Real-world efficacy of bezlotoxumab for prevention of recurrent Clostridium difficile infection: a retrospective study of 46 patients in five university hospitals in Finland.

Reports on real-world experience on efficacy of bezlotoxumab (BEZ) has been lacking thus far. We retrospectively studied the efficacy and safety of BEZ in preventing the recurrence of Clostridium difficile infection (CDI) in five university hospitals in Finland. Seventy-three percent of our 46 patients remained free of recurrence in the following 3 months and the performance remained as 71% effective also among immunocompromised patients. In severe CDI, BEZ prevented recurrence in 63% of cases. From our study patients, 78% had three or more known risk factors for recurrence of CDI. Eight of our patients were waiting for fecal microbiota transplantation but after stopping the antibiotics that were continued to prevent recurrence of CDI and after receiving BEZ, all remained free of recurrence and did not need the procedure. Success with BEZ as an adjunctive treatment in preventing recurrence of CDI in high-risk patients may be rated as high. Among a subgroup of our patients, those already evaluated to be in need of fecal microbiota transplantation, BEZ seems to be an alternative option.

Long-term colonisation with donor bacteriophages following successful faecal microbial transplantation.

BACKGROUND: Faecal microbiota transplantation (FMT) is used in the treatment of recurrent Clostridium difficile infection. Its success is typically attributed to the restoration of a diverse microbiota. Viruses (including bacteriophages) are the most numerically dominant and potentially the most diverse members of the microbiota, but their fate following FMT has not been well studied. RESULTS: We studied viral transfer following FMT from 3 donors to 14 patients. Recipient viromes resembled those of their donors for up to 12 months. Tracking individual bacteriophage colonisation revealed that engraftment of individual bacteriophages was dependent on specific donor-recipient pairings. Specifically, multiple recipients from a single donor displayed highly individualised virus colonisation patterns. CONCLUSIONS: The impact of viruses on long-term microbial dynamics is a factor that should be reviewed when considering FMT as a therapeutic option.

The long-term effects of faecal microbiota transplantation for gastrointestinal symptoms and general health in patients with recurrent Clostridium difficile infection.

BACKGROUND: Faecal microbiota transplantation (FMT) is an effective treatment for recurrent Clostridium difficile infection. In short-term the treatment has been shown to be safe, however, there are no large, long-term follow-up studies looking into the potential adverse effects. AIM: To analyse the long-term effect of FMT treatment in patients with recurrent C. difficile infection and to compare the outcome to antibiotic treated patients. METHODS: Altogether 84 patients of which 45 received a FMT treatment and 39 served as controls receiving antibiotics for the infection were followed on average for 3.8 years. Their recovery and medical status was evaluated using a retrospective questionnaire, determining their quality of life, gastrointestinal symptoms and new diseases potentially related to the FMT. RESULTS: There was no difference in the incidence of severe diseases (inflammatory bowel disease, cancer, autoimmune disease, allergy, neurological diseases) between the patient groups. In addition, weight gain did not differ between treatment groups. The FMT treated patients reported that their bowel habits improved significantly faster, they had less irregular bowel function and less symptoms of upper GI-tract when compared to the patients treated with antibiotics. Significantly more patients in FMT-group reported that their mental health improved after the treatment. The willingness to receive FMT treatment for potential new C. difficile infection was significantly higher in both treatment groups compared to other treatment options. CONCLUSION: Our study highlights that FMT is a durable, safe and acceptable treatment option for patients with recurrent C. difficile infection also in long term, and it shows potential benefits over antimicrobial treatment.

Simple faecal preparation and efficacy of frozen inoculum in faecal microbiota transplantation for recurrent Clostridium difficile infection--an observational cohort study.

BACKGROUND: Faecal microbiota transplantation (FMT) is an effective treatment for recurrent Clostridium difficile infection (rCDI). The finding of suitable donor, donor screening and preparation of faecal transplants are challenging in clinical work. AIM: To develop a practical protocol for preparing frozen transplants and to compare the efficacy of previously frozen and fresh faeces in treating rCDI. METHODS: Two healthy volunteers acted as universal donors for the frozen faecal preparations, which were prepared by suspending faeces into physiological saline, adding glycerol to a final concentration of 10% and storing at -80 °C. We compared the outcomes of patients with rCDI who had undergone FMT at colonoscopy and received infusion of previously prepared, freeze-stored faeces (n = 23) or fresh faeces from individual (n = 15) or universal donors (n = 11) (total n = 49). Clinical failure was defined as persistent or recurrent symptoms with a positive C. difficile toxin stool test, and a need for new therapy. RESULTS: At 12 weeks post-FMT, symptoms were resolved in 22 of 23 patients receiving previously frozen faeces, and in all 11 or 14 of 15 patients receiving fresh faeces from the universal or individual donors respectively (totally 25 of 26; P = ns, success rate 96%). Mild transient fever appeared for two patients receiving frozen faeces, but no other significant side effects were observed. 42 patients were followed up for a year post-FMT and the success rate was 88% in both fresh and frozen faeces groups. CONCLUSIONS: Preparation of frozen transplants simplifies the practical aspects of faecal microbiota transplantation without loss of efficacy or safety.

Rifaximin in the treatment of recurrent Clostridium difficile infection.

BACKGROUND: Clostridium difficile can cause severe antibiotic-associated colitis. Conventional treatments with metronidazole and vancomycin improve symptoms, but after discontinuation of treatment, C. difficile infection (CDI) recurs in a number of patients. Rifaximin is a rifamycin-based non-systemic antibiotic that has effect against C. difficile. AIM: To assess the effectiveness of rifaximin in recurrent C. difficile infection. METHODS: We retrospectively evaluated the records of 32 patients who were treated with rifaximin for recurrent C. difficile infection. The symptoms were evaluated 12 weeks after the start of treatment and patient records were followed up until 1 year after treatment. RESULTS: The mean age of the patients was 55 years (median 64, range: 19-84 years). Before the initiation of rifaximin therapy, the patients had undergone, on the average, 4.4 (range: 2-12) antimicrobial courses for C. difficile infection. C. difficile strain typing was performed in 27 patients. Eight (30%) patients had a strain with a DNA profile compatible with the BI/NAP1/027 ribotype. Antibiotic susceptibilities were determined of isolates from 22 patients. Most isolates (68%) had very low MIC-values for rifampin (<0.002 µg/mL) and the highest MIC value was 3.0 µg/mL. Isolates with a DNA profile compatible with the BI/NAP1/027 ribotype had, on the average, higher MICs of rifampin. After 12 weeks 17 (53%) patients had no relapse. The MIC value of rifampin seemed to predict the response to rifaximin treatment. CONCLUSIONS: Rifaximin is a safe treatment for C. difficile infection. It has a reasonable effect in C. difficile infection and it can be considered as an optional treatment for recurrent C. difficile infection.

Cytokinesis failure due to derailed integrin traffic induces aneuploidy and oncogenic transformation in vitro and in vivo.

Aneuploidy is frequently detected in solid tumors but the mechanisms regulating the generation of aneuploidy and their relevance in cancer initiation remain under debate and are incompletely characterized. Spatial and temporal regulation of integrin traffic is critical for cell migration and cytokinesis. Impaired integrin endocytosis, because of the loss of Rab21 small GTPase or mutations in the integrin ß-subunit cytoplasmic tail, induces failure of cytokinesis in vitro. Here, we describe that repeatedly failed cytokinesis, because of impaired traffic, is sufficient to trigger the generation of aneuploid cells, which display characteristics of oncogenic transformation in vitro and are tumorigenic in vivo. Furthermore, in an in vivo mouse xenograft model, non-transformed cells with impaired integrin traffic formed tumors with a long latency. More detailed investigation of these tumors revealed that the tumor cells were aneuploid. Therefore, abnormal integrin traffic was linked with generation of aneuploidy and cell transformation also in vivo. In human prostate and ovarian cancer samples, downregulation of Rab21 correlates with increased malignancy. Loss-of-function experiments demonstrate that long-term depletion of Rab21 is sufficient to induce chromosome number aberrations in normal human epithelial cells. These data are the first to demonstrate that impaired integrin traffic is sufficient to induce conversion of non-transformed cells to tumorigenic cells in vitro and in vivo.

Personal health promotion through personalized health technologies - Nuadu experience.

Poor lifestyles - overweight, unhealthy diet, physical inactivity, sleep deprivation, and stress - are significant risk factors to chronic illnesses, which cause majority of the health care costs. Hence, behavioral change towards healthy lifestyles is one of the keys to health care cost containment. Personal health systems (PHS) offer tools to support behavioral change. As health risks, personal needs and preferences vary from an individual to another, personalization of the PHS is needed. In Nuadu project we have developed a PHS integrating several different personal health technologies. This system was studied in a large (N=354) randomized controlled trial where employees with several health risks participated in a health promotion program. The study will finish in June 2009. User feedback and technology usage logs reveal that especially simple mobile technologies were actively used during the program. However, usage models varied between individuals and time, and there was a significant number of both active users and non-users. The results emphasize that "one size" does not fit all, and instead of individual "killer applications", PHS with different personalizable and interoperable options should be developed. In addition, screening and profiling methods should be developed to identify those users who would best accept and benefit from technology-supported health promotion. Successful technologies combine high usability and conceptual simplicity to clear and perceivable added value for the end users.

Nuadu concept for personal management of lifestyle related health risks.

Majority of the health risks and diseases in the modern world are related to lifestyles, e.g., overweight, unhealthy diet, physical inactivity, sleep deprivation, and stress. Behavioral change towards healthy lifestyles is the key to the prevention and management of these risks, but early and efficient interventions are scarcely available. We present the Nuadu Concept, an ICT (Information and Communication Technologies) assisted wellness toolbox for the management of multiple, behavior-originated health risks. The concept is based on psychological models, which provide methods and motivation for behavior change. The individual is considered as the best expert of his/her own wellness. Thus, the Nuadu Concept provides a variety of personal wellness technologies and services, among which the user may freely choose the best tools for him/herself. We believe this approach has the potential to provide efficient, acceptable, available, and affordable wellness management support for a significant number of people.

[Patient guidance during the hospitalization--patients' perceptions and experiences]. / Potilaan ohjaus sairaalahoidon aikana--potilaiden käsityksiä ja kokemuksia.

The aims of this study were to describe, firstly the perceptions and the experiences of the patients concerning the holistic guidance in a hospital, and secondly to describe their perceptions about how the guidance of the patients promoted patients' readinesses of self-care. Fifteen somatic and 10 psychiatric patients between 23 to 80 years of age participated in the study. The sample consisted of 12 men and 13 women. The data were collected by theme-interviews in three hospitals. The phenomenographic interpretive analysis was used for analysing the data. The psychiatric patients perceived the guidance as activating and developing the patient. The social management in the daily life was mainly emphasized in the guidance. They wished to discuss more about their feelings and their situation at the beginning and in the end of the nursing care in the hospital. The somatic patients regarded the guidance as informing and advising them how to observe their vital functions. They were dependent on the nursing experts during the hospitalization whereas the psychiatric patients thought they were more dependent when leaving the hospital. The somatic patients wished to discuss with nurses when they felt physically better. The psychiatric nursing emphasized the viewpoint of the human situation and the somatic the viewpoint of the organism. The guidance promoted the self-care readinesses of the patients when they handled their experiences of health and caring with nurses and when their own resources were used. The nurses need continuously to consider the ethical questions with which they could develop the guidance of the patients.

Long-term follow-up of St. Jude Medical valve.

St. Jude Medical bileaflet valve replacement was performed on 182 patients--aortic in 90, mitral in 70, both sites in 20 and tricuspid in two. The 30-day mortality was 4.3%, and was related to poor preoperative condition (NYHA class III or IV). The late mortality during observation up to 8 years was 9.3%, with actuarial survival 87.4% at 5 years and 86.3% at 8 years. For aortic, mitral and double valve replacement the respective 8-year figures were 88, 87.3 and 76.2%. Late death was associated with high preoperative pulmonary vascular resistance in five cases, dysrhythmia in four, myocardial infarction in two, thromboembolism, paravalvular leakage, prosthetic endocarditis or bleeding, each in one case, and was accidental in two cases. Calculated per 100 patient years the incidence of late thromboembolic events was 1.0, of bleeding complications 0.9 and of prosthetic valve endocarditis and paravalvular leak 0.26 (8, 7, 2 and 2 cases). The NYHA class in the 144 cases available for follow-up was I in 63%, II in 27% and III in 10%. The St. Jude Medical prosthesis thus was reliable, with good long-term performance.

EEG spectral analysis in delirium.

Spectral analysis of EEG was conducted for 51 elderly delirious patients meeting the Diagnostic and Statistical Manual of Mental Disorders III (DSM-III) criteria and for 19 controls. As a whole group, and also when subdivided according to the type of delirium, severity of cognitive decline or the type of central nervous system disease, delirious patients showed significant reductions of alpha percentage, increased theta and delta activity and slowing of the peak and mean frequencies and these changes were also obvious in individual recordings. The alpha percentage and various ratio parameters correlated significantly with Mini Mental State score, and delta percentage and mean frequency with the lengths of delirium and hospitalisation. The results indicate an association between spectral EEG changes and severity of cognitive deterioration in delirium.

Cerebrospinal fluid somatostatin in delirium.

Cerebrospinal fluid somatostatin-like immunoreactivity (CSF SLI) was determined for 67 elderly patients who met the DSM-III criteria for delirium and for 19 age-matched controls. As a group, and also when subdivided according to the type of delirium, severity of cognitive decline or the type of central nervous system disease, the delirious patients showed significant reductions of SLI compared with the controls, together with a declining trend associated with increasing cognitive dysfunction. These findings are in accordance with previous observations that reduced CSF SLI is associated with diseases in which cognitive function is disturbed and they extend this finding to delirium.

Delirium among elderly persons admitted to a psychiatric hospital: clinical course during the acute stage and one-year follow-up.

Seventy elderly patients meeting the DSM-III criteria for delirium were examined during the acute stage and followed up to one year. The mean age of the patients was 75 years (range 60-88), their delirium lasted on average 20 days (range 3-81) and the psychiatric hospitalization on average 30 days (range 8-365). The most common etiologies for delirium were stroke, infections and metabolic disorders. For 57 cases (81%) a predisposing structural brain disease was found. During the index admission, the cognitive dysfunction associated with delirium ameliorated significantly (the mean +/- SD Mini-Mental State Examination score 9.7 +/- 6.6 at admission and 13.9 +/- 7.2 at discharge; P less than 0.001), but during the one-year follow-up progression of the basic central nervous system disease was seen together with declining cognition and deterioration of functions of daily living.

CSF beta-endorphin-like immunoreactivity in delirium.

Cerebrospinal fluid beta-endorphin-like immunoreactivity (CSF BLI) was determined for 69 patients who met DSM-III criteria for delirium and for 8 controls. The CSF BLI was significantly lower in the delirious patient group than in the controls (12.5 +/- 3.0 pg/ml versus 15.0 +/- 3.4 pg/ml, p less than 0.05). CSF BLI had no correlation with age or neuroleptic drug dosage, but did have a significant positive correlation with cognitive functioning as evaluated by the Mini-Mental State. Our findings suggest a role for beta-endorphinergic dysfunction in the development of delirium.

Computed tomography findings in delirium.

Computerized tomography of the head was carried out on 69 elderly patients who met the DSM-III criteria for delirium and 31 neurological controls in order to evaluate the focal changes and generalized brain atrophy associated with delirium. Neither the difference between the mean ages nor the sex distribution in these groups was statistically significant. The delirious patients differed from the controls significantly in ventricular dilatation and cortical atrophy, and there was a statistically significant correlation between the width of the sylvian fissure and Mini-Mental State Examination score. Focal changes were also statistically more common in the delirious patients, and these changes tended to concentrate in the high-order association areas of the right hemisphere. Results suggest a marked predisposing role for the structural brain diseases (primary degenerative and multi-infarct type dementias, parkinsonism) in the development of delirium in elderly patients.

Lack of evidence of HTLV-I antibodies in the Finnish population.

5,287 serum samples from 2 different sources in Finland, people possibly at risk and healthy blood donors, were tested for the presence of HTLV-I antibodies. No positive cases were found. The result suggests that this virus is not endemic in Finland. 10 cases gave repeatedly a low positive value in the enzyme immune assay (EIA) test but were confirmed negative with other tests that included western blot, passive agglutination and immunofluorescence. Four of these samples originated from healthy blood donors, 6 from other categories. Several of them showed restricted reactivity in western blots. Five HIV-positive sera, discovered during the study from people with possible risk factors, were also tested for HTLV-I but showed no reactivity.