Dose-dependent naloxone-induced morphine withdrawal symptoms in opioid-dependent males-a double-blinded, randomized study.

AIMS: Oral opioid preparations combined with naloxone are intended to induce a transient acute withdrawal syndrome to avoid intravenous misuse. This trial aimed to establish an appropriate morphine-naloxone dose ratio for an abuse-deterrent oral opioid formulation. METHODS: In a randomized, double-blinded, 2 × 2 cross-over trial, 43 patients with opioid use disorder were challenged with intravenous morphine HCl Ph.Eur. (75 mg; [morphine mono]) or morphine HCl Ph.Eur. and naloxone HCl Ph.Eur. at ratios of 100:1 (75 mg: 0.75 mg; [morphine-naloxone 100:1]) or 200:1 (75 mg: 0.375 mg; [morphine-naloxone 200:1]). Acute naloxone-induced opioid withdrawal was evaluated using subjective (Short Opiate Withdrawal Scale-German [SOWS-G]) and observer-rated (Objective Opiate Withdrawal Scale [OOWS], Wang scale) questionnaires, and physiological parameters. For statistical analysis, the area under the curve between baseline and 20 minutes after drug administration of the outcome variables was calculated. RESULTS: Intravenous morphine-naloxone caused rapid withdrawal symptoms. Coadministration of naloxone dose-dependently (morphine-naloxone 100:1 > morphine-naloxone 200:1) increased SOWS-G, OOWS and Wang Scale area under the curve when compared to morphine mono, respectively (all P < .0001). A similar response was detectable for changes of pupil diameter. Blood pressure and respiratory rate changed heterogeneously, and heart rate was unaltered by morphine without or with naloxone. CONCLUSION: Morphine-naloxone 100:1 effectively suppresses the pleasurable effects of intravenous morphine and results in an aversive withdrawal reaction. A lower naloxone concentration as used in morphine-naloxone 200:1 does not appear to be appropriate to prevent intravenous morphine misuse.

Treatment of acute rhinitis with a nasal spray containing tramazoline and essential oils: a multicenter, uncontrolled, observational trial.

BACKGROUND: In this observational trial, data were collected on the effectiveness and tolerability/safety of a nasal spray containing tramazoline and essential oils (trade name Rhinospray(®) Plus) used for symptomatic treatment of acute rhinitis due to common cold. METHODS: The trial was performed in 300 children, adolescents and adults, who were to be treated with Rhinospray(®) Plus for up to 4 times per day for up to 10 days. Primary endpoints were the change from baseline to final visit in the mean of three single symptom scores (blocked nose, sneezing, and runny nose) and the mean improvement in two quality-of-life parameters (ability to perform normal daytime activities and quality of sleep). RESULTS: A total of 108 children, 30 adolescents and 162 adults were treated with Rhinospray(®) Plus. No patient discontinued prematurely. There was a mean reduction of 2.0 ± 0.6 (standard deviation) in nasal symptom scores from baseline to final visit; 297 of 300 of patients (99.0 %) reported an improvement. The mean value for improvement in quality-of-life parameters was 1.3 ± 0.5. Improvement in daytime activities was reported by all 300 patients (100.0 %) and in quality of sleep by 292 patients (97.4 %). Effectiveness and tolerability were rated as 'very good' or 'good' by 95.4 % and 97.4 % of patients, respectively; the investigators rated effectiveness and tolerability as 'very good' or 'good' for 97.4 % and 100.0 % of patients, respectively. No adverse events were reported. CONCLUSIONS: Community-based patients reported a relief in acute rhinitis symptoms and improvement in quality of life as a result of treatment with Rhinospray(®) Plus. Treatment was well-tolerated.

Cardiovascular risk stratification and antihypertensive therapy according to guidelines in the outpatient setting.

UNLABELLED: BASIC CONCEPTS AND METHODOLOGY: Acceptance of the ESH/ESC 2007 hypertension guidelines and their reappraisal 2009 are not known by Austrian practitioners. Therefore, within the frame of a noninterventional trial we investigated 3,488 ambulatory hypertensive patients. Primary goal was the evaluation of the assignment to cardiovascular risk categories according to the ESH/ESC charts by office-based physicians compared to an independent risk adjudication using the same data and method. Further goals were assessment of compliance with the recommendation to start combination treatment in grade 2 and 3 hypertension and efficacy and tolerability of treatment with candesartan. RESULTS: The comparison revealed incorrect physicians' risk assessment for approximately 60% of the patients with a strong tendency for underestimation. Despite guidelines recommending an initial combination therapy for hypertension ≥160/90 mmHg, 15.4% of these patients still received candesartan as a monotherapy. Target blood pressure ≤140/90 mmHg could be well achieved (in 81.6%) with candesartan as monotherapy or combined with hydrochlorothiazide (HCTZ) for hypertension grade 1-3. CONCLUSIONS: Guidelines for assessment of individual risk and derived therapy algorithms should be better communicated in the outpatient setting. Candesartan alone or combined with HCTZ is an effective and well tolerated therapeutic option to control blood pressure in the majority of patients.

Prevalence of vertebral fracture in elderly men and women with osteopenia.

The objective of our cross-sectional, not population-based, observational study was to determine the prevalence of patients with osteopenia in relation to bone mineral density (BMD) and vertebral fractures and to identify risk factors for vertebral fractures above the osteoporotic BMD T-score threshold of -2.5. A total of 698 consecutive hospitalized and ambulatory white patients with T-scores between -1.0 and -2.5 were investigated in an academic medical center in Austria between January 2005 and June 2006. Measurements of BMD (T-score at spine and hip) by DXA, spinal X-ray, laboratory data of bone metabolism and vitamin D, and sex-specific data were assessed. A multivariate general linear model was used to calculate vertebral and non-vertebral fractures, age, BMI and lowest T-score at measured anatomic sites. Overall, 218 patients (31.2%) with a mean age of 72.2 years and mean BMI of 26.0 presented with vertebral fractures; in comparison, patients with non-vertebral fractures had a mean age of 62.6 years and BMI 24.6, and patients without fractures had a mean age of 61.3 years and BMI 24.0 (P < 0.001). Serum markers of bone resorption and formation had no influence on fracture occurrence but 73% of the patients had vitamin D deficiency (25.2 +/- 9.8 ng/ml). The lowest T-score in all fracture patients was found at the femoral neck. At this site 64.3% patients with vertebral fractures had a T-score within the range -1.0 to -2.0 (95% CI 57.3-70.8). The prevalence of vertebral fractures increased stepwise (P < 0.05) and at T-scores between -1.5 and -2.0 the increase was linear. We conclude that a significant proportion of non-osteoporotic elderly men and women with mean age 72 years, BMI 26.0 and a threshold T-score above -2.0 are susceptible to osteoporotic vertebral fractures. These patients are not adequately detected by BMD measurements based on WHO thresholds. Early assessment, prior to their first fracture, is important for identifying individuals with clinical risk factors.