Is Long-Term Low-Dose Aspirin Therapy Associated with Renal Dysfunction in Patients with Type 2 Diabetes? JPAD2 Cohort Study

Background

Low-dose aspirin is widely recommended for patients at high risk for cardiovascular disease (CVD); however, it remains uncertain whether long-term treatment adversely affects renal function in patients with diabetes.We investigated whether long-term low-dose aspirin affects renal dysfunction in patients with diabetes.

Methods

We conducted a randomized controlled trial (RCT), the Japanese Primary Prevention of Atherosclerosis with Aspirin for Diabetes (JPAD) trial, to evaluate low-dose aspirin as primary prevention for CVD in patients with type 2 diabetes. We followed the patients with negative urine dipstick albumin of the JPAD trial in a cohort study after the RCT period was completed. Patients were randomly allocated to receive aspirin (81 mg or 100 mg daily, aspirin group) or no aspirin (no aspirin group). After the RCT, the treating physician decided whether to administer aspirin. We evaluated the incidence of positive urine dipstick albumin and annual changes in estimated glomerular filtration rate (eGFR).

Results

Positive urine dipstick albumin developed in 297 patients in the aspirin group (n = 1,075) and 270 patients in the no aspirin group (n = 1,098) during follow-up (median, 8.5 years). Intention-to-treat analysis showed low-dose aspirin did not increase the incidence of positive urine dipstick albumin (hazard ratio [HR], 1.17; 95% confidence interval [CI], 0.995–1.38). On-treatment analysis yielded similar results (HR, 1.08; 95% CI, 0.92–1.28). Multivariable analysis showed the incidence of positive urine dipstick albumin was higher among the elderly and those with elevated serum creatinine, high hemoglobin A1c, or high blood pressure; however, low-dose aspirin did not increase the risk of positive urine dipstick albumin. There were no significant differences in annual changes in eGFR between the groups (aspirin, −0.8 ± 2.9; no aspirin, −0.9 ± 2.5 ml/min/1.73m²/year).

Conclusion

Long-term low-dose aspirin does not affect eGFR and positive urine dipstick albumin in patients with type 2 diabetes.     

Is Cardiac Resynchronisation Therapy Proarrhythmic?

It is well established that cardiac resynchronisation therapy (CRT) using biventricular pacing prolongs survival by its effects on pump failure. The rate of sudden cardiac death in patients undergoing CRT, however, remains high. Animal and human studies have shown that reversal of normal sequence of myocardial activation during epicardial pacing, as applied during CRT, increases the transmural dispersion of repolarisation (TDR), a substrate for ventricular arrhythmias. Cohort studies in humans suggest that CRT has a differential effect on the arrhythmogenic substrate, antiarrhythmic in some and proarrhythmic in others. This review the focuses on the possibility that CRT may, under certain circumstances, promote arrhythmogenesis.     

Is Body Mass Index a Measure of Adiposity in Elderly Women?

Objective: To evaluate the accuracy of body mass index (BMI) as a predictor of body fat in elderly women. Research Methods and Procedures: A total of 1423 women aged 67 ± 5 (mean ± SD, range: 60 to 88) years were consecutively enrolled into the study. Fat mass (FM) was measured using DXA. Results: BMI explained 72.9% of FM variance (p < 0.0001), with a root mean square error of estimate (RMSE) of 3.5 kg. After standardization of RMSE on the dependent variable as RMSE%, the prediction error equaled 15%. BMI explained 54.8% of FM% variance (p < 0.0001), with an RMSE of 4.1%, corresponding to an RMSE% of 11%. Discussion: The relatively high RMSE% of the FM and FM%‐BMI associations caution against the use of BMI as an adiposity index in individual elderly women. However, an error corresponding to 11% of FM% may be accepted for population studies of body fat in elderly women.     

Is DL-Fenfluramine a Potentially Helpful Drug Therapy in Overweight Adolescent Subjects?

We have studied the therapeutic effects of two different doses (30 mg and 60 mg, twice daily) of DL-fen-fluramine (DL-F) in, respectively, prepuberal (11–13 years old) and adolescent subjects (14–17 years old). Sixty-eight obese subjects were recruited for this study (22 boys, 36 girls, aged 10–17 years old) with body mass index ranging from 24.5 to 44.0 kg/m², absolute weight ranging from 37.0 to 119.5 kg and % over IBW ranging from 122% to 260%. Results were compared to a placebo treated group of obese adolescent patients (n=17), 6 boys and 11 girls, aged 10–17 years old, BMI ranging from 26–44 kg/m², absolute weight 53.1 to 96.5 kg, and with 129% to 253% over IBW. In the DL-F-treated subjects most patients (n=41) had a continuous weight loss during 12 months but 27 individuals were unable to lose any additional weight after the initial 6 months of the trial. Taken together 65% of all patients lost weight during DL-F treatment (12 months) whereas only 17.4% of the placebo group lost a significant (>10% BMI) amount of excess weight. Also the placebo group had a higher withdrawal rate (57%) as compared with the DL-F-treated group (24%). There was a significant (p<0.05) decrease of the mean & SD of the BMI (at 6 and 12 months of therapy). No significant change of the BMI was observed for control group. Minor adverse side effects consisted of a brief period of drowsiness and dry mouth. Our findings indicated that the continuous administration of DL-Fenfluramine might help obese adolescent subjects adhere to a diet and to maintain the weight loss achieved without major or harmful adverse effects .     

Breeding without Breeding: Is a Complete Pedigree Necessary for Efficient Breeding?

Complete pedigree information is a prerequisite for modern breeding and the ranking of parents and offspring for selection and deployment decisions. DNA fingerprinting and pedigree reconstruction can substitute for artificial matings, by allowing parentage delineation of naturally produced offspring. Here, we report on the efficacy of a breeding concept called "Breeding without Breeding" (BwB) that circumvents artificial matings, focusing instead on a subset of randomly sampled, maternally known but paternally unknown offspring to delineate their paternal parentage. We then generate the information needed to rank those offspring and their paternal parents, using a combination of complete (full-sib: FS) and incomplete (half-sib: HS) analyses of the constructed pedigrees. Using a random sample of wind-pollinated offspring from 15 females (seed donors), growing in a 41-parent western larch population, BwB is evaluated and compared to two commonly used testing methods that rely on either incomplete (maternal half-sib, open-pollinated: OP) or complete (FS) pedigree designs. BwB produced results superior to those from the incomplete design and virtually identical to those from the complete pedigree methods. The combined use of complete and incomplete pedigree information permitted evaluating all parents, both maternal and paternal, as well as all offspring, a result that could not have been accomplished with either the OP or FS methods alone. We also discuss the optimum experimental setting, in terms of the proportion of fingerprinted offspring, the size of the assembled maternal and paternal half-sib families, the role of external gene flow, and selfing, as well as the number of parents that could be realistically tested with BwB.     

Is Antiretroviral Therapy Causing Long-Term Liver Damage? A Comparative Analysis of HIV-Mono-Infected and HIV/Hepatitis C Co-Infected Cohorts

The effects of highly active antiretroviral therapy (HAART) on progression of hepatic fibrosis in HIV-hepatitis C virus (HCV) co-infection are not well understood. Deaths from liver diseases have risen in the post-HAART era, yet some cross-sectional studies have suggested that HAART use is associated with improved fibrosis rates. In a retrospective cohort of 533 HIV mono-infected and 127 HIV/HCV co-infected patients, followed between January 1991 and July 2005 at a university-based HIV clinic, we investigated the relationship between cumulative HAART exposure and hepatic fibrosis, as measured by the aspartate aminotransferase-to-platelet ratio index (APRI). We used a novel methodological approach to estimate the dose-response relationship of the effect of HAART exposure on APRI. HAART was associated with increasing APRI over time in HIV/HCV co-infected patients suggesting that they may be experiencing cumulative hepatotoxicity from antiretrovirals. The estimated median change (95% confidence interval) in APRI per one year of HAART intake was of −0.46% (−1.61% to 0.71%) in HIV mono-infected compared to 2.54% (−1.77% to 7.03%) in HIV/HCV co-infected patients. Similar results were found when the direct effect of HAART intake since the last visit was estimated on the change in APRI. HAART use associated is with increased APRI in patients with HIV/HCV co-infection. Therefore treatment for HCV infection may be required to slow the growing epidemic of end-stage liver disease in this population.     

Is Peri-Operative Steroid Replacement Therapy Necessary for the Pituitary Adenomas Treated with Surgery? A Systematic Review and Meta Analysis

Background

Patients with pituitary adenomas usually receive “stress dose” steroids in the peri-operative peroids. Though randomized controlled trials(RCT) have not been performed to assess the necessity of steroid coverage, there are several studies that explained the changes of adrenal function during peri-operative peroids. The aim of the present study is to investigate whether it is necessary to employ conventional peri-operative glucocorticoid replacement therapy to all the patients undergoing surgery.

Methods

We searched studies addressing peri-operative steroids coverage for pituitary adenomas in the Web of Science, Medline and the Cochrane Library. Then we extracted studies about peri-operative morning serum cortisol(MSC) levels, morbidity of early postoperative adrenal insufficiency, postoperative diabetes insipidus, relationships between MSC levels and adrenal integrity. We used RevMan Software to combine the results for meta-analysis. We used fixed-effects models for there was no significant heterogeneity existed.

Findings

There are 18 studies from 11 countries published between 1987 and 2013 including 1224 patients. The postoperative serum cortisol levels were significantly increased compared with the preoperative one in hypothalamic-pituitary-adrenal axis(HPAA) functions preserved patients(P<0.00001). The morbidity of early postoperative adrenal insufficiency ranged from 0.96% to 12.90%, with the overall morbidity of 5.55%(41/739). There was no significant differences of early postoperative diabetes insipidus between no supplementation patients and in supplementation patients(P=0.82). Conversely, there may be some disadvantages of high levels of cortisols such as high incidence of osteopenia and bone derangement and even the increased mortality rate. The patients with MSC levels of less than 60 nmol/l at 3 days after operation is considered as adrenal insufficient and more than 270 nmol/l as adrenal sufficient. To patients with MSC levels of 60–270 nmol/l, we need more clinical data to establish further cortisol supplementation criteria.     

Are Additional Trace Elements Necessary in Total Parenteral Nutrition for Patients with Esophageal Cancer Receiving Cisplatin-Based Chemotherapy?

It is known that cisplatin induces the excretion of zinc from the urine and thereby reduces its serum concentration. However, the fluctuation of these trace elements during or after cisplatin-based chemotherapy has not been evaluated. To answer this question, we performed a clinical study in esophageal cancer patients undergoing cisplatin-based chemotherapy. Eighteen patients with esophageal cancer who were not able to swallow food or water orally due to complete stenosis of the esophagus were evaluated. The patients were divided into a control group [total parenteral nutrition (TPN) alone for 28?days, ten cases] and an intervention group (TPN with additional trace elements for 28?days, eight cases). The serum concentrations of zinc, iron, copper, manganese, triiodothyronin (T3), and thyroxin (T4), as alternative indicators of iodine, were measured on days?0, 14, and 28 of treatment, and statistically analyzed on day?28. In the control group, the serum concentration of copper was significantly decreased from 135.4 (day?0) to 122.1???g/ml (day?14), and finally to 110.6???g/ml (day?28, p?=?0.015). The concentration of manganese was also significantly decreased from 1.34 (day?0) to 1.17???g/ml (day?14) and finally to 1.20 (day?28, p?=?0.049). The levels of zinc, iron, T3, and T4 were not significantly changed. In the intervention group, the supplementation with trace elements successfully prevented these decreases in their concentrations. TPN with supplementary trace elements is preferable and recommended for patients who are undergoing chemotherapy in order to maintain the patients?? nutrient homeostasis.     

Is Liraglutide A Useful Addition to Diabetes Therapy?

ObjectiveTo evaluate liraglutide as an antidiabetic agent.MethodsThe pertinent English-language medical literature was reviewed for the period from 1985 to April 2010 with use of data from MEDLINE.ResultsLiraglutide is a glucagonlike peptide-1 receptor analogue that stimulates insulin secretion, reduces postprandial glucagon release, causes a mild delay in gastric emptying, and may slightly decrease appetite. Mean reductions in hemoglobin A1c levels with liraglutide therapy range from 1.0% to 1.5% in comparison with baseline and are 1.0% and 1.3% in comparison with placebo. Head-to-head trials suggest that liraglutide may be more effective than glimepiride, rosiglitazone, insulin glargine, and exenatide. Some of the previous trials, however, are limited by use of submaximal doses of comparator drugs and an open-label design. The use of liraglutide is associated with a mean weight loss of 0.2 to 3.2 kg relative to baseline and 0.1 to 2.6 kg relative to placebo. Liraglutiderelated hypoglycemia is generally mild, but its incidence and severity substantially increase in conjunction with sulfonylureas. Gastrointestinal adverse effects such as nausea, diarrhea, or vomiting occurred in 44% to 56% of patients who received liraglutide versus 17% to 19% with placebo. Premature withdrawal from trials occurred in 4% to 15% of liraglutide-treated patients (mainly attributable to gastrointestinal adverse effects), in comparison with 3% to 5% of those receiving placebo.ConclusionThe 2 main advantages of liraglutide are mild degrees of weight loss and hypoglycemia. Important limitations, however, are the frequent occurrence of gastrointestinal adverse effects, the requirement of subcutaneous injection once daily, and the lack of long-term efficacy and safety data. Liraglutide may be a useful add-on therapy in patients with type 2 diabetes uncontrolled with metformin, when hypoglycemia, weight gain, or both are major concerns. (Endocr Pract. 2010;16:1028-1037)     

Group I mGluRs and Long-Term Depression: Potential Roles in Addiction?

Addiction is an enormous societal problem. A number of recent studies have focused on adaptations at glutamatergic synapses that may play a role in the behavioral responses to drugs of abuse. These studies have largely focused on NMDA receptor-dependent forms of synaptic plasticity such as NMDA receptor-dependent long-term potentiation (LTP) and long-term depression (LTD). A growing body of evidence, however, suggests that metabotropic glutamate receptors (mGluRs) also play important roles in the behavioral responses to drugs of abuse and participate in producing synaptic plasticity at glutamate synapses. In this review, we focus first on the evidence supporting a role for mGluRs in addiction and then on the properties of mGluR-dependent forms of synaptic plasticity, focusing in particular on Gq-linked receptor-induced LTD.     

Is Large Body Size always Advantageous for Terrestrial Adaptation?

Sesarmops intermedium de Haan (1835) is a semi-terrestrial crab inhabiting the areas around a forest creek at Heng-chun Peninsula in southern Taiwan. Small and large individuals excavate tunnels near the waterline, while those individuals with medium body size are more distant from the water. This unusual distribution pattern might reflect the habitat preference related to physiological requirement of crabs with different body sizes. In natural conditions, the animals keep their haemolymph osmolality at a relatively low level near those of fully-rehydrated individuals. In dehydrated conditions, the haemolymph osmolality of the animal was much higher and was negatively related to the body size. Both the rates of water loss and uptake decrease with increasing body size. While, both the potential time exposed in air and the rehydration time increase with increasing body size. The low water loss rate of large individuals may prolong the potential time exposed in air, but this advantage may be offset by their low efficiency in water uptake simultaneously. Small crabs, with a high water uptake rate and a small amount of water requirement, may have a shorter time needed for rehydration. However, those small crabs, smaller than about 2 g in living weight, due to their extremely fast loss of body water, have to access water more frequently and thus have a lower potential for terrestrial activity also. For medium sized crabs, the advantages of high water uptake rate, less water requirement and better ability to utilize interstitial water may allow them to emancipate from the water body. Due to the constraints of performance in water balance, the optimum size for extending terrestrial activity of S. intermedium is below 14 g in weight (=28.5 mm in carapace width) at which the crabs may have a higher potential for terrestrial activity. In the terrestrial adaptation regarding the water balance of S. intermedium, how to increase water uptake efficiency and the capability to use various interstitial water on land seem to be more important than how to reduce the water loss rate. Large body size and hence the low water loss rate may not be always advantageous for the terrestrial adaptation of S. intermedium and possibly other crustaceans.     

Is Repeat Biopsy for Isolated High-Grade Prostatic Intraepithelial Neoplasia Necessary?

Numerous studies have cited the positive predictive value of isolated highgrade prostatic intraepithelial neoplasia (HGPIN) to the detection of cancer. Epidemiological, morphological, and molecular data support the potential for malignant transformation of HGPIN, yet no current method can discriminate which lesions will progress to clinically significant prostate cancer versus more latent lesions. Recent analyses of multiple retrospective studies have found similar rates of cancer detection following either diagnosis of isolated HGPIN or an initial negative biopsy. This may reflect increased use of extended biopsy techniques involving 10 or more cores rather than the true ability of HGPIN to undergo malignant transformation. This article discusses controversies surrounding management of an isolated diagnosis of HGPIN and whether repeat biopsy of HGPIN should be mandatory or selective in the context of other predictive values such as rising prostate-specific antigen or lesion on digital rectal examination.     

Is the Medial Prefrontal Cortex Necessary for Theory of Mind?

Background

Successful social interaction relies on the ability to attribute mental states to other people. Previous functional neuroimaging studies have shown that this process, described as Theory of Mind (ToM) or mentalization, is reliably associated with activation of the medial prefrontal cortex (mPFC). However, this study presents a novel and surprising finding that provides new insight into the role of the mPFC in mentalization tasks.

Methodology/Principal Findings

Twenty healthy individuals were recruited from a wide range of ages and social backgrounds. Participants underwent functional magnetic resonance imaging (fMRI) while viewing a well-established ToM visual paradigm involving moving triangles. Functional MRI data were analyzed using a classical general linear model. No activation was detected in the medial prefrontal cortex (mPFC) during movement patterns that typically elicit ToM. However, increased activity was observed in the right middle occipital gyrus, right temporoparietal junction (TPJ), left middle occipital gyrus and right inferior frontal gyrus. No correlation was found between participants’ age and BOLD response.

Conclusions/Significance

In contrast with previous neuroimaging research, our findings support the notion that mPFC function is not critical for reasoning about the mental states of others; furthermore, our data indicate that the right TPJ and right inferior frontal gyrus are able to perform mentalization without any contributions from the mPFC.     

Is Zooplankton Body Size an Indicator of Water Quality in (Sub)tropical Reservoirs in China?

Ecosystems - Large zooplankton can efficiently graze on algae and thereby improve water quality. However, zooplankton body size is considered to decrease with decreasing latitude because of the...