Prevalence, risk factors and evolution of diabetes mellitus after treatment in primary aldosteronism. Results from the SPAIN-ALDO registry.

PURPOSE: To evaluate the prevalence, risk factors and evolution of diabetes mellitus (DM) after targeted treatment in patients with primary aldosteronism (PA). METHODS: A retrospective multicenter study of PA patients in follow-up at 27 Spanish tertiary hospitals (SPAIN-ALDO Register). RESULTS: Overall, 646 patients with PA were included. At diagnosis, 21.2% (n = 137) had DM and 67% of them had HbA1c levels < 7%. In multivariate analysis, family history of DM (OR 4.00 [1.68-9.53]), the coexistence of dyslipidemia (OR 3.57 [1.51-8.43]) and advanced age (OR 1.04 per year of increase [1.00-1.09]) were identified as independent predictive factors of DM. Diabetic patients were on beta blockers (46.7% (n = 64) vs. 27.5% (n = 140), P < 0.001) and diuretics (51.1% (n = 70) vs. 33.2% (n = 169), p < 0.001) more frequently than non-diabetics. After a median follow-up of 22 months [IQR 7.5-63.0], 6.9% of patients developed DM, with no difference between those undergoing adrenalectomy and those treated medically (HR 1.07 [0.49-2.36], p = 0.866). There was also no significant difference in the evolution of glycemic control between DM patients who underwent surgery and those medically treated (p > 0.05). CONCLUSION: DM affects about one quarter of patients with PA and the risk factors for its development are common to those of the general population. Medical and surgical treatment provides similar benefit in glycemic control in patients with PA and DM.

Effects of direct-fed Bacillus subtilis and Bacillus licheniformis on production performance and milk fatty acid profile in dairy cows.

The aim of the study was to determine the effect of a Bacillus-based direct-fed microbial on performance of mid-lactating Holstein dairy cows and on their milk fatty acid composition. Six multiparous cows fitted with a rumen cannula were used in a randomized replicated crossover design. Cows received 200 g/d of either whey powder as a control or BioPlus 2B (Chr. Hansen), a commercial direct-fed microbial providing Bacillus subtilis and Bacillus licheniformis, representing a daily dose of 6.4 × 1011 cfu, and using whey powder as a carrier. The 2 experimental periods lasted 14 d and were separated by a 7-d washout interval. Samples were collected on d 0, 13, and 14 of each period. Data from d 0 were used as covariate. Significance was declared at P ≤ 0.05 and tendency at 0.05

Effects of lorcaserin on fat and lean mass loss in obese and overweight patients without and with type 2 diabetes mellitus: the BLOSSOM and BLOOM-DM studies.

Body composition was determined using dual-energy X-ray absorptiometry (DXA) in a subset of patients without (BLOSSOM) and with (BLOOM-DM) type 2 diabetes who received diet and exercise counselling along with either lorcaserin 10 mg twice daily or placebo. DXA scans were performed on study day 1 (baseline), week 24 and week 52. Baseline demographics of the subpopulations (without diabetes, n = 189; with diabetes, n = 63) were similar between studies and representative of their study populations. At week 52, patients without diabetes on lorcaserin lost significantly more fat mass relative to those on placebo (-12.06% vs -5.93%; p = 0.008). In patients with diabetes, fat mass was also decreased with lorcaserin relative to placebo (-9.87% vs -1.65%; p < 0.05). More fat mass was lost in the trunk region with lorcaserin compared with placebo (without diabetes: -3.31% vs -2.05%; with diabetes: -3.65% vs -0.36%). Weight loss with lorcaserin was associated with a greater degree of fat mass loss than lean mass loss, and most of the fat mass lost for patients without and with diabetes was from the central region of the body.

Irrigation and phosphorous fertilization management to minimize rice grain arsenic content.

This research sought to minimize inorganic arsenic levels in polished rice grain by using different irrigation and phosphorous fertilization practices while also maintaining crop yield and water productivity. Two experiments were conducted during seasons 2018-2019 and 2019-2020 using a split-plot design with three blocks, five irrigation treatments (main-plots) and two phosphorous levels (sub-plots). Irrigation treatments consisted of a traditional continuous flood (CF) control and four alternatives irrigation techniques with one or two drying events during the irrigation cycle. The phosphorous fertilization levels investigated were an unfertilized control (0 kg P2O5 ha-1) and the recommended fertilization level of 50 kg P2O5 ha-1. Soil pH and redox potentials were measured in each treatment. Strategically-timed, low severity drying events were effective at achieving aerobic soil conditions, resulting in Eh values over 50 mV. The alternative irrigation treatment with two drying events, implemented at panicle initiation and full flowering, was the most effective in reducing inorganic arsenic in grain without affecting grain yield or the amount of irrigation water applied. This irrigation technique could be considered as an alternative management to the traditional continuous flooded to reach minimal inorganic arsenic accumulation in grain in order to attend special quality standards or specific market requirements. Accumulated inorganic arsenic in grain was below international maximum levels in all analyzed samples, with an average value of 0.084 mg kg-1.

Genotoxicity of swine effluents.

This study aimed at the investigation of genotoxic effects of swine effluents from different stages of a treatment system for swine wastes through bioassay of stamen hairs and micronuclei in Tradescantia (clone BNL 4430). No significant differences (p≥0.05) regarding the genic mutations were found in the bioassay of stamen hairs, independently of the effluent analysed. For the genotoxicity test with micronuclei, the plants exposed to raw wastes, to sludge, and to effluent of the biodigester have presented higher rates of chromosomal damages (micronuclei), with significant differences in relation to the control group and other effluent of the waste treatment system (p≤0.05). The association between the chemical parameters and the genotoxicity data have shown that the variables COD and TKN have presented significant correlation (p≤0.05) with the number of mutagenic events in the tetrads.

Adjunctive rufinamide in Lennox-Gastaut syndrome: a long-term, open-label extension study.

OBJECTIVE: This open-label extension evaluated the long-term efficacy and tolerability of rufinamide in patients with Lennox-Gastaut syndrome (LGS) who had previously completed a 12-week double-blind study. MATERIALS AND METHODS: In total, 124 patients (aged 4-37 years), receiving 1-3 concomitant antiepileptic drugs, were treated with rufinamide approximately 25-60 mg/kg/day. Efficacy was assessed by seizure frequency; tolerability by adverse events (AEs) and laboratory tests. RESULTS: Overall, patients were treated with rufinamide for a median (range) of 432 (10-1149) days. Reductions in seizure frequency were observed throughout the study; during the last 12 months of treatment, 41.0% and 47.9% of patients had > or = 50% reduction in total and tonic-atonic seizure frequency, respectively. The most common AEs were vomiting (30.6%) and pyrexia (25.8%). CONCLUSIONS: In this open-label extension, rufinamide appeared to be an effective long-term adjunctive therapy for the treatment of LGS-associated seizures in children and young adults.

Effect of lorcaserin on weight reduction in persons with obstructive sleep apnea (OSA): a combined subgroup analysis from three randomized, controlled clinical trials.

STUDY OBJECTIVES: To evaluate weight loss with lorcaserin in persons with obstructive sleep apnea (OSA). METHODS: This retrospective analysis evaluated weight loss of lorcaserin (10 mg twice daily) versus placebo in persons with obesity or overweight persons with OSA from a pooled database of three randomized, controlled trials. Primary end points were reductions in the baseline body weight of ≥5% and ≥10% at year 1 and overall weight change at year 1. Changes in heart rate and blood pressure were also evaluated. RESULTS: A total of 336 persons with OSA were identified in the overall pooled population (N = 6,636). At year 1, more patients receiving lorcaserin lost ≥5% (47.2% lorcaserin vs. 25.6% placebo; p < 0.0001) and 10% (22.2% lorcaserin vs. 13.1% placebo; p < 0.0354) of their baseline body weight. Weight loss at year 1 was 6.4 kg versus 3.5 kg in the lorcaserin and placebo groups, respectively (p < 0.0001). Similar results were observed for change in blood pressure and heart rate, with responders having larger benefits. Weight loss was similar between persons with and without OSA. CONCLUSIONS: In this retrospective analysis, persons with OSA showed significant and meaningful weight loss, blood pressure and heart rate reductions in patients treated with lorcaserin versus placebo. Persons with OSA lost just as much weight as those without OSA. Health care providers can expect persons with OSA to lose weight by diet, exercise and the weight loss medication lorcaserin comparable with persons without OSA. Further prospective research is warranted to evaluate impact of weight loss on OSA and overall outcomes for patients.

Effect of lorcaserin in different age groups: a post hoc analysis of patients from the BLOOM, BLOSSOM and BLOOM-DM studies.

INTRODUCTION: The elderly population is projected to be the fastest growing group of individuals with obesity group in the United States. As such, there is merit in examining factors that contribute to healthy aging and weight management. The effects of newer weight loss medications approved after 2013 have been studied but are not often assessed specifically in older persons. METHODS: This post hoc analysis evaluated the magnitude of weight loss in adults across age quartiles with lorcaserin, a serotonin (5-HT) 2C receptor agonist indicated as an adjunct to a reduced-caloric diet and increased physical activity for chronic weight management. Data from three lorcaserin pivotal phase 3 studies were used in this analysis. Data for patients with overweight/obesity without type 2 diabetes (T2D; BLOOM/BLOSSOM; body mass index [BMI] 27.0-29.9 kg/m2 and ≥1 comorbidity or BMI 30.0-45.0 kg/m2) and patients with overweight/obesity with T2D (BLOOM-DM; BMI 27.0-45.0 kg/m2) were used. Patients were randomized to receive lorcaserin 10 mg twice daily or placebo in addition to diet and exercise for 52 weeks. Age quartiles between the studies differed as the T2D population was on average, 9 years older. RESULTS: This analysis shows that lorcaserin was associated with improved weight loss relative to placebo regardless of age. Importantly, these results were consistent for patients with and without T2D. Interestingly, the magnitude of weight loss for lorcaserin appeared to increase with increasing age. In patients without T2D, odds of achieving ≥5% and ≥10% reduction in body weight at 52 weeks were significantly higher for patients >36 years. Lorcaserin was well tolerated in all patients across all quartiles including the oldest quartile. CONCLUSIONS: In summary, this post hoc analysis demonstrates that lorcaserin treatment in patients with and without T2D was safe and effective at reducing weight across all age groups analysed. Weight loss appeared to be greater for older patients; additional analyses are warranted to confirm these findings and to better understand the factors for improved weight loss.

Lorcaserin and metabolic disease: weight-loss dependent and independent effects.

OBJECTIVE: Weight management pharmacotherapies can improve metabolic diseases through weight-dependent and weight-independent effects. Lorcaserin is a selective 5-hydroxytryptamine 2C receptor agonist. The objective of this analysis is to quantify the relative contribution of weight loss to the treatment effects of lorcaserin 10 mg twice a day on key metabolic parameters. METHODS: This retrospective analysis evaluated 6,897 patients with overweight or obesity (with or without diabetes mellitus) across three randomized, placebo-controlled, double-blind, 52-week clinical trials that evaluated lorcaserin 10 mg twice daily (BID; NCT00395135, NCT00603902, and NCT00603291); 509 patients from only one of the studies had type 2 diabetes mellitus. A mediation analysis was applied to help rank the relative contribution of weight loss to metabolic study outcomes. RESULTS: According to this mediation analysis, lorcaserin 10 mg BID improved a spectrum of adiposopathic metabolic abnormalities with varying contributions attributable to weight loss. Improvements in waist circumference and blood pressure were almost exclusively attributable to weight loss. Less than 50% of the improvement in glucose parameters (fasting blood glucose and haemoglobin A1c) were attributable to weight loss. CONCLUSIONS: Across Phase III clinical trials, lorcaserin 10 mg BID improved multiple cardiometabolic parameters through both weight-loss dependent and independent mechanisms.

Spontaneous gastric rupture after Sodium Bicarbonate consumption: A case report.

Spontaneous gastric rupture is a rare condition however a prompt diagnosis and treatment are necessary to decrease mortality and morbidity. We report a case of stomach rupture after the ingestion of Sodium Bicarbonate (SB); imaging findings with a brief review of the literature are presented.

Pylephlebitis with splenic abscess following transrectal prostate biopsy: rare complications of intra-abdominal infection.

Pylephlebitis is a rare complication of intra-abdominal infection involving septic thrombosis of the portal system. If the splenic vein is compromised, this can lead to a splenic abscess, an extremely rare complication of pylephlebitis. The pathophysiology behind these clinical entities remains unclear. In both cases, symptoms are highly nonspecific and include fever, malaise and abdominal pain. Here, we discuss a case in which a patient develops both pylephlebitis and a subsequent splenic abscess following a transrectal prostate biopsy. Diagnosis was made by computerized tomography scan; the treatment included broad spectrum antibiotics and laparoscopic splenectomy, after which the patient made a full recovery.

Long-term prevention of erosive or ulcerative gastro-oesophageal reflux disease relapse with rabeprazole 10 or 20 mg vs. placebo: results of a 5-year study in the United States.

BACKGROUND: Erosive gastro-oesophageal reflux disease (GERD) is a chronic condition requiring long-term maintenance treatment. However, few trials of proton pump inhibitors in maintaining healing of erosive or ulcerative GERD are conducted for longer than 1 year. AIM: To compare the efficacy and safety of 10- and 20-mg rabeprazole with placebo in the 5-year maintenance of healing in patients previously diagnosed with erosive/ulcerative GERD healed in an acute efficacy trial. METHODS: Patients (N = 497) were randomized to receive once-daily doses of 10- or 20-mg rabeprazole or placebo. The primary efficacy measure was endoscopically documented absence of oesophageal erosions or ulcerations. RESULTS: After 5 years, relapse rates in both rabeprazole groups were significantly lower than with placebo (rabeprazole 20 mg, 11%; 10 mg, 23%; placebo, 63%; P < 0.001 for rabeprazole vs. placebo; P = 0.005 for rabeprazole 20 mg vs. 10 mg). Both rabeprazole doses were significantly superior to placebo in preventing relapse of heartburn frequency and improving patient quality of life. Analyses of adverse events, biopsy findings and laboratory values showed no evidence of clinically significant effects. CONCLUSIONS: Five-year maintenance therapy with rabeprazole is effective in preventing relapse of erosive or ulcerative GERD and is well tolerated.

Evaluation of sludge from pond system for treatment of piggery wastes.

Stabilization ponds used for the treatment of piggery wastes accumulate sludge over time, which is commonly used in agriculture. The objective of this study was to evaluate the agronomic potential of this kind of sludge. The samplings were collected in two different phases. The first in two anaerobic ponds (AP1 and AP2) and in one facultative pond with 5 transverse baffles and, the second in the same facultative pond with aeration. The removed sludge of AP1 and AP2 was characterized as rich sludge in volatile solids and with low stabilization, there was a great accumulation of the total phosphorus in the sludge of AP2. The facultative pond presented greater retention of nutrients in the sludge in relation to the anaerobic ponds. The annual accumulation of sludge was 13.3 cm/year in the AP1 and 6.70 cm/year in the AP2, while in the pond with aeration this was on the average of 0.5 cm/year, due to the aeration regime. The sludge can be used as a fertilizer in agriculture, if the chemical characteristics of the soil are taken into account so as to avoid the accumulation of nutrients and damage to plants.

Effect of Moxidectin Treatment at Peripartum on Gastrointestinal Parasite Infections in Ewes Raised under Tropical Andes High Altitude Conditions.

This study tested the impact of moxidectin at peripartum on nematode fecal egg count (FEC) and clinical parameters on ewes in the high altitude tropical Andes of Colombia. FEC and clinical evaluations were performed on 9 occasions in 43 naturally infected ewes before and during gestation and after lambing. Moxidectin (Mox, 200 µg kg(-1)) was applied at late pregnancy (T 1, n = 15) or 48 hours after parturition (T 2, n = 14). 14 untreated ewes served as controls (C). Suckling lambs (n = 58) remained untreated and underwent four clinical and parasitological evaluations until 8 weeks after birth. Mox efficacy equaled 99.3% (T 1) and 96.9% (T 2). Highest mean FEC value reflecting periparturient nematode egg rise (PPER) was recorded in C ewes at 4-6 weeks after lambing. Significant FEC reductions were found in T 1 (94.8%) and T 2 (96.7%) ewes (p < 0.05). All lambs showed a significant and ewes-group independent increase in FEC before weaning (p < 0.05). Clinical parameters (anemia and diarrhea) showed time- and treatment-related differences (p < 0.05). Monitoring of FEC and clinical parameters linked to gastrointestinal parasite infections allowed demonstrating that postpartum or preweaning are two critical periods to nematode infection for sheep raised under tropical Andes high altitude conditions. Use of Mox as anthelmintic treatment prevented PPER.

Etodolac, aspirin, and gastrointestinal microbleeding.

The effects of etodolac, a new nonsteroidal anti-inflammatory drug, on gastrointestinal (GI) microbleeding were quantitatively assessed in two studies in healthy adult men. The first was a two-group, open-label, parallel comparison of etodolac, 600 mg/day, aspirin, 2600 mg/day, and placebo in 20 subjects; the second was a four-group, double-blind, parallel comparison of etodolac, 600, 800, and 1200 mg/day, aspirin, 2600 mg/day, and placebo in 41 subjects. Subjects in both studies received a single-blind placebo on days 1 through 7, either etodolac or aspirin on days 8 through 14, and a single-blind placebo on days 15 through 19. GI blood loss (milliliters per day) was estimated by the radiolabeled (51Cr) erythrocyte method and was based on daily radioactivity counts of stool specimens and regression-estimated daily blood radioactivity. Etodolac, 600 mg/day, induced no significant GI blood loss at any time during the experiments, nor was there significant blood loss after 800 and 1200 mg/day in experiment 2. Blood loss was noted after aspirin in both.

Open-label, multicenter, phase 3 extension study of the safety and efficacy of donepezil in patients with Alzheimer disease.

BACKGROUND: Donepezil hydrochloride is a selective acetylcholinesterase inhibitor approved for the symptomatic treatment of mild to moderately severe Alzheimer disease (AD). Controlled clinical trials of up to 24 weeks have demonstrated that donepezil treatment (5 and 10 mg/d) significantly improves cognition and global function. OBJECTIVE: To investigate the long-term benefits of donepezil treatment in patients with AD. DESIGN: Multicenter, open-label, 144-week extension of 2 US phase 3, double-blind, placebo-controlled clinical trials: a 15-week study (12 weeks of treatment followed by a 3-week placebo washout) and a 30-week study (24 weeks of treatment followed by a 6-week placebo washout). INTERVENTIONS: All patients (N = 763) initially received donepezil, 5 mg/d, for 6 weeks, after which an increase to 10 mg/d was encouraged. MEASURES: Primary efficacy measures were the Alzheimer's Disease Assessment Scale-cognitive subscale and the Clinical Dementia Rating-Sum of the Boxes. RESULTS: After the shorter 3-week placebo washout, donepezil-associated benefits remained above original baseline values for an additional 24 weeks of open-label treatment. Benefits on Alzheimer's Disease Assessment Scale-cognitive subscale scores for patients who received 10 mg/d in the double-blind study were evident compared with the other groups for 108 weeks of open-label treatment. In contrast, donepezil-associated benefits were lost after the 6-week placebo washout, and scores decreased below original baseline values for all patient groups. Although scores improved relative to the new open-label study baseline scores after drug use was restarted, patients remained below original baseline values. The most common adverse events were associated with the nervous and digestive systems and were generally mild and transient; 17% of patient discontinuations were associated with adverse events. CONCLUSIONS: Donepezil is an effective and safe drug for the long-term symptomatic treatment of mild to moderately severe AD for up to 144 weeks (2.8 years), and sustained treatment may confer some advantages.

A 1-year, placebo-controlled preservation of function survival study of donepezil in AD patients.

OBJECTIVE: To examine the effects of donepezil compared with placebo on the preservation of function in patients with AD over a 1-year period. METHODS: This was a prospective, 54-week, double-blind, placebo-controlled, survival to endpoint study. Patients were required to have at entry: a diagnosis of probable AD (National Institute of Neurological and Communicative Disorders and Stroke criteria); Mini-Mental State Examination score of 12 to 20; Clinical Dementia Rating of 1 or 2; modified Hachinski ischemia score < or =4; and capability of performing 8 of 10 instrumental activities of daily living and 5 of 6 basic activities of daily living. Patients (n = 431) were randomized to placebo or donepezil (5 mg/day for 28 days, 10 mg/day thereafter). Outcome measures were the AD Functional Assessment and Change Scale, the Mini-Mental State Examination, and Clinical Dementia Rating scale. At each visit, investigators determined whether predefined criteria for clinically evident decline in functional status had been met. Patients who met the endpoint criteria were discontinued per protocol. RESULTS: Donepezil extended the median time to clinically evident functional decline by 5 months versus placebo. The probability of patients treated with donepezil remaining in the study with no clinically evident functional loss was 51% at 48 weeks, compared with 35% for placebo. The Kaplan-Meier survival curves for the two treatment groups were different (p = 0.002, log-rank test). CONCLUSIONS: Patients with AD continue to show detectable disease progression over time, but treatment with donepezil for 1 year was associated with a 38% reduction in the risk of functional decline compared with placebo.

Integrated acidity and rabeprazole pharmacology.

BACKGROUND: Integrated gastric and oesophageal acidity can be calculated from measurements of gastric and oesophageal pH and used to quantify gastric and oesophageal acidity over time. Rabeprazole is a new proton pump inhibitor that is effective in treating gastro-oesophageal reflux disease (GERD). AIM: To use measurement of integrated gastric and oesophageal acidity to determine the onset, duration and overall effect of rabeprazole in subjects with GERD. METHODS: Subjects with GERD were required to have oesophageal pH less-than-or-equal 4 for at least 10% of a 24-h recording. Effects of 20 mg rabeprazole on 24-h gastric and oesophageal pH were measured on days 1 and 7 of dosing. Integrated gastric and oesophageal acidity were calculated from time-weighted average hydrogen ion concentrations at each second of the 24-h record. RESULTS: At steady-state, 20 mg rabeprazole inhibited gastric acidity by 89% and oesophageal acidity by 95%. The first dose of rabeprazole inhibited gastric and oesophageal acidity by at least 70% of the steady-state effect. Oesophageal acidity could be divided into monophasic and biphasic patterns, and rabeprazole had different effects on oesophageal and gastric acidity in these two GERD subpopulations. The onset of action of the first dose of rabeprazole on gastric acidity was 4 h and on oesophageal acidity was 4 h in monophasic subjects and 7 h in biphasic subjects. Integrated acidity was more sensitive than time pH less-than-or-equal 4 in measuring the inhibitory actions of rabeprazole. CONCLUSIONS: Integrated gastric and oesophageal acidity are quantitative measurements that provide useful and novel information regarding the pathophysiology of GERD as well as the impact of antisecretory agents such as rabeprazole.