Dairy Intakes in Older Irish Adults and Effects on Vitamin Micronutrient Status: Data from the TUDA Study.

BACKGROUND: Consumption of dairy products has been associated with positive health outcomes including a lower risk of hypertension, improved bone health and a reduction in the risk of type 2 diabetes. The suggested dairy intake for health in older adults is three servings per day but recent analysis of the NHANES data for older adults reported 98% were not meeting these recommendations. No studies have investigated the consequences of such declines in the dairy intakes of Irish older adults and the subsequent effects on vitamin micronutrient status. OBJECTIVES: To study the daily dairy intakes of older Irish adults and to examine how the frequency of dairy food consumption affects vitamin micronutrient status. METHODS: Participants (n 4,317) were from the Trinity Ulster Department of Agriculture (TUDA) Study, a large study of older Irish adults (aged >60 yrs) designed to investigate gene-nutrient interactions in the development of chronic diseases of aging. The daily intake portion for milk, cheese and yoghurt was calculated from food frequency questionnaire (FFQ) responses. Blood samples were analysed for vitamin biomarkers as follows: vitamin B12 (total serum cobalamin and holotranscobalamin (holoTC)), folate (red cell folate (RCF) and serum folate), vitamin B2 (erythrocyte glutathione reductase activation coefficient (EGRac)), vitamin B6 (serum pyridoxal phosphate) and vitamin D (serum 25(OH)D). RESULTS: The mean total reported dairy intake was 1.16 (SD 0.79) portions per day with males consuming significantly fewer total dairy portions compared to females (1.07 vs 1.21 respectively) (P<0.05). There was no significant difference in total daily dairy serving intakes by age decade (60-69, 70-79, >80 yrs). Overall, only 3.5% of the total population (n 151) achieved the recommended daily dairy intake of three or more servings per day. A significantly higher proportion of females (4%) compared to males (2.4%) met these dairy requirements (P=0.011). Blood concentrations of vitamin B12 biomarkers, RCF, vitamin B2 and vitamin B6 were significantly worse in those with the lowest tertile of dairy intake (0-0.71 servings) compared to those in the highest tertile (1.50-4.50 servings) (P<0.05). CONCLUSION: This study found that more than 96% of the older adults sampled did not meet current daily dairy intake recommendations. The study is the largest to-date examining dairy intakes in older Irish adults, and provides evidence that daily dairy intakes (in particular yogurt) contribute significantly to the B-vitamin and vitamin D biomarker status of older adults. These results suggest that older adults who are already vulnerable to micronutrient inadequacies, are forgoing the nutritional advantages of vitamin-rich dairy products.

Greater yogurt consumption is associated with increased bone mineral density and physical function in older adults.

In this cohort of community dwelling older adults (>60 years), we observed significant positive associations between the frequencies of yogurt intake with measures of bone density, bone biomarkers, and indicators of physical function. Improving yogurt intakes could be a valuable health strategy for maintaining bone health in older adults. INTRODUCTION: The associations of yogurt intakes with bone health and frailty in older adults are not well documented. The aim was to investigate the association of yogurt intakes with bone mineral density (BMD), bone biomarkers, and physical function in 4310 Irish adults from the Trinity, Ulster, Department of Agriculture aging cohort study (TUDA). METHODS: Bone measures included total hip, femoral neck, and vertebral BMD with bone biochemical markers. Physical function measures included Timed Up and Go (TUG), Instrumental Activities of Daily Living Scale, and Physical Self-Maintenance Scale. RESULTS: Total hip and femoral neck BMD in females were 3.1-3.9% higher among those with the highest yogurt intakes (n = 970) compared to the lowest (n = 1109; P < 0.05) as were the TUG scores (-6.7%; P = 0.013). In males, tartrate-resistant acid phosphatase (TRAP 5b) concentrations were significantly lower in those with the highest yogurt intakes (-9.5%; P < 0.0001). In females, yogurt intake was a significant positive predictor of BMD at all regions. Each unit increase in yogurt intake in females was associated with a 31% lower risk of osteopenia (OR 0.69; 95% CI 0.49-0.96; P = 0.032) and a 39% lower risk of osteoporosis (OR 0.61; 95% CI 0.42-0.89; P = 0.012) and in males, a 52% lower risk of osteoporosis (OR 0.48; 95% CI 0.24-0.96; P = 0.038). CONCLUSION: In this cohort, higher yogurt intake was associated with increased BMD and physical function scores. These results suggest that improving yogurt intakes could be a valuable public health strategy for maintaining bone health in older adults.

Vitamin D deficiency is associated with inflammation in older Irish adults.

CONTEXT: Inadequate vitamin D status is common within elderly populations and may be implicated in the etiology of autoimmune disease and inflammation. Few studies have investigated the relationship between vitamin D status and age-related immune dysfunction in humans. OBJECTIVE: The aim of this study was to investigate the association between vitamin D status and immune markers of inflammation in a large sample of older adults. DESIGN, SETTING, AND PARTICIPANTS: An observational investigation of 957 Irish adults (>60 years of age) recruited in Northern Ireland (55°N latitude) as part of the Trinity Ulster Department of Agriculture aging cohort study. MAIN OUTCOME MEASURE: We measured serum 25-hydroxyvitamin D (25(OH)D) by liquid chromatography tandem mass spectrometry and serum cytokines IL-6, TNF-α, IL-10, and C-reactive protein (CRP) by ELISA. RESULTS: Concentrations of IL-6, CRP, and the ratios of IL-6 to IL-10 and CRP to IL-10 were significantly higher in individuals with deficient (<25 nmol/L) serum 25(OH)D compared with those with sufficient (>75 nmol/L) status after adjustment for age, sex, and body mass index (P < .05). Vitamin D status was a significant predictor of the IL-6 to IL-10 cytokine ratio, and those participants defined as deficient were significantly more likely to have an IL-6 to IL-10 ratio >2:1 compared with those defined as sufficient. CONCLUSIONS: This study demonstrated significant associations between low vitamin D status and markers of inflammation (including the ratio of IL-6 to IL-10) within elderly adults. These findings suggest that an adequate vitamin D status may be required for optimal immune function, particularly within the older adult population.

B-vitamins and bone in health and disease: the current evidence.

Osteoporosis, a metabolic skeletal disease characterised by decreased bone mass and increased fracture risk, is a growing public health problem. Among the various risk factors for osteoporosis, calcium and vitamin D have well-established protective roles, but it is likely that other nutritional factors are also implicated. This review will explore the emerging evidence supporting a role for certain B-vitamins, homocysteine and the 677 C → T polymorphism in the gene encoding the folate-metabolising enzyme methylenetetrahydrofolate reductase, in bone health and disease. The evidence, however, is not entirely consistent and as yet no clear mechanism has been defined to explain the potential link between B-vitamins and bone health. Coeliac disease, a common condition of malabsorption, induced by gluten ingestion in genetically susceptible individuals, is associated with an increased risk both of osteoporosis and inadequate B-vitamin status. Given the growing body of evidence linking low bone mineral density and/or increased fracture risk with low B-vitamin status and elevated homocysteine, optimal B-vitamin status may play an important protective role against osteoporosis in coeliac disease; to date, no trial has addressed this possible link.

Comparing the needs of health professional and peer cancer support group facilitators in an Australian context.

This study explored the perceived needs of health professional and peer facilitators of cancer support groups. Participants were facilitators of support groups affiliated with The Cancer Council Victoria (Australia). Facilitators completed questionnaires assessing their experience of support group facilitation, including training and support needs. Data from health professional and peer facilitators (n= 74) were analysed in this paper. The majority of facilitators (88%) were female; 57% had run their group for more than 3 years, and 47% reported between 11 and 20 people attended each group. Although results showed the characteristics of support groups are broadly similar for peers and professionals, there were some distinct differences in perceived needs. Health professional facilitators were more likely than peers to regard training as valuable and beneficial to their role. In addition, health professionals more frequently reported needing debriefing as well as more difficulty accessing debriefing than cancer peers. This study builds on the small body of literature exploring the experiences of cancer support group facilitators. Given the experiences and needs of health professional and peer facilitators may differ, it may be relevant to tailor training and support so that it meets the needs of both health professionals and cancer peers.

Relative activity of triclabendazole metabolites against the liver fluke, Fasciola hepatica.

A study has been carried out to determine the relative activity of triclabendazole (TCBZ) and its sulphoxide (TCBZSO) and sulphone (TCBZSO(2)) metabolites against the adult stage of the liver fluke, Fasciola hepatica. Flukes were incubated for 24h in vitro in 15mug/ml of each of the compounds and prepared for scanning and transmission electron microscopy. All three compounds induced changes to the surface morphology of the fluke, the changes comprising swelling and blebbing to a greater or lesser extent in different regions of the fluke. TCBZSO(2) was more disruptive anteriorly and TCBZSO posteriorly. Internal ultrastructural changes were evident following incubation with each of the compounds, with an order of severity TCBZSO(2)>TCBZSO>TCBZ. Swelling of the basal infolds and mitochondria were observed in the tegumental syncytium. In the tegumental cell bodies, there was a reduction in the number of secretory bodies, disruption of the Golgi complexes and swelling of the mitochondria. Severe flooding of the internal tissues was observed with TCBZSO(2) and, to a lesser extent, with TCBZSO and TCBZ. The results demonstrate that both TCBZ and TCBZSO(2) are capable of disrupting the fluke in vitro and are not the inactive compounds they were assumed to be previously. They may well contribute to drug action in vivo as well, indicating that drug action is due to the additive effects of several metabolites, rather than being due to a single active metabolite, namely, TCBZSO.

Tegumental surface changes in juvenile Fasciola hepatica in response to treatment in vivo with triclabendazole.

Eight indoor-reared crossbred sheep with no pre-exposure to Fasciola hepatica were infected, by oral gavage, with 200 metacercarial cysts of the triclabendazole (TCBZ)-susceptible Cullompton isolate of F. hepatica. Anthelmintic dosing occurred at 4 weeks post-infection with 10 mg/kg triclabendazole. Two treated sheep were euthanized at 48 h, 72 h and 96 h post-treatment with triclabendazole. Two control sheep were euthanized alongside the 48 h triclabendazole-treated sheep. Juvenile flukes were recovered from each of the sheeps' liver and processed for scanning electron microscopy (SEM). Flukes were still active 48 h post-treatment and displayed limited morphological disruption. There was some blebbing and sloughing of the tegument around the oral sucker. In several of the specimens, an extra layer had been deposited on the fluke surface, giving it a flattened appearance. At 72 h post-treatment, only one fluke remained alive and the disruption varied in degree. In the majority of flukes, there was severe swelling of the tegument, accompanied by isolated areas of flattening along the lateral margins of the flukes and in the tail region. Limited areas of sloughing occurred in the tail region. In more seriously affected specimens, the syncytium had been stripped away to reveal the basal lamina and some deeper lesions were also observed. By 96 h post-treatment, all the flukes were dead and were grossly disrupted. They were totally devoid of tegument and deep lesions exposed the internal tissues of the fluke.

Dialysate as food as an option for automated peritoneal dialysis.

Protein-energy malnutrition is frequently found in dialysis patients. Many factors play a role in its development including deficient nutrient intake as a result of anorexia. Peritoneal dialysis (PD) solutions containing a mixture of amino acids and glucose in an appropriate ratio could serve as a source of food. The authors of this article found that such a dialysis solution when administered to fasting patients who were on nightly automated peritoneal dialysis (APD), as part of a regular dialysis schedule, induced an acute anabolic effect. Also in PD patients in the fed state, dialysis solutions containing both amino acids and glucose were found to improve protein metabolism. It appears that the body responds similar to intraperitoneal and oral amino acid:dialysate as food. Like dietary proteins, intraperitoneal amino acids can bring about generation of hydrogen ions and urea as a result of oxidation. No rise of serum urea levels was found and serum bicarbonate remained within the normal range when a total buffer concentration of 40 mmol/L in the mixture was used. The use of this approach may be an option for PD patients who cannot fulfil dietary recommendations.

Wide variation in single, daily-dose aminoglycoside pharmacokinetics in patients with burn injuries.

Five to seven mg/kg single, daily-dose aminoglycoside regimens have been recently advocated as effective alternatives to traditional aminoglycoside regimens. The rationale for single, daily-dose aminoglycoside therapy is to produce an optimal ratio between aminoglycoside peak concentrations (Cmax) and pathogen minimal inhibitory concentration to maximize bacterial killing and to produce an aminoglycoside-free period during the 24-hour dosing interval. Single, daily-dose aminoglycoside therapy has not been recommended to date for use in the population of patients with burn injuries. The purpose of this study was to determine the magnitude and variability of aminoglycoside Cmax and the duration of the aminoglycoside-free period after simulated single, daily-dose regimens in patients with burn injuries. Fifty-two patients receiving gentamicin or tobramycin in the burn unit were studied retrospectively to determine the individualized pharmacokinetic parameters and the simulated Cmax and 24-hour after the dose trough minimum concentrations for 5 and 7 mg/kg single, daily-dose aminoglycoside regimens. Patients were only included in the final analysis if they had been treated for burn wound infections and exhibited a calculated creatinine clearance exceeding 60 ml/min (N = 40). Mean [percentage coefficient of variation] Cmax/minimum concentrations were 15.4[30.5]/0.03[200.0] and 21.6[30.6]/0.04[200.0] mg/L for 5 and 7 mg/kg daily doses, respectively. The mean coefficient of variation time to reach an extrapolated concentration of 0.1 mg/L was 15.9[30.8] hours and 17.0[30.6] hours for the 5 and 7 mg/kg daily doses, respectively. Substantial variability in aminoglycoside Cmax and duration of the aminoglycoside-free period was observed. These data suggest that many patients with burn injuries are not candidates for single, daily-dose aminoglycoside therapy because of restrictive creatinine clearance criteria and pronounced variability in length of the aminoglycoside-free interval. If single, daily-dose aminoglycoside therapy is to be used in this patient population, therapeutic drug monitoring is recommended to screen for appropriate candidates and to optimize Cmax and minimal inhibitory concentration ratios and duration of the aminoglycoside-free interval.

The impact of practice guidelines on prescribing patterns of nondepolarizing neuromuscular blocking agents.

Guidelines for selecting nondepolarizing neuromuscular blocking agents (NNMBAs) were developed and implemented by an interdisciplinary team for use in our intensive care units. They suggest pancuronium as the drug of choice if the patient does not have renal insufficiency and is hemodynamically stable. If either of these criteria is not met and hepatic function is normal, vecuronium is recommended. Atracurium is reserved for patients not meeting either criterion. A 12-month retrospective chart review was performed for 24 patients 18 years of age or older who received continuous infusion of an NNMBA beginning 7 months after the guidelines were implemented. Before the guidelines, atracurium, vecuronium, and pancuronium were prescribed for 68% (17), 24% (6), and 8% (2) of patients, respectively. Their use was inappropriate based on organ function and hemodynamic stability in 88% (15), 83% (5), and 0% of patients, respectively. After guideline implementation, atracurium, vecuronium, and pancuronium were prescribed for 33% (8), 21% (5), and 46% (11) of patients, respectively, and use was inappropriate in 38% (3), 60% (3), and 0% of patients, respectively. Overall, the prevalence of inappropriate NNMBA selection decreased from 80% (20) to 25% (6). Further analysis is necessary to determine the associated pharmacoeconomic impact of decreased inappropriate NNMBA prescribing.

QTc-interval prolongation associated with slow intravenous erythromycin lactobionate infusions in critically ill patients: a prospective evaluation and review of the literature.

Intravenous erythromycin has recently been associated with significant QTc interval prolongation, torsades de pointes, and sudden cardiac death. The prolonged the QTc interval attributed to erythromycin typically is associated with rapid infusion rates in excess of 10 mg/minute. We prospectively assessed the relationship between QTc interval prolongation and erythromycin administration by slow intravenous infusion (mean rate 8.9 +/- 3.5 mg/minute, range 3.9-16.7 mg/minute). Electrocardiographic (ECG) rhythm strips were prospectively obtained in 44 critically ill patients receiving intravenous antibiotics (22 received erythromycin and 22 ceftazidime, cefuroxime, cefotaxime, ceftriaxone, or ampicillin-sulbactam as controls). The ECG recordings were obtained immediately before and within 15 minutes after drug infusions. Only the first available set of ECG strips were evaluated. Two controls had evidence of hepatic dysfunction; no patients receiving erythromycin did. The QTc interval was calculated using Bazett's formula by two blinded investigators. For controls, mean +/- 1 SD (range) QTc intervals were 423 +/- 96 (300-550) msec at baseline and 419 +/- 96 (280-610) msec after infusion (p = 0.712). In contrast, in the erythromycin group, the interval was significantly prolonged from 524 +/- 105 (360-810) msec at baseline to 555 +/- 134 (400-980) msec after infusion (p = 0.034). No patients experienced a dysrhythmia as a consequence of erythromycin infusion. Despite slow rates of infusion, QTc interval prolongation was significant. The clinical importance of this finding remains to be determined.

Resistance to nondepolarizing neuromuscular blocking agents.

Several case reports of resistance to short-term administration of nondepolarizing neuromuscular blocking agents (NNMBAs) have been reported in research and surgical settings. Recently, several reports documented resistance to NNMBAs during therapy for prolonged paralysis in critically ill patients. Adverse outcomes associated with NNMBA resistance may include inadequate ventilatory management or suppression of patient movement, and an increased risk of dose-dependent cardiovascular adverse effects. Pharmacoeconomic issues must be considered in that the cost of NNMBA therapy in a resistant patient may be significant. Although the specific etiologies of resistance are not clear, several pharmacodynamic and pharmacokinetic alterations may occur as a consequence of disease state or concomitant drug therapy. Pharmacodynamic changes include altered acetylcholine receptor physiology or sensitivity, inhibition of serum cholinesterase activity, and interaction with plasma constituents. Alterations in distribution volume, protein binding, and clearance may also contribute to resistance in several disease states.

Lorazepam stability in parenteral solutions for continuous intravenous administration.

OBJECTIVE: To determine the stability of lorazepam over a 24-hour period when prepared in polyvinyl chloride (PVC) bags at initial concentrations of 0.08 and 0.5 mg/mL. DESIGN: Each concentration was studied at room (21 degrees C) and refrigerator (4 degrees C) temperatures in dextrose 5% (D5W) and NaCl 0.9% solutions. Duplicate test solution admixtures were prepared for each lorazepam concentration, diluent, and temperature. At 0, 1, 4, 8, and 24 hours, duplicate samples were obtained for visual inspection, pH determination, and concentration determination by stability-indicating, reverse-phase HPLC analysis. Compared with baseline, peaks for lorazepam degradation products were not found on any of the study chromatograms. RESULTS: In D5W and NaCl 0.9% solutions, lorazepam loss in excess of 10% by HPLC analysis occurred for concentrations of 0.08 and 0.5 mg/mL at 1 and 4 hours, respectively. CONCLUSIONS: These data suggest that significant loss of lorazepam occurs as the probable result of sorption to PVC bags when admixed in both D5W and NaCl 0.9% solutions at 21 and 4 degrees C.

A retrospective study of sodium nitroprusside use and assessment of the potential risk of cyanide poisoning.

Sodium nitroprusside (SNP) is an effective vasodilator but is potentially dangerous due to its cyanide content. Infusion rates above 2 micrograms/kg/minute may cause cyanide to accumulate to toxic concentrations in critically ill patients. Coadministration of thiosulfate with SNP effectively and safely prevents cyanide toxicity. This study determined if patients at our institution were treated with SNP infusion rates that could cause cyanide toxicity and whether those patients were administered thiosulfate. We reviewed the charts of 36 critically ill patients treated with SNP during the previous 12 months. In 72% of patients the SNP infusion rates were above 2 micrograms/kg/minute. In 47% the rates were greater than 2 micrograms/kg/minute for 6 hours or more, and in 20% they were greater than 5 micrograms/kg/minute for up to 11 hours. None of the patients was administered thiosulfate. In a significant number of patients the infusion rates of SNP potentially exposed them to significant risk of cyanide toxicity including death.

Inappropriate vancomycin prescribing based on criteria from the Centers for Disease Control and Prevention.

Increasing reports of vancomycin resistance have raised concerns about the future effectiveness of this drug in treatment of critically ill patients with gram-positive infections. Due to these concerns the Centers for Disease Control and Prevention (CDC) recently published criteria that delineate the prudent use of vancomycin. Using these criteria, we attempted to determine the appropriateness of vancomycin prescribing patterns at our institution. A retrospective chart review was performed for 135 hospitalized patients treated between May 1993 and April 1994. Inappropriate empiric vancomycin use was documented in 81 (60%) of these patients. When culture results were available, 28 (21%) patients inappropriately received the drug. Results of this study are similar to those of other studies of vancomycin use in hospitals based on non-CDC criteria. If CDC criteria are to have a positive impact on physicians' vancomycin prescribing patterns, significant educational efforts will be required.

Atracurium resistance in a critically Ill patient.

A previously healthy 25-year-old man with metastatic testicular teratocarcinoma became resistant to atracurium-induced neuromuscular blockade as evidenced by train-of-four (TOF) monitoring combined with clinical assessment. Subsequently he had an adequate response with a standard dosage of pancuronium. During the first 10 days of neuromuscular blockade, the atracurium requirements escalated from 0.31 to 1.7 mg/kg/hour, guided by TOF monitoring, movement, and spontaneous respirations. The infusion was discontinued but later reinstituted. Despite a total atracurium loading dose of 1.4 mg/kg followed by an infusion rate titrated to 1.7 mg/kg/hour, inadequate paralysis persisted. Atracurium was terminated and an intravenous infusion of pancuronium 0.10 mg/kg/hour was started. Over the next 3 days the pancuronium infusion was titrated down to a range of 0.04-0.06 mg/kg/hour, followed by a maintenance infusion of 0.01-0.05 mg/kg/hour for 5 days. A pharmacokinetic alteration, such as increased metabolism or elimination, may have caused the atracurium resistance.

Inconsistency with train-of-four monitoring in a critically ill paralyzed patient.

Problems occurred with train-of-four (TOF) monitoring during prolonged therapy with nondepolarizing neuromuscular blocking agents (NNMBAs). A previously healthy 25-year-old male with metastatic testicular teratocarcinoma was paralyzed with an atracurium infusion to facilitate mechanical ventilation. Dosage titration was initially based on clinical assessment; however, on day 4 of atracurium, TOF monitoring was initiated. During days 4 to 10 of atracurium therapy, TOF monitoring correlated well with clinical assessment of the depth of paralysis. On day 13, atracurium was discontinued and a pancuronium infusion was initiated. During the 9 days of pancuronium therapy, TOF monitoring suggested overparalysis on several occasions (no thumb twitch at 80 mamp of ulnar nerve stimulation) despite clinical evidence of spontaneous movement or respirations. The patient was edematous and had extremely dry skin during some of these instances of inappropriate TOF response. Although these problems were rectified, TOF response continued to be erroneous. Thus we had to rely primarily on clinical assessment to monitor the duration of NNMBA therapy. This case demonstrates that TOF data and clinical assessment of neuromuscular blockade may not always correlate.