Randomized placebo-controlled trial of the activity of the morphine glucuronides

BACKGROUND: Morphine-6-glucuronide (M6G) is an active metabolite of morphine with potent analgesic activity. Morphine-3-glucuronide (M3G), the most prevalent metabolite, has minimal affinity for opioid receptors. It has been suggested from animal model data and by examination of metabolite ratios in humans that M3G may functionally antagonize the respiratory depressant and analgesic actions of morphine and M6G. METHODS: We performed a double-blind placebo-controlled trial with 10 healthy volunteers. The trial had 6 arms: (1) placebo, (2) 10 mg/70 kg of morphine, (3) 3.3 mg/70 kg of M6G, (4) 30.6 mg/70 kg of M3G, (5) 30.6 mg/70 kg of M3G with 10 mg/70 kg of morphine, and (6) 30.6 mg/70 kg of M3G with 3.3 mg/70 kg of M6G; all were give by slow intravenous bolus. Analgesia was assessed with the use of the submaximal ischemic pain model. The effects were quantified on numerical and visual analogue scales. Respiratory parameters and response to steady state 5% carbon dioxide challenge were assessed with spirometry, mass spectroscopy, and earlobe blood gas analysis. RESULTS: Morphine and M6G produced significant pain relief compared with placebo (morphine, P < .0001; M6G, P = .033). Pain relief after M6G was less than after morphine (P = .009) and M3G was no better than placebo (P = .26). Pain relief with morphine and M6G were not significantly altered by M3G (P = .59 and P = .28, respectively). Significant and similar dysphoria and sedation occurred with both morphine (P < .002) and M6G (P < .016) but were absent with both M3G and placebo. Respiratory parameters suggested that M6G produced less respiratory depression than morphine. Both morphine and M6G caused a significant reduction in respiratory drive compared with placebo (morphine, P = .002; M6G, P = .013); this effect was not reversed by M3G (P = .35 and P = .83, respectively). CONCLUSIONS: M3G appears to be devoid of significant activity; in these circumstances and at these doses, it does not antagonize either the analgesic or respiratory depressant effects of M6G or morphine.     

Provision of alternating air-pressure mattresses in the community

The presence of pressure ulcers is seen as a key indicator of quality (Department of Health, 1993) and they are both costly to the patient (Franks, 2001) and the NHS. It is important that resources are directed towards prevention rather than treatment, which makes the provision of pressure-relieving equipment an integral part of any strategy for the prevention and management of pressure ulcers.     

Randomized controlled trial of a family problem-solving intervention

Adaptive problem solving contributes to individual and family health and development. In this article, the effect of the cooperative family learning approach (CFLA) on group family problem solving and on cooperative parenting communication is described. A pretest or posttest experimental design was used. Participant families were recruited from Head Start programs and exhibited two or more risk factors. Participant preschool children were screened to have two or more developmental delays. Direct behavioral observation measures were used to determine group family problem solving and cooperative parenting communication outcomes. Few group family problem-solving behaviors were coded, and they displayed little variability. However, intervention parents increased the length of time they played and extended the cooperative parent-child interactions. The evidence shows that CFLA has the potential to enhance parental-modeling of cooperative behavior while engaged in play activities with preschoolers. Direct measurement of group family problem solving was difficult. Solutions are suggested.     

Randomized crossover trial studying the effect of music on examination anxiety

The purpose of this study was to assess the effect of lento music on examination anxiety among nursing students. A randomized crossover classroom-based trial was conducted. Thirty-eight students with a mean age of 19.4 years (SD = .54) were randomly assigned to either a music/silence or a silence/music group sequence. The students in the music group were given a 40-min group-based music intervention in a classroom, whereas the students in the silence group received the regular test without music. Using paired t-tests, there were no significant different in pretest scores for state anxiety, examination anxiety, finger temperature and pulse rate between the two conditions. Nonetheless, the findings indicated that music intervention did effectively decrease examination anxiety and state anxiety as well as reducing pulse rate and increasing higher finger temperature (p = 0.05 to 0.001). In addition, significant differences were detected between the pretest and posttest measures for silence (p = 0.001). The results suggest that lento music is effective at anxiety reduction. This study provides evidence for nursing faculty and clinical educators to foster nursing students' mastering over the anxiety of examination by using lento music.     

Randomized comparison of J-shaped and straight atrial screw-in pacing leads

OBJECTIVE: To study the importance of a J shape in atrial pacing leads. PATIENTS AND METHODS: We compared in a randomized controlled study acute and chronic results with 2 steroid-eluting, polyurethane, screw-in atrial lead models that differ only in shape. A total of 208 patients were randomized to have implantation of either a straight atrial lead (n = 105) or a J-shaped atrial lead (n = 103). Patients were followed up for 1 year. RESULTS: On implantation, there were no significant differences between leads in rates of failure to implant, implant measurements, number of attempts to achieve an acceptable position, and fluoroscopy times. Before discharge and at 3-month and 1-year follow-up, electrical measurements showed no statistical differences between leads. During the first year after implantation, there were 2.9% early dislodgments (< 1 week after implantation) and 2.9% late dislodgments in the straight lead group (5.9% rate of all dislodgments) vs no dislodgments in the J-shaped lead group (P = .01). There was a trend toward higher rates of exit block and lead malfunction in the J-shaped lead group. Rates of pericardial complications, subclavian/axillary thrombosis, and chronic atrial fibrillation were the same in both groups. CONCLUSIONS: Both leads appear to have an equally favorable performance profile for 1 year of follow-up. The J-shaped lead seems to be more stable and have fewer dislodgments, although it may have a somewhat higher malfunction rate.     

Randomized pharmacokinetic and pharmacodynamic comparison of fluoroquinolones for tuberculous meningitis

Tuberculous meningitis (TBM) is the most lethal form of tuberculosis, and new treatments that improve outcomes are required. We randomly assigned adults with TBM to treatment with standard antituberculosis treatment alone or in combination with ciprofloxacin (750 mg/12 h), levofloxacin (500 mg/12 h), or gatifloxacin (400 mg/24 h) for the first 60 days of therapy. Fluoroquinolone concentrations were measured with plasma and cerebrospinal fluid (CSF) specimens taken at predetermined, randomly assigned times throughout treatment. We aimed to describe the pharmacokinetics of each fluoroquinolone during TBM treatment and evaluate the relationship between drug exposure and clinical response over 270 days of therapy (Controlled Trials number ISRCTN07062956). Sixty-one patients with TBM were randomly assigned to treatment with no fluoroquinolone (n = 15), ciprofloxacin (n = 16), levofloxacin (n = 15), or gatifloxacin (n = 15). Cerebrospinal fluid penetration, measured by the ratio of the plasma area under the concentration-time curve from 0 to 24 h (AUC(0-24)) to the cerebrospinal fluid AUC(0-24), was greater for levofloxacin (median, 0.74; range, 0.58 to 1.03) than for gatifloxacin (median, 0.48; range, 0.47 to 0.50) or ciprofloxacin (median, 0.26; range, 0.11 to 0.77). Univariable and multivariable analyses of fluoroquinolone exposure against a range of different treatment responses revealed worse outcomes among patients with lower and higher plasma and CSF exposures than for patients with intermediate exposures (a U-shaped exposure-response). TBM patients most likely to benefit from fluoroquinolone therapy were identified, along with exposure-response relationships associated with improved outcomes. Fluoroquinolones add antituberculosis activity to the standard treatment regimen, but to improve outcomes of TBM, they must be started early, before the onset of coma.     

Randomized controlled trial of exercise for chronic whiplash-associated disorders

Whiplash-associated disorders are common and incur considerable expense in social and economic terms. There are no known effective treatments for those people whose pain and disability persist beyond 3 months. We conducted a randomized, assessor-blinded, controlled trial at two centres in Australia. All participants received 3 advice sessions. In addition the experimental group participated in 12 exercise sessions over 6 weeks. Primary outcomes were pain intensity, pain bothersomeness and function measured at 6 weeks and 12 months. Exercise and advice was more effective than advice alone at 6 weeks for all primary outcomes but not at 12 months. The effect of exercise on the 0-10 pain intensity scale was -1.1 (95%CI -1.8 to -0.3, p=0.005) at 6 weeks and -0.2 (0.6 to -1.0, p=0.59) at 12 months; on the bothersomeness scale the effect was -1.0 (-1.9 to -0.2, p=0.003) at 6 weeks and 0.3 (-0.6 to 1.3, p=0.48) at 12 months. The effect on function was 0.9 (0.3 to 1.6, p=0.006) at 6 weeks and 0.6 (-0.1 to 1.4, p=0.10) at 12 months. High levels of baseline pain intensity were associated with greater treatment effects at 6 weeks and high levels of baseline disability were associated with greater treatment effects at 12 months. In the short-term exercise and advice is slightly more effective than advice alone for people with persisting pain and disability following whiplash. Exercise is more effective for subjects with higher baseline pain and disability.     

Randomized clinical trial of distraction for infant immunization pain

Distraction has been shown to be an effective technique for managing pain in children; however, few investigations have examined the utility of this technique with infants. The goal of the current study was to investigate the effectiveness of movie distraction in reducing infants' immunization distress. Participants were 136 infants (range=1-21 months; M=7.6 months, SD=5.0 months) and their parents, all of whom were recruited when presenting for routine vaccinations. The parent-child dyads were randomly assigned to either a Distraction or Typical Care control condition. Infant and adult behaviors were assessed using a visual analog scale and a behavioral observation rating scale. Results indicated parents in the Distraction group engaged in higher rates of distraction than those in the Typical Care group, whereas there was no difference in the behavior of nurses in the Distraction and Typical Care groups. In addition, infants in the Distraction group displayed fewer distress behaviors than infants in the Typical Care group both prior to and during recovery from the injection. Findings suggest that a simple and practical distraction intervention can provide some distress relief to infants during routine injections.     

Randomized trial of two mind-body interventions for weight-loss maintenance

OBJECTIVE: Regain of weight after initial weight loss constitutes a major factor contributing to the escalating obesity epidemic. The objective of this study was to determine the feasibility and clinical impact of two mind-body interventions for weight-loss maintenance. DESIGN: Randomized, balanced, controlled trial. SETTING: Large-group model health maintenance organization. PARTICIPANTS: Overweight and obese adults were recruited to a 12-week behavioral weight-loss program. Participants meeting threshold weight loss and attendance requirements were eligible for randomization. INTERVENTIONS: The three weight-loss maintenance interventions were qigong (QI), Tapas Acupressure Technique (TAT (registered trademark of Tapas Fleming, L.Ac.), and a self-directed support (SDS) group as an attention control. OUTCOMES: The main outcome measure was weight loss maintenance at 24 weeks postrandomization. Patient interviews explored additional benefits of the interventions, as well as barriers and facilitators to compliance. RESULTS: Eighty-eight percent (88%) of randomized patients completed the study. There were no significant study-related adverse events. At 24 weeks, the TAT group maintained 1.2 kg more weight loss than the SDS group did (p = 0.09), and 2.8 kg more weight loss than the QI group did (p = 0.00), only regaining 0.1 kg. A separation test (0.05 level, 0.95 power) indicated that TAT merits further study. A secondary analysis revealed that participants reporting a previous history of recurrent unsuccessful weight loss were more likely to regain weight if assigned to the SDS arm, but this effect was suppressed in both the QI and TAT groups (p = 0.03). Although QI participants reported important general health benefits, the instruction sequence was too brief, given the complexity of the intervention. CONCLUSIONS: TAT warrants further research for weight-loss maintenance. Any further research on qigong should use a modification of our protocol.     

Randomized controlled trial of a lay-facilitated angina management programme

furze g., cox h., morton v., chuang l.-h., lewin r.j.p., nelson p., carty r., norris h., patel n. & elton p. (2012)?Randomized controlled trial of a lay-facilitated angina management programme. Journal of Advanced Nursing68(10), 2267-2279. ABSTRACT: Aims. This article reports a randomized controlled trial of lay-facilitated angina management (registered trial acronym: LAMP). Background. Previously, a nurse-facilitated angina programme was shown to reduce angina while increasing physical activity, however most people with angina do not receive a cardiac rehabilitation or self-management programme. Lay people are increasingly being trained to facilitate self-management programmes. Design. A randomized controlled trial comparing a lay-facilitated angina management programme with routine care from an angina nurse specialist. Methods. Participants with new stable angina were randomized to the angina management programme (intervention: 70 participants) or advice from an angina nurse specialist (control: 72 participants). Primary outcome was angina frequency at 6?months; secondary outcomes at 3 and 6?months included: risk factors, physical functioning, anxiety, depression, angina misconceptions and cost utility. Follow-up was complete in March 2009. Analysis was by intention-to-treat; blind to group allocation. Results. There was no important difference in angina frequency at 6?months. Secondary outcomes, assessed by either linear or logistic regression models, demonstrated important differences favouring the intervention group, at 3?months for: Anxiety, angina misconceptions and for exercise report; and at 6?months for: Anxiety; Depression; and angina misconceptions. The intervention was considered cost-effective. Conclusion. The angina management programme produced some superior benefits when compared to advice from a specialist nurse.     

Evaluation of an electric bed frame and pressure-reducing mattresses

Pressure ulcers remain a challenge to all healthcare professionals. With the trend towards caring for ill patients in the community there is a need to ensure that equipment used to prevent pressure ulcers in these patients is effective. It is not always appropriate to simply use equipment designed for hospital. This article describes the evaluation of an electric bed frame and three mattresses specifically designed for patients in the community, in either their own homes or nursing home/residential care. The location of this research can reduce the number of participants recruited. In order to compensate for this, three different methods of evaluation were employed - clinical, laboratory and anecdotal - which have produced results relevant to both purchasers and users of the system tested.     

Randomized trial of the anti-FGF23 antibody KRN23 in X-linked hypophosphatemia

Background. X-linked hypophosphatemia (XLH) is the most common heritable form of rickets and osteomalacia. XLH-associated mutations in phosphate-regulating endopeptidase (PHEX) result in elevated serum FGF23, decreased renal phosphate reabsorption, and low serum concentrations of phosphate (inorganic phosphorus, Pi) and 1,25-dihydroxyvitamin D [1,25(OH)₂D]. KRN23 is a human anti-FGF23 antibody developed as a potential treatment for XLH. Here, we have assessed the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD), and immunogenicity of KRN23 following a single i.v. or s.c. dose of KRN23 in adults with XLH. Methods. Thirty-eight XLH patients were randomized to receive a single dose of KRN23 (0.003–0.3 mg/kg i.v. or 0.1–1 mg/kg s.c.) or placebo. PK, PD, immunogenicity, safety, and tolerability were assessed for up to 50 days. Results. KRN23 significantly increased the maximum renal tubular threshold for phosphate reabsorption (TmP/GFR), serum Pi, and 1,25(OH)₂D compared with that of placebo (P < 0.01). The maximum serum Pi concentration occurred later following s.c. dosing (8–15 days) compared with that seen with i.v. dosing (0.5–4 days). The effect duration was dose related and persisted longer in patients who received s.c. administration. Changes from baseline in TmP/GFR, serum Pi, and serum 1,25(OH)₂D correlated with serum KRN23 concentrations. The mean t_1/2 of KRN23 was 8–12 days after i.v. administration and 13–19 days after s.c. administration. Patients did not exhibit increased nephrocalcinosis or develop hypercalciuria, hypercalcemia, anti-KRN23 antibodies, or elevated serum parathyroid hormone (PTH) or creatinine. Conclusion. KRN23 increased TmP/GFR, serum Pi, and serum 1,25(OH)₂D. The positive effect of KR23 on serum Pi and its favorable safety profile suggest utility for KRN23 in XLH patients. Trial registration. Clinicaltrials.gov NCT00830674. Funding. Kyowa Hakko Kirin Pharma, Inc.     

Randomized trial of buprenorphine for treatment of concurrent opiate and cocaine dependence

BACKGROUND: Buprenorphine is a partial mu-opiate agonist and kappa-opiate antagonist with established efficacy in the treatment of opiate dependence. Its efficacy for cocaine dependence is uncertain. This study evaluated buprenorphine for the treatment of concomitant cocaine and opiate dependence. METHODS: Two hundred outpatients currently dependent on both cocaine and opiates were randomly assigned to double-blind groups receiving a sublingual solution of buprenorphine (2, 8, or 16 mg daily, or 16 mg on alternate days, or placebo), plus weekly individual drug abuse counseling, for 13 weeks. The chief outcome measures were urine concentrations of opiate and cocaine metabolites (quantitative) and proportion of urine samples positive for opiates or cocaine (qualitative). Group differences were assessed by use of mixed regression modeling. RESULTS: The target dose of buprenorphine was achieved in 179 subjects. Subjects receiving 8 or 16 mg buprenorphine daily showed statistically significant decreases in urine morphine levels (P =.0135 for 8 mg and P <.001 for 16 mg) or benzoylecgonine concentrations (P =.0277 for 8 mg and P =.006 for 16 mg) during the maintenance phase of the study. For the 16-mg group, mean benzoylecgonine concentrations fell from 3715 ng/mL during baseline to 186 ng/mL during the withdrawal phase; mean morphine concentrations fell from 3311 ng/mL during baseline to 263 ng/mL during withdrawal. For the 8-mg group, mean benzoylecgonine concentrations fell from 6761 ng/mL during baseline to 676 ng/mL during withdrawal; mean morphine concentrations fell from 3890 ng/mL during baseline to 661 ng/mL during withdrawal. Qualitative urinalysis showed a similar pattern of results. Subjects receiving the highest dose showed concomitant decreases in both urine morphine and benzoylecgonine concentrations. There were no significant group differences in treatment retention or adverse events. CONCLUSIONS: A sublingual buprenorphine solution at 16 mg daily is well tolerated and effective in reducing concomitant opiate and cocaine use. The therapeutic effect on cocaine use appears independent of that on opiate use.     

Randomized comparison of nasojejunal and nasogastric feeding in critically ill patients

OBJECTIVE: Critically ill patients often develop large gastric residual volumes during nasogastric feeding as a result of poor gastroduodenal motility. Nasojejunal feeding may decrease the severity of this complication. The aim of this study was to determine whether nasojejunal feeding improved tolerance of enteral nutrition by reducing gastric residual volumes. DESIGN: Randomized, prospective, clinical study. SETTING: Intensive care unit of a university-affiliated hospital. PATIENTS: Seventy-three intensive care unit patients expected to require nutritional support for at least 3 days. INTERVENTIONS: Patients were randomized to receive enteral nutrition via a nasojejunal tube (placed endoscopically) (34 patients) or a nasogastric tube (39 patients). A strict protocol was followed, which included regular gastric residual volume measurement (in both groups), the use of predetermined criteria for intolerance, and an attempt at nasojejunal feeding for those nasogastrically fed patients who were intolerant of enteral nutrition. MEASUREMENTS AND MAIN RESULTS: Endoscopic placement of nasojejunal tubes was successful in 98% with no complications of insertion. Patients fed via a nasojejunal tube had 1) a reduced total gastric residual volume in both the first 24 (197 vs. 491 mL, p = .02) and 48 hrs (517 vs. 975 mL, p = .02); 2) a reduced incidence of a single gastric residual volume >150 mL (32% vs. 74%, p = .001); and 3) a trend toward a reduced incidence of intolerance of enteral nutrition (13% vs. 31%, p = .09). Only 13% of those nasogastrically fed patients who were initially intolerant of enteral nutrition remained intolerant once fed via a nasojejunal tube, and only 1.4% of all patients met criteria for commencement of parenteral nutrition. CONCLUSIONS: Enteral nutrition delivered via a nasojejunal tube is associated with a significant reduction in gastric residual volume, a strong trend toward improved tolerance of enteral nutrition, and an extremely low requirement for parenteral nutrition.