A NOVEL MUTATION IN BCS1L IN A PATIENT WITH AN ISOLATED MITOCHONDRIAL COMPLEX III DEFICIENCY

Background: Isolated complex III deficiencies are caused by mutations in the mitochondrial CytB gene, in the BCS1L gene coding for a CIII assembly factor and in the UQCRQ gene that codes for the ubiquinone binding protein of complex III. Objective: Description of clinical features, mitochondrial function and molecular genetic analysis in a patient with an isolated complex III deficiency. Patient: A 17 year old boy, born to consanguineous parents who presented with hypoglycemia, glycosuria, deafness, growth retardation, Fanconi Syndrome and severe lactic acidosis in the neonatal period. Methods: Activities and assembly of OXPHOS complexes were investigated spectrophotometrically and by BN-PAGE. mt-DNAwas screened for deletions. Cytochrome b (CytB) and the BCS1L gene were sequenced. Results: Isolated complex III deficiency was detected in the patient's skeletal muscle. Using BN-PAGE blotting a complex III of lower molecular weight was detected. Staining the 2D reveals a missing subunit. No mutation was detected in the mitochondrial CytB gene. Sequence analysis of BCS1L revealed a novel homozygous point mutation p.M48V. Conclusion: The patients decreased complex III activity is most likely caused by incomplete assembly of complex III due to the homozygous p. M48V mutation in the BCS1L gene.

BrainCheck - a very brief tool to detect incipient cognitive decline: optimized case-finding combining patient- and informant-based data.

INTRODUCTION: Optimal identification of subtle cognitive impairment in the primary care setting requires a very brief tool combining (a) patients' subjective impairments, (b) cognitive testing, and (c) information from informants. The present study developed a new, very quick and easily administered case-finding tool combining these assessments ('BrainCheck') and tested the feasibility and validity of this instrument in two independent studies. METHODS: We developed a case-finding tool comprised of patient-directed (a) questions about memory and depression and (b) clock drawing, and (c) the informant-directed 7-item version of the Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE). Feasibility study: 52 general practitioners rated the feasibility and acceptance of the patient-directed tool. Validation study: An independent group of 288 Memory Clinic patients (mean ± SD age = 76.6 ± 7.9, education = 12.0 ± 2.6; 53.8% female) with diagnoses of mild cognitive impairment (n = 80), probable Alzheimer's disease (n = 185), or major depression (n = 23) and 126 demographically matched, cognitively healthy volunteer participants (age = 75.2 ± 8.8, education = 12.5 ± 2.7; 40% female) partook. All patient and healthy control participants were administered the patient-directed tool, and informants of 113 patient and 70 healthy control participants completed the very short IQCODE. RESULTS: Feasibility study: General practitioners rated the patient-directed tool as highly feasible and acceptable. Validation study: A Classification and Regression Tree analysis generated an algorithm to categorize patient-directed data which resulted in a correct classification rate (CCR) of 81.2% (sensitivity = 83.0%, specificity = 79.4%). Critically, the CCR of the combined patient- and informant-directed instruments (BrainCheck) reached nearly 90% (that is 89.4%; sensitivity = 97.4%, specificity = 81.6%). CONCLUSION: A new and very brief instrument for general practitioners, 'BrainCheck', combined three sources of information deemed critical for effective case-finding (that is, patients' subject impairments, cognitive testing, informant information) and resulted in a nearly 90% CCR. Thus, it provides a very efficient and valid tool to aid general practitioners in deciding whether patients with suspected cognitive impairments should be further evaluated or not ('watchful waiting').

Early major worsening in ischemic stroke: predictors and outcome.

INTRODUCTION: We aimed to investigate the characteristics and outcome of patients suffering early major worsening (EMW) after acute ischemic stroke (AIS) and assess the parameters associated with it. METHODS: All consecutive patients with AIS in the ASTRAL registry until 10/2010 were included. EMW was defined as an NIHSS increase of ≥8 points within the first 24 h after admission. The Bootstrap version of the Kolmogorov-Smirnov test and the χ(2)-test were used for the comparison of continuous and categorical covariates, respectively, between patients with and without EMW. Multiple logistic regression analysis was performed to identify independent predictors of EMW. RESULTS: Among 2155 patients, 43 (2.0 %) had an EMW. EMW was independently associated with hemorrhagic transformation (OR 22.6, 95 % CI 9.4-54.2), cervical artery dissection (OR 9.5, 95 % CI 4.4-20.6), initial dysarthria (OR 3.7, 95 % CI 1.7-8.0), and intravenous thrombolysis (OR 2.1, 95 % CI 1.1-4.3), whereas a negative association was identified with initial eye deviation (OR 0.4, 95 % CI 0.2-0.9). Favorable outcome at 3 and 12 months was less frequent in patients with EMW compared to patients without (11.6 vs. 55.3 % and 16.3 vs. 50.7 %, respectively), and case fatality was higher (53.5 vs. 12.9 % and 55.8 vs. 16.8 %, respectively). Stroke recurrence within 3 months in surviving patients was similar between patients with and without EMW (9.3 vs. 9.0 %, respectively). CONCLUSIONS: Worsening of ≥8 points in the NIHSS score during the first 24 h in AIS patients is related to cervical artery dissection and hemorrhagic transformation. It justifies urgent repeat parenchymal and arterial imaging. Both conditions may be influenced by targeted interventions in the acute phase of stroke.

Monitoring compliance in resistant hypertension: an important step in patient management.

Poor compliance with antihypertensive drug regimens is one recognized cause of inadequate blood pressure control. Compliance is difficult to measure, so poor adherence to treatment remains largely undiagnosed in clinical practice. When the therapeutic response to a drug is not the one expected, it is a major challenge for many physicians to decide whether the patient is a non-responder or a non-complier. Poor compliance is therefore often incorrectly interpreted as a lack of response to treatment. Not detecting non-compliance can lead to the wrong measures being taken. Electronic monitoring of compliance provides important longitudinal information about drug-intake behaviour that cannot be obtained in the clinic. Such monitoring can improve both compliance and blood pressure control, and help physicians to make more rational therapeutic decisions. A reliable assessment of compliance could have a great impact on medical costs by preventing unnecessary investigations or dose adaptations in patients who are not taking their drugs adequately, or potentially reducing the number of hospitalizations. Side-effects and lack of effectiveness are two frequent causes of poor compliance. The right choice of antihypertensive drug can therefore contribute to compliance. In this respect, it is important to find a drug regimen that is effective, long-acting and well tolerated. Long-acting antihypertensive drugs that provide good blood pressure control beyond the 24-h dosing period should perhaps be considered as drugs of choice in non-compliant patients with hypertension because they help to prevent the consequences of occasional drug omissions.

Relation soignant-soigné quand les blogs s'en mêlent [Patient-caregiver relationship: when illness blogs step in].

The use of social media as a communication tool is rapidly growing in the community, and more specifically in patients, through illness blogs. This has been true for several years in North America, but is becoming a reality in Europe as well. We report here the first results of studies on the putative psychological benefits and risks of illness blogs for their authors. We also explore the possible impact of blogging on the patient-caregiver relationship. Social media are expected to have a growing influence in certain areas of health care. Physicians should therefore stay informed about them, take advantage of their benefits, and anticipate their risks.

High-dose intravenous immunoglobulin treatment and cerebral vasospasm : a possible mechanism of ischemic encephalopathy?

A 46-year-old woman with a severe polyradiculoneuropathy treated with high-dose intravenous immunoglobulin (IVIg) presented an encephalopathy with increased blood flow velocities of the middle cerebral arteries (MCAs) detected by transcranial Doppler (TCD) studies. The similitude between this observation and another case recently reported of a patient suffering from Guillain-Barré syndrome (GBS) and cerebral blood flow abnormalities after IVIg treatment prompted us to investigate the responsibility of the IVIg therapy in the genesis of these blood flow alterations. We studied therefore by TCD 10 consecutive patients who underwent this treatment for different reasons. In 1 case we observed an asymptomatic, spontaneously reversible increase in the blood flow velocities of the MCAs consistent with a vasospasm and occurring 3-10 days after completion of the therapy. Stroke and ischemic encephalopathy have been reported as possible complications of IVIg treatment. In the case under discussion, clinical events appeared shortly after the administration of the IVIg therapy and responded favorably to a treatment with nimodipine. Other etiopathogenic mechanisms, in particular a CNS vasculopathic process related to the GBS itself, have to be considered as well. Further studies, with a larger number of patients, are therefore needed to evaluate the underlying mechanisms of blood flow abnormalities occurring sometimes in GBS patients after IVIg treatment.

Patient dose management in fluoroscopy : the use of DRL : P123

Purpose: To set local dose reference levels (DRL) that allow radiologists to control stochastic and deterministic effects. Methods and materials: Dose indicators for cerebral angiographies and hepatic embolizations were collected during 4 months and analyzed in our hospital. The data were compared when an image amplifier was used instead of a flat panel detector. The Mann and Whitney test was used. Results: For the 40 cerebral angiographies performed the DRL for DAP, fluoroscopy time and number of images were respectively: 166 Gy.cm2, 19 min, 600. The maximum DAP was 490 Gy.cm2 (fluoroscopy time: 84 min). No significant difference for fluoroscopy time and DAP for image amplifier and flat panel detector (p = 0.88) was observed. The number of images was larger for flat panel detector (p = 0.004). The values obtained were slightly over the present proposed DRL: 150 Gy.cm2, 15 min, 400. Concerning the 13 hepatic embolizations the DRL for DAP fluoroscopy time and number of images were: 315 Gy.cm2, 25 min, 370. The maximum DAP delivered was 845 Gy.cm2 (fluoroscopy time of 48 min). No significant difference between image amplifier and flat panel detector was observed (p = 0.005). The values obtained were also slightly over the present proposed DRL: 300 Gy.cm2, 20 min, 200. Conclusion: These results show that the introduction of flat panel detector did not lead to an increase in patient dose. A DRL concerning the cumulative dose (that allow to control the deterministic effect) should be introduced to allow radiologists to have full control on the risks associated with ionizing radiations. Results of this on going study will be presented.

General practitioners can evaluate the material, social and health dimensions of patient social status

OBJECTIVE: To identify which physician and patient characteristics are associated with physicians' estimation of their patient social status.DESIGN: Cross-sectional ulticentric survey. SETTING: Fourty-seven primary care private offices in Western Switzerland. PARTICIPANTS: Random sample of 2030 patients ≥ 16, who encountered a general practitioner (GP) between September 2010 and February 2011. MAIN MEASURES: PRIMARY OUTCOME: patient social status perceived by GPs, using the MacArthur Scale of Subjective Social Status, ranging from the bottom (0) to the top (10) of the social scale.Secondary outcome: Difference between GP's evaluation and patient's own evaluation of their social status. Potential patient correlates: material and social deprivation using the DiPCare-Q, health status using the EQ-5D, sources of income, and level of education. GP characteristics: opinion regarding patients' deprivation and its influence on health and care. RESULTS: To evaluate patient social status, GPs considered the material, social, and health aspects of deprivation, along with education level, and amount and type of income. GPs declaring a frequent reflexive consideration of their own prejudice towards deprived patients, gave a higher estimation of patients' social status (+1.0, p = 0.002). Choosing a less costly treatment for deprived patients was associated with a lower estimation (-0.7, p = 0.002). GP's evaluation of patient social status was 0.5 point higher than the patient's own estimate (p<0.0001). CONCLUSIONS: GPs can perceive the various dimensions of patient social status, although heterogeneously, according partly to their own characteristics. Compared to patients' own evaluation, GPs overestimate patient social status.

Intégrer les préférences des patients dans les projets thérapeutiques de médecine intensive [To integrate patient's preferences in intensive care treatment plans]

An increasing number of terminally ill patients are admitted into the intensive care unit, and decisions of limitation, or of palliative care are made to avoid medical futility. The principle of autonomy states that the patient (or in case of necessity his relatives) should make end of life decision after detailed information. The exercise of autonomy is difficult due to the disease of the patient and the nature of invasive treatments, but also due to organisational and communication barriers. The latter can be surmounted by a proactive approach. Early communication with the patient and relatives about the sometimes-limited expectations of an invasive treatment plan, and the possibility of palliative care allow to integer patient's preferences in the formulation of a therapeutical plan.