Are health states ‘timeless’? A case study of an acute condition: post‐chemotherapy nausea and vomiting1

Rationale, aims and objectives The objective was to test whether individuals’ responses to standard gamble (SG) and visual analogue scale (VAS) questions do not depend on the time horizon of the health scenario presented. Methods Face‐to‐face interviews were conducted in a convenience sample of 18 women aged 22–50 years with no history of breast cancer or cancer requiring chemotherapy. Data were collected from March 2000 to June 2000 at a university in the Midwest of the United States of America. Preference weights were estimated using SG top‐down titration method and VAS scaled from zero (death) to one (perfect health). Subjects were asked to rate their preferences if faced with two scenarios: post‐chemotherapy nausea and vomiting (PCNV) occurring for 3 days (scenario 1), and PCNV lasting for the rest of their lives (scenario 2). Three PCNV health states of varying severity were tested: complete alleviation, partial alleviation, and no alleviation. Results Paired‐t‐test analysis showed statistically significantly lower preference weights (P < 0.05) when the health state was for the rest of the respondent's life vs. 3 days. Mean SG weights for scenario 1 vs. scenario 2 were: 0.968 vs. 0.927 (complete alleviation), 0.942 vs. 0.810 (partial alleviation) and 0.866 vs. 0.644 (no alleviation). Mean VAS weights for scenario 1 vs. scenario 2 were: 0.741 vs. 0.676 (complete alleviation), 0.490 vs. 0.307 (partial alleviation) and 0.276 vs. 0.136 (no alleviation). Discussion and conclusions For the majority of respondents the utility independence assumption for SG and VAS did not hold. Similar to Bala et al., the results of this study indicated that preference weights as measured by SG and VAS techniques were not ‘timeless’. Regardless of the preference measure used, both SG and VAS yielded higher scores when PCNV lasted for a shorter period of time.     

A randomized double‐blind study of low‐molecular‐weight heparin (parnaparin) for superficial vein thrombosis: STEFLUX (Superficial ThromboEmbolism and Fluxum)

Summary. Background: Optimal doses and duration of low‐molecular‐weight heparin (LMWH) for the treatment of superficial vein thrombosis (SVT) are still uncertain. Objectives: To compare the efficacy and safety of different doses and durations of LMWH parnaparin for symptomatic lower limb SVT. Patients and methods: Outpatients with at least a 4‐cm‐long SVT of long or short saphenous veins or their collaterals were randomized to receive parnaparin either 8500 UI once daily ( o.d.) for 10 days followed by placebo for 20 days (group A) or 8500 UI o.d. for 10 days followed by 6400 UI once daily (o.d.) for 20 days (group B) or 4250 UI o.d. for 30 days (group C) in a double‐blind fashion in 16 clinics. Primary outcome was the composite of symptomatic and asymptomatic deep vein thrombosis (DVT), symptomatic pulmonary embolism (PE) and relapse and/or symptomatic or asymptomatic SVT recurrence in the first 33 days with 60 days follow‐up. Results: Among 664 patients, primary outcome occurred in 33/212 (15.6%), 4/219 (1.8%) and 16/217 (7.3%) subjects in groups A, B and C, respectively (B vs. A: absolute risk reduction [ARR]: 13.7%, 95% confidence intervals [CI]: 8–18.9 P < 0.001; B vs. C: ARR: 5.5%; 95% CI: 1.6–9.4 P = 0.011; C vs. A: ARR: 8.2%, 95% CI: 2–14 P = 0.012). During days 0–93, the event rate was higher in group A (22.6%) than either in group B (8.7%; P = 0.001) or C (14.3%, P = 0.034). No major hemorrhages occurred. Conclusions: An intermediate dose of parnaparin for 30 days is superior to either a 30‐day prophylactic dose or a 10‐day intermediate dose for lower limb SVT treatment.     

Frequency and outcomes of painful physical symptoms in a naturalistic population with major depressive disorder: an analysis of pooled observational studies focusing on subjects aged 65 years and over

Aims: To estimate the frequency of painful physical symptoms (PPS) in elderly subjects (≥ 65 years) with major depressive disorder (MDD) in real‐world clinical conditions and to establish whether PPS are associated with poor depression outcomes, including more severe depression and worse health‐related quality of life (HRQoL). Methods: Observational studies of MDD that included assessment of PPS and elderly subjects were screened. Measures of PPS were based on the Somatic Symptom Inventory (SSI) or Visual Analogue Scale (VAS). Data from a variety of depressive symptom severity and HRQoL scales were used. Analysis cohorts were based on age [aged ≥ 65 years (elderly) or < 65 years (younger)] and/or PPS status (presence or absence); five subsets were used to examine specific outcomes in matched elderly subjects. Results: Data from seven studies (representing 26 countries) were collated. Of the 11,477 subjects, 14% were aged ≥ 65 years and 71% were classified as having PPS (PPS+). PPS were more frequent in elderly subjects (74% vs. 70% of younger subjects) and were positively associated with being female and Hispanic, and negatively associated with being East Asian in the elderly. The presence of PPS was associated with more severe clinical symptomatology and comparatively poorer HRQoL in elderly subjects. Conclusions: PPS, although frequent in younger MDD patients, were slightly more frequent in elderly MDD patients and associated with comparatively poorer clinical and functional outcomes. As elderly patients report somatic symptoms more readily than emotional symptoms, physicians should consider depression in addition to physical causes when PPS are present.     

Effect of polymerized-type I collagen in knee osteoarthritis. II. In vivo study

Background Polymerized‐Type I Collagen (Polymerized‐Collagen) is an anti‐inflammatory and a tissue regenerator biodrug. The aim of the study was to evaluate the efficacy and safety of intra‐articular injections of Polymerized‐Collagen in patients with knee osteoarthritis (OA). Methods and design Patients (n = 53) were treated with 12 intra‐articular injections of 2 mL of Polymerized‐Collagen (n = 27) or 2 mL of placebo (n = 26) during 6 months. Follow up period was 6 months. The primary endpoints included Western Ontario and McMaster University Osteoarthritis Index, Lequesne index, and pain intensity on a visual analogue scale (VAS). Secondary outcomes were patient global score, investigator global score and drug evaluation. Clinical improvement was determined if the decrease in pain exceeds 20 mm on a VAS and patients achieved at least 20% of improvement from baseline. Urinary levels of C‐terminal crosslinking telopeptide of collagen type II (CTXII) and serum high‐sensitivity C‐reactive protein (hsCRP) were determined by enzyme immunoassays. Statistical analysis was performed by intention to treat. Results Polymerized‐Collagen was safe and well tolerated. Patients had a statistically significant improvement (P < 0·05) from baseline vs. Polymerized‐Collagen and vs. placebo at 6 months in: Lequesne Index (13·1 ± 0·5 vs. 7·1 ± 0·7 vs. 9·6 ± 0·8; P = 0·027), WOMAC (9·0 ± 0·5 vs. 4·0 ± 0·6 vs. 5·80 ± 0·8; P = 0·032), patient VAS (60·0 ± 2·6 vs. 20·6 ± 2·4 vs. 36·1 ± 4·5; P = 0·003), physician VAS (49·8 ± 1·9 vs. 16·8 ± 2·9 vs. 29·8 ± 2·9; P = 0·002), patient global score (1·08 ± 0·1 vs. 2·7 ± 0·1 vs. 1·9 ± 0·2; P = 0·028) and analgesic usage (30·1 ± 9·4 vs. 11·0 ± 3·4 vs. 17·9 ± 4·9; P = 0·001). This improvement was persistent during the follow up. A threefold increase in CTXII was determined in placebo group. No differences were found on hs CRP and incidence of adverse events between groups. Conclusion Polymerized‐Collagen is safe and effective in the treatment of knee OA.     

The Short-Term Effects of Acupuncture on Myofascial Pain Patients After Clenching

Aim: Short‐term pain reduction from acupuncture in chronic myofascial pain subjects was evaluated using an 11‐point (0 to 10) numeric rating scale, visual analog scale (VAS), and pain rating of mechanical pressure on the masseter muscle. Methods: A single‐blind, randomized, controlled, clinical trial with an independent observer was performed. Fifteen chronic myofascial pain subjects over the age of 18 were randomly assigned into groups: nine subjects received real acupuncture; six subjects received sham acupuncture. Each subject clenched his/her teeth for 2 minutes. Acupuncture or sham acupuncture was administered at the Hegu Large Intestine 4 acupoint. Sham acupuncture was conducted by lightly pricking the skin with a shortened, blunted acupuncture needle through a foam pad, without penetrating the skin. The foam pad visually conceals the needle's point of the entry, so that the subject cannot discern which technique is being used. The subjects rated their general pain on a numeric rating scale. A mechanical pain stimulus was applied with an algometer and the subject rated his/her pain on a VAS. Statistical analysis was performed using the repeated measures anova , paired t‐tests, and Fisher's exact test as appropriate. Results: There was a statistically significant difference in pain tolerance with acupuncture (P = 0.027). There was statistically significant reduction in face pain (P = 0.003), neck pain (P = 0.011), and headache (P = 0.015) with perception of real acupuncture. Conclusion: Pain tolerance in the masticatory muscles increased significantly more with acupuncture than sham acupuncture.     

Comparison of the tolerability of recombinant human hyaluronidase + normal saline and recombinant human hyaluronidase + lactated ringer's solution administered subcutaneously: A phase IV, double-blind, randomized pilot study in healthy volunteers

Background: Recombinant human hyaluronidase (rHuPH20) (150 U) is approved by the US Food and Drug Administration to facilitate subcutaneous fluid administration in adults and children.Objective: This Phase IV, double-blind, randomized pilot study was designed to compare the tolerability, flow rate, and safety profile of subcutaneous infusions of normal saline (NS) and lactated Ringer's (LR) solutions following subcutaneous administration of rHuPH20.Methods: Healthy volunteers received 1 mL rHuPH20 (150 U) in each thigh, followed by simultaneous gravity-driven subcutaneous infusions of 500 mL of LR solution into 1 thigh and NS solution into the contralateral thigh. Subjects rated infusion-site discomfort in each thigh using a 100-mm (0 = no pain to 100 = most severe pain) visual analog scale (VAS) at baseline (ie, after catheter placement/ rHuPH20 injection and just prior to the start of the infusions) and at the following times: after infusion of 250 mL, after infusion of 500 mL (end of infusion), and when thigh circumference returned to within 5% of baseline. Adverse events (AEs) were recorded throughout the study. The primary tolerability end point was the maximal increase from baseline in infusion-site discomfort on the VAS. Secondary end points included infusion flow rate, change in thigh circumference, subject preference for leftversus right-thigh infusion, and safety profile measures.Results: Fifteen subjects (14 women, 1 man; mean age, 41 years [range, 20–60 years]) were included in the study. Mean (SD) maximal increase from baseline VAS pain score was significantly greater with NS solution than with LR solution (20.0 [19.4] vs 9.4 [18.3] mm, respectively; P = 0.005). Mean infusion flow rate was not significantly different between the NS and LR solutions (384.1 [118.1] vs 395.8 [132.8] mL/h). No significant differences between solutions were observed in mean maximal change in thigh circumference (5.2% [1.6%] vs 5.3% [1.5%]). All subjects expressed global preference for LR infusion over NS infusion. All subjects experienced ≥1 AE; the majority of AEs were mild, localized infusion-site reactions. Of all AEs (regardless of their relationship to study drug or procedure), 81% were mild injectionsite reactions that were similar in nature for the NS and LR solutions. Although the types of mild local AEs were similar for the 2 infusions, they were numerically more common with NS infusions (15 subjects [100%]) than with LR infusions (9 subjects [60%]). For the NS and LR solutions, the most frequent infusion-site AEs were pain (67% vs 40%, respectively), erythema (47% vs 13%), and irritation (27% vs 20%).Conclusions: This small pilot study found that the mean maximal increase from baseline in self-assessed pain VAS scores was statistically significantly higher with NS solution than LR solution. In addition, all subjects preferred LR solution to NS solution, and the incidence of some infusion-site AEs was numerically greater with NS solution. Although the VAS score indicated a statistically significant difference in tolerability favoring LR, the modest changes from baseline suggest both solutions were generally well tolerated and support the use of both NS and LR, as appropriate, for rHuPH20-facilitated subcutaneous isotonic fluid infusion in healthy adults. These results need to be confirmed in larger, controlled clinical studies.     

Statins after recent stroke reduces recurrence and improves survival in an aging Mediterranean population without known coronary heart disease

What is known and Objective: The effect of a statin‐based medical intervention on prevention of fatal and non‐fatal stroke recurrence and the incidence of all‐causes mortality have been explored previously in aging populations within the scope of clinical trials research. However, such evidence needs to be explored under conditions of routine clinical practice. The objective of this study was to determine whether statin therapy in patients with a first stroke episode reduces the incidence of 6‐year recurrent fatal or non‐fatal stroke and all‐cause mortality in an aging Mediterranean population without known coronary heart disease followed in routine medical practice. Methods: A retrospective study was carried out using records on death, hospitalizations owing to stroke and history of statin therapy included in the Badalona Serveis Assistencials (BSA) database. The cohort studied consisted of consecutive patients covered by the BSA health provider plan with a first‐ever acute stroke episode during January 2003 until December 2008, for whom there was available information covering the 6‐year follow‐up period. Recurrence rate (RR) and incidence rate (IR) of fatal/non‐fatal stroke and all‐causes mortality were computed. Association with statin therapy was assessed by means of calculation of relative risk (RR) and hazard ratio (HR) using multivariate logistic regression and Cox proportional hazards models controlling for confounding covariates. Results and Discussion: The cohort comprised a series of 601 consecutive patients [57% men, 75·9 (12·4) years old (88% >60 years)]. Of these, 32% received statins, which were associated with lower fatal/non‐fatal recurrent stroke RR; 7% vs. 18% [adjusted RR = 0·32 (CI: 0·16–0·61), P = 0·001] and lower IR; 16·78 vs. 45·22 events/year‐1000 subjects [adjusted HR = 0·35 (0·19–0·64), P = 0·001]. Similarly, observed all‐causes mortality was lower in the cohort receiving statins; 11% vs. 16% [adjusted RR = 0·29 (CI: 0·08–1·12), P = 0·072], and also mortality rate; 26·09 vs. 36·25 deaths/year‐1000 subjects [adjusted HR = 0·23 (0·08–0·67), P = 0·007]. What is new and Conclusions:  Statin therapy in patients with first‐ever acute stroke lowers the risk of 6‐year stroke recurrence and improves survival in an aging Mediterranean cohort. These results add additional evidence in routine clinical practice to the observed effects of statins in clinical trials.     

Interactions between glutamate and capsaicin in inducing muscle pain and sensitization in humans

The aim of the study was to investigate the interaction between glutamate and capsaicin in inducing muscle pain and sensitization in humans. Fifteen male volunteers participated. Glutamate or capsaicin or isotonic saline, in a paired‐sequence order, was injected randomly into the right or left masseter muscle. Two injections were given in a double‐blinded design 25min apart in 1session/week over 4 weeks: saline (A1) followed by glutamate (A2), capsaicin (B1) followed by glutamate (B2), saline (C1) followed by capsaicin (C2), and glutamate (D1) followed by capsaicin (D2). The subjects drew the area of perceived pain and scored pain intensity on a 0–10 visual analogue scale (VAS). Pressure pain threshold (PPT) at the injection site, at a site 2‐cm away, and on the contralateral side, as well as pressure pain tolerance (PPTol) at the injection site and contralateral site, were also measured before and after injection and subsequently at 5‐min intervals. Paired t‐test analyses showed that the pain drawing area was significantly smaller in the B2 compared to the A2 condition (P=0.028), and significantly larger in the D2 compared to the C2 condition (P=0.027). It also revealed significantly lower VAS peak pain intensity (P=0.008) and smaller VAS area under the curve (P=0.003) for the B2 compared to the A2 condition, and significantly higher VAS peak pain (P=0.015) and larger VAS area under the curve (P=0.037) for the D2 compared to the C2 condition. There was a significant PPT and PPTol decrease at the injection site after glutamate or capsaicin injection (ANOVA: P<0.028). The percentage decrease in PPT or PPTol (at the injection site) was not significantly different for the B2 compared to the A2 condition (Paired t‐test: P>0.682) or for the D2 compared to the C2 condition (P>0.133). Significant PPT changes were also observed at the site 2cm away, but not on the contralateral side. In conclusion, these findings indicate that intramuscular administrations of glutamate and capsaicin interact and influence pain and sensitization of muscle nociceptors: glutamate causes a sensitization to subsequent administration of capsaicin, whereas capsaicin is associated with a desensitization to subsequent injection of glutamate. These findings support previous animal data.     

Hypertension control, predictors for medication adherence and gender differences in older Chinese immigrants

Title. Hypertension control, predictors for medication adherence and gender differences in older Chinese immigrants Aim. This paper is a report of a study to explore the relationship between demographic and cultural factors and antihypertensive medication adherence in older Chinese immigrants. Background. Hypertension is a well‐known controllable risk factor for cardiovascular diseases worldwide, but only 20–80% of patients who take antihypertensive medications adhere adequately to their treatment regimen. Methods. A cross‐sectional study was conducted between 2002 and 2003, with a convenience sample of 75 older men and 69 older women (n = 144, response rate 80%). Medication adherence was defined as ≥80% of the total score on the Morisky scale. Findings. Age (75·2 ± 5·7 vs. 75·9 ± 7·0 years, P = 0·51) and length of stay in the United States of America (12·7 ± 6·4 vs. 12·7 ± 6·6 years, P = 0·97) were similar for men and women. More men were married (85% vs. 46%, P < 0·01). A smaller proportion of men were poor (39% vs. 65%, P < 0·01), believed in religion (49% vs. 70%, P = 0·01), and could speak no English (32% vs. 57%, P < 0·01). Fewer men used Chinese herbs to treat hypertension (4% vs.13%). Hypertension control was low for men and women (53% and 48%, P = 0·51). Adherence in men and women was 69% and 75% (P = 0·42) respectively. For men, shorter length of stay in the United States of America was negatively associated with non‐adherence (OR = 0·16; 95% CI: 0·05, 0·57). No association between length of stay and non‐adherence was found for women. Conclusion. More research, including gender‐specific studies, is needed to understand better how to develop an effective and culturally sensitive strategy to help older Chinese immigrants manage their hypertension.     

Withdrawal of inhaled steroids in children with non‐cystic fibrosis bronchiectasis

Background: To study the effects of inhaled steroid withdrawal on bronchial hyperreactivity, sputum inflammatory markers and neutrophilic apoptosis in children with non‐cystic fibrosis (non‐CF) bronchiectasis. Objectives: To evaluate the role of inhaled steroids in the treatment of children with non‐CF bronchiectasis with specific emphasis on the bronchial hyperreactivity and neutrophilic apoptosis. Methods: Twenty‐seven children with steady‐state non‐CF bronchiectasis were evaluated primarily with metacholine challenge tests and apoptotic neutrophil ratios in induced sputum and secondarily with symptom scores, pulmonary function tests and tumour necrosis factor‐alpha (TNF‐α), interleukin‐8 (IL‐8) levels and neutrophil ratios in induced sputum before and after 12‐week withdrawal of inhaled steroids. Results: There were 16 girls and 11 boys. Median (interquartile range) age was 11·4 (9·5–13·6) years, follow‐up duration was 3·5 (2–6·5) years. Symptom scores (4 vs. 3; P = 0·27), oxygen saturation (95% vs. 97%; P = 0·06), pulmonary function tests (FEV1: 82% predicted vs. 83% predicted; P = 0·73), sputum neutrophil ratios (29·9% vs. 46·8%; P = 0·20), TNF‐α (58 pg/mL vs. 44·5 pg/mL; P = 0·55) and IL‐8 (2·7 ng/mL vs. 2·4 ng/mL; P = 0·82) levels in induced sputum were similar before and after 12‐week withdrawal of inhaled steroids. However, the number of patients with bronchial hyperreactivity increased (37% vs. 63% of patients; P = 0·016) and neutrophilic apoptosis in induced sputum decreased (42·8% vs. 20·2%; P = 0·03) after withdrawal. Conclusion: In this study, 12 week‐withdrawal of inhaled steroid treatment resulted in a significant increase in bronchial hyperreactivity and decrease in neutrophil apoptosis, but no change in sputum inflammatory markers in children with non‐CF bronchiectasis was observed.     

A new method to quantify postexercise ST‐deviation – the ST‐deficit. A study in men at high and low‐risk for coronary heart disease

Background Quantitative heart rate adjusted exercise ST criteria like μV/beats per minute (bpm) improve the diagnostic accuracy of the exercise ECG. However, there are few quantitative HR adjusted postexercise variables available. The aim of the present exercise study was to evaluate a new such variable from computerized averaging of the postexercise ECG. Methods The presence of possible myocardial ischaemia in a population based sample of 74 elderly male hypertensives at high‐risk of coronary heart disease, and in 42 age‐matched clinically healthy males (reference group) at low‐risk was assessed by exercise ECG. All men had a normal resting ECG without signs of ischaemia. Variables studied: standard ST‐criteria, ST/HR slope ≤–2·4 μV · bpm^–1, shape of the rate‐recovery loop, the latter also with a new quantitative variable, the ST‐deficit. Results In spite of a normal resting ECG many subjects showed an abnormal ST/HR slope during exercise, 43% in the hypertension group and 26% in the reference group. An abnormal rate‐recovery loop (ST‐deficit) also contributed substantially to identify patients with possible myocardial ischaemia, 30 vs. 10%, respectively (P<0·02); cumulatively for the two HR adjusted criteria 53% vs. 29%, respectively (P<0·02). Mean ST‐deficit was significantly lower in the high‐risk group. Conclusions Effort‐related myocardial ischaemia is frequently silent in elderly high‐risk hypertensives and necessitates testing, preferably with computerized exercise ECG and heart rate adjusted ST criteria. A new quantitative variable to assess the postexercise rate‐recovery loop in the time domain, the ST‐deficit is described. This variable seems to effectively discriminate between subjects with low and high‐risk for coronary heart disease and thus provides new information. Further studies are warranted to validate this variable against myocardial perfusion scintigraphy and coronary angiography.     

Clinical Science (42)

Intravenous clodronate in the treatment of reflex sympathetic dystrophy syndrome: a randomized, double blind, placebo‐controlled study. (Istituto Ortopedico Gaetano Pini, Milan, Italy) J Rheumatol 2000;27:1477–1483. This study evaluated the efficacy of intravenous (IV) clodronate in patients with reflex sympathetic dystrophy syndrome (RSDS) and assessed the urinary excretion of type 1 collagen crosslinked N‐telopeptide (NTx) before and after treatment. Thirty‐two patients with RSDS were randomized to receive either IV Clodronate 300 mg daily for 10 consecutive days or placebo. Forty days later, the placebo treated patients received the clodronate treatment. Outcome measures included as a primary endpoint the visual analog scale of pain (VAS, range 0–100); secondary endpoints were a clinical global assessment (CGA, range 0–3) and an efficacy verbal score (EVS, range 0–3). Clinical and biochemical assessments were performed before the treatment, 40 (T40), 90 (T90), and 180 (T180) days later. At T40 the 15 patients randomized to clodronate treatment showed significant decreases of VAS and CGA (P = 0.002, P = 0.001, respectively). Compared with the placebo group (17 patients), significant differences were found in all clinical variables. A further clinical improvement was observed throughout the study. Pooling the results of all 32 patients after clodronate treatment, at T180 the overall percentage decrease of VAS was 9.32 ± 15.6% with 30 patients significantly improved or asymptomatic. Significant inverse correlations between baseline NTx values and decreases of VAS were found at T90 (P = 0.03) and T180 (P = 0.01). No adverse events related to treatment occurred. Conclude that a 10‐day IV clodronate course is better than placebo and effective in the treatment of RSDS. NTx seems to be a predictive factor for clodronate efficacy. Comment by Susan Anderson, MD. This is a randomized double blind placbo controlled study to evaluate the efficacy of intravenous clodronate in patients with reflex sympathetic dystrophy syndrome (RSDS) or complex regional pain syndrome type I. It is also to assess the urinary excretion of type I collogen crosslink N‐telopeptide (NTx) before and after the treatment. Thirty‐two patients with complex regional pain syndrome type I were randomized to receive either a placebo or IV clodronate 300mg daily for 10 consecutive days. At the end of 40 days, the placebo group was then treated with the clodronate. The primary endpoint measures with the visual analog scale (VAS, range 0–100) and a secondary endpoint was the clinical global assessment (CGA, range 0–3), and an efficacy vocal score (EVS, range 0–3). In addition, the patient had clinical and biochemical assessments performed before the treatment at 40 days, at 90 days, and at 180 days later. The purpose of the study was valued at the efficacy of the IV clodronate in pain relief. The second purpose was to evaluate the possibility of using NTx as a predicting factor for evaluating complex regional pain syndrome type I or the clodranate efficacy. On day 40, 15 patients that were randomized to the clodronate treatment showed significant decreases in their VAS and CGA when compared with the placebo group with 17 patients. In addition, the patients who had originally received placebo infusions showed decreased VAS and CGA scores after 40 days of treatment with the clodronate when compared to their VAS and CGA scores after placebo. At 180 days, the patients continued to show significant improvement or were asymptomatic. Bisphosphonates have been proposed since 1988 for the treatment of CRPS type I. The most frequently used is pamidronate, which is given intravenously showing varied results. The pamidronate did not seem to be well tolerated. Alendronate is also given intravenously demonstrating good efficacy. It, however, has a high relapse rate. Clodronate was chosen for this study because it was efficacious in treatment of various painful skeletal disorders and was more tolerable and safe than the pamidronate. The length of the time of the study was chosen to be 10 consecutive days so that it followed the study with successful use of pamidronate. These results suggest that a 10‐day IV clodronate course is better than placebo and is an effective complex regional pain syndrome type I treatment that may induce prompt and long lasting improvement. This study also attempted to demonstrate NTx as a predictive factor for clodranate efficacy. While NTx has shown to be a specific and sensitive marker of bone resorption, in this study, they found a low association between high NTx values and the complex regional pain syndrome type I. This finding could weaken the relationship between NTx baseline values and the responsiveness to clodronate treatment. It should be noted, however, that there were significant immerse correlations found between the baseline NTx values and in the pain improvement measured on the percentage change of VAS at 90 days and 180 days. Therefore, while significant inverse correlations may have been determined, and the NTx may be a promising tool, it is not yet possible to determine the predictive rolls of NTx as a marker.     

Australian triage tags: A prospective,randomised cross‐over trial and evaluation of user preference

Objective: The aim of this study was to determine if any disaster triage tag is superior to others, based on objective parameters (time, accuracy) and subjective parameters (user preference). A secondary aim was to determine the average time to perform triage assessment using ‘sieve and sort’. Methods: This was a prospective, randomised cross‐over trial comparing triage cards currently used, or being implemented, across Australia. De‐identified patient information from a trauma database was used to create 125 cases. Volunteer participants were selected from Major Incident Medical Management and Support certified doctors, nurses, paramedics and defence medics and randomised into five groups. Participants completed timed ‘sieve and sort’ triage exercises on 25 different cases with each of the five triage tags and were then asked to rank the tags in order of preference. Participants also performed timed practical triage assessments (sieve and sort) on two healthy volunteers. Results: Based on the objective measures we did not find that one card was superior to others; however, the Northern Territory card was significantly slower and less accurate (P < 0.001). Doctors were the fastest and most accurate ‘sorters’ (P < 0.001); however, inaccuracy was the same for all professional groups for the ‘sieve’. Participants preferred the SMART card to any other tag. Participants' time to carry out a sieve was approximately 30 s, and 60 s for a sort. Conclusion: The SMART card was preferred by participants based on design issues, which supports its implementation. We suggest that doctors are best used in the casualty clearing post.     

Health‐related quality of life and aerobic fitness in people with schizophrenia

The purpose of this cross‐sectional study was to investigate whether aerobic fitness contributes to the health‐related quality of life (HRQoL) in people with schizophrenia, while adjusting for other previously‐established contributory factors. Thirty‐four male (34.1 ± 12.0 years) and 13 female (34.3 ± 9.2 years) participants performed a submaximal Astrand–Rhyming cycle ergometer test and completed the 36‐item Short‐Form Health Survey, the International Physical Activity Questionnaire, and the Psychosis Evaluation tool for Common Use by Caregivers. After controlling for age and sex, illness duration (12.4 ± 11.2 years, r² = 0.38, P < 0.001), fewer positive (9.3 ± 4.3, r² = 0.30, P = 0.006) and cognitive (8.4 ± 3.8, r² = 0.28, P = 0.011) symptoms, and higher aerobic fitness (34.5 ± 8.7 ml O₂ min^?1 kg^?1, r² = 0.36, P = 0.001) were found to be independent significant predictors of physical HRQoL (mean score 66.6 ± 18.5). However, when all variables were included in the same regression model, only illness duration (P = 0.004) and positive symptoms (P = 0.045) remained significant predictors, while there was a trend (P < 0.10) for age and aerobic fitness. The final model explained 54% of the variability in physical HRQoL. No significant correlates for mental HRQoL (54.9 ± 18.5) were found. People with schizophrenia might improve their physical HRQoL by improving their aerobic fitness. Mental health nurses should assist in facilitating improvements in aerobic fitness through facilitating physical activity participation in patients with schizophrenia.     

Paracetamol and opioid pathways: a pilot randomized clinical trial

Previous studies suggest that the antinociceptive action of paracetamol (acetaminophen, APAP) might involve descending inhibitory pain pathways and the opioidergic system: this study explores this issue in humans with naloxone, the opioid antagonist. After ethical approval, 12 healthy male volunteers were included in this randomized, controlled, double‐blind, crossover, four‐arm study. They were administered intravenous paracetamol (APAP 1 g) or saline (placebo, pl) followed at 100 min with IV naloxone (Nal 8 mg) or saline, every week for 4 weeks. The amplitude of cerebral potentials evoked by thermal/painful stimuli applied on the arm was recorded nine times over 150 min, witnessing of pain integration at central level. Amplitude changes as well as areas under the curve (AUCs) over 150 min were compared for the four treatments by repeated measures anova (significance 0.05). Amplitude changes were significant for APAP/pl vs. pl/pl at t₁₅₀: ?44% (95%CI ?58 to ?30) vs. ?27% (95%CI ?37 to ?17; P < 0.05) but not vs. APAP/Nal. AUC (0–150) of APAP/pl is significantly different from pl/pl (?3452%.min (95%CI ?4705 to ?2199) vs. ?933% min (95%CI ?2273 to 407; P = 0.015) but not from APAP/Nal (?1731% min (95%CI ?3676 to 214; P = 0.08) and other treatments. AUC (90–150) is not significantly different. This pilot study shows for the first time in human volunteers that naloxone does not inhibit paracetamol antinociception, suggesting no significant implication of the opioid system in paracetamol mechanism of action: this needs be confirmed on a larger number of subjects.     

Improvement of glycaemic control by nateglinide decreases systolic blood pressure in drug-naive patients with type 2 diabetes

Background It has been speculated that oral hypoglycaemic agents that block K‐ATP channels could potentially increase blood pressure by blocking such channels in vascular myocytes. No information about this issue exists regarding nateglinide. Design A multicentre, double‐blind, placebo‐controlled, randomized trial was conducted in 109 drug‐naive 30‐ to 75‐year‐old patients with type 2 diabetes and < 5 years of diabetes diagnosis, who are not taking antihypertensive drugs. These patients were assigned to receive placebo or fixed doses of nateglinide (120 mg before each main meal: breakfast, lunch and dinner) and evaluated at weeks 0 and 12 for (i) body mass index and blood pressure; (ii) standard laboratory tests, including haemoglobin A1c (HbA1c) and fasting plasma glucose; and (iii) incremental area under the curve for glucose and C‐peptide after a standardized liquid breakfast challenge, homeostasis model assessment (HOMA)‐B% (as surrogate of β‐cell activity) and HOMA‐S% (as surrogate of insulin sensitivity). Results At the end of the follow‐up period, patients in the nateglinide group (n = 55), compared to patients in the placebo group (n = 54), showed lower values of HbA1c (6·7 ± 0·6 vs. 7·2 ± 0·7%, respectively; P < 0·001), fasting plasma glucose (7·9 ± 2·1 vs. 8·5 ± 2·0 mmol L^?1; P = 0·023) and systolic blood pressure (125·3 ± 15·4 vs. 129·3 ± 18·7 mmHg; P = 0·015), and higher values of HOMA‐B%[75·7 (51·8–99·4) vs. 57·7 (42·2–83·4); P = 0·033]. A positive correlation was found between changes in HbA1c and systolic blood pressure in the nateglinide group (r = 0·355, P = 0·011). Conclusions In drug‐naive patients with type 2 diabetes, the improvement in glycaemic control with nateglinide is associated with a decrease in systolic blood pressure.     

Serum sialic acid changes in type 2 diabetic patients on metformin or rosiglitazone treatment

What is known and objective: Serum sialic acid is a recently investigated potential risk‐marker for cardiovascular complications. There is a known association between sialic acid and cardiovascular complications in diabetes mellitus. We aimed to investigate the effect of antidiabetic drugs on the serum concentration of sialic acid. Methods: We investigated the effect of metformin and rosiglitazone on the concentration of sialic acid in 120 type 2 diabetic patients, divided into a group (n = 60) receiving metformin and a group (n = 60) receiving rosiglitazone treatment. Results: Serum sialic acid was significantly higher in patients on rosiglitazone (66·90 ±8·80 mg/dL vs. 57·6 ± 8·46 mg/dL, P <0·01) and metformin (61·95 ± 10·49 mg/dL vs. 57·6 ±8·46mg/dL, P < 0·04) when compared with control subjects. In addition, rosiglitazone‐treated patients showed a significant increase in cardiovascular risk factors, notably total cholesterol (246·45 ± 20·2 mg/dL vs. 170·6 ± 15·1 mg/dL, P =0·01), triglyceride (178 ± 9·20 mg/dL vs. 149·35 ±6·31 mg/dL, P < 0·04) and glycohemoglobin (HbA1‐c) concentration (8·17 ± 1·43% vs. 4·38 ±0·96%, P < 0·02) compared with normal control subjects. The patients on metformin also showed significantly higher levels of serum glucose (133·7 ± 9·63 mg/dL vs. 88·35 ± 6·31 mg/dL, P <0·04) and glycohemoglobin (HbA1‐c) (8·23 ±1·75% vs. 4·38 ± 0·96%, P < 0·02) when compared with control subjects. Comparison of the two groups of patients revealed a significantly higher serum sialic acid (66·90 ± 8·80 mg/dL vs. 61·95 ±10·49 mg/dL, P < 0·05), total cholesterol (246·45 ±20·2 mg/dL vs. 192 ± 14·23 mg/dL, P <0·02) and triglyceride (178 ± 9·20 mg/dL vs. 158 ± 14·51mg/dL, P < 0·05) concentrations in the rosiglitazone‐treated patients. What is new and conclusions: This study suggests significantly higher levels of serum sialic acid and other cardiovascular risk factors in rosiglitazone‐treated patients than in metformin‐treated patients. The lower sialic acid concentration may explain a better metformin antidiabetic effect than with rosiglitazone.