibited similar differences. After 2 years of treatment, there were no significant differences in annualized relapse rate, sustained disability progression, time to sustained disability progression, or number of MRI-identified gadolinium-enhanced lesions between age groups in either analysis. The cumulative probability of relapse was significantly lower in patients ≥ 40 years versus patients <40 years (0.601 vs. 0.702; P < 0.001). Adverse event incidence did not differ significantly between age groups in either analysis. CONCLUSIONS: IM IFNß-1a is effective and well tolerated in patients with MS ≥ 40 and ≥ 50 years as well as younger patients.

[Generation 55+: leadership and motivation of generations in hospitals]. / Generation 55 + : Führung und Motivation von Generationen im Krankenhaus.

BACKGROUND: Demographic changes in Germany are leading towards a decrease of the population from the current 82 million to 74 million in the year 2050. As a consequence the shortage of qualified staff will be aggravated and intensifying recruiting efforts will increase competition among employers. An alternative is to utilize the potential of jobholders older than 55 years, the so-called generation 55 +. However, little is known about the hospital workforce generation 55 +. METHODS: An internet search was conducted using google.de, yahoo.de and altavista.de for "generation 55 + and medicine" and "demographics, personnel and hospital" In Medline/pubmed a search was conducted for the key words "aging workforce" (949 sources) and in combination with AND "doctors" (134 sources), "demographic changes", "staff" (794 sources) as well as for "generation 55 + AND doctors" (312 sources). Finally, sources from reputable public institutions and academic medical societies were analyzed. The data were sorted by main categories and relevance for hospitals. Statistical analysis was done mainly using descriptive measures. RESULTS: From initially more than 530,000 sources, a total of 289 studies and reports on the topic were plotted. There was no evidence for a negative correlation between age and work ability or fitness. Jobholders senior to 55 years can be divided into the "economic miracle generation" and into the so-called baby-boomers. Both groups have differences in values, communication needs and leadership requirements. They jointly prefer direct communication and seek appreciation for their experience on the job. CONCLUSIONS: Generation 55 + is not asking for an upscaled position in hospitals. They expect respect and appreciation for their sound experience of work and life. Generation 55 + wants to be integrated and sought after. Keeping these employees fit, motivated and qualified is a sound approach to fight the foreseeable shortage of qualified staff in hospitals.

Brain stem activation in spontaneous human migraine attacks.

Evidence from animal experiments shows that the brain stem is involved in the pathophysiology of migraine. To investigate human migraine, we used positron emission tomography to examine the changes in regional cerebral blood flow as an index of neuronal activity in the human brain during spontaneous migraine attacks. During the attacks, increased blood flow was found in the cerebral hemispheres in cingulate, auditory and visual association cortices and in the brain stem. However, only the brain stem activation persisted after the injection of sumatriptan had induced complete relief from headache and phono- and photophobia. These findings support the idea that the pathogenesis of migraine is related to an imbalance in activity between brain stem nuclei regulating antinociception and vascular control.

[Generation Y : recruitment, retention and development]. / Generation Y : Rekrutierung, Entwicklung und Bindung.

BACKGROUND: There is a significant shortage of highly qualified personnel in medicine, especially skilled doctors and nurses. This shortage of qualified labor has led to competition between hospitals. Analyzing the circumstances of the competition, nurses and doctors of the so-called generation Y are of importance. Recruitment and retention of these staff members will become a critical success factor for hospitals in the future. METHOD: An internet search was conducted using the key words "generation Y and medicine, demography, personnel and hospitals". A search in Medline/pubmed for scientific studies on the topics of labor shortage was performed using the key words "personnel, shortage doctors, generation X, baby boomer, personnel and demographic changes, staff". Finally, sources from public institutions and academic medical societies were analyzed. The data were sorted by main categories and relevance for hospitals. Statistical analysis was done using descriptive measures. RESULTS: The analysis confirmed the heterogeneous and complex flood of information on the topic demography and generation. A comparison of the generations showed that they can be separated into baby boomers (born 1946-1964 live to work), generation X (born 1965-1980 work to live) and generation Y (born 1981 and after, live while working). Members of generation Y "live while working" are oriented to competence and less with hierarchies. They exchange information using modern communication methods and within networks. Internet and computers are part of their daily routine. CONCLUSION: Employees of generation Y challenge leadership in hospitals by increasing the demands. However, generation Y can significantly increase professionalization and competitiveness for hospitals.

Efficacy of natalizumab in second line therapy of relapsing-remitting multiple sclerosis: results from a multi-center study in German speaking countries.

BACKGROUND: Natalizumab has been recommended for the treatment of relapsing-remitting multiple sclerosis (RRMS) in patients with insufficient response to interferon-beta/glatiramer acetate (DMT) or aggressive MS. The pivotal trials were not conducted to investigate natalizumab monotherapy in this patient population. METHOD: Retrospective, multicenter study in Germany and Switzerland. Five major MS centers reported all RRMS patients who initiated natalizumab >or=12 months prior to study conduction. RESULTS: Ninety-seven RRMS patients were included [69% female, mean age 36.5 years, mean Expanded Disability Status Scale (EDSS) 3.4; 93.8% were pre-treated with DMT], mean treatment duration with natalizumab was 19.3 +/- 6.1 months. We found a reduction of the annualized relapse rate from 2.3 to 0.2, 80.4% were relapse free with natalizumab. EDSS improved in 12.4% and 89.7% were progression free (change of >or= 1 EDSS point). Eighty-six per cent of patients with highly active disease (>or= 2 relapses in the year and >or= 1 Gadolinium (Gd)+ lesion at study entry, n = 20) remained relapse free. The mean number of Gd enhancing lesions was reduced to 0.1 (0.8 at baseline). Discontinuation rate was 8.2% (4.1% for antibody-positivity). CONCLUSION: Natalizumab is effective after insufficient response to other DMT and also in patients with high disease activity.

Natalizumab is effective as second line therapy in the treatment of relapsing remitting multiple sclerosis.

BACKGROUND: Natalizumab has been recommended for the treatment of patients with relapsing remitting multiple sclerosis with insufficient response to interferon-beta (IFN-beta) or glatiramer acetate (GA). METHOD: Prospective, observational study. RESULTS: We found a reduction of the annualized relapse rate from 2.1 under IFN-beta or GA to 0.2 one year after switching to natalizumab. There were 94% fewer gadolinium enhancing lesions with natalizumab. CONCLUSION: Natalizumab reduced short term clinical and MRI activity in second line therapy and efficacy is comparable to first line therapy as demonstrated in the pivotal trials.

Prevalence of migraine, tension-type headache and trigeminal neuralgia in multiple sclerosis.

BACKGROUND: Prevalence rates of headache in multiple sclerosis (MS) patients varied widely in recent studies. This study aimed to investigate the 1 year prevalence of headache in MS compared with the general population. METHODS: Population-based case-control study in Germany. RESULTS: We included 491 patients with definite MS (68% female, mean age 45.3 years, 63.7% relapsing remitting MS, mean Expanded Disability Status Scale (EDSS) 3.2, 106 treated with interferon-beta, 53 with glatiramer acetate, 271 untreated) and 447 age and gender matched controls. Headache was diagnosed with a validated questionnaire according to the International Headache Society Criteria. Headache prevalence was 56.2% (tension type headache 37.2%, migraine 24.6%). Headache prevalence rates did not differ from controls. Headache was not associated with disability or treatment. Trigeminal neuralgia was found in 6.3% of MS cases. CONCLUSION: Results suggest that headache in MS patients reflects comorbidity in most conditions.

Prednisone vs. placebo in withdrawal therapy following medication overuse headache.

This proof-of-concept study evaluated the efficacy of prednisone for the treatment of withdrawal symptoms in patients with medication overuse headache (MOH) in a randomized, placebo-controlled, double-blind design. Twenty patients were randomized and underwent in-patient withdrawal therapy. The total number of hours with severe or moderate headache within the first 72 and 120 h was significantly lower in the prednisone group. The results show that prednisone might be effective in the treatment of medication withdrawal headache.

Guidelines for controlled trials of prophylactic treatment of chronic migraine in adults.

In 1991 the Clinical Trials Subcommittee of the International Headache Society (IHS) developed and published its first edition of the Guidelines on controlled trials of drugs in episodic migraine because only quality trials can form the basis for international collaboration on drug therapy, and these Guidelines would 'improve the quality of controlled clinical trials in migraine'. With the current trend for large multinational trials, there is a need for increased awareness of methodological issues in clinical trials of drugs and other treatments for chronic migraine. These Guidelines are intended to assist in the design of well-controlled clinical trials of chronic migraine in adults, and do not apply to studies in children or adolescents.

[Current diagnosis and treatment of migraine]. / Aktuelle Diagnostik und Therapie der Migräne.

Headaches are one of the most common disorders and symptoms in daily medical practice. The prevalence of migraine is 8% in men and 12-15% in women. Dramatic progress in the areas of epidemiology, pathophysiology, and acute and preventive therapy of migraine has been made over the past 100 years, with triptans being the breakthrough for treating acute migraine attacks. Beta blockers, calcium antagonists, and neuromodulators are available for preventive migraine therapy. Nonpharmacologic treatment also plays an important role in migraine prevention. New medical care structures such as integrated headache care provide better support for patients with migraine, particularly those with chronic migraine.

Autoinjector preference among patients with multiple sclerosis: results from a national survey.

PURPOSE: Autoinjectors are well-established in supporting multiple sclerosis (MS) therapy. This market survey was aimed at investigating patients' rating of three devices for subcutaneous interferon beta formulations: the electronic autoinjectors Betaconnect® and RebiSmart™ as well as the mechanical ExtaviPro™ device. PATIENTS AND METHODS: Organization and conduction of structured face-to-face interviews in five German cities were managed through an independent external market research company. After questionnaire validation (n=15), 85 participants currently either using the Betaconnect (n=39), the RebiSmart (n=36) or the ExtaviPro injector (n=10) were asked 22 questions in the same order. First, patients named their current device in use, watched the corresponding instruction video, and were queried about their device. Second, patients were asked about their opinion of an ideal autoinjector. Third, instruction videos for the two non-used devices were presented and participants could dummy-inject into a pillow. Last, patients evaluated device features and indicated their preferred autoinjector. RESULTS: Before having been presented the two other autoinjectors not in use, evaluation of patients' satisfaction with their own device revealed that 82% of the Betaconnect users, 67% of the RebiSmart and 60% of the ExtaviPro users were highly satisfied. All patients desired some improvement of their own device particularly concerning optimization of size and handling. Subsequent to testing and watching instruction videos of all devices, the Betaconnect received the best rating regarding different functions. Finally, participants indicated their preferred autoinjector, provided their own medication was suitable for all three devices: 56.5% of the participants (n=48/85) chose the Betaconnect, 36.5% the RebiSmart (n=31/85), and 5% the ExtaviPro device (n=4/85); 2% did not answer (n=2/85). CONCLUSION: In this survey, the Betaconnect device was the preferred autoinjector and may currently best meet patients' needs. As it was closest to participants' opinion of an ideal device, the Betaconnect might contribute to treatment adherence. Our results need to be confirmed in further studies.

Costs and quality of life of multiple sclerosis in Germany.

This cost-of-illness analysis based on information from 2973 patients with multiple sclerosis (MS) in Germany is part of a Europe-wide study on the costs of MS. The objective was to analyze the costs and quality of life (QOL) related to the level of disease severity. Patients from six centres (office- and hospital-based physicians) and patients enrolled in a database were asked to participate in the survey; 38% answered a mail questionnaire. In addition to details on the disease (type of disease, relapses, level of functional disability), the questionnaire asked for information on all resource consumption, medical, non-medical, work absence, informal care, as well as QOL (measured as utility). The mean age of the cohort was 45 years, and 18% of patients were 65 years of age or older. Forty-seven percent of patients had mild disease (Expanded Disability Status Scale [EDSS] score 0-3), 36% had moderate disease (EDSS score 4-6.5) and 12% had severe disease (EDSS score > or =7). The mean EDSS score in the sample was 3.8 (median 4.0), with a mean utility of 0.62. Costs and utility are highly correlated with disease severity. Workforce participation decreases from 73% in very early disease to less than 10% in the very late stages, leading to a tenfold rise in productivity losses in the late stages of disease. Hospitalisation and ambulatory visits rise by a factor of 5-6 between early and late disease; investments and services increase from basically no cost to euro 2700; and informal care increases by a factor of 27 for patients with an EDSS score of 7 and by a factor of 50 for patients at the very severe end of the EDSS scale (8-9). Hence, total mean costs per patient are determined essentially by the distribution of the severity levels in the sample, increasing from approximately euro 18 500 at an EDSS score of 0-1 to euro 70 500 at an EDSS score of 8-9. The same is true for utility, which decreases from 0.86 to 0.10 as the disease becomes severe. However, the utility loss compared to the general population is high at all levels of the disease, leading to an estimated loss of 0.2 quality-adjusted life-years per patient. Relapses are associated with a cost of approximately euro 3 000 and a utility loss of 0.1 during the quarter in which they occur. Compared with a similar study performed in 1999, resource consumption, with the exception of drugs, is somewhat lower. This is most likely due to a difference in the severity distribution of the two samples and to changes in health-care consumption overall in the country, such as the introduction of diagnosis-related groups (DRGs, Fallpauschalen).

MRI changes associated with partial status epilepticus.

Neurological disorders of different etiology may cause identical clinical symptoms requiring additional diagnostic procedures for a precise differential diagnosis. Focal epileptic seizures have been shown to cause increased signal intensities in T2 and diffusion-weighted magnetic resonance images (MRI), mimicking other neurological disorders or diseases such as viral encephalitis. In some cases even the combination of neuroimaging and cerebrospinal fluid (CSF) analysis is not sufficient to obtain the final diagnosis, since epileptic seizures may cause pleocytosis as well. Some epilepsy centers presented cases of focal status epilepticus with severe but reversible MRI changes. These cases indicate that MRI-changes following focal seizures are reversible over a different time window compared to MRI changes associated with other etiologies, such as viral infection. This data further suggest that in cases where focal seizures can not be ruled out, a follow-up MRI scan within a few days following the onset of symptoms significantly improves the precision of the differential diagnosis. Recently new scientific data were reported in this review.

The NOS inhibitor, 7-nitroindazole, decreases focal infarct volume but not the response to topical acetylcholine in pial vessels.

We examined whether 7-nitroindazole (7-NI), a putative inhibitor of neuronal nitric oxide synthase (nNOS), decreases cerebral infarction 24 h after proximal middle cerebral artery (MCA) occlusion. In preliminary experiments, we determined that 7-NI (25, 50, and 100 mg/kg i.p.) decreased nitric oxide synthase (NOS) activity within cerebral cortex by 40-60% when measured up to 120 min, but not 240 min after administration. At 25 or 50 mg/kg, 7-NI did not alter the systemic arterial blood pressure or the dilation of pial arterioles after topical acetylcholine (10 and 100 microM). To examine the effect of 7-NI on infarct size, 55 Sprague-Dawley halothane-anesthetized rats were subjected to proximal MCA occlusion (modified Tamura method). Five minutes after occlusion, 7-NI (25 or 50 mg/kg i.p.) or vehicle was injected. Animals treated with 25 or 50 mg/kg showed 25 and 27% reductions in infarct volume, respectively. Coadministration of L-arginine (300 mg/kg i.p.) plus 7-NI (25 mg/kg i.p.) reversed the effect. If, indeed, the effects of 7-NI are mediated by inhibition of nNOS activity, these results suggest that enzymatic products of the neuronal isoform promote ischemic injury and that they do so at least within the first few hours after permanent occlusion. The results also emphasize the importance of developing strategies to selectively inhibit the neuronal isoform inasmuch as we observed previously that administering the less selective NOS inhibitor, N omega-nitro-L-arginine (L-NA), in the same model either caused no change or increased the volume of ischemic injury.