Nutrition Intervention Informed by Indirect Calorimetry Compared to Predictive Equations to Achieve Weight Goals in Geriatric Rehabilitation Inpatients: The NEED Study.

OBJECTIVES: To assess if nutritional interventions informed by indirect calorimetry (IC), compared to predictive equations, show greater improvements in achieving weight goals, muscle mass, strength, physical and functional performance. DESIGN: Quasi-experimental study. SETTING AND PARTICIPANTS: Geriatric rehabilitation inpatients referred to dietitian. INTERVENTION AND MEASUREMENTS: Patients were allocated based on admission ward to either the IC or equation (EQ) group. Measured resting metabolic rate (RMR) by IC was communicated to the treating dietitian for the IC group but concealed for the EQ group. Achieving weight goals was determined by comparing individualised weight goals with weight changes from inclusion to discharge (weight gain/loss: >2% change, maintenance: ≤2%). Muscle mass, strength, physical and functional performance were assessed at admission and discharge. Food intake was assessed twice over three-days at inclusion and before discharge using plate waste observation. RESULTS: Fifty-three patients were included (IC n=22; EQ n=31; age: 84.3±8.4 years). The measured RMR was lower than the estimated RMR within both groups [mean difference IC -282 (95%CI -490;-203), EQ -273 (-381;-42) kcal/day)] and comparable between-groups (median IC 1271 [interquartile range 1111;1446] versus EQ 1302 [1135;1397] kcal/day, p=0.800). Energy targets in the IC group were lower than the EQ group [mean difference -317 (95%CI -479;-155) kcal/day]. There were no between-group differences in energy intake, achieving weight goals, changes in muscle mass, strength, physical and functional performance. CONCLUSIONS: In geriatric rehabilitation inpatients, nutritional interventions informed by IC compared to predictive equations showed no greater improvement in achieving weight goals, muscle mass, strength, physical and functional performance. IC facilitates more accurate determination of energy targets in this population. However, evidence for the potential benefits of its use in nutrition interventions was limited by a lack of agreement between patients' energy intake and energy targets.

Patient preference for eletriptan 80 mg versus subcutaneous sumatriptan 6 mg: results of a crossover study in patients who have recently used subcutaneous sumatriptan.

This current randomized, open-label, crossover study evaluated preference for oral eletriptan 80 mg compared with subcutaneous sumatriptan 6 mg (suma-sc) amongst patients (n = 311) meeting IHS criteria for migraine who had recently used suma-sc, and found it well tolerated. Three attacks were treated on each study medication. Assessment of subjective preference was evaluated, after which patients freely chose which study medication they wished to use to treat each of three additional migraine attacks. A slight majority (50.6%) preferred or greatly preferred eletriptan, whilst 43% preferred suma-sc. When permitted to choose between eletriptan and suma-sc for subsequent treatment, 78% of patients who had preferred eletriptan took eletriptan during the extension phase for all three of their attacks, whilst only 37% of patients who preferred suma-sc took suma-sc for all of their extension-phase attacks (P < 0.05). Secondary efficacy measures showed comparable efficacy for each study medication, except for faster headache response and pain-free rates favor of suma-sc, and a significantly lower recurrence rate on eletriptan (25% vs. 40%; P < 0.05). The results of this study suggest that eletriptan is a strong alternative option for patients who have been prescribed suma-sc.

No effect of eletriptan administration during the aura phase of migraine.

Migraine aura is a warning sign readily recognized by patients. From the onset of aura it takes 30-60 min before the headache phase starts. Administration of acute medication during aura should provide sufficient time to achieve therapeutic plasma levels, counteracting the headache. To test this hypothesis we evaluated the efficacy of eletriptan 80 mg taken during aura. Patients met International Headache Society diagnostic criteria for migraine with aura, with an attack frequency of at least one per month and with aura occurring in > 50% of recent attacks. Of 123 patients randomized, 87 (71%) were treated with a double-blind, one attack, during the aura phase before headache, dose of either eletriptan 80 mg (n = 43; 74% female; mean age, 40 years), or placebo (n = 44; 82% female; mean age, 40 years). The primary outcome measure was the proportion of patients not developing moderate-to-severe headache within 6 h post-dose. There was no significant difference in the proportion of patients developing moderate-to-severe headache on eletriptan (61%) versus placebo (46%). Eletriptan was well tolerated and did not prolong the aura phase. Typical transient triptan adverse events were observed; most were mild-to-moderate in intensity. This study confirms the findings of two studies showing that triptans are ineffective but safe when given during the migraine aura phrase.

Effect of high-dose intravenous eletriptan on coronary artery diameter.

The goal of this study was to evaluate the coronary vasoconstrictive effects of high doses of eletriptan compared with a standard dose of sumatriptan. Patients with no clinically significant coronary artery disease were randomized to receive high-dose intravenous eletriptan (n = 24) vs a standard dose of sumatriptan (n = 18; 6 mg subcutaneously) vs placebo (n = 18). Serial angiograms were obtained. The primary non-inferiority analysis found equivalence between the mean maximum change in left anterior descending coronary artery diameter for eletriptan, -22%[95% confidence interval (CI) -26, -19], and sumatriptan, -19% (95% CI -22, -16). The change due to placebo was -16% (95% CI -20, -12). No individual cases of clinically significant vasoconstriction were observed. The results confirm that eletriptan has a broad cardiovascular safety margin, with plasma concentrations comparable to three to five times the Cmax of an oral 80-mg dose associated with modest vasoconstriction equivalent to standard therapeutic doses of sumatriptan.

Comparative efficacy of eletriptan vs. naratriptan in the acute treatment of migraine.

This was a randomized, double-blind study designed to evaluate the comparative efficacy and tolerability of the 40-mg dose of eletriptan and the 2.5-mg dose of naratriptan. Patients (n = 548) meeting International Headache Society (IHS) criteria for migraine were randomized to treat a single migraine attack with either eletriptan 40 mg, naratriptan 2.5 mg, or placebo. Headache response rates at 2 h and 4 h, respectively, were 56% and 80% for eletriptan, 42% and 67% for naratriptan (P < 0.01 for both time-points vs. eletriptan), and 31% and 44% for placebo (P < 0.0001 vs. both active drugs at both time-points). Eletriptan also showed a significantly greater pain-free response at 2 h (35% vs. 18%; P < 0.001) as well as lower use of rescue medication (15% vs. 27%; P < 0.01) and higher sustained headache response at 24 h (38%) compared with naratriptan (27%; P < 0.05) and placebo (19%; P < 0.01). Both eletriptan and naratriptan were well tolerated. The results confirm previous meta-analyses that have suggested the superiority of eletriptan vs. naratriptan in the acute treatment of migraine.

A self-administered screener for migraine in primary care: The ID Migraine validation study.

BACKGROUND: Migraine is a highly prevalent and disabling illness that remains substantially undiagnosed in primary care. Because of the potential value of a screening tool, the current study was designed to establish the validity and reliability of a brief, self-administered migraine screener in patients with headache complaints in the primary care setting. METHODS: A total of 563 patients presenting for routine primary care appointments and reporting headaches in the past 3 months completed a self-administered migraine screener. All patients were then referred for an independent diagnostic evaluation by a headache expert, of whom 451 (80%) completed a full evaluation. Migraine diagnosis was assigned based on International Headache Society criteria after completing a semi-structured diagnostic interview. RESULTS: Of nine diagnostic screening questions, a three-item subset of disability, nausea, and sensitivity to light provided optimum performance, with a sensitivity of 0.81 (95% CI, 0.77 to 0.85), a specificity of 0.75 (95% CI, 0.64 to 0.84), and positive predictive value of 0.93 (95% CI, 89.9 to 95.8). Test-retest reliability was good, with a kappa of 0.68 (95% CI, 0.54 to 0.82). The sensitivity and specificity of the three-item migraine screener was similar regardless of sex, age, presence of other comorbid headaches, or previous diagnostic status. CONCLUSIONS: The three-item ID Migraine migraine screener was found to be a valid and reliable screening instrument for migraine headaches. Its ease of use and operating characteristics suggest that it could significantly improve migraine recognition in primary care.

Efficacy, safety and tolerability of oral eletriptan in the acute treatment of migraine: results of a phase III, multicentre, placebo-controlled study across three attacks.

The efficacy, safety and tolerability of the 5-HT1B/D receptor agonist eletriptan (40 mg and 80 mg) in acute treatment of migraine was evaluated in a multinational, randomized, double-blind, parallel-group, placebo-controlled, three-attack study treating 1153 patients. In the initial attack, significantly more eletriptan patients reported headache relief and complete pain relief at 2 h vs. placebo (40 mg 62% and 32%, 80 mg 65% and 34%, placebo 19% and 3%; P < 0.0001). Headache relief occurred faster after eletriptan, with more patients at both doses reporting relief 30 min (P < 0.01) and 1 h (P < 0.0001) after treatment than after placebo. There was a significantly lower recurrence rate with eletriptan 80 mg compared with placebo (P < 0.01). Adverse events for all treatments were generally mild or moderate and self-limiting. Eletriptan 40 mg and eletriptan 80 mg both appear to be effective and well-tolerated acute migraine treatments.

Malignant priapism associated with metastatic urethral carcinoma.

We present a 40-year-old man with malignant priapism secondary to urethral squamous cell carcinoma. Magnetic resonance imaging revealed the tumor originating from the bulbous urethra, extending into the penile urethra and corpora spongiosa and cavernosa. A penile biopsy confirmed poorly differentiated squamous cell carcinoma of the urethra. Despite administration of systemic chemotherapy, the prognosis of the patient has worsened due to the extensive metastatic disease.

No acute antimigraine efficacy of CP-122,288, a highly potent inhibitor of neurogenic inflammation: results of two randomized, double-blind, placebo-controlled clinical trials.

CP-122,288 is a highly potent inhibitor of neurogenic plasma extravasation in animal models at doses without vasoconstrictor effect. We evaluated the acute antimigraine efficacy of intravenous and oral CP-122,288 in two double-blind studies. In a crossover design, patients randomly received 31.25 microg of CP-122,288 intravenously, placebo, or both. In the oral study, patients received placebo or one of four doses of CP-122,288 between 3.125 and 312.5 microg, using a novel "up and down" design for randomization. Both studies were stopped prematurely when target efficacy could not be achieved. Responder rates were 29% for CP-122,288 versus 30% for placebo (difference, -1%; 95% CI, -24-22%; intravenous study) and an overall rate of 25% for CP-122,288 versus 0% for placebo (difference, 25%; 95% CI; 10-40%; oral study). CP-122,288 was not clinically effective at doses and plasma concentrations in excess of those required to inhibit neurogenic plasma extravasation in animals. Neurogenic plasma extravasation is unlikely to play a crucial role in the pathophysiology of migraine headache.

Combined inhibition of neutral endopeptidase and angiotensin-converting enzyme by sampatrilat in essential hypertension.

BACKGROUND: The antihypertensive response to angiotensin-converting enzyme (ACE) inhibitors may be attenuated by a compensatory decrease in atrial natriuretic factor production. If so, inhibition of atrial natriuretic factor breakdown by neutral endopeptidase (NEP) may enhance the antihypertensive effects of ACE inhibition. We compared effects of the combined ACE-NEP inhibitor sampatrilat, lisinopril, and placebo on blood pressure, plasma ACE, and renin activity and urinary cyclic guanosine monophosphate (cGMP) of patients with hypertension. METHODS AND RESULTS: After a 4-week placebo run-in period, 124 patients with a mean blood pressure of 162/102 mm Hg were randomized in a double-blind parallel-group design to 1 of 5 treatments, given once daily for 10 days: 50 mg, 100 mg, or 200 mg sampatrilat; 20 mg lisinopril; or placebo. The first dose of sampatrilat did not lower clinic or ambulatory blood pressure. Lisinopril had an immediate antihypertensive effect that differed significantly from all doses of sampatrilat. After 10 days of treatment, sampatrilat lowered clinic and ambulatory blood pressure significantly at all doses, with a trend toward a dose response for systolic ambulatory blood pressure. Sampatrilat inhibited plasma ACE in a dose-dependent fashion but significantly less so than lisinopril on days 1 and 10 of treatment. Lisinopril but not sampatrilat significantly increased plasma renin activity, whereas sampatrilat but not lisinopril significantly increased urinary cGMP excretion. CONCLUSION: The increasing efficacy of sampatrilat compared with lisinopril over 10 days could not be attributed to an increase in plasma ACE inhibition, suggesting that the NEP inhibitor activity of sampatrilat may have contributed to its antihypertensive action. NEP inhibition may enhance the antihypertensive effect of ACE inhibition.

Can a hydrophilic guidewire be resterilized?

The Glidewire (Microvasive, Natick, MA) or Terumo wire (Terumo, Japan) is constructed with a hydrophilic polymer surface that enables easier passage through narrowed lumens in the urinary tract. This study examined the effects of gas sterilization on Glidewire surface structure, slipperiness, and ability to support bacterial growth. Light microscopy at 100x and 400x and scanning electron microscopy at 100 to 1300x were used to compare the surface tips of five new 0.038-inch Glidewires with those resterilized one or three times. The tips were immersed in water prior to standard gas sterilization for operating room equipment. Subjective evaluation of slipperiness involved asking 10 blinded urologists to assess the nature of new and resterilized wires by feel. Support of bacterial growth was assessed by comparing cultures performed on new wires (control) with those of wires incubated with Bacillus stearothermophilus. Microscopy, reviewed by a pathologist, revealed no perceivable surface differences after one and three gas sterilizations. Eight of the urologists noted similar or improved slipperiness of resterilized wires compared with new wires. Bacterial cultures of intentionally infected wire segments showed no growth after standard gas sterilization in all cases. In this study, gas sterilization did not adversely affect the lubricious nature or the surface coating of the hydrophilic coating of Glidewires. Also, gas resterilization was bactericidal to new and used wires that had been infected with a heat-tolerant organism.

Self-poisoning in Sri Lanka: factors determining the choice of the poisoning agents.

Sri Lanka is a developing agricultural country with a high fatality rate due to self-poisoning with very toxic agrochemicals as the main poisoning agents. A prospective study of 97 consecutive admissions following self-poisoning reveals that easy availability of the agrochemicals together with the lack of knowledge regarding their lethality were the main causative factors determining the choice of poisoning agents. Developing community awareness of the lethality of these substances, educating the farmers with regards to proper storage and disposal of agrochemicals together with stricter legislation regarding their sale and distribution may reduce the incidence of self-poisoning due to these agents with a consequent reduction in mortality due to self-poisoning.

Pattern of poisoning in rural Sri Lanka.

An epidemiology study of poisoning was done in a geographically defined area in rural Sri Lanka, a developing agricultural country. The incidence of poisoning was 75 per 100,000 population and the death rate was very high (22 per 100,000 population). Both were highest in the age group 15-34 and there were significant ethnic differences in the incidence of poisoning. Agrochemicals were responsible for 59% of all poisonings. Paraquat was the commonest poisoning agent with a high fatality rate of 68%. Use of highly toxic agents may have resulted in deaths where there was no intention to commit suicide. Strict legislation regarding the sale, distribution and storage of agrochemicals could result in the reduction of mortality and perhaps the incidence of poisoning, in developing agricultural countries.

Self poisoning in Sri Lanka: motivational aspects.

Sri Lanka is a developing Asian country with high suicide rate due to self poisoning, related to a high fatality rate. A study of motivational aspects of self poisoning in 97 consecutive patients showed that there is no greater intention of suicide in them than those from the developed countries. Interpersonal disputes involving domestic problems and love affairs are the main precipitating causes. Improving family relations may help in the prevention of self-poisoning. However the impulsive nature of the act might prove prevention a difficult task.

Spironolactone in thiazide-induced hypokalaemia: variable response between patients.

1 The influence of spironolactone 25, 50, 100 and 200 mg daily, and placebo, on plasma potassium and other variables was examined in a random crossover study of 15 hypertensive patients taking bendrofluazide 10 mg daily. 2 Spironolactone produced significant dose-related increases in plasma potassium and aldosterone, and reductions in plasma sodium and bicarbonate. 3 In 14 compliant patients plasma concentrations of the major metabolite canrenone were related linearly to the dose of spironolactone, and there was less than twofold variation between patients. The plasma canrenone concentration correlated negatively with body weight (r = -0.77, P less than 0.001). 4 The plasma potassium response to spironolactone varied sevenfold between compliant patients. The response correlated negatively with placebo plasma potassium (r = -0.62, P less than 0.02), positively with plasma canrenone (r = +0.55, P less than 0.05), but was unrelated to plasma aldosterone (r = -0.22). In one patient relative resistance to spironolactone was attributed to exaggerated secondary hyperaldosteronism induced by the drug. 5 The variability in response to spironolactone between patients is such that fixed dose thiazide-spironolactone combination tablets are unlikely to prevent hypokalaemia reliably.