Prevalence of the metabolic syndrome in the Seychelles according to different definitions, contribution of components, and agreement between different definitions

Background: The metabolic syndrome (MS) represents a cluster of metabolic disorders that predicts diabetes and cardiovascular disease. Several definitions exist and further descriptive and prospective data are needed to compare these definitions and their significance in different populations. Objective: We examined, in a country of the African region, i) the prevalence of MS according to three major definitions (ATP, IDF, WHO); ii) the contribution of individual MS components; and iii) the agreement between the three considered definitions. We also examined the prevalence among diabetics and non-diabetics. Methods: We conducted an examination survey in a sample representative of the general population aged 25-64 of the Seychelles (Indian Ocean, African region), attended by 1255 persons (participation rate of 80.2%). Results: The prevalence of MS was similar with either definition of MS in men (24%-25%) but differed in women (WHO: 25%, ATP: 32%; IDF: 35%). Upon exclusion of diabetic persons, the prevalence was 5-10% lower for all three MS definitions: most diabetic persons had MS although a substantial proportion of diabetic men aged 45-64 did not have MS. The following components were found most often among persons with MS: 90% had high blood pressure (HBP) and 78% had obesity (ATP); 95% had obesity and 84% had HBP (WHO), and 89% had HBP and 75% had impaired glucose regulation (IDF) -not considering impaired glucose regulation and obesity that are compulsory components of the WHO and IDF definitions, respectively. Among persons with MS based on either of the three definitions (37% of total population), less than 80% met both ATP and IDF criteria, 67% both WHO and IDF criteria, 54% both WHO and ATP criteria and only 37% met all three definitions. Conclusions. We found a fairly high prevalence of MS in an African population. However, because there was only poor agreement between the 3 MS definitions, the fairly similar proportions of MS based on ATP, IDF or WHO definitions identified, to a substantial extent, different subjects as having MS.

Konsensusempfehlungen zur Beurteilung der medizinischen Mindestanforderungen für Fahreignung bei kognitiver Beeinträchtigung [Consensus recommendations for the assessment of fitness to drive in cognitively impaired patients].

Memory Clinics provide evidence based diagnosis and treatment of dementia. Whenever a diagnosis of dementia is made, it is important to inform the patients about the possible impact of dementia on driving. Patients and their next of kin require competent advice whenever this difficult question is addressed and the mobility desire and the risks related to driving need to be carefully weight up. The time of diagnosis does not necessarily equate to the time when a person with dementia becomes an unsafe driver. The cause and severity of dementia, comorbidities and the current medication need to be carefully taken into account for this decision. On behalf of the association of the Swiss Memory Clinics, a group of experts has developed recommendations to assess fitness to drive in cognitively impaired older adults.

A New Large Deletion in the DFNB1 Locus Causes Nonsyndromic Hearing Loss.

Mutations in the GJB2 gene encoding the gap junction protein connexin 26 are responsible for up to 30% of all cases of autosomal recessive nonsyndromic hearing impairment (HI) with prelingual onset in most populations. The corresponding locus DFNB1, located on chromosome 13q11-q12, is also affected by three distinct deletions. These deletions extended distally to GJB2, which remains intact. We report a novel large deletion in DFNB1 observed in a patient presenting profound prelingual HI. This deletion was observed in trans to a GJB2 mutated allele carrying the p.Val84Met (V84M) mutation and was shown to be associated with hearing loss. The deletion caused a false homozygosity of V84M in the proband. Quantification of alleles by quantitative fluorescent multiplex PCR (QFM-PCR) enabled us to study the breakpoints of the deletion. The deleted segment extended through at least 920kb and removed the three connexin genes GJA3, GJB2 and GJB6. The distal breakpoint inside intron 2 of CRYL1 gene differed from the breakpoints of the known DFNB1 deletions. This case highlights the importance of screening for large deletions in molecular studies of GJB2.

Genetic variation near IRS1 associates with reduced adiposity and an impaired metabolic profile.

Genome-wide association studies have identified 32 loci influencing body mass index, but this measure does not distinguish lean from fat mass. To identify adiposity loci, we meta-analyzed associations between ∼2.5 million SNPs and body fat percentage from 36,626 individuals and followed up the 14 most significant (P < 10(-6)) independent loci in 39,576 individuals. We confirmed a previously established adiposity locus in FTO (P = 3 × 10(-26)) and identified two new loci associated with body fat percentage, one near IRS1 (P = 4 × 10(-11)) and one near SPRY2 (P = 3 × 10(-8)). Both loci contain genes with potential links to adipocyte physiology. Notably, the body-fat-decreasing allele near IRS1 is associated with decreased IRS1 expression and with an impaired metabolic profile, including an increased visceral to subcutaneous fat ratio, insulin resistance, dyslipidemia, risk of diabetes and coronary artery disease and decreased adiponectin levels. Our findings provide new insights into adiposity and insulin resistance.

The return of increased blood pressure after discontinuation of antihypertensive treatment is associated with an impaired post-ischemic skin blood flow response.

OBJECTIVE: To assess the post-ischemic skin blood flow response after withdrawal of antihypertensive therapy in hypertensive patients with normal blood pressure during treatment. DESIGN AND METHODS: Twenty hypertensive patients (group A) with a normal clinic blood pressure (<140/ 90 mmHg) receiving antihypertensive treatment (any monotherapy; one pill per day for at least 6 months) had their treatment discontinued. Before medication withdrawal and 2, 4, 12 and 24 weeks thereafter, the following measurements were made: clinic blood pressure, home blood pressure (three times per week, morning and evening) and skin blood flow response to a 5 min forearm arterial occlusion (using laser Doppler flowmetry). The patients were asked to perform an ambulatory blood pressure recording at any time if home blood pressure was > or =160/95 mmHg on two consecutive days, and treatment was initiated again, after determination of the skin hyperemic response, if daytime ambulatory blood pressure was > or =140/90 mmHg. The same studies were performed in 20 additional hypertensive individuals in whom antihypertensive treatment was not withdrawn (group B). The allocation of patients to groups A and B was random. RESULTS: The data fom 18 patients in group A who adhered strictly to the procedure were available for analysis. Seven of them had to start treatment again within the first 4 weeks of follow-up; four additional patients started treatment again during the next 8 weeks (group A1). The seven other patients remained untreated (group A2). The skin hyperemic response decreased significantly in patients in group A1 and returned to baseline values at the end of the study, when there were again receiving antihypertensive treatment. In patients in group A2 a significant attenuation of the hyperemic response was also observed. This impaired response was present even at the end of the 6 month follow-up, at which time the patients were still untreated but exhibited a significantly greater blood pressure than before drug discontinuation. The hyperemic response of patients who did not stop treatment (group B) did not change during the course of the study. CONCLUSIONS: Our findings show a decrease in the postischemic skin blood flow response after withdrawal of antihypertensive treatment in hypertensive patients. This impaired response may be due to the development of endothelial dysfunction, vascular remodeling, or both, and might contribute to the return of blood pressure to hypertensive values after withdrawal of antihypertensive therapy.

Gender differences in HIV-positive persons in use of cardiovascular disease-related interventions : D:A:D study

INTRODUCTION: There is a lack of data on potential gender differences in the use of interventions to prevent and treat cardiovascular disease (CVD) in HIV-positive individuals. We investigated whether such differences exist in the D:A:D study. MATERIALS AND METHODS: Follow-up was from 01/02/99 until the earliest of death, 6 months after last visit or 01/02/13. Rates of initiation of lipid-lowering drugs (LLDs), angiotensin-converting enzyme inhibitors (ACEIs), anti-hypertensives and receipt of invasive cardiovascular procedures (ICPs; bypass, angioplasty, endarterectomy) were calculated in those without a myocardial infarction (MI) or stroke at baseline, overall and in groups known to be at higher CVD risk: (i) age >50, (ii) total cholesterol >6.2 mmol/l, (iii) triglyceride >2.3 mmol/l, (iv) hypertension, (v) previous MI, (vi) diabetes, or (vii) predicted 10-year CVD risk >10%. Poisson regression was used to assess whether rates of initiation were higher in men than women, after adjustment for these factors. RESULTS: At enrolment, women (n=13,039; median (interquartile range) 34 (29-40) years) were younger than men (n=36,664, 39 (33-46) years, p=0.001), and were less likely to be current smokers (29% vs. 39%, p=0.0001), to have diabetes (2% vs. 3%, p=0.0001) or to have hypertension (7% vs. 11%, p=0.0001). Of 49,071 individuals without a MI/stroke at enrolment, 0.6% women vs. 2.1% men experienced a MI while 0.8% vs. 1.3% experienced a stroke. Overall, women received ICPs at a rate of 0.07/100 person-years (PYRS) compared to 0.29/100 PYRS in men. Similarly, the rates of initiation of LLDs (1.28 vs. 2.46), anti-hypertensives (1.11 vs. 1.38) and ACEIs (0.82 vs. 1.37) were all significantly lower in women than men (Table 1). As expected, initiation rates of each intervention were higher in the groups determined to be at moderate/high CVD risk; however, within each high-risk group, initiation rates of most interventions (with the exception of anti-hypertensives) were generally lower in women than men. These gender differences persisted after adjustment for potential confounders (Table 1). CONCLUSION: Use of most CVD interventions was lower among women than men in the D:A:D study. Our findings suggest that actions should be taken to ensure that both men and women are monitored for CVD and, if eligible, receive appropriate CVD interventions.

Measurement with an automated oscillometric wrist device with position sensor leads to lower values than measurements obtained with an automated oscillometric arm device from the same manufacturer in elderly persons

Introduction : Le monitoring de la tension artérielle à domicile est recommandé par plusieurs guidelines et a été montré être faisable chez la personne âgée. Les manomètres au poignet ont récemment été proposés pour la mesure de la tension artérielle à domicile, mais leur précision n'a pas été au préalable évaluée chez les patients âgés. Méthode : Quarante-huit participants (33 femmes et 15 hommes, moyenne d'âge 81.3±8.0 ans) ont leur tension artérielle mesurée avec un appareil au poignet avec capteur de position et un appareil au bras dans un ordre aléatoire et dans une position assise. Résultats : Les moyennes de mesures de tension artérielle étaient systématiquement plus basses avec l'appareil au poignet par rapport à celui du bras pour la pression systolique (120.1±2.2 vs. 130.5±2.2 mmHg, P < 0.001, moyenneidéviation standard) et pour la pression diastolique (66.011.3 vs. 69.7±1.3 mmHg, P < 0.001). De plus, une différence de lOmmHg ou plus grande entre l'appareil au bras et au poignet était observée dans 54.2 et 18,8% des mesures systoliques et diastoliques respectivement. Conclusion : Comparé à l'appareil au bras, l'appareil au poignet avec capteur de position sous-estimait systématiquement aussi bien la tension artérielle systolique que diastolique. L'ampleur de la différence est cliniquement significative et met en doute l'utilisation de l'appareil au poignet pour monitorer la tension artérielle chez la personne âgée. Cette étude indique le besoin de valider les appareils de mesures de la tension artérielle dans tous les groupes d'âge, y compris les personnes âgées.

Non-pharmacological interventions for chronic pain in people with spinal cord injury.

BACKGROUND: Chronic pain is frequent in persons living with spinal cord injury (SCI). Conventionally, the pain is treated pharmacologically, yet long-term pain medication is often refractory and associated with side effects. Non-pharmacological interventions are frequently advocated, although the benefit and harm profiles of these treatments are not well established, in part because of methodological weaknesses of available studies. OBJECTIVES: To critically appraise and synthesise available research evidence on the effects of non-pharmacological interventions for the treatment of chronic neuropathic and nociceptive pain in people living with SCI. SEARCH METHODS: The search was run on the 1st March 2011. We searched the Cochrane Injuries Group's Specialised Register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE (OvidSP), Embase (OvidSP), PsycINFO (OvidSP), four other databases and clinical trials registers. In addition, we manually searched the proceedings of three major scientific conferences on SCI. We updated this search in November 2014 but these results have not yet been incorporated. SELECTION CRITERIA: Randomised controlled trials of any intervention not involving intake of medication or other active substances to treat chronic pain in people with SCI. DATA COLLECTION AND ANALYSIS: Two review authors independently extracted data and assessed risk of bias in the included studies. The primary outcome was any measure of pain intensity or pain relief. Secondary outcomes included adverse events, anxiety, depression and quality of life. When possible, meta-analyses were performed to calculate standardised mean differences for each type of intervention. MAIN RESULTS: We identified 16 trials involving a total of 616 participants. Eight different types of interventions were studied. Eight trials investigated the effects of electrical brain stimulation (transcranial direct current stimulation (tDCS) and cranial electrotherapy stimulation (CES); five trials) or repetitive transcranial magnetic stimulation (rTMS; three trials). Interventions in the remaining studies included exercise programmes (three trials); acupuncture (two trials); self-hypnosis (one trial); transcutaneous electrical nerve stimulation (TENS) (one trial); and a cognitive behavioural programme (one trial). None of the included trials were considered to have low overall risk of bias. Twelve studies had high overall risk of bias, and in four studies risk of bias was unclear. The overall quality of the included studies was weak. Their validity was impaired by methodological weaknesses such as inappropriate choice of control groups. An additional search in November 2014 identified more recent studies that will be included in an update of this review.For tDCS the pooled mean difference between intervention and control groups in pain scores on an 11-point visual analogue scale (VAS) (0-10) was a reduction of -1.90 units (95% confidence interval (CI) -3.48 to -0.33; P value 0.02) in the short term and of -1.87 (95% CI -3.30 to -0.45; P value 0.01) in the mid term. Exercise programmes led to mean reductions in chronic shoulder pain of -1.9 score points for the Short Form (SF)-36 item for pain experience (95% CI -3.4 to -0.4; P value 0.01) and -2.8 pain VAS units (95% CI -3.77 to -1.83; P value < 0.00001); this represented the largest observed treatment effects in the included studies. Trials using rTMS, CES, acupuncture, self-hypnosis, TENS or a cognitive behavioural programme provided no evidence that these interventions reduce chronic pain. Ten trials examined study endpoints other than pain, including anxiety, depression and quality of life, but available data were too scarce for firm conclusions to be drawn. In four trials no side effects were reported with study interventions. Five trials reported transient mild side effects. Overall, a paucity of evidence was found on any serious or long-lasting side effects of the interventions. AUTHORS' CONCLUSIONS: Evidence is insufficient to suggest that non-pharmacological treatments are effective in reducing chronic pain in people living with SCI. The benefits and harms of commonly used non-pharmacological pain treatments should be investigated in randomised controlled trials with adequate sample size and study methodology.

Expanding view of phenotype and oxidative stress in Friedreich's ataxia patients with and without idebone.

Friedreich's ataxia (FRDA), the most common autosomal recessive ataxia, is characterised by progressive ataxia with dysarthria of speech, loss of deep-tendon reflexes, impaired vibratory and proprioceptive sensations and corticospinal weakness with a Babinski's sign. Patients eventually also develop kyphoscoliosis, cardiomyopathy and diabetes mellitus. The disease is a GAA repeat disorder resulting in severely reduced levels of frataxin, with secondary increased sensitivity to oxidative stress. The anti-oxidative drug, idebenone, is effective against FRDA-associated cardiomyopathy. We provide detailed clinical, electrophysiological and biochemical data from 20 genetically confirmed FRDA patients and have analysed the relationship between phenotype, genotype and malondialdehyde (MDA), which is a marker of superoxide formation. We assessed the effects of idebenone biochemically by measuring blood MDA and clinically by serial measurements of the International Cooperative Ataxia Rating Scale (ICARS). The GAA repeat length influenced the age at onset (p <0.001), the severity of ataxia (p = 0.02), the presence of cardiomyopathy (p = 0.04) and of low-frequency hearing loss (p = 0.009). Multilinear regression analysis showed (p = 0.006) that ICARS was dependent on the two variables of disease duration (p = 0.01) and size of the GAA expansion (p = 0.02). We found no correlation to bilateral palpebral ptosis, visual impairment, diabetes mellitus or skeletal deformities, all of which appear to be signs of disease progression rather than severity. We discuss more thoroughly two underrecognised clinical findings: palpebral ptosis and GAA length-dependent low-frequency hearing loss. The average ICARS remained unchanged in 10 patients for whom follow-up on treatment was available (mean 2.9 years), whereas most patients treated with idebenone reported an improvement in dysarthria (63%), hand dexterity (58%) and fatigue (47%) after taking the drug for several weeks or months. Oxidative stress analysis showed an unexpected increase in blood MDA levels in patients on idebenone (p = 0.04), and we discuss the putative underlying mechanism for this result, which could then explain the unique efficacy of idebenone in treating the FRDA-associated cardiomyopathy, as opposed to other antioxidative drugs. Indeed, idebenone is not only a powerful stimulator of complexes II and III of the respiratory chain, but also an inhibitor of complex I activity, then promoting superoxide formation. Our preliminary clinical observations are the first to date supporting an effect of idebenone in delaying neurological worsening. Our MDA results point to the dual effect of idebenone on oxidative stress and to the need for controlled studies to assess its potential toxicity at high doses on the one hand, and to revisit the exact mechanisms underlying the physiopathology of Friedreich's ataxia on the other hand, while recent reports suggest non-oxidative pathophysiology of the disease.

An integrated genetic and functional analysis of the role of type II transmembrane serine proteases (TMPRSSs) in hearing loss.

Building on our discovery that mutations in the transmembrane serine protease, TMPRSS3, cause nonsyndromic deafness, we have investigated the contribution of other TMPRSS family members to the auditory function. To identify which of the 16 known TMPRSS genes had a strong likelihood of involvement in hearing function, three types of biological evidence were examined: 1) expression in inner ear tissues; 2) location in a genomic interval that contains a yet unidentified gene for deafness; and 3) evaluation of hearing status of any available Tmprss knockout mouse strains. This analysis demonstrated that, besides TMPRSS3, another TMPRSS gene was essential for hearing and, indeed, mice deficient for Hepsin (Hpn) also known as Tmprss1 exhibited profound hearing loss. In addition, TMPRSS2, TMPRSS5, and CORIN, also named TMPRSS10, showed strong likelihood of involvement based on their inner ear expression and mapping position within deafness loci PKSR7, DFNB24, and DFNB25, respectively. These four TMPRSS genes were then screened for mutations in affected members of the DFNB24 and DFNB25 deafness families, and in a cohort of 362 sporadic deaf cases. This large mutation screen revealed numerous novel sequence variations including three potential pathogenic mutations in the TMPRSS5 gene. The mutant forms of TMPRSS5 showed reduced or absent proteolytic activity. Subsequently, TMPRSS genes with evidence of involvement in deafness were further characterized, and their sites of expression were determined. Tmprss1, 3, and 5 proteins were detected in spiral ganglion neurons. Tmprss3 was also present in the organ of Corti. TMPRSS1 and 3 proteins appeared stably anchored to the endoplasmic reticulum membranes, whereas TMPRSS5 was also detected at the plasma membrane. Collectively, these results provide evidence that TMPRSS1 and TMPRSS3 play and TMPRSS5 may play important and specific roles in hearing.