Nasal decongestants for the common cold.

BACKGROUND: The common cold is a major and recurrent cause of morbidity, on average affecting children and adults two or more times each year. Nasal congestion is its commonest symptom and many therapies are marketed for its relief. There is no meta-analysis of controlled clinical trials on the effects of nasal decongestants in the common cold. OBJECTIVES: To assess the efficacy of nasal decongestants at reducing the symptom of nasal congestion in adults and children with the common cold and to identify possible adverse effects associated with their use. SEARCH STRATEGY: In this updated review in 2006, the following databases were searched: the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library, Issue 3, 2006); MEDLINE (January 1996 to September 2006); OLDMEDLINE (1951 to 1965); EMBASE (1980 to Week 36, 2006). We contacted known principal investigators and pharmaceutical companies. SELECTION CRITERIA: Randomised, placebo controlled trials of single-active oral and topical nasal decongestants in adults and children suffering from common cold. DATA COLLECTION AND ANALYSIS: Two review authors (DT and GJL) independently extracted data. All outcomes variables were continuous. Subjective outcomes were normalised to a common scale and a weighted mean difference (WMD) was calculated. A standardised mean difference (SMD) was calculated for the objective outcomes. MAIN RESULTS: Seven studies in adults, but none in children, fitted all inclusion criteria. There was a small but statistically significant 6% decrease in subjective symptoms after a single dose of decongestant compared with placebo. This was supported by a significant decrease in nasal airways resistance. With repeated doses, nasal decongestants produce a very small statistical benefit of 4% over three to five days, again supported by a decrease in nasal airways resistance. Two studies provided safety data for this meta-analysis, showing a relatively small number of adverse events and only a small increased risk of insomnia with pseudoephedrine compared to placebo. AUTHORS' CONCLUSIONS: A single oral dose of nasal decongestant in the common cold is modestly effective for the short term relief of congestion in adults, and these drugs also provide benefit in some individuals after regular use over three to five days. Adverse events in adults are rare and mild. There is insufficient data on the use of these medications in children and therefore they are not recommended for use in children younger than 12 years of age with the common cold.

Nasal decongestants for the common cold.

BACKGROUND: The common cold is a major and recurrent cause of morbidity, affecting children and adults two or more times each year. Nasal congestion is its commonest symptom and many therapies are marketed for its relief. There is no meta-analysis of controlled clinical trials on the effects of nasal decongestants in the common cold. OBJECTIVES: To assess the efficacy of nasal decongestants at reducing the symptom of nasal congestion in adults and children with the common cold and to identify possible adverse effects associated with their use. SEARCH STRATEGY: In updating this review in 2004, the following databases were searched: the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library, Issue 1, 2004) which contains the Cochrane Acute Respiratory Infections Group's specialised register; MEDLINE (January 1996 to February week 1 2004); EMBASE (1996 to February week 7 2004); and Current Contents (February 2004). We handsearched review citations from other references and contacted known principal investigators and pharmaceutical companies. SELECTION CRITERIA: Randomised controlled trials with placebo of single-active oral and topical nasal decongestants in adults and children suffering from common cold. DATA COLLECTION AND ANALYSIS: Data were independently extracted by two reviewers (DT and GJL). All outcomes variables were continuous. Subjective outcomes were normalised to a common scale and a weighted mean difference (WMD) was calculated. We calculated a standardised mean difference (SMD) for the objective outcomes. MAIN RESULTS: Five studies involving 286 adults were included, none in children. There was a significant 13% decrease in subjective symptoms after decongestants were compared with placebo. This was supported by a significant decrease in nasal airways resistance. Repeated doses of nasal decongestant were not significantly better than placebo at relieving symptoms of nasal congestion. REVIEWERS' CONCLUSIONS: A single dose of nasal decongestant in the common cold is moderately effective for the short term relief of congestion in adults, while there is no evidence available to show benefit after repeated use over several days. There is insufficient data on the use of these medications in children and therefore they are not recommended for use in young children with the common cold.

Nasal decongestants for the common cold.

BACKGROUND: The common cold is a major and recurrent cause of morbidity, affecting children and adults two or more times each year. Nasal congestion is its commonest symptom, and many therapies are marketed for its relief. There is no meta-analysis of controlled clinical trials on the effects of nasal decongestants for the common cold. OBJECTIVES: To assess the efficacy of nasal decongestants at reducing the symptom of nasal congestion in adults and children with the common cold and to identify possible adverse effects associated with their use. SEARCH STRATEGY: MEDLINE, EMBASE and Current Contents were searched up to May 1999. Searching the Cochrane Acute Respiratory Infections Group's trials register, following the review citation trail from other references and contacting known principal investigators and pharmaceutical companies was also done. SELECTION CRITERIA: Randomised, placebo controlled trials of single-active oral and topical nasal decongestants in adults and children suffering from the common cold. DATA COLLECTION AND ANALYSIS: Data were independently extracted by two reviewers (DT and LB). All outcomes variables were continuous. Subjective outcomes were normalised to a common scale and a weighted mean difference (WMD) was calculated. A standardised mean difference (SMD) was calculated for the objective outcomes. MAIN RESULTS: Four studies in adults, but none in children, fitted all inclusion criteria. There was a significant 13% decrease in subjective symptoms after decongestant compared with placebo. This was supported by a significant decrease in nasal airways resistance. Repeated doses of nasal decongestant were not significantly better than placebo at relieving symptoms of nasal congestion. REVIEWER'S CONCLUSIONS: A single dose of nasal decongestant in the common cold is moderately effective for the short term relief of congestion in adults, while there is no evidence available to show benefit after repeated use over several days. These medications are not recommended for use in young children with the common cold.

Comparison of methods for teaching clinical skills in assessing and managing drug-seeking patients.

AIMS: New medical graduates lack clinical skills in assessing and managing patients seeking drugs of dependence. This study compares the effectiveness of three different clinical skills training methods, with similar content, which were developed to teach these skills to senior medical students. METHODS: A preliminary survey indicated that common problems seen by primary care practitioners included both new and previously known patients seeking either benzodiazepines or opiates. The common content of the teaching was determined from this survey. A didactic small group tutorial (DT), a video-based tutorial (VBT) using professional actors, and a computer-aided instruction package using digitized video (CAI) were developed with this common content, and trialled with undergraduate medical students over 2 years in a parallel-group design. Outcome was assessed by student feedback, performance on a case-based written examination and by a structured evaluation of interviews with simulated patients requesting drugs. Comparison was also made between methods on the basis of knowledge tests. RESULTS: No difference was seen in written examination and simulated patient outcomes between the three groups. However, the VBT was thought by the students to be preferable to other methods. The estimated development costs of CAI were higher, but total costs over a 6-year period were lower than for the DT and VBT. The results suggest that clinical skills can be taught equally effectively through several different methods. Collaboration between institutions in the development of widely applicable CAI tools should be an efficient and economical mode of teaching with a wide range of applications.

Cross-over comparison of nifedipine Oros and felodipine extended release with blind 24 h ambulatory blood pressure assessments.

1. The aim of the present study was to compare the efficacy of nifedipine Oros and felodipine extended release (ER) in controlling 24 h ambulatory blood pressures (ABP) in hypertensive patients. 2. The study was a randomized cross-over design with a 2 week open placebo run-in phase and two observer-blind treatment periods. 3. Subjects were males and females, aged between 18 and 65 years, suffering from mild to moderate essential hypertension with a sitting mean diastolic blood pressure (DBP) within the range of 95-114 mmHg. Twenty-three subjects were randomized to treatment; 15 patients completed the study. 4. Treatment intervention was 2 weeks of placebo followed by either 30 mg nifedipine OROS once daily or 5 mg felodipine ER once daily for 6 weeks, which was titrated up to 60 mg nifedipine OROS daily or 10 mg felodipine ER daily after 2 weeks of treatment on the lower doses if the DBP was > 90 mmHg. The main outcome measure was 24 h ABP after 6 weeks of active treatment, evaluated by an independent observer blinded as to treatment allocation. 5. Compared with placebo, mean (+/- SD) 24 h DBP was reduced by 6.2 +/- 6.8 and 5.2 +/- 5.1 mmHg after nifedipine and felodipine, respectively. The 24 h mean systolic blood pressure (SBP) fell by 11.8 +/- 10.9 and 10.1 +/- 8.2 mmHg for nifedipine and felodipine, respectively, compared with placebo. There were no significant differences between the two active treatments in the reduction of DBP or SBP during the 24 h period, daytime or night-time. 6. Similar antihypertensive effects are achieved with nifedipine Oros and felodipine ER when doses are individually titrated, with no significant differences between the two treatments.

Evaluation of the dose-response relationship for intra-nasal oxymetazoline hydrochloride in normal adults.

OBJECTIVES: To evaluate the dose-response relationship of increasing doses of oxymetazoline compared with placebo in normal subjects, and to determine the sensitivities of rhinomanometry, acoustic rhinometry and symptoms in discriminating between differing doses of oxymetazoline in normal subjects. METHODS: The study had a randomized, double-blind, placebo-controlled, parallel group, dose-response design. One hundred and twenty-five healthy volunteers with no nasal obstruction were randomized to administration of a single intra-nasal dose of oxymetazoline (6.25 microg, 12.5 microg, 25 microg or 50 microg) or placebo to each nasal cavity. Nasal airway resistance (NAR) was measured by active posterior rhinomanometry. Total minimum cross-sectional area (tMCA) and volume (tVOL) were measured by acoustic rhinometry. Symptoms of congestion (CON) were assessed on a visual analogue scale. RESULTS: The two highest doses of oxymetazoline produced a significant decrease in NAR compared with placebo (P = 0.015) but not between placebo and 12.5 microg or 6.25 microg. There was a dose-response relationship for tVOL, which increased significantly after all doses compared with placebo (P < 0. 001) and showed differences between 6.25-microg and 25-microg (P < 0. 014) and 12.5-microg and 50-microg (P < 0.05) doses. tMCA increased compared with placebo after all treatments (P = 0.028), but there were no significant differences between any of the active doses. There were no significant changes in CON after any treatments compared with placebo. CONCLUSIONS: tVOL shows a clear dose-response relationship for the range of doses of oxymetazoline administered. tVOL provides a sensitive and discriminatory measure of small nasal changes after low doses of oxymetazoline. NAR is able to discriminate between doses, but is less sensitive than tVOL and tMCA, requiring a higher threshold dose before significant changes are seen in nasal patency.

The nasal airways response in normal subjects to oxymetazoline spray: randomized double-blind placebo-controlled trial.

AIMS: The effects of a single dose of oxymetazoline nasal spray on nasal patency have been compared with placebo using three separate measuring systems in normal subjects. METHODS: The study was a placebo-controlled, randomised double-blind crossover trial. Subjects without ear, nose or throat disease and with resting nasal airways resistance >0.15 Pa s cm-3 were selected so that a fall in airways resistance could be detected. Nasal airways resistance (NAR) was measured by NR6-2 rhinomanometer. Acoustic rhinometry (SR-2000 rhinometer) provided the sum of the minimum cross-sectional areas (tMCA) and volume (tVOL) of the left and right nasal cavities. Symptoms of congestion were assessed on a visual analogue scale (CON, range 0-100). Measurements were made for 60 min before and for 120 min after bilateral administration of oxymetazoline nasal spray (0.9 mg) or placebo (0.9% saline). Crossover occurred 7-21 days later. Results for all measures were analysed as change from average baseline value by trapezoidal AUC, and statistical significance was tested by 2-way anova. RESULTS: NAR, tMCA, tVOL and CON did not change after placebo, but NAR and CON fell and tMCA and tVOL increased significantly at all timepoints after oxymetazoline. NAR_AUC, tVOL_AUC, tMCA_AUC were significantly different between placebo and oxymetazoline (P<0.001) as was CON_AUC (P=0.012). The day-to-day intraindividual repeatability of baseline NAR tMCA and tVOL was <10%. CONCLUSIONS: Normal subjects can be used to detect the effects of nasally vasoactive drugs with a variety of complementary systems, with the advantages of easy subject recruitment and low variability.

The effects of oral pseudoephedrine on nasal patency in the common cold: a double-blind single-dose placebo-controlled trial.

A placebo-controlled double-blind randomized trial was carried out to assess the efficacy of pseudoephedrine in relieving nasal congestion in the common cold. Fifty-four previously healthy persons who had a common cold for at least 5 days or less at the start of the study with moderate to severe nasal congestion were recruited, 52 completed the trial. Following a single dose of oral pseudoephedrine (60 mg capsule) or placebo, symptoms of congestion improved significantly compared with placebo at times 60, 90, 120, and 150 min after the dose. Total nasal minimum cross-sectional area and nasal volume measured by acoustic rhinometry increased significantly compared to placebo (P = 0.018 and P = 0.003, respectively) after the dose. There was no significant change in nasal area as measured by active posterior rhinomanometry after pseudoephedrine compared to placebo. We conclude that in the acute common cold, a single 60 mg dose of pseudoephedrine produces significant increases in the dimensions of the nasal cavity compared to placebo and this is associated with a reduction in the symptom of congestion.

High-power chirped-pulse all-fiber amplification system based on large-mode-area fiber gratings.

We describe the fabrication of chirped gratings in a specially developed photosensitive large-mode-area fiber and report the use of these components in a picosecond all-fiber chirped-pulse-amplification circuit. We demonstrate the generation of microjoule energy pulses with peak powers in excess of 500 kW, which we believe to be a record peak power from an all-fiber system.

Highly efficient second-harmonic and sum-frequency generation of nanosecond pulses in a cascaded erbium-doped fiber:periodically poled lithium niobate source.

By combining erbium-doped fiber sources based on a large mode-area design and periodically poled lithium niobate, we have obtained single-pass conversion efficiencies of as much as 83% (energy efficiency) for second-harmonic generation into the near IR (768 nm) and of 34% for sum-frequency generation into the green (512 nm) for nanosecond pulses, using first-order quasi-phase matching. Pulse energies in excess of 80microJ of second harmonic have been obtained from systems pumped by a single laser diode.

All-optical AND gate based on coupled gap-soliton formation in a fiber Bragg grating.

We experimentally demonstrate an all-optical AND gate based on coupled gap-soliton formation in an apodized fiber Bragg grating. A switching contrast of better than 17 dB is obtained with an incident pulse peak power of 2.5 kW.

Nonlinear self-switching and multiple gap-soliton formation in a fiber Bragg grating.

We report, for the first time to our knowledge, the experimental observation of quasi-cw nonlinear switching and multiple gap-soliton formation within the bandgap of a fiber Bragg grating. As many as five gap solitons with 100-500-ps durations were generated from a 2-ns pulse at a launched peak intensity of approximately 27 GW/cm(2). A corresponding increase in the grating transmission from 3% to 40% of the incident pulse energy was observed.

Optical parametric oscillation in periodically poled lithium niobate driven by a diode-pumped Q-switched erbium fiber laser.

We describe what is to our knowledge the first nanosecond periodically poled lithium niobate (PPLN) optical parametric oscillator (OPO) driven by a fiber laser. The source was frequency doubled by a PPLN sample before pumping a second, 20-mm-long, PPLN crystal. The OPO threshold was <10muJ, with pump depletions of as much as 45% and a tunable signal range of 945-1450 nm (1690-4450-nm idler range). We demonstrated 130-nm signal tuning by varying the pump wavelength and doubling crystal's temperature. Also, we achieved 15-nm tuning with all crystals at a constant temperature. The results demonstrate the potential of the fiber laser:PPLN combination for practical, versatile, and tunable sources.

Nonlinear switching in fibre Bragg gratings.

We report on our recent experiments on nonlinear switching in fibre Bragg gratings. Using an all-fibre source we show an increase in transmission of a FBG from 4% to 40% at high powers. This switching is associated with the formation of gap solitons inside the grating. We also demonstrate an all-optical AND gate using polarization coupled gap solitons and the optical pushbroom.

158-microJ pulses from a single-transverse-mode, large-mode-area erbium-doped fiber amplifier.

We report the amplification of 10-100-pJ semiconductor diode pulses to an energy of 158 microJ and peak powers >100 kW in a multistage fiber amplifier chain based on a single-mode, large-mode-area erbium-doped amplifier design. To our knowledge these results represent the highest single-mode pulse energy extracted from any doped-fiber system.

Classification of heart rate variability in patients with mild hypertension.

The diagnostic performance of two pattern classification methods to detect hypertension was evaluated in a population of 29 mildly hypertensive and 20 normal subjects. The heart rate variability (HRV) signal of each subject was recorded during rest and isometric handgrip exercise. Feature vectors composed of up to 6 features from both the time and frequency domain representation of the HRV signal were constructed and applied to a Bayes' likelihood classifier and a voting k-nearest neighbours classifier. Each subject was classified as hypertensive or normal, and the classification compared to the clinical diagnosis for each subject. The diagnostic performance of each classifier/feature vector combination was evaluated using the leave-one-out method. The best performance of 90% correct classifications was achieved using a nearest neighbour classifier, a Euclidean distance metric and 3 features. The Bayes' classifier achieved a best performance of 84% correct classification. The work shows promise for the detection of the autonomic disturbance which precedes and accompanies the hypertensive state.

Experimental observation of nonlinear pulse compression in nonuniform Bragg gratings.

We demonstrate a scheme for optical pulse compression by cross-phase modulation that utilizes a nonuniform Bragg grating to work in reflection. Our scheme is similar to the conventional optical pushbroom, which works in transmission. This reflection geometry has the advantage of allowing the compressed signal to be observed easily, as it is spatially separate from the pump. This is to our knowledge the first nonlinear effect to be observed that requires a nonuniform grating.

Reproducibility of conventional and power spectral measurements of cardiovascular sympathetic activation in normal subjects.

1. Normal subjects (n = 5; age 20-42 years; mean resting blood pressure (+/- 1 s.d.) 116 +/- 21/61 +/- 11 mmHg) underwent cardiovascular reflex testing five times each. On every occasion systolic blood pressure (SBP) responses to sustained handgrip (GRIP) and cold pressor (COLD) tests were measured and continuous non-invasive SBP and heart period (RRINT) data were analysed in the frequency domain using fast Fourier transforms. Power spectral (PS) density estimates of high frequency/total power (HF%; a measured of vagal activity), low frequency/HF ratio (LF/HF; a measure mainly of cardiovascular sympathetic activity for heart period) and low frequency/total power (LF%; a proposed measure of sympathetic activity for SBP) at rest, during and 2 min after the end of stimuli were calculated. 2. The data from the rest and recovery periods did not differ and showed that cardiovascular recovery to baseline measures following sympathetic stimulation occurred within 2 min. 3. There was a significant rise in SBP with GRIP and COLD. The LF/HF(RRINT) rose significantly with GRIP, but not with COLD. The LF%(SBP) did not change significantly with GRIP or COLD. 4. The SBP and PS analyses showed low intra-individual reproducibility of responses to reflex tests, with coefficients of variation for PS measures at rest of 25-41% and on sympathetic stimulation of up to 80%. 5. The high variability of these observations indicates that PS methods may not be suitable for the analysis of transient cardiovascular reflexes.

Experimental investigation of picosecond pulse reflection from fiber gratings.

The dispersion of picosecond pulses on reflection from efficient photorefractive fiber gratings is explored experimentally. Unlike simple measurements of reflectivity, this approach allows both the amplitude and the phase of the grating response to be probed as a function of frequency.