Identifying the cognitive underpinnings of voice-hearing by comparing never, past and current voice-hearers.

OBJECTIVE: The current study aimed to compare specific cognitive profiles corresponding to auditory verbal hallucinations (AVH) status and elucidate which pattern of cognitive deficits may predict voice-hearing status. METHOD: Clinical participants with schizophrenia spectrum disorders were partitioned into: (i) current voice-hearers (n = 46), (ii) past voice-hearers (n = 37) and (iii) never voice-hearers (n = 40), and compared with 319 non-clinical controls. Cognitive assessment employed the MATRICS Consensus Cognitive Battery (MCCB), supplemented by the Delis-Kaplan Executive Function System (D-KEFS) Colour-Word Interference Test (Stroop) as a robust measure of executive function. RESULTS: On the Visual Learning domain, current and past voice-hearers had significantly poorer performance relative to never voice-hearers, who in turn had significantly poorer performance than non-clinical controls. Current and never voice-hearers had significantly poorer performance on the Social Cognition domain relative to non-clinical controls. Current voice-hearers also had significantly poorer performance on the Inhibition domain relative to non-clinical controls. Binary logistic regression revealed that Visual Learning was the only significant cognitive predictor of AVH presence. CONCLUSION: Visual learning, and potentially inhibition, may be viable therapeutic targets when addressing cognitive mechanisms associated with AVHs. Future research should focus on investigating additional cognitive mechanisms, employing diverse voice-hearing populations and embarking on related longitudinal studies.

Inguinal and Ilio-inguinal Lymphadenectomy in Management of Palpable Melanoma Lymph Node Metastasis: A Long-Term Prospective Evaluation of Morbidity and Quality of Life.

PURPOSE: Prospective data are lacking on long-term morbidity of inguinal lymphadenectomy including the influence of extent of surgery, use of radiotherapy, and patient factors. The aim of this study is to evaluate the effects of these factors on patient outcome, quality of life (QOL), regional symptoms, and limb volumes after inguinal or ilio-inguinal lymphadenectomy for melanoma. METHODS: Analysis of the subgroup of patients with inguinal lymph node field relapse of melanoma, treated by inguinal or ilio-inguinal lymphadenectomy in the ANZMTG/TROG randomized trial of adjuvant radiotherapy versus observation. RESULTS: Sixty-nine patients, 46 having undergone inguinal and 23 ilio-inguinal lymphadenectomy, with median follow-up of 73 months were analyzed. Mean limb volume increased rapidly after surgery (7% by 3 months) and continued to increase for at least another 18 months. Patients with body mass index (BMI) ≥ 25 kg/m2 had greater limb volume increase than normal-weight patients (13.3% versus 6.9%, P = 0.030). QOL improved over the first 18 months, but despite initial improvement, regional symptoms persisted long term. Type of surgery (inguinal or ilio-inguinal lymphadenectomy) had no demonstrably significant effect on limb volume (9.9% versus 13.4%, P = 0.35), QOL (P = 0.68), or regional symptoms (P = 0.65). There was no difference in overall survival between inguinal and ilio-inguinal lymphadenectomy [hazard ratio (HR) 0.75, 95% confidence interval (CI) 0.40-1.40, P = 0.43]. CONCLUSIONS: Inguinal lymphadenectomy for melanoma is a potentially morbid procedure with significant increases in limb volume. Patients report reasonable QOL but may have ongoing regional symptoms. Overweight/obesity is associated with poorer QOL, increased limb volume, and regional symptoms.

Prospective randomized trial of neoadjuvant chemotherapy during the 'wait period' following preoperative chemoradiotherapy for rectal cancer: results of the WAIT trial.

AIM: The aim was to determine whether the addition of additional cycles of chemotherapy during the 'wait period' following neoadjuvant chemoradiotherapy for rectal cancer improves the pathological complete response (pCR) rate. METHOD: Rectal cancer patients were randomly allocated either to a standard 10 week wait period before surgery (standard chemoradiotherapy, SCRT) or to receive three cycles of fluorouracil based chemotherapy following chemoradiotherapy during a similar 10 week wait (extended chemoradiotherapy, XCRT). The primary end-point was pCR as determined by blinded pathological assessment. RESULTS: Forty-nine patients were randomized (SCRTn = 24, XCRTn = 25). pCR occurred in 10 patients overall but there was no significant difference in pCR between the groups (SCRTn = 6, XCRTn = 4, P = 0.49). CONCLUSION: The addition of three cycles of 5-fluorouracil/leucovorin in a 10 week wait period after conventional chemoradiotherapy seems to result in similar pCR rates in patients with locally advanced rectal cancer based on this small randomized trial.

The 2010 Canadian Hypertension Education Program recommendations for the management of hypertension: part 2 - therapy.

OBJECTIVE: To update the evidence-based recommendations for the prevention and treatment of hypertension in adults for 2010. OPTIONS AND OUTCOMES: For lifestyle and pharmacological interventions, randomized trials and systematic reviews of trials were preferentially reviewed. Changes in cardiovascular morbidity and mortality were the primary outcomes of interest. However, for lifestyle interventions, blood pressure lowering was accepted as a primary outcome given the general lack of long-term morbidity and mortality data in this field. Progressive renal impairment was also accepted as a clinically relevant primary outcome among patients with chronic kidney disease. EVIDENCE: A Cochrane Collaboration librarian conducted an independent MEDLINE search from 2008 to August 2009 to update the 2009 recommendations. To identify additional studies, reference lists were reviewed and experts were contacted. All relevant articles were reviewed and appraised independently by both content and methodological experts using prespecified levels of evidence. RECOMMENDATIONS: For lifestyle modifications to prevent and treat hypertension, restrict dietary sodium to 1500 mg (65 mmol) per day in adults 50 years of age or younger, to 1300 mg (57 mmol) per day in adults 51 to 70 years of age, and to 1200 mg (52 mmol) per day in adults older than 70 years of age; perform 30 min to 60 min of moderate aerobic exercise four to seven days per week; maintain a healthy body weight (body mass index 18.5 kg/m(2) to 24.9 kg/m(2)) and waist circumference (less than 102 cm for men and less than 88 cm for women); limit alcohol consumption to no more than 14 standard drinks per week for men or nine standard drinks per week for women; follow a diet that emphasizes fruits, vegetables and low-fat dairy products, dietary and soluble fibre, whole grains and protein from plant sources, and that is low in saturated fat and cholesterol; and consider stress management in selected individuals with hypertension. For the pharmacological management of hypertension, treatment thresholds and targets should be predicated on the patient's global atherosclerotic risk, target organ damage and comorbid conditions. Blood pressure should be decreased to less than 140/90 mmHg in all patients, and to less than 130/80 mmHg in patients with diabetes mellitus or chronic kidney disease. Most patients will require more than one agent to achieve these target blood pressures. Antihypertensive therapy should be considered in all adult patients regardless of age (caution should be exercised in elderly patients who are frail). For adults without compelling indications for other agents, considerations for initial therapy should include thiazide diuretics, angiotensin- converting enzyme (ACE) inhibitors (in patients who are not black), long-acting calcium channel blockers (CCBs), angiotensin receptor blockers (ARBs) or beta-blockers (in those younger than 60 years of age). A combination of two first-line agents may also be considered as initial treatment of hypertension if systolic blood pressure is 20 mmHg above target or if diastolic blood pressure is 10 mmHg above target. The combination of ACE inhibitors and ARBs should not be used, unless compelling indications are present to suggest consideration of dual therapy. Agents appropriate for first-line therapy for isolated systolic hypertension include thiazide diuretics, long-acting dihydropyridine CCBs or ARBs. In patients with coronary artery disease, ACE inhibitors, ARBs or betablockers are recommended as first-line therapy; in patients with cerebrovascular disease, an ACE inhibitor/diuretic combination is preferred; in patients with proteinuric nondiabetic chronic kidney disease, ACE inhibitors or ARBs (if intolerant to ACE inhibitors) are recommended; and in patients with diabetes mellitus, ACE inhibitors or ARBs (or, in patients without albuminuria, thiazides or dihydropyridine CCBs) are appropriate first-line therapies. In selected high-risk patients in whom combination therapy is being considered, an ACE inhibitor plus a long-acting dihydropyridine CCB is preferable to an ACE inhibitor plus a thiazide diuretic. All hypertensive patients with dyslipidemia should be treated using the thresholds, targets and agents outlined in the Canadian lipid treatment guidelines. Selected patients with hypertension who do not achieve thresholds for statin therapy, but who are otherwise at high risk for cardiovascular events, should nonetheless receive statin therapy. Once blood pressure is controlled, low-dose acetylsalicylic acid therapy should be considered. VALIDATION: All recommendations were graded according to the strength of the evidence and voted on by the 63 members of the Canadian Hypertension Education Program Evidence-Based Recommendations Task Force. All recommendations reported here achieved at least 80% consensus. These guidelines will continue to be updated annually. SPONSORS: The Canadian Hypertension Education Program process is sponsored by the Canadian Hypertension Society, Blood Pressure Canada, the Public Health Agency of Canada, the College of Family Physicians of Canada, the Canadian Pharmacists Association, the Canadian Council of Cardiovascular Nurses, and the Heart and Stroke Foundation of Canada.

A truncated erythropoietin receptor EPOR-T is associated with hypertension susceptibility.

Erythropoietin (EPO) and its analogs increase blood pressure (BP) in susceptible patients. The ratio of truncated to full EPO receptors (EPORs) in endothelial progenitor cells harvested from anemic patients receiving EPO while undergoing hemodialysis is related to the increased BP observed in these patients. Truncated EPORs exert a hypertensive effect by opposing full EPOR stimulation that augments cyclic guanosine monophosphate (GMP) in vascular endothelium. The contribution of this discovery to clinical practice is debatable.

Association of TCF7L2 polymorphism with diabetes mellitus, metabolic syndrome, and markers of beta cell function and insulin resistance in a population-based sample of Emirati subjects.

AIMS: The prevalence of type 2 diabetes mellitus (DM) among Emirati subjects is one of the highest in the world. This has been attributed to rising prevalence of obesity acting on genetically susceptible individuals. We analyzed the associations between TCF7L2 polymorphism and DM, metabolic syndrome, and markers of beta cell function and insulin resistance in a population-based sample of Emirati subjects. METHODS: We genotyped the two TCF7L2 single nucleotide polymorphisms (SNPs) rs12255372 and rs7903146 in 368 adult subjects. Homeostatic model assessment (HOMA) was used to assess beta cell function (HOMA2-%B) and insulin resistance (HOMA2-IR). The SNP genotypes were analyzed against disease stage [normal glucose=0 (n=188), pre-diabetes=1 (n=85), and DM=2 (n=95)] and against clinical and biochemical measures. Age and sex were included as covariates in all association analyses. Additional adjustments were made for body mass index (BMI) and waist circumference in several analyses. RESULTS: Diabetes disease stage was marginally significantly associated with the frequency of the T variant at rs12255372 (p=0.057; adjusted p=0.017) but not at rs7903146 (p=0.5; adjusted p=0.2). Comparison between subjects with normal glucose and the combined DM/pre-diabetes showed a significant association with rs12255372 (OR 1.47, CI 1.04-2.08; p=0.03) but not with rs7903146 (OR 1.16, CI 0.81-1.64; p=0.4). We found no association with metabolic syndrome, or with insulin and glucose levels, HOMA2-%B or HOMA2-IR. The age-standardized prevalence rate for metabolic syndrome was 43.9% in men and 42.1% in women. CONCLUSION: These data suggest that TCF7L2 variants are associated with increased risk for DM in Emirati subjects. We also demonstrate a high prevalence of the metabolic syndrome in this population.

Prevalence of diabetes mellitus and its complications in a population-based sample in Al Ain, United Arab Emirates.

AIMS: To determine the prevalence of diabetes mellitus (DM) and its complications in the adult population of the United Arab Emirates (UAE) and assess the degree of metabolic control in subjects with diagnosed DM. METHODS: A random sample of houses of Emirati citizens living in Al Ain, UAE was surveyed. Fasting blood glucose was determined by glucose meter and an oral glucose tolerance test (OGTT) was conducted if blood sugar was <7 mmol/l. DM was defined according to the WHO criteria. Pre-diabetes status was based on fasting venous blood glucose concentration of 5.6-6.9 mmol/l or 2h post-OGTT venous blood glucose level of 7.8-11.0 mmol/l. RESULTS: There were 2455 adults (>18) living in the 452 surveyed houses of which 10.2% reported having the diagnosis of DM. A total of 373 men and non-pregnant women underwent testing, and after adjustment for factors affecting participation probability the prevalence of diagnosed DM, undiagnosed DM and pre-diabetes was 10.5, 6.6 and 20.2%, respectively. Age-standardized rates for DM (diagnosed and undiagnosed) and pre-diabetes among 30-64 years old were 29.0 and 24.2%, respectively. Logistic regression analysis showed that only age and body mass index (BMI) were significantly independently related to undiagnosed DM. In patients with diagnosed DM, the prevalence rates for retinopathy, neuropathy, nephropathy, peripheral vascular disease and coronary heart disease were 54.2, 34.7, 40.8, 11.1 and 10.5%, respectively. A significant proportion of subjects with undiagnosed DM and pre-diabetes also had micro- and macro-vascular complications. The proportion of subjects with diagnosed DM who achieved internationally recognized targets for HbA1c (<7%), LDL-C (<2.6 mmol/l) and blood pressure (<130/80 mmHg) was 33.3, 30.8 and 42.1%, respectively. CONCLUSION: This study confirms the previously reported high prevalence of DM in the UAE. Diabetic complications were highly prevalent among subjects with diagnosed and undiagnosed DM. Metabolic control was suboptimal in most subjects with diagnosed DM. Greater efforts are urgently needed to screen early and effectively treat DM in the UAE in order to prevent long-term complications.

Persistence with teriparatide in patients with osteoporosis: the UK experience.

INTRODUCTION: The objective of this paper was to determine the persistence with teriparatide at 12 months in all patients in the UK who were prescribed the treatment since its launch. METHODS: Virtually all patients prescribed teriparatide in the UK receive treatment through Healthcare at Home, Basingstoke, UK. Data was obtained to assess the start date, discontinuation date and reason for discontinuation in all patients receiving teriparatide since its launch. Persistence was defined as the number of patients continuing treatment. RESULTS: A total of 1,104 patients were included in the analysis. The median duration of use in all patients was 252 days. Of the 435 patients who were at least 12 months post-initiation of treatment, persistence was 87%. Forty-two patients (3.8%) had discontinued treatment due to adverse events. CONCLUSIONS: This study demonstrates that persistence with teriparatide at 12 months is very high and is probably greater than that of existing oral therapies for osteoporosis. The reasons for the high persistence rates seen with teriparatide are likely to be multi-factorial. The high persistence rates should help to optimise the effectiveness of therapy in this group of high-risk patients.

Total body irradiation and pneumonitis risk: a review of outcomes.

A review was undertaken of all patients treated at Royal Adelaide Hospital, South Australia with total body irradiation (TBI) for the purpose of assessing the incidence of interstitial pneumonitis (IP) and possible prognostic factors for its development. The aim was also to assess the impact of IP and other prognostic factors on long-term survival outcome following bone marrow transplantation. A total of 84 patients received TBI, with 12 Gy in six fractions delivered using two different instantaneous dose rates of 7.5 and 15 cGy min(-1). This series included 26 cases of acute lymphoblastic leukaemia, 26 of multiple myeloma and 15 of acute myelogenous leukaemia. On multivariate analysis, a higher dose rate was independently significant for an increased risk of IP.

Induced sputum: time from expectoration to processing.

One of the limitations in the use of induced sputum to measure indices of airway inflammation is the perceived need to process the sample within 2 h. Therefore, the authors investigated whether the processing of induced sputum could be delayed. Induced sputum samples obtained from asthmatic subjects (n=30) were examined. Each sample was stored at 4 degrees C. A portion was selected and processed within 2 h and the remaining expectorate (sputum plus saliva) was refrigerated. Later an equal amount was selected and processed at either 9 (n=15) or 18 (n=15) h. The sputum was examined for cell counts and viability, fluid-phase eosinophil cationic protein (ECP), interleukin-8 (IL-8) and fibrinogen. Repeatability of measurements was assessed by the interclass correlation coefficient (ICC). Measurements obtained at 9 h did not differ from those made at 2 h and the repeatability was excellent (ICC 0.88-0.99). However, by 18 h the median cell viability was reduced from 65.0% to 43.0% and the ICC was generally lower: 0.10 for total cell count, 0.24 for viability, 0.60 for neutrophils, 0.90 for eosinophils, 0.56 for macrophages, 0.76 for ECP, 0.82 for IL-8 and 0.84 for fibrinogen. The results indicate that when induced sputum from subjects with asthma is kept at 4 degrees C, examination of cell counts can be delayed for < or = 9 h and for the fluid-phase indices measured for < or = 18 h. Further investigation of this issue is required for spontaneous sputum, other airway diseases and other inflammatory markers.

Increased detection of interleukin-5 in sputum by addition of protease inhibitors.

The measurement of interleukin (IL)-5 in sputum is problematic, with interfering factors affecting immunoassay. The authors investigated whether sputum proteases could be acting as interfering factors by studying the effect of protease inhibitors (PI) on sputum IL-5 measurement. Induced sputa from 20 subjects with asthma were divided into aliquots, processed with and without protease inhibitors (in low and high concentrations) and the levels of IL-5 (spiked and endogenous) measured by enzyme immunoassay were compared. The concentration of sputum IL-5 was significantly increased by PI, with median (interquartile range) levels processed with no, low and high PI concentrations being 0 (0), 41.8 (75.6) and 66.1 (124.4) pg x mL(-1), respectively. There was also a significant increase in percentage recovery of spiked IL-5. Although high concentrations of PI reduced cell viability, there was no effect on total or differential cell counts and low concentrations of PI had no effect on cell counts or viability. Levels of endogenous interleukin-5 in sputum of asthmatic subjects can be significantly increased by the addition of protease inhibitors, and samples which would be regarded as negative for interleukin-5 without protease inhibitors may instead have considerable amounts of interleukin-5 detected.