Communication, Coordination, and Security for People with Multiple Sclerosis (COCOS-MS): a randomised phase II clinical trial protocol.

INTRODUCTION: Patients with multiple sclerosis (MS) have complex needs that range from organising one's everyday life to measures of disease-specific therapy monitoring to palliative care. Patients with MS are likely to depend on multiple healthcare providers and various authorities, which are often difficult to coordinate. Thus, they will probably benefit from comprehensive cross-sectoral coordination of services provided by care and case management (CCM). Though studies have shown that case management improves quality of life (QoL), functional status and reduces service use, such benefits have not yet been investigated in severely affected patients with MS. In this explorative phase ll clinical trial, we evaluated a CCM with long-term, cross-sectoral and outreaching services and, in addition, considered the unit of care (patients and caregivers). METHODS AND ANALYSIS: Eighty patients with MS and their caregivers will be randomly assigned to either the control (standard care) or the intervention group (standard care plus CCM (for 12 months)). Regular data assessments will be done at baseline and then at 3-month intervals. As primary outcome, we will evaluate patients' QoL. Secondary outcomes are patients' treatment-related risk perception, palliative care needs, anxiety/depression, use of healthcare services, caregivers' burden and QoL, meeting patients' and caregivers' needs, and evaluating the CCM intervention. We will also evaluate CCM through individual interviews and focus groups. The sample size calculation is based on a standardised effect of 0.5, and one baseline and four follow-up assessments (with correlation 0.5). Linear mixed models for repeated measures will be applied to analyse changes in quantitative outcomes over time. Multiple imputation approaches are taken to assess the robustness of the results. The explorative approach (phase ll clinical trial) with embedded qualitative research will allow for the development of a final design for a confirmative phase lll trial. ETHICS AND DISSEMINATION: The trial will be conducted under the Declaration of Helsinki and has been approved by the Ethics Commission of Cologne University's Faculty of Medicine. Trial results will be published in an open-access scientific journal and presented at conferences. TRIAL REGISTRATION NUMBER: German Register for Clinical Studies (DRKS) (DRKS00022771).

Alemtuzumab as rescue therapy in a cohort of 50 relapsing-remitting MS patients with breakthrough disease on fingolimod: a multi-center observational study.

BACKGROUND: Relapsing-remitting multiple sclerosis (RRMS) requires efficient immunomodulatory treatment to reach "no evidence of disease activity" status at best. Alemtuzumab and fingolimod have proved to be efficient options in RRMS with active disease course. Yet, side effects and break-through disease may limit long-time treatment and necessitate switch of medication. Data on efficacy and safety of alemtuzumab following fingolimod treatment are limited, but useful for clinical practice. METHODS: Clinical and MRI data of 50 RRMS patients with a history of therapy switch from fingolimod to alemtuzumab were retrospectively analyzed. Data were acquired from nine large German MS Centers from 2013 to 2016 and analyzed using descriptive statistics. RESULTS: On average, patients with disease duration of 12.9 years and median EDSS of 3.0 at baseline switched to alemtuzumab after 68 weeks of fingolimod treatment. Thereafter, patients on alemtuzumab were followed for a mean of 64 weeks. The annualized relapse rate decreased from 2.2 in the year prior to 0.34 in the following year after switching to alemtuzumab and EDSS stabilized. In a subgroup of patients (n = 23), MRI data point to a reduction in enhancing (4.47 vs. 0.26) and new/enlarging T2 lesions (5.8 vs. 0.27) after treatment adjustment. Side effects were generally as expected from published data for alemtuzumab (autoimmunity 2/50, severe infections 1/50). One patient suffered combined lethal necrotizing leukoencephalopathy and hemolytic anemia. DISCUSSION: Therapy switch was highly effective in reducing clinical and MRI surrogates of disease activity and was mainly well tolerated within one year of follow-up. Hence, alemtuzumab constitutes a promising therapy in RRMS with refractory disease activity despite fingolimod treatment. Further studies are warranted to confirm these beneficial findings and to reveal safety concerns in the longer-term follow-up.

Electrocardiographic assessments and cardiac events after fingolimod first dose - a comprehensive monitoring study.

BACKGROUND: First dose observation for cardiac effects is required for fingolimod, but recommendations on the extent vary. This study aims to assess cardiac safety of fingolimod first dose. Individual bradyarrhythmic episodes were evaluated to assess the relevance of continuous electrocardiogram (ECG) monitoring. METHODS: START is an ongoing open-label, multi-center study. At the time of analysis 3951 patients were enrolled. The primary endpoints are the incidence of bradycardia (heart rate < 45 bpm) and second-/third-degree AV blocks during treatment initiation. The relevance of Holter was assessed by matching ECG findings with the occurrence of clinical symptoms as well as by rigorous analysis of AV blocks with regard to the duration of pauses and the minimal heart rate recorded during AV block. RESULTS: Thirty-one patients (0.8%) developed bradycardia (<45 bpm), 62 patients (1.6%) had second-degree Mobitz I and/or 2:1 AV blocks with a lowest reading (i.e. mean of ten consecutive beats) of 35 bpm and the longest pause lasting for 2.6 s. No Mobitz II or third-degree AV blocks were observed. Only one patient complained about mild chest discomfort and fatigue. After 1 week, there was no second-/third-degree AV block. CONCLUSIONS: Continuous Holter ECG monitoring in this large real-life cohort revealed that bradycardia and AV conduction abnormalities were rare, transient and benign. No further unexpected abnormalities were detected. The data presented here give an indication that continuous Holter ECG monitoring does not add clinically relevant value to patients' safety. TRIAL REGISTRATION: NCT01585298 ; registered April 23, 2012.

Case Report: Human Bocavirus Associated Pneumonia as Cause of Acute Injury, Cologne, Germany.

Although the human bocavirus (HBoV) is known since a decade, limited information about its pathogenesis is available due to the lack of an animal model. Thus, clinical cases and studies are the major source of novel information about the course of infection and the related pathophysiology.In this context, a clinical case of an adult patient suffering from severe HBoV-pneumonia is described that was associated with loss of consciousness followed by acute rib fracture and subsequent neurological disorder.Following initial global respiratory dysfunction the clinical respiratory symptoms recovered but the neurological symptoms maintained after weaning and intensive care in the stroke unit. During the initial phase, an acute active HBoV infection was confirmed by positive polymerase chain reactions from bronchoalveolar lavage fluid and serum.The case further demonstrates that HBoV can cause severe pneumonia, induce secondary disease also in adults, and may be associated with neurological symptoms as previously assumed.

Single-use autoinjector for once-weekly intramuscular injection of IFNß-1a.

INTRODUCTION: IFNß products and glatiramer acetate are established treatment first-line options in long-term disease-modifying therapy of multiple sclerosis (MS). These self-injectable medications are used once weekly to once daily. Injection-related issues are common patient-cited reasons for nonadherence. Autoinjectors have been shown to support long-term adherence to injectable medications. The ability to self-inject in MS patients has been associated with a reduced risk of missed injections and drug discontinuation, and a beneficial effect on patient independence. AREAS COVERED: The recently introduced easy-to-use prefilled once-weekly pen is a safe and effective device for intramuscular (IM) IFNß-1a application and provides a convenient method for self-injection. We reviewed the available published evidence on the characteristics of this device. The once-weekly pen facilitates self-injection and was preferred over prefilled syringes by patients in a prospective open-label, multicenter Phase IIIb trial in MS patients who had been using IM IFNß-1a in prefilled syringes. EXPERT OPINION: The simple and safe handling, shielded short needle, single-use disposable design and virtually painless injection by the device may contribute to adherence, quality of life and independence in patients using IM IFNß-1a.

Experience of gratitude, awe and beauty in life among patients with multiple sclerosis and psychiatric disorders.

BACKGROUND: Feelings of gratitude and awe facilitate perceptions and cognitions that go beyond the focus of illness and include positive aspects of one's personal and interpersonal reality, even in the face of disease. We intended to measure feelings of gratitude, awe, and experiences of beauty in life among patients with multiple sclerosis and psychiatric disorders, particularly with respect to their engagement in specific spiritual/religious practices and their life satisfaction. METHODS: We conducted a cross-sectional survey with standardized questionnaires to measure engagement in various spiritual practices (SpREUK-P) and their relation to experiences of Gratitude, Awe and Beauty in Life and life satisfaction (BMLSS-10). In total, 461 individuals (41 ± 13 years; 68% women) with multiple sclerosis (46%) and depressive (22%) or other psychiatric disorders (32%) participated. RESULTS: Among participants, 23% never, 43% rarely, 24% often, and 10% frequently experienced Gratitude. In contrast, 41% never, 37% rarely, 17% often, and 6% frequently experienced Awe. Beauty in Life was never experienced by 8% of the sample, and 28% rarely, 46% often, and 18% frequently experienced it. Gratitude (F = 9.2; p = .003) and Beauty in Life (F = 6.0; p = .015) were experienced significantly more often by women than men. However, the experience of Awe did not differ between women and men (F = 2.2; n.s.). In contrast to our hypothesis, Gratitude/Awe cannot explain any relevant variance in patients' life satisfaction (R2 = .04). Regression analyses (R2 = .42) revealed that Gratitude/Awe can be predicted best by a person's engagement in religious practices, followed by other forms of spiritual practices and life satisfaction. Female gender was a weak predictor and underlying disease showed no effect. CONCLUSIONS: Gratitude/Awe could be regarded as a life orientation towards noticing and appreciating the positive in life--despite the symptoms of disease. Positive spirituality/religiosity seems to be a source of gratitude and appreciation in life, whereas patients with neither spiritual nor religious sentiments (R-S-) seem to have a lower awareness for these feelings.

Faith as a resource in patients with multiple sclerosis is associated with a positive interpretation of illness and experience of gratitude/awe.

The aim of this cross-sectional anonymous survey with standardized questionnaires was to investigate which resources to cope were used by patients with multiple sclerosis (MS). We focussed on patients' conviction that their faith might be a strong hold in difficult times and on their engagement in different forms of spirituality. Consecutively 213 German patients (75% women; mean age 43 ± 11 years) were enrolled. Fifty-five percent regarded themselves as neither religious nor spiritual (R-S-), while 31% describe themselves as religious. For 29%, faith was a strong hold in difficult times. This resource was neither related to patients' EDSS scores, and life affections, fatigue, negative mood states, life satisfaction nor to Positive attitudes. Instead it was moderately associated with a Reappraisal strategy (i.e., and positive interpretation of illness) and experience of gratitude/awe. Compared to spiritual/religious patients, R-S- individuals had significantly (P < .0001) lower Reappraisal scores and lower engagement in specific forms of spiritual practices. The ability to reflect on what is essential in life, to appreciate and value life, and also the conviction that illness may have meaning and could be regarded as a chance for development was low in R-S- individuals which either may have no specific interest or are less willing to reflect these issues.

Pain prevalence and risk distribution among inpatients in a German teaching hospital.

OBJECTIVES: This study was designed to provide a cross-sectional analysis of pain prevalence, chronicity, and severity as well as the impact of pain on psychological and social variables in inpatients in various departments of a German teaching hospital. METHODS: Patients were asked to complete a questionnaire including sections on sociodemographic and socioeconomic data, pain variables, recent and past health care utilization, and screening questionnaires for depression, anxiety, and health-related quality of life. RESULTS: Of the 438 patients, 386 (88.1%) had experienced pain in the past 12 months; 367 (83.8%) reported having pain in the previous 3 months. Sixty-four percent of the pain patients stated that pain was the main reason for hospital admission; 48% reported having three or more pain sites. The most common location of pain was the back (26.9%). Pain patients showed significantly higher depression and anxiety scores and markedly reduced physical health when compared to non-pain patients. DISCUSSION: The results of this study indicate that in most medical disciplines pain is more than merely a symptom of disease. In many instances pain should be considered a serious comorbidity that can influence the outcome of medical and surgical treatment. Recent research has shown that prevention of the pain chronification process is the most promising strategy for avoiding the development of intractable pain. Acceptance, recognition, and assessment of pain as a risk factor at an early stage are essential factors. A first step might involve routine screening for pain on admission to any hospital facility, and subsequently evaluating the impact of pain on biopsychosocial functions.

Risk factors for acute and chronic postoperative pain in patients with benign and malignant renal disease after nephrectomy.

AIMS: This longitudinal study was performed in order to analyze the incidence of and perioperative risk factors for the development of chronic postsurgical pain (CPSP) in patients after nephrectomy. METHODS: For baseline data acquisition, valid instruments were used for scoring sociodemographic, psychological, psychosocial, pain, pain treatment, and comorbidity factors: the Mainz Pain Staging System (MPSS) for pain chronicity, the Chronic Pain Grading Questionnaire (CPGQ), the Neuropathic Pain Scale (NPS), the Hospital Anxiety and Depression Scale (HADS), the Short Form 12 (SF-12) for health-related quality of life, the Habitual Well-Being Questionnaire (HWBQ), the Symptom Check List (SCL-8) for detecting psychosomatic dysfunction, and the Weighted Illness Check List (WICL) for evaluation of comorbidities and their impact on activities of daily living. Pain intensities were recorded over the first 6 postoperative days after nephrectomy. A sample of 35 patients was followed up for 3 and 6 months. RESULTS: Patients with more intense postoperative pain during the first 6 days had significantly higher preoperative anxiety scores. The incidence of CPSP 3 and 6 months after nephrectomy was 28.6% and 8.6%, respectively. Preoperatively increased anxiety scores, reduced physical health-related quality of life (SF-12), multiple comorbid conditions, and increased comorbidity-related disability were significantly associated with the occurrence of CPSP after 3 months. These patients also reported more severe pain during the first week after surgery. Preoperative "current pain intensity" was significantly increased in CPSP patients. CONCLUSIONS: Our results demonstrate a multifactorial development of CPSP. This process may contribute not only to the occurrence of chronic postsurgical pain but also to the biopsychosocial impairment in these patients as often seen in other chronic pain populations.

Pain therapy in german neurology. Structures and standards of evaluation.

In order to analyze aspects of pain patient care in neurology, we conducted a survey among German neurology departments that aimed to determine different structural aspects of neurological pain medicine. A 5-page questionnaire was sent to 391 neurological departments, and a return rate of 59.8% was achieved. Some 70% of university-based neurology departments have established their own outpatient clinic, and some 80% of these departments actively take part in interdisciplinary pain services. University hospitals operate an interdisciplinary pain clinic in 94.7%. Almost all neurological departments admit pain patients, especially for further diagnosis and neurological treatment. These fields are accepted as important neurological tasks. The quality of care is reported to be excellent. Routine questioning for pain of all admitted patients is carried out by 85% of all hospitals, and an extensive pain history is taken by almost 90% of departments. Our survey data confirm that the documentation of medical, psychological and psychosocial pain histories and the process of pain patient care are partly fulfilled, yet need improvement. Routine application of validated instruments and regular inquiry of the presence/course of pain may improve the process of care and--as the basis of outcome--pain management in neurology.

Prevalence and impact of pain in neurological inpatients of a German teaching hospital.

OBJECTIVES: The authors sought to determine the prevalence of pain among neurological inpatients and the impact of pain on psychological and social variables depending on severity and chronicity of pain. PATIENTS AND METHODS: 400 consecutive newly referred inpatients to a neurological department who were 18 years and older and able to speak German were asked to complete a self-administered epidemiological questionnaire containing demographics and socioeconomics, pain variables, health care utilization, screening for depression and anxiety, habitual well-being, and health-related quality of life. RESULTS: 320 patients (80%) complained of pain in the past 3 months. 43% showed higher pain severity -- mirroring severely disabling pain with additionally moderate to high interferences with daily activities. Two-thirds of the neurological patients suffering from pain have to be considered "chronic pain patients". Pain patients had significantly higher depression scores, bodily complaints, more severe disabilities and lower well-being scores compared to patients without pain. CONCLUSION: This study documents a high prevalence of pain with high grades of pain severity and chronicity in neurological inpatients. Pain presents a major problem as a secondary comorbid condition among neurological inpatients.

Prevalence, severity, and chronicity of pain and general health-related quality of life in patients with localized prostate cancer.

AIMS: To analyze the prevalence and the severity spectrum of pain and its relationships to health-related quality of life and the bio-psycho-social consequences of pain among patients scheduled for radical prostatectomy. METHODS: Urological inpatients completed an epidemiological pain questionnaire extensively exploring pre-operative acute and chronic pains in 21 body regions. The severity of pain was determined using von Korff's Pain Grading (CPGQ). Pain chronicity was estimated employing the Mainz Pain Staging System (MPSS). Anxiety and depressive symptoms were identified with the HADS and the Habitual Well-Being Questionnaire (FW-7). Health-related quality of life was measured using the SF-12. Comorbidities and comorbidity-related interferences with daily activities were ascertained with the Weighted Illness Checklist (WICL). RESULTS: Eighty of 115 patients (69.6%) reported about pain during the last 3 months pre-operatively. 28.7% of the pain patients had pain related to urological disease. Severe dysfunctional pain was identified by pain Grades 3 and 4 of the CPGQ in 20% and 13.8%, respectively. Advanced pain chronicity characterized by pain Stages II and III of the MPSS was present in 38.8% and 11.3%. Patients with localized prostate cancer without pain complaints had significantly better health-related quality of life and habitual well-being and lower anxiety and depression scores and fewer comorbidities. Patients with cancer-related and non-cancer pain did not differ in pain chronicity, pain severity, pain intensities, anxiety, comorbidities and physical health (SF12-PCS). CONCLUSIONS: The high prevalence of severe and chronic pain in cancer patients before scheduled radical prostatectomy--combined with considerable disability effects and markedly reduced quality of life necessitate a short routine screening-analysis of the severity spectrum of pain and psychopathology. Patient self-rated pain chronicity staging and psychological distress analysis will allow a disorder severity-guided treatment and the prevention of suffering and additional new chronic post-surgical pain.

Rapid geographical clustering of wound botulism in Germany after subcutaneous and intramuscular injection of heroin.

BACKGROUND: Wound infections due to Clostridium botulinum in Germany are rare and occur predominantly in heroin injectors, especially after subcutaneous or intramuscular injection of heroin ("skin popping"), which is contaminated with spores of C. botulinum. We report a rapid geographical clustering of cases in Germany in a region between Cologne, Bonn, and Aachen with wound botulism and consecutive systemic C. botulinum intoxication in intravenous drug users (IDUs) within 6 weeks in October and November 2005. PATIENTS: A group of 12 IDUs with wound botulism after "skin popping." RESULTS: Clinical data were available in 11 (92%) of 12 patients; in 7 (58%) of the 12 cases, there was cranial nerve involvement including mydriasis, diplopia, dysarthria, and dysphagia, followed by progressing symmetric and flaccid paralysis of proximal muscles of the neck, arms, trunk, and respiratory muscles. Mechanical respiratory support was necessary. Five of the IDUs were treated with antitoxin, but mechanical respiratory support could not be avoided. The mean ventilation duration was 27.4 days (range 6-77 days). In 4 patients (33%), mechanical ventilation could be avoided; two were treated with antitoxin. CONCLUSIONS: This report describes rapid geographical clustering of wound botulism with severe respiratory complications in IDUs after "skin popping," which has not previously been reported either in Germany or any other European country. Based on these observations and those in other European countries, we conclude that there is a trend towards "skin popping," suggesting a change in injection practices in IDUs. Secondly, we conclude that the total number of cases with wound botulism is likely to increase because "skin popping" is the main risk factor.