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Kinds of Vs. Terms modified by Vs. Selected AbstractsSpatial Distribution and Frequency Dependence of Arrhythmogenic Vagal Effects in Canine AtriaJOURNAL OF CARDIOVASCULAR ELECTROPHYSIOLOGY, Issue 9 2000OLEG F. SHARIFOV Ph.D. Arrhythmogenic Vagal Effects in Dog Atria. introduction: Prior studies in isolated canine atria demonstrated that acetylcholine-induced reentrant atrial fibrillation (AF) was triggered by multifocal activity in the area of normal impulse origin (sinus node-crista terminalis). The aim of this study was to investigate the activation sequence in AF induced by vagal stimulation (VS) in intact dog hearts. Methods and Results: VS (10 to 50 Hz, 1 msec, 15 V, 5-sec trains) induced single or multiple atrial premature depolarizations (APDs), and/or AF in 8 of 10 open chest dogs. Occurrence of APDs and AF increased with increasing VS intensity. Epicardial mapping (254 unipolar electrodes) of both atria showed that APDs as a rule emerged from ectopic sites, often from the right atrial appendage. Activation mapping of the first 10 cycles of AF showed that only a small number (<3 to 4) of unstable reentrant circuits were possible at the same moment. Moreover, most sustained VS-induced AFs were accounted for by a single leading stable reentrant circuit that activated the remainder of the atria. Conclusion: (1) Occurrence of vagally induced APDs and AF increases with increasing frequency of VS. (2) VS-induced focal ectopic APDs are widely distributed over the atria. (3) A single APD can be sufficient for initiation of reentrant AF. (4) Despite its high rate of sustained AF, it may be maintained by single stable reentrant circuit. (5) The atrial septum can play an important role in both the initiation and the maintenance of VS-induced AF. [source] Neurodevelopmental Outcomes in Infants after Surgery for Congenital Heart Disease: A Comparison of Single-Ventricle vs.CONGENITAL HEART DISEASE, Issue 2 2010Two-Ventricle Physiology ABSTRACT Introduction., The neurodevelopmental outcome of children with repaired congenital heart defect has risen in importance with improved survival. This study compares neurodevelopmental outcomes of children who had CHD with single ventricle physiology with those who had CHD with two-ventricle physiology. Patients and Methods., Participants included 112 infants discharged from the NICU between February 1999 to August 2006. The 12 infants who had a known genetic defect were excluded. Of the 100 infants 26 had single ventricle physiology and 74 had CHD with two-ventricle physiology. The children were seen in a follow-up clinic and growth parameters and standardized instruments were used to evaluate development. The referral rate to early intervention services was also compared. Results., The number of functional ventricles did not significantly differentiate growth parameters at 6,8 months of age. Early cognitive outcomes were relatively unimpaired in both the groups (single ventricle vs. two ventricle physiology). Early motor outcomes were worse in (p < 0.05) CHD with single ventricle physiology. The rate of referral for early intervention services was high in both groups compared to the average rate of referral in the state, but there was not a significant difference between the CHD groups. Conclusion., Significant differences noted on motor outcomes at the 6,8 month visit were no longer apparent in later visits. Referral to early intervention services is high in both the groups. These findings are important to those caring for infants with CHD because many of these patients may need referral for early intervention. [source] Persistent Orthopnea and the Prognosis of Patients in the Heart Failure ClinicCONGESTIVE HEART FAILURE, Issue 4 2004Luís Beck Da Silva MD Heart failure (HF) is a public health problem with ever-growing costs. Signs such as jugular venous pressure and third heart sound have been associated with disease prognosis. Symptoms of heart failure are frequently subjective, and their real value is often overlooked. The authors aimed to assess the relationship between orthopnea and left ventricular ejection fraction (LVEF) and hospitalization rate in patients referred to the HF clinic. One hundred fifty-three new consecutive patients referred to the HF clinic from September 2001 to July 2002 were reviewed. Information about orthopnea was available at baseline and at a 6-month to 1-year follow-up. One hundred thirty-one patients had a baseline multigated radionuclide ventriculogram scan, and 68 patients had a follow-up multigated radionuclide ventriculogram scan available. The patients were divided into groups by presence of orthopnea and compared with respect to LVEF and hospitalization rate. Patients with or without orthopnea had similar LVEFs at baseline (32%±17% vs. 33%±15%, respectively; p=NS). However, patients who were orthopnea-free at the follow-up visit had a significant LVEF improvement whereas patients with ongoing orthopnea at follow-up had no LVEF improvement (11%±13% vs. ,1%±6%; p<0.001). Patients who presented with persistent orthopnea had a significantly higher rate of hospitalization (64% vs. 15.3%; p=0.0001). Persistent orthopnea in HF patients is associated with a significantly higher rate of hospitalization and with worsening or no improvement in LVEF. Patients with persistent orthopnea may require a more aggressive approach to improve their outcome. This result may help centers with limited access to LVEF measurements to better stratify HF patients' risk. [source] Impaired contractile function and mitochondrial respiratory capacity in response to oxygen deprivation in a rat model of pre-diabetesACTA PHYSIOLOGICA, Issue 4 2009M. F. Essop Abstract Aim:, Obesity is a major contributor to the global burden of disease and is closely associated with the development of type 2 diabetes and cardiovascular diseases. This study tested the hypothesis that mitochondrial respiratory capacity of the pre-diabetic heart is decreased leading to impaired contractile function and tolerance to ischaemia/reperfusion. Methods:, Eight-week-old male Wistar rats were fed a high caloric diet for 16 weeks after which anthropometric, metabolic, cardiac and mitochondrial parameters were evaluated vs. age-matched lean controls. Cardiac function (working heart perfusions) and mitochondrial respiratory capacity were assessed at baseline and in response to acute oxygen deprivation. Results:, Rats fed the high caloric diet exhibited increased body weight and visceral fat vs. the control group. Heart weights of obese rats were also increased. Triglyceride, fasting plasma insulin and free fatty acid levels were elevated, while high-density lipoprotein cholesterol levels were reduced in the obese group. Contractile function was attenuated at baseline and further decreased after subjecting hearts to ischaemia-reperfusion. Myocardial infarct sizes were increased while ADP phosphorylation rates were diminished in obese rats. However, no differences were found for mtDNA levels and the degree of oxidative stress-induced damage. Conclusions:, These data show that decreased mitochondrial bioenergetic capacity in pre-diabetic rat hearts may impair respiratory capacity and reduce basal contractile function and tolerance to acute oxygen deprivation. [source] Circulatory effects of apnoea in elite breath-hold diversACTA PHYSIOLOGICA, Issue 1 2009F. Joulia Abstract Aim:, Voluntary apnoea induces several physiological adaptations, including bradycardia, arterial hypertension and redistribution of regional blood flows. Elite breath-hold divers (BHDs) are able to maintain very long apnoea, inducing severe hypoxaemia without brain injury or black-out. It has thus been hypothesized that they develop protection mechanisms against hypoxia, as well as a decrease in overall oxygen uptake. Methods:, To test this hypothesis, the apnoea response was studied in BHDs and non-divers (NDs) during static and dynamic apnoeas (SA, DA). Heart rate, arterial oxygen saturation (SaO2), and popliteal artery blood flow were recorded to investigate the oxygen-conserving effect of apnoea response, and the internal carotid artery blood flow was used to examine the mechanisms of cerebral protection. Results:, The bradycardia and peripheral vasoconstriction were accentuated in BHDs compared with NDs (P < 0.01), in association with a smaller SaO2 decrease (,2.7% vs. ,4.9% during SA, P < 0.01 and ,6% vs. ,11.3% during DA, P < 0.01). Greater increase in carotid artery blood flow was also measured during apnoea in BHDs than in controls. Conclusion:, These results confirm that elite divers present a potentiation of the well-known apnoea response in both SA and DA conditions. This response is associated with higher brain perfusion which may partly explain the high levels of world apnoea records. [source] AMP-activated protein kinase in the regulation of hepatic energy metabolism: from physiology to therapeutic perspectivesACTA PHYSIOLOGICA, Issue 1 2009B. Viollet Abstract As the liver is central in the maintenance of glucose homeostasis and energy storage, knowledge of the physiology as well as physiopathology of hepatic energy metabolism is a prerequisite to our understanding of whole-body metabolism. Hepatic fuel metabolism changes considerably depending on physiological circumstances (fed vs. fasted state). In consequence, hepatic carbohydrate, lipid and protein synthesis/utilization are tightly regulated according to needs. Fatty liver and hepatic insulin resistance (both frequently associated with the metabolic syndrome) or increased hepatic glucose production (as observed in type 2 diabetes) resulted from alterations in substrates oxidation/storage balance in the liver. Because AMP-activated protein kinase (AMPK) is considered as a cellular energy sensor, it is important to gain understanding of the mechanism by which hepatic AMPK coordinates hepatic energy metabolism. AMPK has been implicated as a key regulator of physiological energy dynamics by limiting anabolic pathways (to prevent further ATP consumption) and by facilitating catabolic pathways (to increase ATP generation). Activation of hepatic AMPK leads to increased fatty acid oxidation and simultaneously inhibition of hepatic lipogenesis, cholesterol synthesis and glucose production. In addition to a short-term effect on specific enzymes, AMPK also modulates the transcription of genes involved in lipogenesis and mitochondrial biogenesis. The identification of AMPK targets in hepatic metabolism should be useful in developing treatments to reverse metabolic abnormalities of type 2 diabetes and the metabolic syndrome. [source] Human soleus muscle protein synthesis following resistance exerciseACTA PHYSIOLOGICA, Issue 2 2004T. A. Trappe Abstract Aim:, It is generally believed the calf muscles in humans are relatively unresponsive to resistance training when compared with other muscles of the body. The purpose of this investigation was to determine the muscle protein synthesis response of the soleus muscle following a standard high intensity bout of resistance exercise. Methods:, Eight recreationally active males (27 ± 4 years) completed three unilateral calf muscle exercises: standing calf press/heel raise, bent-knee calf press/heel raise, and seated calf press/heel raise. Each exercise consisted of four sets of 15 repetitions (,15 repetition maximum, RM, or ,70% 1RM). Fractional rate of muscle protein synthesis (FSR) was determined with a primed constant infusion of [2H5]phenylalanine coupled with muscle biopsies immediately and 3 h following the exercise in both the exercise and non-exercise (resting control) leg. Results:, FSR was elevated (P < 0.05) in the exercise (0.069 ± 0.010) vs. the control (0.051 ± 0.012) leg. Muscle glycogen concentration was lower (P < 0.05) in the exercise compared with the control leg (Decrease from control; immediate post-exercise: 54 ± 5; 3 h post-exercise: 36 ±4 mmol kg,1 wet wt.). This relatively high amount of glycogen use is comparable with previous studies of resistance exercise of the thigh (i.e. vastus lateralis; ,41,49 mmol kg,1 wet wt.). However, the exercise-induced increase in FSR that has been consistently reported for the vastus lateralis (,0.045,0.060% h,1) is on average ,200% higher than reported here for the soleus (0.019 ± 0.003% h,1). Conclusions:, These results suggest the relatively poor response of soleus muscle protein synthesis to an acute bout of resistance exercise may be the basis for the relative inability of the calf muscles to respond to resistance training programs. [source] Twenty-four-hour non-invasive monitoring of systemic haemodynamics and cerebral blood flow velocity in healthy humansACTA PHYSIOLOGICA, Issue 1 2002M. DIAMANT ABSTRACT Acute short-term changes in blood pressure (BP) and cardiac output (CO) affect cerebral blood flow (CBF) in healthy subjects. As yet, however, we do not know how spontaneous fluctuations in BP and CO influence cerebral circulation throughout 24 h. We performed simultaneous monitoring of BP, systemic haemodynamic parameters and blood flow velocity in the middle cerebral artery (MCAV) in seven healthy subjects during a 24-h period. Finger BP was recorded continuously during 24 h by Portapres and bilateral MCAV was measured by transcranial Doppler (TCD) during the first 15 min of every hour. The subjects remained supine during TCD recordings and during the night, otherwise they were seated upright in bed. Stroke volume (SV), CO and total peripheral resistance (TPR) were determined by Modelflow analysis. The 15 min mean value of each parameter was assumed to represent the mean of the corresponding hour. There were no significant differences between right vs. left, nor between mean daytime vs. night time MCAV. Intrasubject comparison of the twenty-four 15-min MCAV recordings showed marked variations (P < 0.001). Within each single 15-min recording period, however, MCAV was stable whereas BP showed significant short-term variations (P < 0.01). A day,night difference in BP was only observed when daytime BP was evaluated from recordings in the seated position (P < 0.02), not in supine recordings. Throughout 24 h, MCAV was associated with SV and CO (P < 0.001), to a lesser extent with mean arterial pressure (MAP; P < 0.005), not with heart rate (HR) or TPR. These results indicate that in healthy subjects MCAV remains stable when measured under constant supine conditions but shows significant variations throughout 24 h because of activity. Moreover, changes in SV and CO, and to a lesser extent BP variations, affect MCAV throughout 24 h. [source] Diagnostic utility of the Quick Inventory of Depressive Symptomatology (QIDS-C16 and QIDS-SR16) in the elderlyACTA PSYCHIATRICA SCANDINAVICA, Issue 3 2010P. M. Doraiswamy Doraiswamy PM, Bernstein IH, Rush AJ, Kyutoku Y, Carmody TJ, Macleod L, Venkatraman S, Burks M, Stegman D, Witte B, Trivedi MH. Diagnostic utility of the Quick Inventory of Depressive Symptomatology (QIDS-C16 and QIDS-SR16) in the elderly. Objective:, To evaluate psychometric properties and comparability ability of the Montgomery-Åsberg Depression Rating Scale (MADRS) vs. the Quick Inventory of Depressive Symptomatology,Clinician-rated (QIDS-C16) and Self-report (QIDS-SR16) scales to detect a current major depressive episode in the elderly. Method:, Community and clinic subjects (age ,60 years) were administered the Mini-International Neuropsychiatric Interview (MINI) for DSM-IV and three depression scales randomly. Statistics included classical test and Samejima item response theories, factor analyzes, and receiver operating characteristic methods. Results:, In 229 elderly patients (mean age = 73 years, 39% male, 54% current depression), all three scales were unidimensional and with nearly equal Cronbach , reliability (0.85,0.89). Each scale discriminated persons with major depression from the non-depressed, but the QIDS-C16 was slightly more accurate. Conclusion:, All three tests are valid for detecting geriatric major depression with the QIDS-C16 being slightly better. Self-rated QIDS-SR16 is recommended as a screening tool as it is least expensive and least time consuming. [source] Employer burden of mild, moderate, and severe major depressive disorder: mental health services utilization and costs, and work performance,DEPRESSION AND ANXIETY, Issue 1 2010Howard G. Birnbaum Ph.D. Abstract Background: Treatment utilization/costs and work performance for persons with major depressive disorder (MDD) by severity of illness is not well documented. Methods: Using National Comorbidity Survey-Replication (2001,2002) data, US workforce respondents (n=4,465) were classified by clinical severity (not clinically depressed, mild, moderate, severe) using a standard self-rating scale [Quick Inventory of Depressive Symptomatology Self-Report (QIDS-SR)]. Outcomes included 12-month prevalence of medical services/medications use/costs and workplace performance. Treatment costs (employer's perspective) were estimated by weighing utilization measures by unit costs obtained for similar services used by MDD patients in claims data. Descriptive analysis across three severity groups generated ,2 results. Results: Using a sample of 539 US workforce respondents with MDD, 13.8% were classified mild, 38.5% moderate, and 47.7% severe cases. Mental health services usage, including antidepressants, increased significantly with severity, with average treatment costs substantially higher for severe than for mild cases both regarding mental health services ($697 vs. $388, ,2=4.4, P=.019) and antidepressants ($256 vs. $88, ,2=9.0, P=.001). Prevalence rates of unemployment/disability increased significantly (,2=11.7, P=.003) with MDD severity (15.7, 23.3, and 31.3% for mild, moderate, and severe cases). Severely and moderately depressed workers missed more work than nondepressed workers; the monthly salary-equivalent lost performance of $199 (severely depressed) and $188 (moderately depressed) was significantly higher than for nondepressed workers (,2=10.3, P<.001). Projected to the US workforce, monthly depression-related worker productivity losses had human capital costs of nearly $2 billion. Conclusions: MDD severity is significantly associated with increased treatment usage/costs, treatment adequacy, unemployment, and disability and with reduced work performance. Depression and Anxiety, 2010. © 2009 Wiley-Liss, Inc. [source] Does occasional cannabis use impact anxiety and depression treatment outcomes?: results from a randomized effectiveness trialDEPRESSION AND ANXIETY, Issue 6 2007Jonathan B. Bricker Ph.D. Abstract This study investigated the extent to which occasional cannabis use moderated anxiety and depression outcomes in the Collaborative Care for Anxiety and Panic (CCAP) study, a combined cognitive-behavioral therapy (CBT) and pharmacotherapy randomized effectiveness trial. Participants were 232 adults from six university-based primary care outpatient clinics in three West Coast cities randomized to receive either the CCAP intervention or the usual care condition. Results showed significant (P<.01) evidence of an interaction between treatment group (CCAP vs. usual care) and cannabis use status (monthly vs. less than monthly) for depressive symptoms, but not for panic disorder or social phobia symptoms (all P>.05). Monthly cannabis users' depressive symptoms improved in the CCAP intervention just as much as those who used cannabis less than monthly, whereas monthly users receiving usual care had significantly more depressive symptoms than those using less than monthly. A combined CBT and medication treatment intervention may be a promising approach for the treatment of depression among occasional cannabis users. Depression and Anxiety 24:392,398, 2007. © 2006 Wiley-Liss, Inc. [source] Cognitive mediation of panic reduction during an early intervention for panicACTA PSYCHIATRICA SCANDINAVICA, Issue 1 2010P. Meulenbeek Meulenbeek P, Spinhoven P, Smit F, van Balkom A, Cuijpers P. Cognitive mediation of panic reduction during an early intervention for panic. Objective:, This study investigated cognitive mediation of improvement in panic disorder (PD) symptomatology during and after an early intervention for panic symptoms in subthreshold and mild PD. Method:, We executed a pragmatic, pre-post, two-group, multi-site, randomized trial of an early intervention for panic symptoms, based on cognitive-behavioural therapy, vs. a wait-list control group in a sample of 217 participants with subthreshold PD or mild PD. Results:, First, two of the three subscales of the mediator variable Panic Appraisal Inventory (PAI-anticipation and PAI-coping) significantly mediated residual change in PD symptomatology on the PD Severity Scale-Self Report. Second, preintervention to postintervention PAI-anticipation and PAI-coping change scores significantly predicted postintervention to follow-up change in PD symptomatology after controlling for other change scores. However, the converse association was also significant. Conclusion:, The results suggest that changes in cognitions may mediate changes in PD symptomatology and that the process of change is circular. [source] Mania associated with antidepressant treatment: comprehensive meta-analytic reviewACTA PSYCHIATRICA SCANDINAVICA, Issue 6 2010L. Tondo Tondo L, Vázquez G, Baldessarini RJ. Mania associated with antidepressant treatment: comprehensive meta-analytic review. Objective:, To review available data pertaining to risk of mania,hypomania among bipolar (BPD) and major depressive disorder (MDD) patients with vs. without exposure to antidepressant drugs (ADs) and consider effects of mood stabilizers. Method:, Computerized searching yielded 73 reports (109 trials, 114 521 adult patients); 35 were suitable for random effects meta-analysis, and multivariate-regression modeling included all available trials to test for effects of trial design, AD type, and mood-stabilizer use. Results:, The overall risk of mania with/without ADs averaged 12.5%/7.5%. The AD-associated mania was more frequent in BPD than MDD patients, but increased more in MDD cases. Tricyclic antidepressants were riskier than serotonin-reuptake inhibitors (SRIs); data for other types of ADs were inconclusive. Mood stabilizers had minor effects probably confounded by their preferential use in mania-prone patients. Conclusion:, Use of ADs in adults with BPD or MDD was highly prevalent and moderately increased the risk of mania overall, with little protection by mood stabilizers. [source] The relationship between childhood trauma history and the psychotic subtype of major depressionACTA PSYCHIATRICA SCANDINAVICA, Issue 6 2010B. A. Gaudiano Gaudiano BA, Zimmerman M. The relationship between childhood trauma history and the psychotic subtype of major depression. Objective:, Increasing evidence exists linking childhood trauma and primary psychotic disorders, but there is little research on patients with primary affective disorders with psychotic features. Method:, The sample consisted of adult out-patients diagnosed with major depressive disorder (MDD) at clinic intake using a structured clinical interview. Patients with MDD with (n = 32) vs. without psychotic features (n = 591) were compared as to their rates of different types of childhood trauma. Results:, Psychotic MDD patients were significantly more likely to report histories of physical (OR = 2.81) or sexual abuse (OR = 2.75) compared with non-psychotic MDD patients. These relationships remained after controlling for baseline differences. Within the subsample with comorbid post-traumatic stress disorder, patients with psychotic MDD were significantly more likely to report childhood physical abuse (OR = 3.20). Conclusion:, Results support and extend previous research by demonstrating that the relationship between childhood trauma and psychosis is found across diagnostic groups. [source] Microprocessor-Controlled Local Anesthesia vs. the Conventional Syringe Technique in Hair TransplantationDERMATOLOGIC SURGERY, Issue 7 2002Dow B. Stough MDArticle first published online: 24 JUL 200 No abstract is available for this article. [source] Comparison of Endovenous Radiofrequency Versus 810 nm Diode Laser Occlusion of Large Veins in an Animal ModelDERMATOLOGIC SURGERY, Issue 1 2002Robert A. Weiss MDArticle first published online: 27 FEB 200 background. Endovenous occlusion using radiofrequency (RF) energy has been shown to be effective for the elimination of sapheno-femoral reflux and subsequent elimination of varicose veins. Recently, endovenous laser occlusion has been introduced with initial clinical reports indicating effective treatment for varicose veins. However, in our practice we note increased peri-operative hematoma and tenderness with the laser. Little is known regarding the mechanism of action of this new laser vein therapy. objective. To better understand the mechanism of action of endovenous laser vs. the endovenous RF procedure in the jugular vein of the goat model. methods. A bilateral comparison was performed using 810 nm diode laser transmitted by a bare-tipped optical fiber vs. the RF delivery by engineered electrodes with a temperature feedback loop using a thermocouple (Closure procedure) in three goat jugular veins. Immediate and one-week results were studied radiographically and histologically. Temperature measurements during laser treatment were performed by using an array of up to five thermocouples, spaced 2 mm apart, placed adjacent to a laser fiber tip during goat jugular vein treatment. results. Immediate findings showed that 100% of the laser-treated veins showed perforations by histologic examination and immediate contrast fluoroscopy. The RF-treated side showed immediate constriction with maintenance of contrast material within the vein lumen and no perforations. The difference in acute vein shrinkage was also dramatic as laser treatments resulted in vein shrinkage of 26%, while RF-treated veins showed a 77% acute reduction in diameter. At one week, extravasated blood that leaked into the surrounding tissue of laser treated veins acutely, continued to occupy space and impinge on surrounding structures including nerves. For the laser treatment, the highest average temperature was 729°C (peak temperature 1334°C) observed flush with the laser fiber tip, while the temperature feedback mechanism of the RF method maintains temperatures at the electrodes of 85°C. conclusion. Vein perforations, extremely high intravascular temperatures, failure to cause significant collagen shrinkage, and intact endothelium in an animal model justify a closer look at the human clinical application of the 810 nm endovenous laser technique. Extravasated blood impinging on adjacent structures may theoretically lead to increased peri-operative hematoma and tenderness. Further study and clinical investigation is warranted. [source] The efficacy of nicotinamide gel 4% as an adjuvant therapy in the treatment of cutaneous erosions of pemphigus vulgarisDERMATOLOGIC THERAPY, Issue 3 2010Fariba Iraji ABSTRACT The high rate of morbidity and mortality resulting from long-term use of corticosteroids in pemphigus vulgaris (PV) warrants discovery of a new treatment strategy. Based on the pathophysiology of PV, nicotinamide can block the process of blister formation through its anti-inflammatory properties. This study was conducted to evaluate the clinical effectiveness of nicotinamide gel in the treatment of skin lesions of PV. In a double-blind, placebo-controlled study, eight PV patients with a total of 60 skin lesions were treated by either nicotinamide or placebo gel. After 30 days of treatment, epithelialization index of the two groups was compared. The mean of the epithelialization index in skin lesions that received nicotinamide was significantly higher than that of the placebo group (26 vs. ,5.8, p < 0.001). Our results were suggestive that nicotinamide gel can effectively be used as an adjunctive treatment for PV lesions. [source] A randomized study of massed three-week cognitive behavioural therapy schedule for panic disorderACTA PSYCHIATRICA SCANDINAVICA, Issue 3 2009M. K. Bohni Objective:, To compare the efficacy of massed vs. spaced group cognitive behavioural therapy (CBT) for patients with panic disorder with or without agoraphobia (PD). Method:, Thirty-nine PD patients were randomly assigned to massed group CBT (daily 4-h sessions in week 1, two 2-h sessions in week 2 and one 2-h session in week 3) or traditional spaced weekly group CBT (13 consecutive, weekly 2-h sessions). The content and number of hours in the two treatment schedules were identical. Outcome was assessed after treatment, and at 3, 6 and 18 months of follow-up. Results:, Both treatment groups achieved significant improvement on all measures with large pre- to post-treatment and pre-treatment to follow-up effect sizes. No between-group differences were registered. Adherence and patient satisfaction did not differ between groups. Conclusion:, The massed, 3-week group CBT schedule proved to be effective and feasible for PD patients with outcomes comparable with that of standard, spaced group CBT. [source] The first steps in word learning are easier when the shoes fit: comparing monolingual and bilingual infantsDEVELOPMENTAL SCIENCE, Issue 1 2010Karen Mattock English, French, and bilingual English-French 17-month-old infants were compared for their performance on a word learning task using the Switch task. Object names presented a /b/ vs. /g/ contrast that is phonemic in both English and French, and auditory strings comprised English and French pronunciations by an adult bilingual. Infants were habituated to two novel objects labeled ,bowce' or ,gowce' and were then presented with a switch trial where a familiar word and familiar object were paired in a novel combination, and a same trial with a familiar word,object pairing. Bilingual infants looked significantly longer to switch vs. same trials, but English and French monolinguals did not, suggesting that bilingual infants can learn word,object associations when the phonetic conditions favor their input. Monolingual infants likely failed because the bilingual mode of presentation increased phonetic variability and did not match their real-world input. Experiment 2 tested this hypothesis by presenting monolingual infants with nonce word tokens restricted to native language pronunciations. Monolinguals succeeded in this case. Experiment 3 revealed that the presence of unfamiliar pronunciations in Experiment 2, rather than a reduction in overall phonetic variability was the key factor to success, as French infants failed when tested with English pronunciations of the nonce words. Thus phonetic variability impacts how infants perform in the switch task in ways that contribute to differences in monolingual and bilingual performance. Moreover, both monolinguals and bilinguals are developing adaptive speech processing skills that are specific to the language(s) they are learning. [source] Managing childhood obesity: when lifestyle change is not enoughDIABETES OBESITY & METABOLISM, Issue 11 2010C. Hearnshaw The management of childhood obesity is a clinical dilemma. Paediatricians will see those children whose weight is at the severe end of the spectrum with obesity-related co-morbidities and for whom more intensive weight loss therapies may be appropriate. A literature review was performed (January 1995,January 2010) of the roles of pharmacotherapy or bariatric surgery in the management of childhood obesity. Three hundred and eighty-three abstracts were reviewed and 76 full-text articles were requested. Of these, 34 were excluded and a total of 21 pharmacotherapy papers and 22 papers on surgery were reviewed in detail. All studies involved adolescents. Pharmacotherapy: Most studies were small and of short duration, the notable exceptions being two large RCTs of sibutramine and orlistat. Sibutramine led to a mean estimated change in BMI from baseline of ,3.1 kg/m2 vs. ,0.3 kg/m2 for placebo over 12 months. Orlistat was also beneficial with a mean reduction in BMI of 0.55 vs. an increase of 0.31 kg/m2 in the placebo group at 12 months. Bariatric surgery: Most papers presented clinical observations and there were no randomised controlled trials (RCTs). Robust selection criteria were not used and ideal candidate selection remains unclear. Most papers showed a significant benefit of surgery in severely obese adolescents in the short term but long-term data were sparse. There were a surprisingly large number of papers examining the benefits of intensive weight management in obese adolescents. The study design of many was inadequate and the role of pharmacotherapy or surgery in childhood obesity remains unclear. [source] Bariatric surgery vs. advanced practice medical management in the treatment of type 2 diabetes mellitus: rationale and design of the Surgical Therapy And Medications Potentially Eradicate Diabetes Efficiently trial (STAMPEDE)DIABETES OBESITY & METABOLISM, Issue 5 2010Sangeeta R. Kashyap Obesity and Type 2 diabetes mellitus (T2DM) are closely interrelated, and are two of the most common chronic, debilitating diseases worldwide. Surgical approaches to weight loss (bariatric surgery) result in marked improvement of T2DM, however randomized trials directly comparing the efficacy of surgical and medical approaches are lacking. The Surgical Therapy and Medications Potentially Eradicate Diabetes Efficiently (STAMPEDE) trial was designed to evaluate the efficacy of two bariatric surgery procedures involving gastric restriction only (laparascopic sleeve gastrectomy) and gastric bypass (Roux-en-Y) to advanced medical therapy in patients with T2DM with modest obesity with BMI of 27,42 kg/m2. This single site, prospective, randomized controlled trial will enroll 150 subjects who will be followed. The primary end point will be the rate of biochemical resolution of T2DM at 1 year as measured by HbA1c < 6%. The safety and adverse event rates will also be compared between the three arms of the study. [source] Vildagliptin plus metformin combination therapy provides superior glycaemic control to individual monotherapy in treatment-naive patients with type 2 diabetes mellitusDIABETES OBESITY & METABOLISM, Issue 5 2009E. Bosi Aim:, To compare the efficacy and safety of vildagliptin and metformin initial combination therapy with individual monotherapies in treatment-naive patients with type 2 diabetes mellitus (T2DM). Methods:, This was a 24-week, randomized, double-blind, active-controlled study. Treatment-naive patients with T2DM who had a glycated haemoglobin (HbA1c) of 7.5,11% (N = 1179) were randomized equally to receive vildagliptin plus high-dose metformin combination therapy (50 mg + 1000 mg twice daily), vildagliptin plus low-dose metformin combination therapy (50 mg + 500 mg twice daily), vildagliptin monotherapy (50 mg twice daily) or high-dose metformin monotherapy (1000 mg twice daily). The primary objective was to demonstrate that HbA1c reduction from baseline with either combination therapy is superior to both monotherapies at the week 24 endpoint. Patients who failed glycaemic-screening criteria [HbA1c >11% or fasting plasma glucose (FPG) >15 mmol/l (270 mg/dl)] could enter a 24-week, single-arm substudy. These patients (N = 94) received open-label vildagliptin plus high-dose metformin combination therapy (100 mg + 1000 mg twice daily). Results:, From comparable baseline values (8.6,8.7%), HbA1c decreased in all four treatment groups, to the greatest extent with vildagliptin plus high-dose metformin combination therapy. Mean (SE) HbA1c change from baseline was ,1.8% (0.06%), ,1.6% (0.06%), ,1.1% (0.06%) and ,1.4% (0.06%) with vildagliptin plus high-dose metformin combination therapy, vildagliptin plus low-dose metformin combination therapy, and vildagliptin and metformin monotherapies respectively. The between-group difference was superior with vildagliptin plus high-dose metformin combination therapy (p < 0.001 vs. both monotherapies) and vildagliptin plus low-dose metformin combination therapy (p < 0.001 and p = 0.004, vs. vildagliptin and metformin monotherapies, respectively). Higher baseline HbA1c values were linked to greater HbA1c reductions, with changes of ,3.2% (0.22%), ,2.7% (0.22%), ,1.5% (0.24%) and ,2.6% (0.26%) respectively, occurring in patients with baseline HbA1c,10%. Reductions in FPG were superior with vildagliptin plus high-dose metformin combination therapy [change from baseline ,2.63 (0.13) mmol/l] compared with both monotherapies [,1.26 (0.13) mmol/l and ,1.92 (0.13) mmol/l, respectively; p < 0.001]. There was no incidence of hypoglycaemia or severe hypoglycaemia with either combination therapy, and neither was associated with weight gain. All treatments were well tolerated and displayed a comparable incidence of adverse events overall. Despite superior HbA1c lowering, the vildagliptin plus low-dose metformin combination therapy group demonstrated a favourable gastrointestinal (GI) tolerability profile compared with metformin monotherapy. Conclusions:, In treatment-naive patients, combinations of vildagliptin and both high-dose and low-dose metformin provide superior efficacy to monotherapy treatments with a comparable overall tolerability profile and low risk of hypoglycaemia. The potential dose-sparing effect of adding vildagliptin to low-dose metformin in preference to the up-titration of metformin may allow patients to achieve equivalent or superior HbA1c lowering without the GI tolerability issues associated with higher doses of metformin. [source] Orlistat 120 mg improves glycaemic control in type 2 diabetic patients with or without concurrent weight lossDIABETES OBESITY & METABOLISM, Issue 4 2009S. Jacob Background:, Both obesity and type 2 diabetes are associated with increased morbidity and mortality. Published data suggest that orlistat 120 mg, a lipase inhibitor used to treat obesity, may improve glycaemic parameters through weight loss,independent effects. Aim:, To investigate the effect of orlistat 120 mg on weight loss, and assess whether changes in glycaemic parameters [fasting plasma glucose (FPG) and haemoglobin A1c (HbA1c)] are independent of weight loss. Methods:, This retrospective analysis of pooled data from seven multicentre, double-blind, placebo-controlled studies involved overweight or obese patients with type 2 diabetes (aged 18,70 years). Patients were required to have a body mass index of 27,43 kg/m2, HbA1c of 6.5 to <13%, and stable weight for ,3 months. Subjects received orlistat 120 mg tid or placebo for 6 or 12 months. Results:, A total of 2550 overweight or obese patients with type 2 diabetes were enrolled and randomized to treatment with orlistat 120 mg tid (n = 1279) or placebo (n = 1271). For the whole population, patients treated with orlistat 120 mg had significantly greater mean decreases in FPG compared with placebo-treated patients (,1.39 mmol/l vs. ,0.47 mmol/l; p < 0.0001). In addition, orlistat 120 mg provided significantly larger mean decreases in HbA1c compared with placebo (,0.74% vs. ,0.31%; p < 0.0001). For patients with minimal weight loss (,1% of baseline body weight), orlistat 120 mg still provided a significantly greater decrease in the least squares mean value for both FPG (,0.83 mmol/l vs. ±0.02 mmol/l; p = 0.0052) and HbA1c,0.29% vs. ±0.14%; p = 0.0008). This suggested that the improvement of glycaemic control with orlistat 120 mg was independent of weight loss. Using linear regression analysis, improvement in glycaemic control (FPG and HbA1c) with orlistat 120 mg was less strongly correlated with weight loss than for placebo. Conclusion:, Orlistat 120 mg appears to improve glycaemic control more than would be predicted by weight loss alone in overweight or obese patients with type 2 diabetes. Postulated mechanisms underlying this effect include an improvement of insulin sensitivity, a slower and incomplete digestion of dietary fat, reduction of postprandial plasma non-esterified fatty acids, decreased visceral adipose tissue, and stimulation of glucagon-like peptide-1 secretion in the lower small intestine. [source] Inhaled insulin as adjunctive therapy in subjects with type 2 diabetes failing oral agents: a controlled proof-of-concept studyDIABETES OBESITY & METABOLISM, Issue 5 2006M. Hausmann Aim:, This controlled proof-of-concept study investigated inhaled insulin (INH) as adjunctive therapy to existing oral antidiabetic agents in subjects with type 2 diabetes. Methods:, Twenty-four subjects with type 2 diabetes [19 men and 5 women, 56.1 ± 6.6 years, body mass index 32.7 ± 4.2 kg/m2, glycosylated haemoglobin (HbA1c) 8.4 ± 0.8% (mean ± s.d.)] inadequately controlled by metformin and/or sulfonylureas were randomized to receive additional therapy with either INH administered preprandially using a metered-dose inhaler (MDI), or insulin glargine (GLA) injected subcutaneously at bedtime for 4 weeks. Both inhaled and injected insulin doses were titrated to predefined blood glucose (BG) targets. Results:, INH and GLA improved metabolic control to a similar extent. Mean daily BG decreased by 2.8 mmol/l in the INH group (p < 0.001) and by 2.4 mmol/l in the GLA group (p < 0.001). Accordingly, fasting BG (,2.7 vs. ,3.6 mmol/l for INH vs. GLA), preprandial- and 2-h postprandial BG, HbA1c (,1.23 vs. ,1.05%), body weight (,1.9 vs. ,2.3 kg) and serum fructosamine were similarly and significantly reduced in both groups (p < 0.05). Triglycerides decreased significantly with INH (,1.15 ,mol/l; p < 0.001) but not with GLA [,0.52 ,mol/l; not significant (NS)]. Incidence rates of adverse events did not differ significantly, and there were no indications of respiratory tract irritation. Conclusions:, In subjects with type 2 diabetes inadequately controlled by oral agents, preprandial administration of INH delivered by a MDI provided a comparable metabolic control to bedtime GLA and did not show any safety concerns during a 4-week treatment. These results warrant a more extensive investigation of preprandial treatment with INH in longer term studies. [source] Degradation in insulin sensitivity with increasing severity of the metabolic syndrome in obese postmenopausal womenDIABETES OBESITY & METABOLISM, Issue 3 2006A. D. Karelis Aim:, We investigated the relationship between insulin sensitivity and the graded increase in the number of features of the metabolic syndrome in a cross-sectional sample of obese postmenopausal women. We hypothesized that insulin sensitivity would deteriorate with an increased number of metabolic syndrome phenotypes. Methods:, Insulin sensitivity was measured in 75 obese postmenopausal women (age: 57.3 ± 5.3 years; BMI: 32.8 ± 4.5 kg/m2) by using both the hyperinsulinaemic,euglycaemic clamp and the homeostasis model assessment (HOMA-IR). Features of the metabolic syndrome included visceral fat (>130 cm2), HDL-cholesterol (<1.29 mmol/l), fasting triglycerides (,1.7 mmol/l), blood pressure (,130/,85 mmHg) and fasting glucose (,6.1 mmol/l). Participants were classified into three categories based on the presence of metabolic syndrome phenotypes: 0,1 vs. 2 vs. ,3 features of the metabolic syndrome. Results:, We found that insulin sensitivity decreased in a graded fashion (12.19 ± 3.2 vs. 11.80 ± 2.3 vs. 9.29 ± 2.6 mg/min/FFM) and HOMA-IR increased in a similar manner (2.95 ± 1.1 vs. 3.28 ± 1.3 vs. 4.65 ± 2.2), as the number of features of the metabolic syndrome increased from 0,1 to ,3. When insulin sensitivity was statistically adjusted for visceral fat (as measured by computed tomography) and plasma triglycerides, the differences among groups were abolished. Conclusions:, These findings suggest that a decreased insulin sensitivity is associated with increased features of the metabolic syndrome in obese postmenopausal women and that visceral fat as well as plasma triglyceride accumulation might be potential mediators of this relationship. [source] Efficacy and safety of ezetimibe co-administered with simvastatin in thiazolidinedione-treated type 2 diabetic patientsDIABETES OBESITY & METABOLISM, Issue 1 2005L. M. Gaudiani Aim:, In patients with type 2 diabetes mellitus (T2DM), combination therapy is usually required to optimize glucose metabolism as well as to help patients achieve aggressive targets for low-density lipoprotein cholesterol (LDL-C) and other lipid parameters associated with cardiovascular risk. The thiazolidinediones (TZDs) are increasingly being used for both their blood glucose-lowering properties and their modest beneficial effects on triglycerides (TG) and high-density lipoprotein cholesterol (HDL-C). Ezetimibe, an intestinal cholesterol absorption inhibitor, has a mechanism of action that differs from that of statins, which inhibit hepatic cholesterol synthesis. We compared the lipid-modifying efficacy and safety of adding ezetimibe to simvastatin, vs. doubling the dose of simvastatin, in TZD-treated T2DM patients. Methods:, This was a randomized, double-blind, parallel group, multicentre study in T2DM patients, 30,75 years of age, who had been on a stable dose of a TZD for at least 3 months and had LDL-C > 2.6 mmol/l (100 mg/dl) prior to study entry. Other antidiabetic medications were also allowed. Following 6 weeks of open-label simvastatin 20 mg/day, patients were randomized to the addition of either blinded ezetimibe 10 mg/day (n = 104) or an additional blinded simvastatin 20 mg/day (total simvastatin 40 mg/day; n = 110) for 24 weeks. Patients were stratified according to TZD type and dose (pioglitazone 15,30 vs. 45 mg/day; rosiglitazone 2,4 vs. 8 mg/day). Results:, LDL-C was reduced more (p < 0.001) by adding ezetimibe 10 mg to simvastatin 20 mg (,20.8%) than by doubling the dose of simvastatin to 40 mg (,0.3%). Ezetimibe plus simvastatin 20 mg also produced significant incremental reductions in non-HDL-C (p < 0.001), very low-density lipoprotein cholesterol (p < 0.05) and apolipoprotein B (p < 0.001) relative to simvastatin 40 mg. There were no differences between the groups with respect to changes in TG and HDL-C levels, and both treatments were well tolerated. Conclusions:, Co-administration of ezetimibe with simvastatin, a dual inhibition treatment strategy targeting both cholesterol synthesis and absorption, is well tolerated and provides greater LDL-C-lowering efficacy than increasing the dose of simvastatin in T2DM patients taking TZDs. [source] Prophylactic use of anti-emetic medications reduced nausea and vomiting associated with exenatide treatment: a retrospective analysis of an open-label, parallel-group, single-dose study in healthy subjectsDIABETIC MEDICINE, Issue 10 2010C. Ellero Diabet. Med. 27, 1168,1173 (2010) Abstract Aims, Transient nausea and, to a lesser extent, vomiting are common adverse effects of exenatide that can be mitigated by dose titration and usually do not result in treatment discontinuation. This retrospective analysis of data from a phase 1, open-label, parallel-group, single-dose study in healthy subjects evaluated the effect of oral anti-emetics on exenatide-associated nausea and vomiting and on the pharmacokinetics of exenatide. Methods, A single subcutaneous dose (10 ,g) of exenatide was administered to 120 healthy subjects (19,65 years, BMI 23,35 kg/m2). Incidences of nausea and vomiting were compared between 60 subjects premedicated with two oral anti-emetics 30 min before the exenatide dose and 60 non-premedicated subjects. Similarly, the area under the concentration-time curve (AUC) and the maximum observed concentration (Cmax) of plasma exenatide concentrations over 8 h post-dose were compared. Results, Among all subjects [61% male, 32 ± 12 years, body mass index (BMI) 29.1 ± 3.4 kg/m2 (mean ± sd)], mild to moderate nausea was the most frequent adverse event after exenatide dosing. Vomiting was also observed. Subjects premedicated with anti-emetics experienced significantly less nausea and vomiting (16.7 and 6.7%, respectively) vs. non-premedicated subjects (61.7 and 38.3%, respectively; P -value < 0.0001 for both nausea and vomiting). The mean area under the concentration-time curve and the maximum observed concentration AUC and Cmax of plasma exenatide concentrations during 8 h post-dose were not significantly different between groups. Conclusion, Administration of oral anti-emetics before a single 10-,g exenatide dose was associated with significant reductions in treatment-emergent nausea and vomiting, with no discernible effect on the pharmacokinetics of exenatide. Use of anti-emetic therapy may provide a short-term strategy to minimize the nausea and vomiting associated with exenatide treatment. [source] Original Article: Treatment: Dose-dependent effects of the once-daily GLP-1 receptor agonist lixisenatide in patients with Type 2 diabetes inadequately controlled with metformin: a randomized, double-blind, placebo-controlled trialDIABETIC MEDICINE, Issue 9 2010R. E. Ratner Diabet. Med. 27, 1024,1032 (2010) Abstract Aims, To evaluate the dose,response relationship of lixisenatide (AVE0010), a glucagon-like peptide-1 (GLP-1) receptor agonist, in metformin-treated patients with Type 2 diabetes. Methods, Randomized, double-blind, placebo-controlled, parallel-group, 13 week study of 542 patients with Type 2 diabetes inadequately controlled [glycated haemoglobin (HbA1c) , 7.0 and < 9.0% (, 53 and < 75 mmol/mol)] on metformin (, 1000 mg/day) treated with subcutaneous lixisenatide doses of 5, 10, 20 or 30 ,g once daily or twice daily or placebo. The primary end-point was change in HbA1c from baseline to 13 weeks in the intent-to-treat population. Results, Lixisenatide significantly improved mean HbA1c from a baseline of 7.55% (59.0 mmol/mol); respective mean reductions for 5, 10, 20 and 30 ,g doses were 0.47, 0.50, 0.69 and 0.76% (5.1, 5.5, 7.5 and 8.3 mmol/mol), on once-daily and 0.65, 0.78, 0.75 and 0.87% (7.1, 8.5, 8.2 and 9.5 mmol/mol) on twice-daily administrations vs. 0.18% (2.0 mmol/mol) with placebo (all P < 0.01 vs. placebo). Target HbA1c < 7.0% (53 mmol/mol) at study end was achieved in 68% of patients receiving 20 and 30 ,g once-daily lixisenatide vs. 32% receiving placebo (P < 0.0001). Dose-dependent improvements were observed for fasting, postprandial and average self-monitored seven-point blood glucose levels. Weight changes ranged from ,2.0 to ,3.9 kg with lixisenatide vs. ,1.9 kg with placebo. The most frequent adverse event was mild-to-moderate nausea. Conclusions, Lixisenatide significantly improved glycaemic control in mildly hyperglycaemic patients with Type 2 diabetes on metformin. Dose,response relationships were seen for once- and twice-daily regimens, with similar efficacy levels, with a 20 ,g once-daily dose of lixisenatide demonstrating the best efficacy-to-tolerability ratio. This new, once-daily GLP-1 receptor agonist shows promise in the management of Type 2 diabetes to be defined further by ongoing long-term studies. [source] Initiating insulin therapy in elderly patients with Type 2 diabetes: efficacy and safety of lispro mix 25 vs. basal insulin combined with oral glucose-lowering agentsDIABETIC MEDICINE, Issue 11 2009B. H. R. Wolffenbuttel Abstract Aims, To compare starter insulins in the elderly subgroup of the DURABLE trial 24-week initiation phase. Methods, In a post-hoc analysis of the , 65 years subgroup enrolled in the DURABLE trial, we compared the safety and efficacy of lispro mix 25 (LM25: lispro 25%/insulin lispro protamine suspension 75%), n = 258, vs. glargine, n = 222, added to oral glucose-lowering agents. Results, Baseline glycated hemoglobin (HbA1c) was similar (LM25 8.7 ± 1.2, glargine 8.8 ± 1.1%, P = 0.612). At 24-weeks, LM25 patients had lower HbA1c (7.0 ± 0.9 vs. 7.3 ± 0.9%, P < 0.001), greater HbA1c reduction (,1.7 ± 1.2 vs. ,1.5 ± 1.1%, P < 0.001), and more patients reaching HbA1c < 7.0% (55.6 vs. 41.0%, P = 0.005). LM25 patients were on more insulin (0.40 ± 0.19 vs. 0.33 ± 0.19 u/kg/day, P < 0.001) and experienced more weight gain (3.6 ± 3.6 vs. 1.8 ± 3.2 kg, P < 0.001). Additionally, LM25-treated patients reported a higher mean overall hypoglycaemia rate than glargine patients (40.8 ± 47.6 vs. 31.1 ± 48.5 episodes/patient/year, P = 0.037), while nocturnal hypoglycaemia rates were similar. Over 24 weeks, incidence of severe hypoglycaemia was higher for LM25 (4.3% vs. 0.9%, P = 0.018); however, by 24-week endpoint incidence was similar (0.8% vs. 0.0%P = 0.125). Conclusions, In this elderly subgroup post-hoc analysis, LM25 demonstrated a lower endpoint HbA1c and a higher % of patients reaching HbA1c target of < 7.0%, but with more weight gain and higher rates of hypoglycaemia compared to glargine. [source] Long-term glycaemic control with metformin,sulphonylurea,pioglitazone triple therapy in PROactive (PROactive 17)DIABETIC MEDICINE, Issue 10 2009A. J. Scheen Abstract Aims, We assessed the long-term glycaemic effects and the safety profile of triple therapy with the addition of pioglitazone vs. placebo in patients with Type 2 diabetes treated with combined metformin,sulphonylurea therapy in the PROspective pioglitAzone Clinical Trial In macroVascular Events (PROactive). Methods, In a post-hoc analysis, we identified patients treated with metformin plus sulphonylurea combination therapy and not receiving insulin at baseline (n = 1314). In those patients, we compared the effects of pioglitazone (force-titrated to 45 mg/day, n = 654) vs. placebo (n = 660) on glycated haemoglobin (HbA1c) reduction, concomitant changes in medications and initiation of permanent insulin use (defined as daily insulin use for a period of , 90 days or ongoing use at death/final visit). Results, Significantly greater reductions in HbA1c and greater proportions of patients with HbA1c at target were noted with pioglitazone vs, placebo, despite a decrease in the use of other oral glucose-lowering agents. There was an approximate twofold increase in progression to permanent insulin use in the placebo group vs. the pioglitazone group: 31.1 vs. 16.1%, respectively, when added to combination therapy. The overall safety of the metformin,sulphonylurea,pioglitazone triple therapy was good. Conclusions, Intensifying an existing dual oral therapy regimen to a triple oral regimen by adding pioglitazone to the classical metformin,sulphonylurea combination resulted in sustained improvements in glycaemic control and reduced progression to insulin therapy. The advantages and disadvantages of adding pioglitazone instead of adding basal insulin should be assessed further. [source] | |||||||||||||||||||||||||||||||||||||||||||||||||