Medication taking in a national sample of dependent older people.

BACKGROUND: Polypharmacy is associated with inappropriate medication use, and subsequently increasing older persons' risk of drug-related harm and health-related costs to individuals and society. OBJECTIVE: To examine and describe, using a national sample of patient-level medication data, the prevalence of older people's polypharmacy and medication use across dependency levels. To examine oral and general pain prevalence and associated analgesic usage. METHODS: Medication data from the 2012 New Zealand Older People's Oral Health Survey, a nationally-representative, cross-sectional study of dependent older people's oral health, were analysed descriptively, comparing classes and sub-classes of drugs and nutrient supplements taken across four categories of dependency: very low (own homes receiving in-home support), low, high and psychogeriatric (all receiving aged residential care). Self-reported current general pain and frequency of orofacial pain data were cross-tabulated by sub-classes of analgesics taken. RESULTS: All participants were taking at least one medication overall, 53.2% (95% CI: 50.4, 56.0) took between five and nine (polypharmacy), and 13.9% (95% CI: 17.4, 22.5) took 10 or more (hyperpolypharmacy). Antihypertensives, analgesics, antiulcer drugs, aspirin, laxatives, statins and antidepressants were the most common drug classes taken, the proportions differing between psychogeriatric level care and all other dependency groups. Overall, simple analgesics were taken (34.5%; 95%CI: 30.8, 38.4) more commonly than other analgesics; the use of nonsteroidal anti-inflammatory drugs was low (3.6%; 95% CI: 2.7, 4.7). Of those reporting experiencing extreme general bodily pain, 63.3% (95% CI: 56.6, 69.4) took an analgesic, more than those experiencing mouth pain occasionally or often. Fat-soluble vitamins were the most common vitamin supplement taken (32.0%; 95%CI: 27.0, 37.4). CONCLUSIONS: Polypharmacy and hyperpolypharmacy are common among older people, regardless of dependency level, and pain may be undertreated.

Modest hypothermia preserves cerebral energy metabolism during hypoxia-ischemia and correlates with brain damage: a 31P nuclear magnetic resonance study in unanesthetized neonatal rats.

Recent studies have shown that mild to moderate (modest) hypothermia decreases the damage resulting from hypoxic-ischemic insult (HI) in the immature rat. To determine whether suppression of oxidative metabolism during HI is central to the mechanism of neuroprotection, 31P nuclear magnetic resonance (NMR) spectroscopy was used to measure high energy metabolites in 7-d postnatal rats under conditions of modest hypothermia during the HI. The rats underwent unilateral common carotid artery ligation followed by exposure to hypoxia in 8% oxygen for 3 h. Environmental temperature was decreased by 3 or 6 degrees C from the control temperature, 37 degrees C, which reliably produces hemispheric damage in over 90% of pups. The metabolite parameters and tissue swelling (edema) at 42 h recovery varied very significantly with the three temperatures. Tissue swelling was 26.9, 5.3, and 0.3% at 37, 34, and 31 degrees C, respectively. Core temperature and swelling were also measured, with similar results, in parallel experiments in glass jars. Multislice magnetic resonance imaging, histology, and triphenyltetrazolium chloride staining confirmed the fairly uniform damage, confined to the hemisphere ipsilateral to the ligation. The NMR metabolite levels were integrated over the last 2.0 h out of 3.0 h of HI, and were normalized to their baseline for all surviving animals (n = 25). ATP was 47.9, 69.0, and 83.0% of normal, whereas the estimator of phosphorylation potential (phosphocreatinine/inorganic phosphorus) was 16.9, 27.8, and 42.6% of normal at 37, 34, and 31 degrees C, respectively. There was a significant correlation of both phosphocreatinine/inorganic phosphorus (p < 0.0001) and ATP levels (p < 0.0001) with brain swelling. Abnormal brain swelling and thus damage can be reliably predicted from a threshold of these metabolite levels (p < 0.0001). Thus for all three temperatures, a large change in integrated high energy metabolism during HI is a prerequisite for brain damage. With a moderate hypothermia change of 6 degrees C, where there is an insufficient change in metabolites, there is no subsequent HI brain damage. In general, treatment for HI in our 7-d-old rat model should be aimed at preserving energy metabolism.

The development and reliability of the Recovery Attitude and Treatment Evaluator-Questionnaire I (RAATE-QI).

A reliability study was performed on a new 94-item true-false report instrument called the Recovery Attitude And Treatment Evaluator-Questionnaire I (RAATE-QI). The RAATE-QI consists of five dimensions which assess a patient's status in five clinically relevant areas for making admission assessment, treatment placement/matching and planning decisions, and discharge/follow-up outcome assessments. The five dimensions measure: resistance to treatment (treatment motivation and denial), resistance to continuing care (long-term denial), biomedical acuity, psychiatric/psychological acuity, and social/family environmental support status. Data on 143 inpatients who completed the RAATE-QI from a public sector chemical dependency/dual diagnosis treatment unit demonstrated test-retest reliabilities in the range from .73 to .87, and internal consistency reliabilities in the range from .63 to .78 across the five dimensions. These preliminary data suggest that the RAATE-QI may be a clinically reliable assessment/placement tool.

Simultaneous determination of intracellular magnesium and pH from the three 31P NMR Chemical shifts of ATP.

The simultaneous determination of intracellular [MgT]/[ATPT] and pH from the three 31P NMR chemical shifts of ATP has been demonstrated using two-dimensional calibrations. The resulting pH will more accurately represent that of healthy tissue than by using the standard NMR technique. As a result of other possible complexes of MgATP and uncertainties in intracellular pH, errors in the values of KMgATPD (pH), the MgATP NMR shift limits, and thus intracellular magnesium levels are reduced by using this self-consistent analytical method. Direct determination of free magnesium from the (gamma-beta) shifts of ATP may be more sensitive in the alkaline pH range than with the commonly used (alpha-beta) shifts. In addition, the calibration data sets allow for a graphical representation of the uncertainty in magnesium due to the uncertainty in the measured chemical shifts and pH. Our results indicate that KMgATPD is consistent with the literature and favors a value near 50 microM at pH 7.2, but that free magnesium levels will be lower than most prior estimates.

Allopurinol preserves cerebral energy metabolism during perinatal hypoxia-ischemia: a 31P NMR study in unanesthetized immature rats.

The effects of high dose allopurinol (ALLOP) pretreatment on the cerebral energy metabolism of unanesthetized 7-day-postnatal rats during exposure to 3 h of cerebral hypoxia-ischemia were serially quantitated using non-invasive 31P NMR spectroscopy. Adenosine triphosphate, integrated over the last 2 h of hypoxia and expressed as a fraction of baseline, was 0.73 +/- 0.16 with ALLOP pretreatment (200 mg/kg s.c.) compared to 0.52 +/- 0.05 for saline pretreatment (P = 0.001). Inorganic phosphate/phosphocreatine (Pi/PCr), integrated over the same time interval, was 2.63 +/- 1.23 relative to baseline with ALLOP versus 5.13 +/- 1.45 for saline-treated pups (P less than 0.0005). We suggest that the neuroprotection achieved with high dose ALLOP pretreatment may be attributed in part to preservation of energy metabolites.

31P NMR spectroscopy of perinatal hypoxic-ischemic brain damage: a model to evaluate neuroprotective drugs in immature rats.

Cerebral energy metabolism can be measured non-invasively in unanesthetized neonatal rats with 31P NMR spectroscopy. Using this technique, serial changes in high energy phosphates were determined from the right cerebral hemispheres of 7 day postnatal rat pups during a hypoxic-ischemic insult known to produce focal brain injury. During 3 h of hypoxia-ischemia the concentration of ATP dropped to 33 +/- 8% of prehypoxic (baseline) levels, phosphocreatine (PCr)/Pi decreased from 1.5 +/- 0.51 to 0.16 +/- 0.06, while pH decreased nominally by 0.2 units. After 2.5 h of recovery in air, ATP returned to 75 +/- 10% of baseline levels, PCr/Pi rose to 1.1 +/- 0.28, and pH returned to its normal value of 7.16 +/- 0.06. This model was used to test the efficacy of the adenosine deaminase inhibitor, 2-deoxycoformycin (DCF) as a potential neuroprotective drug. The data for the drug- and saline-treated populations were analyzed by integrating ATP and Pi/PCr levels over specific time intervals, expressing it relative to baseline levels, and modeling it with cubic splines. Pretreatment with 500 micrograms/kg DCF shows a small, but statistically significant, preservation of both ATP and phosphorylation potential during hypoxia and initial recovery. Brain water content (edema) at 42 h recovery was apparently associated with both mean ATP and mean Pi/PCr in the last 2 h of hypoxia-ischemia. When ATP fell below 70% of baseline, brain edema was evident at 42 h of recovery. This methodology is suitable for extension to human infants.

Error in the calibration of the MgATP chemical-shift limit: effects on the determination of free magnesium by 31P NMR spectroscopy.

The measurement of free intracellular magnesium (Mg2+) using the 31P chemical shifts of ATP requires the use of appropriate calibration solutions to determine the chemical-shift limits delta ATP alpha beta and delta MgATP alpha beta. Solutions containing excess Mg2+ contain significant amounts of Mg2ATP and yield positive errors in the value of delta MgATP alpha beta. For physiological applications this may overestimate free intracellular Mg2+ by as much as 300%. This error may be minimized if appropriate mole ratios of Mg2+/ATP are used to calibrate delta MgATP alpha beta.

31P NMR saturation-transfer study of the in situ kinetics of the mitochondrial adenine nucleotide translocase.

The exchange of intramitochondrial ATP (ATP(in)) for extramitochondrial ATP (ATP(out)) was measured by using 31P NMR spectroscopy over a range of temperatures in isolated rat liver mitochondria oxidizing glutamate and succinate in the presence of external ATP but no added ADP (state 4). The rate of this exchange is more than an order of magnitude faster than rates reported previously that were determined by using isotopic techniques in the presence of oligomycin, the potent ATPase inhibitor. Differences are ascribed in part to the low levels of matrix ATP present in oligomycin-treated mitochondria. The addition of oligomycin to mitochondrial suspensions decreases intramitochondrial ATP levels from 17 +/- 3 (SEM) nmol/mg of protein in state 4 to 1.51 +/- 0.1 nmol/mg of protein in the presence of inhibitor at 8 degrees C. Simultaneously, transporter flux falls from 960 +/- 55 nmol/min.mg to undetectable levels (less than 300 nmol/min.mg). Although transport rates are much faster when measured by saturation-transfer than by conventional isotopic methods, the enthalpy values obtained by determining the effect of temperature on flux are very similar to those reported in the past that were determined by using isotopic techniques. Intramitochondrial ATP content regulates the rate of the ATP(in)/ATP(out) exchange. At 18 degrees C, the concentration of internal ATP that produces half-maximal transport rate is 6.6 +/- 0.12 nmol/mg of mitochondrial protein. The relationship between substrate concentration and flux is sigmoidal and is 90% saturated at 11.3 +/- 0.18 nmol/mg of mitochondrial protein.(ABSTRACT TRUNCATED AT 250 WORDS)

Suppression of the human mucosal-related colonic microflora with prophylactic parenteral and/or oral antibiotics.

The purpose of this investigation was to assess the effects of preoperative administration of parenteral antibiotics with or without concomitant preoperative administration of oral antibiotics on the colonic mucosal-related microflora. Thirty-one patients were studied in a prospective fashion. Group A patients (n = 8) had colonoscopic mucosal biopsies performed after mechanical bowel preparation. Group B patients (n = 5) received neomycin and erythromycin (NE), 1 g each following mechanical bowel preparation, at 1, 2, and 11 p.m. the evening prior to either elective colon resection (n = 2) or prior to colonoscopic biopsy (n = 3). Emergent trauma patients who had left colon or sigmoid perforations due to gunshot wounds requiring segmental resection comprised group C (n = 7). These patients received cefoxitin or cefotetan 2 g intravenously preoperatively. Individuals in group D (n = 11) all had elective left hemicolectomies or sigmoid resections due to nonobstructing malignancies. These patients underwent the same regimen as group B patients in addition to receiving intravenous cefoxitin perioperatively. Quantitative and qualitative bacterial cultures as well as scanning electron microscopy (SEM) were used to study the mucosa-associated flora. Tissue for culture and SEM were obtained from the pathologic specimen immediately after removal. The interval between the dosage of parenteral antibiotics to tissue removal was 3 hours in both groups. Anaerobic and aerobic counts were suppressed the greatest in patients receiving both oral and parenteral antibiotics (p = 0.0001). Mean anaerobic counts decreased from 3.4 X 10(7) in group A to 1.8 X 10(2) (mean cfu/g) in group D patients. Mean aerobic counts in group A decreased from 3.7 X 10(6) to 64 (mean cfu/g) in group D.(ABSTRACT TRUNCATED AT 250 WORDS)

In vivo functioning of creatine phosphokinase in human forearm muscle, studied by 31P NMR saturation transfer.

31P nuclear magnetic resonance (NMR) saturation transfer has been used to measure enzymatic flux through the creatine phosphokinase reaction in the direction of ATP synthesis in the human forearm muscle flexor digitorum superficialis. Modification of the ratio method for measurement of spin-lattice relaxation (R. Freeman, H.D.W. Hill, and R. Kaptein, J. Magn. Reson. 7, 82(1972]was tested and used to appreciably shorten the duration of the measurement. Under conditions of steady state work intracellular pH decreased slightly by 0.06 units and the spin-lattice relaxation time of phosphocreatine in muscle was unchanged, while flux from phosphocreatine to ATP was 64 +/- 10% of the resting value. This is contrary to the increase in flux of 155% predicted from previous saturation transfer studies carried out in vitro on rabbit skeletal muscle creatine phosphokinase using metabolite concentrations to mimic those in vivo (E.A. Shoubridge, J.L. Bland, and G.K. Radda, Biochim. Biophys. Acta 805, 72 (1984]. This discrepancy could be accounted for by an underestimation of the ADP concentrations to which the enzyme is exposed due to inaccurate assumptions about the total metabolite concentrations, or possibly by compartmentation of creatine phosphokinase and its reactants.

Urinary and serum silicon in normal and uraemic individuals.

The urinary excretion of silicon (Si) in humans was studied in normal subjects on a low Si diet, a normal diet, and after ingestion of silicate antacid. Measurements of 24-hour urinary excretion of Si showed that urinary Si was derived mainly from dietary intake. The serum concentration of Si was determined in normal individuals and in patients with chronic renal failure. In health, serum Si is maintained within a narrow range, but a significant hypersilicaemia occurs in uraemia. The concentration of Si was measured in the water supply, dialysate and pre-dialysis and post-dialysis serum in patients on regular haemo-dialysis in three areas with low, intermediate and high concentrations of Si in the water supply. Si was removed during dialysis in the region where it was naturally low in the water or where reverse osmosis was used, but it was dialysed into patients in regions with intermediate and high concentrations in the water. Serum Si levels returned to normal after renal transplantation. Preliminary analysis of the geographical variation in the Si content of tap water suggests that uraemic hypersilicaemia may protect haemodialysed patients from the development of aluminium dementia. The kidney would appear from these studies to be the major organ for elimination of absorbed Si.

Thermal transitions in the low-density lipoprotein and lipids of the egg yolk of hens.

1. Differential sanning calorimetry and light-scattering have been used to investigate temperature-dependent transitions in low-density lipoprotein and in lipids from hens' egg yolk. Yolks of different fatty acid composition were obtained by varying the dietary lipid and by adding methyl sterculate to the hen's diet. 2. Lipoprotein solutions in 50 percent glycerol/water gave characteristic melting curves between -25 degrees C and 50 degrees C, and on cooling showed increases in light-scattering between 10 degrees C and -20 degrees C. The temperatures at which major changes occurred depended on the proportions of saturated and unsaturated fatty acids. 3. The thermal transitions in the intact lipoprotein in glycerol solution were reversible, but with marked hysteresis. Lipid extracted from the lipoprotein did not show temperature hystersis but the transition heats and melting curves similar to those of the intact lipoprotein. The results support the hypothesis of a "lipid-core" structure for low-density lipoproteins. 4. Scanning calorimetry of egg-yolk lecithins indicated a strong dependence of transition temperature on water content in the rane 3 percent-20 percent water. A rise in the mid-temperature of the liquid-crystalline to gel transition as the water content is lowered on freezing may be the primary event in the irreversible gelation of egg yolk and aggregation of lipoprotein.