Guidelines for the clinical management of atrial fibrillation: a practical perspective.

Since the management of atrial fibrillation may be difficult in the individual patient, our purpose was to develop simple clinical recommendations to help the general internist manage this common clinical problem. Systematic review of the literature with evaluation of data-related evidence and framing of graded recommendations. Atrial fibrillation affects some 1% of the population in Western countries and is linked to a significant increase in morbidity and mortality. The management of atrial fibrillation requires individualised evaluation of the risks and benefits of therapeutic modalities, relying whenever possible on simple and validated tools. The two main points requiring a decision in clinical management are 1) whether or not to implement thromboembolic prevention therapy, and 2) whether preference should be given to a "rate control" or "rhythm control" strategy. Thromboembolic prophylaxis should be prescribed after individualised risk assessment: for patients at risk, oral anticoagulation with warfarin decreases the rate of embolic complications by 60% and aspirin by 20%, at the expense of an increased incidence of haemorrhagic complications. "Rate control" and "rhythm control" strategies are probably equivalent, and the choice should also be made on an individualised basis. To assist the physician in making his choices for the care of an atrial fibrillation patient we propose specific tables and algorithms, with graded recommendations. On the evidence of data from the literature we propose simple algorithms and tables for the clinical management of atrial fibrillation in the individual patient.

Clinical experience with Adalimumab in a multicenter Swiss cohort of patients with Crohn's disease

Background. Des études précédentes ont démontré l'efficacité et la tolérance de l'adalimumab chez les patients avec maladie de Crohn modérée ou sévère. Les patients qu'on rencontre dans la pratique quotidienne peuvent être différents des patients rigoureusement sélectionnés dans les études contrôlées.But. Dans ce travail, nous résumons notre expérience avec l'adalimumab durant une période de 3 ans.Méthodes. Nous avons analysé rétrospectivement les dossiers de 55 patients atteints d'une maladie de Crohn modérée ou sévère et traités par adalimumab dans les hôpitaux universitaires de Bâle, Zurich, Genève et Lausanne, ainsi que dans un cabinet médical à Olten. Les informations collectées étaient les suivantes : données démographiques, localisation, phénotype et durée de la maladie, traitements chirurgicaux précédents, traitements précédents par anti-TNF alpha ou immunosuppresseur, le traitement concomitant et l'activité de la maladie à la « baseline » et durant le traitement. La sévérité de la maladie à l'inclusion a été établie en utilisant le score Harvey- Bradshaw Index (HBI). Durant le traitement, la rémission a été définie avec un HBI<4 et la réponse comme une réduction de l'HBI de plus de 3 points. L'analyse de régression logistique univariée a été utilisée pour déterminer si les variables étudiées étaient associées à la réponse ou à la rémission durant le traitement.Résultats. L'âge moyen des patients a été de 37.5 ± 11.4 ans et la durée moyenne de maladie à été de 12.7 ans. 29 des 55 patients étaient des fumeurs. Le traitement d'induction a été effectué chez 31 patients avec l'adalimumab en sous-cutané 160 mg à la semaine 0 et 80 mg à la semaine 2 et chez 24 patients avec 80 mg à la semaine 0 et 40 mg à la semaine 2. Le traitement d'entretien a été de 40 mg en sous-cutané toutes les 2 semaines. 13 patients (23.6%) ont nécessité l'augmentation de la dose d'adalimumab pour maintenir la rémission ou la réponse.Le taux de rémission et de réponse à la semaine 4-6 était de 52.7%, respectivement 83.6%. La rémission a été maintenue aux semaines 12, 24 et 52 chez 89.6%, 72.4%, respectivement 44.7% des patients. Le taux de rémission et de réponse n'a pas été influencé par le tabagisme, la location ou la durée de la maladie, la dose totale donnée durant le premier mois de traitement, la dose d'adalimumab par kilogramme-corps ou par le traitement précédent par infliximab. La rémission à la semaine 4-6 a été significativement plus élevée chez les patients intolérants à l'infliximab comparativement à ceux qui avaient perdu la réponse à l'infliximab (78.9% vs 42.1%, p=0.02). Le traitement par adalimumab a été bien toléré. Les effets secondaires les plus signalés ont été : la douleur au site d'injection (10.9%), l'asthénie (9%) et des infections (7.2%).Conclusions. L'adalimumab a démontré une bonne efficacité et tolérance dans la pratique quotidienne chez les patients avec une maladie de Crohn modérée ou sévère.

Clinical and genetic findings in a large cohort of patients with congenital myopathies due to mutations in the skeletal muscle ryanodine receptor (RYR1) gene

RYR1 mutations are the most common cause of structural congenital myopathies and may exhibit both dominant and recessive inheritance. Histopathological findings are variable and include central cores, multi-minicores, type 1 predominance/ uniformity, fibre type disproportion, increased internal nucleation and fatty and connective tissue. Until recently, diagnostic RYR1 sequencing was limited to mutational hotspots due to the large size of the gene. Since the introduction of full RYR1 sequencing in 2007 we have detected pathogenic mutations in 77 families: 39 had dominant inheritance and 38 recessive inheritance. In some cases with presumably recessive inheritance, only one heterozygous mutation inherited from an asymptomatic parent was identified. Of 28 dominant mutations, 6 were novel; 37 of the 59 recessive mutations were also novel. Dominant mutations were more frequently in recognized hotspot regions, while recessive mutations were distributed throughout the coding sequence. Dominant mutations were predominantly missense, whereas recessive mutations included many nonsense and splice mutations expected to result in reduced RyR1 protein. There was wide clinical variability in patients with both dominant and recessive inheritance. As a group, those with dominant mutations were generally more mildly affected than those with recessive inheritance, who had earlier onset and were weaker with more functional limitations. Extraocular muscle involvement was almost exclusively observed in the recessive group. Bulbar involvement was also more prominent in this group, resulting in a larger number requiring gastrostomy insertion. In conclusion, genomic sequencing of the entire RYR1 leads to the detection of many novel mutations, but may miss large genetic rearrangements in some cases. Assigning pathogenicity to novel mutations is often difficult and interpretation of genetic results in the context of clinical, histological and, increasingly, muscle MRI findings is essential.

Tibial or hip BMD predict clinical fracture risk equally well: results from a prospective study in 700 elderly Swiss women.

SUMMARY: In a randomly selected cohort of Swiss community-dwelling elderly women prospectively followed up for 2.8 +/- 0.6 years, clinical fractures were assessed twice yearly. Bone mineral density (BMD) measured at tibial diaphysis (T-DIA) and tibial epiphysis (T-EPI) using dual-energy X-ray absorptiometry (DXA) was shown to be a valid alternative to lumbar spine or hip BMD in predicting fractures. INTRODUCTION: A study was carried out to determine whether BMD measurement at the distal tibia sites of T-EPI and T-DIA is predictive of clinical fracture risk. METHODS: In a predefined representative cohort of Swiss community-dwelling elderly women aged 70-80 years included in the prospective, multi-centre Swiss Evaluation of the Methods of Measurement of Osteoporotic Fracture risk (SEMOF) study, fracture risk profile was assessed and BMD measured at the lumbar spine (LS), hip (HIP) and tibia (T-DIA and T-EPI) using DXA. Thereafter, clinical fractures were reported in a bi-yearly questionnaire. RESULTS: During 1,786 women-years of follow-up, 68 clinical fragility fractures occurred in 61 women. Older age and previous fracture were identified as risk factors for the present fractures. A decrease of 1 standard deviation in BMD values yielded a 1.5-fold (HIP) to 1.8-fold (T-EPI) significant increase in clinical fragility fracture hazard ratio (adjusted for age and previous fracture). All measured sites had comparable performance for fracture prediction (area under the curve range from 0.63 [LS] to 0.68 [T-EPI]). CONCLUSION: Fracture risk prediction with BMD measurements at T-DIA and T-EPI is a valid alternative to BMD measurements at LS or HIP for patients in whom these sites cannot be accessed for clinical, technical or practical reasons.

Intra-articular osteoid osteoma of the knee: clinical and therapeutical particularities

The intra-articular osteoid osteoma (10-13% of the cases) is often difficult to identify. They present frequent atypical clinical signs and radiological images that eventually lead to inadequate treatment. For example, it has been observed that this pathology leads to inappropriate arthroscopies (up to 40%). Meniscal tear and then osteochondritis were initially suspected on a patient with an intra-articular osteoid osteoma at the tibia level. For the treatment, any damage of the cartilage has to be avoided. Thermoablation with radiofrequency is the treatment of choice

Analysis of Respiratory Syncytial Virus in Clinical Samples by Reverse Transcriptase-Polymerase Chain Reaction Restriction Mapping

The aim of this study was to develop a polymerase chain reaction (PCR) for the detection of respiratory syncytial virus (RSV) genomes. The primers were designed from published sequences and selected from conserved regions of the genome encoding for the N protein of subgroups A and B of RSV. PCR was applied to 20 specimens from children admitted to the respiratory ward of "William Soler" Pediatric Hospital in Havana City with a clinical diagnosis of bronchiolitis. The PCR was compared with viral isolation and with an indirect immunofluorescence technique that employs monoclonal antibodies of subgroups A and B. Of 20 nasopharyngeal exudates, 10 were found positive by the three assayed methods. In only two cases, samples that yielded positive RNA-PCR were found negative by indirect immunofluorescence and cell culture. Considering viral isolation as the "gold standard" technique, RNA-PCR had 100% sensitivity and 80% specificity. RNA-PCR is a specific and sensitive technique for the detection of the RSV genome. Technical advantages are discussed

Initial clinical experience with the admiral oxygenator combined with separated suction.

The Admiral, a new microporous membrane oxygenator with a low surface area, decreased priming volume and two separate reservoirs, was tested in 30 adult patients. This study was undertaken to evaluate blood path resistance, gas exchange capabilities and blood trauma in clinical use, with and without shed blood separation. Patients were divided into 3 groups. Group 1 had valve surgery without separation of suction, Group 2 had coronary artery bypass grafting (CABG) with direct blood aspiration and Group 3 had coronary artery bypass grafting with shed blood separation. The suctioned, separated, cardiotomy blood in Group 3 was treated with an autotransfusion device at the end of bypass before being returned to the patient. Theoretical blood flow could be achieved in all cases without problem. The pressure drop through the oxygenator averaged 88 +/- 13 mmHg at 4 l/min and 109 +/- 12 mmHg at 5 l/min. O(2) transfer was 163 +/- 27 ml/min. Free plasma haemoglobin rose in all groups, but significantly less in group 3. Lactate dehydrogenase (LDH) rose significantly in Groups 1 and 2. Platelets decreased in all groups without significant differences. Clinical experience with this new oxygenator was safe, the reduced membrane surface did not impair gas exchange and blood trauma could be minimized easily by separating shed blood, using the second cardiotomy reservoir.

Role of Immune Complexes from Pacients with Different Clinical Forms of Schistosomiasis in the Modulation of In Vitro Granuloma Reaction

Schistosomiasis is a disease whose pathology is strongly related to the granulomatous reaction formed around parasite eggs trapped in host tissues. Studies have shown that the chronic intestinal form (INT) of this infection is associated with a variety of immunoregulatory mechanisms which lead to a diminished granulomatous reaction. Using an in vitro model of granuloma reaction, we show that immune complexes (IC) isolated from sera of INT patients are able to reduce granulomatous reaction developed by peripheral blood mononuclear cells (PBMC) from acute (AC), INT and hepatosplenic (HE) patients to soluble egg antigen (SEA)-conjugated polyacrylamide beads (PB-SEA). This inhibitory activity is also observed in cell proliferation assay of PBMC from INT and HE patients stimulated with SEA and adult worm antigen (SWAP). Furthermore, IC isolated from sera of patients with different clinical forms of the disease are also able to suppress INT patients PBMC reactivity. Therefore, our results show that circulating IC present in sera of patients with different clinical forms of schistosomiasis may down-regulate PBMC reactivity to parasite antigens resulting in a diminished granuloma reaction to parasite eggs

Immunological mechanism of action and clinical profile of disease-modifying treatments in multiple sclerosis.

Multiple sclerosis (MS) is a life-long, potentially debilitating disease of the central nervous system (CNS). MS is considered to be an immune-mediated disease, and the presence of autoreactive peripheral lymphocytes in CNS compartments is believed to be critical in the process of demyelination and tissue damage in MS. Although MS is not currently a curable disease, several disease-modifying therapies (DMTs) are now available, or are in development. These DMTs are all thought to primarily suppress autoimmune activity within the CNS. Each therapy has its own mechanism of action (MoA) and, as a consequence, each has a different efficacy and safety profile. Neurologists can now select therapies on a more individual, patient-tailored basis, with the aim of maximizing potential for long-term efficacy without interruptions in treatment. The MoA and clinical profile of MS therapies are important considerations when making that choice or when switching therapies due to suboptimal disease response. This article therefore reviews the known and putative immunological MoAs alongside a summary of the clinical profile of therapies approved for relapsing forms of MS, and those in late-stage development, based on published data from pivotal randomized, controlled trials.

Familial aplasia of the trapezius muscle: clinical and MRI findings.

A 5-year-old boy was referred to our neurology clinic for suspected myopathy. His parents reported normal upper extremity strength and no limitation in daily activities; however, he was unable to raise his arms above his head. On examination, both shoulders were down-slanting and anteriorly displaced, leading to a webbed neck appearance. Muscle MRI demonstrated isolated bilateral aplasia of the trapezius muscles. His father was found to have a unilateral partial trapezius hypoplasia with no functional consequences. Conclusion:  Congenital aplasia of the trapezius muscle is a rare condition; bilateral aplasia of the muscle, having been reported in only five cases, is most often associated with aplasia of the pectoralis major. This is the first report to our knowledge to demonstrate bilateral isolated trapezius aplasia by MRI.

Does previous hip arthroscopy negatively influence the short term clinical result of total hip replacement?

INTRODUCTION: The risk that hip preserving surgery may negatively influence the performance and outcome of subsequent total hip replacement (THR) remains a concern. The aim of this study was to identify any negative impact of previous hip arthroscopy on THR. METHODS: Out of 1271 consecutive patients who underwent primary THR between 2005 and 2009, 18 had previously undergone ipsilateral hip arthroscopy. This study group (STG) was compared with two control groups (CG, same approach, identical implants; MCG, paired group matched for age, BMI and Charnley categories). Operative time, blood loss, evidence of heterotopic bone and implant loosening at follow-up were compared between the STG and the MCG. Follow-up WOMAC were compared between the three groups. RESULTS: Blood loss was not found to be significantly different between the STG and MCG. The operative time was significantly less (p < 0.001) in the STG. There was no significant difference in follow-up WOMAC between the groups. No implant related complications were noted in follow-up radiographs. Two minor complications were documented for the STG and three for the MCG. CONCLUSION: We have found no evidence that previous hip arthroscopy negatively influences the performance or short-term clinical outcome of THR.

Clinical benefits of an adherence monitoring program in the management of secondary hyperparathyroidism with cinacalcet: results of a prospective randomized controlled study.

BACKGROUND/AIMS: One of the causes of uncontrolled secondary hyperparathyroidism (sHPT) is patient's poor drug adherence. We evaluated the clinical benefits of an integrated care approach on the control of sHPT by cinacalcet. METHODS: Prospective, randomized, controlled, multicenter, open-label study. Fifty hemodialysis patients on a stable dose of cinacalcet were randomized to an integrated care approach (IC) or usual care approach (UC). In the IC group, cinacalcet adherence was monitored using an electronic system. Results were discussed with the patients in motivational interviews, and drug prescription adapted accordingly. In the UC group, drug adherence was monitored, but results were not available. RESULTS: At six months, 84% of patients in the IC group achieved recommended iPTH targets versus 55% in the UC group (P = 0.04). The mean cinacalcet taking adherence improved by 10.8% in the IC group and declined by 5.3% in the UC group (P = 0.02). Concomitantly, the mean dose of cinacalcet was reduced by 7.2 mg/day in the IC group and increased by 6.4 mg/day in the UC group (P = 0.03). CONCLUSIONS: The use of a drug adherence monitoring program in the management of sHPT in hemodialysis patients receiving cinacalcet improves drug adherence and iPTH control and allows a reduction in the dose of cinacalcet.