Endoscopic grading systems for nasal polyps: are we comparing apples to oranges?

Endoscopic grading of nasal polyps (NP) is typically a coprimary endpoint in clinical trials evaluating treatments for chronic rhinosinusitis with nasal polyps (CRSwNP). However, a consensus on the most effective way to grade nasal polyps has not been reached. Different scales have been used, hampering the interpretation of data across trials. This review compares the characteristics of NP grading systems used in registration trials for approved NP treatments. These fundamental differences in grading systems make quantitative comparison of outcomes between trials inaccurate and potentially misleading. In lieu of a universal grading system, reporting the baseline distribution of polyp grades (unilateral and/or summed/total grades), as well as changes from baseline over time by baseline grade may help improve interpretability of outcomes and reduce inaccuracy when attempting cross-trial comparisons and making therapeutic decisions.

Deposition of drugs in the nose and sinuses with an exhalation delivery system vs conventional nasal spray or high-volume irrigation in Draf II/III post-surgical anatomy.

BACKGROUND: Endoscopic sinus surgery is often performed to improve delivery of topical medication into sinus cavities. Intranasal steroids are guideline recommended in post-surgical patients, and experiments with cadavers suggest that surgery improves delivery of drug into sinuses. Exhalation delivery systems (EDS) use a new mechanism for intranasal delivery and have been shown to reach superior/posterior regions of the nasal cavity better than nasal sprays in unoperated patients. METHODS: Silicone casts of the nasal cavity and sinuses from a patient after Draf II, and then Draf III, were made from high-resolution computed tomography (CT) data using 3D printing. Internal surfaces were coated with liquid-sensitive, color-changing gel. Color changes were evaluated following conventional nasal spray delivery (0.1 mL x 2) (Nasonex), EDS delivery (0.1 mL x 2) (XHANCE), and high-volume, low-flow (HVLF) delivery (80 mL) with head tilted either 45° or 90°. RESULTS: Conventional nasal spray deposited liquid only in anterior nasal segments. EDS deposited liquid throughout the nasal cavity, in surgically opened ethmoid and maxillary spaces, at entrances of the frontal sinuses in Draf II geometry, and into frontal sinuses in Draf III. Tilted 45° HVLF delivery enters the maxillary sinuses but not the frontal sinuses or the ethmoid region. At full 90° inclination, HVLF delivery reaches most of the frontal and maxillary sinuses but not the roof and posterior wall of the ethmoid region. CONCLUSIONS: HVLF and EDS produced a deep intranasal/intrasinal deposition in the silicone cast compared with conventional nasal spray delivery; both deposited liquid inside the surgically opened sinuses. HVLF offers the benefit of lavage, whereas EDS may be more efficient and convenient.

EXHANCE-3: a cohort study of the exhalation delivery system with fluticasone for chronic sinusitis with or without nasal polyps.

BACKGROUND: Inhaled nasal corticosteroid sprays (INS) are often inadequate to treat chronic rhinosinusitis (CRS). The exhalation delivery system with fluticasone (EDS-FLU; XHANCE®) may improve outcomes in CRS by increasing medication delivery to target superior/posterior anatomic sites. This study assessed safety and efficacy of EDS-FLU in a large population with moderate-to-severe CRS with or without nasal polyps (CRSwNP, CRSsNP). METHODS: Prospective, multicenter, 12-week, single-arm study of EDS-FLU 372 Â#181;g twice daily (BID) at 38 U.S. sites. Safety was assessed by adverse-event evaluations, nasal endoscopy, and ocular examinations. Efficacy was serially assessed by outcomes including nasal endoscopy (Lund-Kennedy Score, polyp grade), patient- and physician-reported outcomes (22-item Sinonasal Outcome Test [SNOT-22]), study-defined surgical indicator assessment, and Patient Global Impression of Change (PGIC). RESULTS: 705 comparatively refractory subjects were enrolled, 603 CRSsNP and 102 CRSwNP [moderate-to-severely symptomatic; baseline SNOT-22 ~43, high rates of prior INS use (92.3%) and/or prior surgery (27.5%)]. More than 90% reported improvement on treatment by PGIC. SNOT-22 scores improved substantially and similarly in patients with NP (-23.7) and without NP (-24.4). Among patients with baseline Lund-Kennedy edema scores >0, 33.3% (CRSwNP) and 54.8% (CRSsNP) had complete resolution of edema. In CRSwNP patients, 48% had polyp elimination in ?1 nostril, 63% had ?1-point improvement in polyp grade, mean bilateral polyp grade decreased from 2.9 to 1.6, and study-defined surgical eligibility decreased. EDS-FLU was generally well tolerated, with a safety profile similar to conventional INS sprays when used to treat CRS CONCLUSION: EDS-FLU 372 #181;g BID in the treatment of CRS with or without polyps was safe, well-tolerated, and produced substantial improvement across a broad range of both objective and subjective measures.

Dose-dependent social-cognitive effects of intranasal oxytocin delivered with novel Breath Powered device in adults with autism spectrum disorder: a randomized placebo-controlled double-blind crossover trial.

The neuropeptide oxytocin has shown promise as a treatment for symptoms of autism spectrum disorders (ASD). However, clinical research progress has been hampered by a poor understanding of oxytocin's dose-response and sub-optimal intranasal delivery methods. We examined two doses of oxytocin delivered using a novel Breath Powered intranasal delivery device designed to improve direct nose-to-brain activity in a double-blind, crossover, randomized, placebo-controlled trial. In a randomized sequence of single-dose sessions, 17 male adults with ASD received 8 international units (IU) oxytocin, 24IU oxytocin or placebo followed by four social-cognitive tasks. We observed an omnibus main effect of treatment on the primary outcome measure of overt emotion salience as measured by emotional ratings of faces (η2=0.18). Compared to placebo, 8IU treatment increased overt emotion salience (P=0.02, d=0.63). There was no statistically significant increase after 24IU treatment (P=0.12, d=0.4). The effects after 8IU oxytocin were observed despite no significant increase in peripheral blood plasma oxytocin concentrations. We found no significant effects for reading the mind in the eyes task performance or secondary outcome social-cognitive tasks (emotional dot probe and face-morphing). To our knowledge, this is the first trial to assess the dose-dependent effects of a single oxytocin administration in autism, with results indicating that a low dose of oxytocin can significantly modulate overt emotion salience despite minimal systemic exposure.

Low-dose oxytocin delivered intranasally with Breath Powered device affects social-cognitive behavior: a randomized four-way crossover trial with nasal cavity dimension assessment.

Despite the promise of intranasal oxytocin (OT) for modulating social behavior, recent work has provided mixed results. This may relate to suboptimal drug deposition achieved with conventional nasal sprays, inter-individual differences in nasal physiology and a poor understanding of how intranasal OT is delivered to the brain in humans. Delivering OT using a novel 'Breath Powered' nasal device previously shown to enhance deposition in intranasal sites targeted for nose-to-brain transport, we evaluated dose-dependent effects on social cognition, compared response with intravenous (IV) administration of OT, and assessed nasal cavity dimensions using acoustic rhinometry. We adopted a randomized, double-blind, double-dummy, crossover design, with 16 healthy male adults completing four single-dose treatments (intranasal 8 IU (international units) or 24 IU OT, 1 IU OT IV and placebo). The primary outcome was social cognition measured by emotional ratings of facial images. Secondary outcomes included the pharmacokinetics of OT, vasopressin and cortisol in blood and the association between nasal cavity dimensions and emotional ratings. Despite the fact that all the treatments produced similar plasma OT increases compared with placebo, there was a main effect of treatment on anger ratings of emotionally ambiguous faces. Pairwise comparisons revealed decreased ratings after 8 IU OT in comparison to both placebo and 24 IU OT. In addition, there was an inverse relationship between nasal valve dimensions and anger ratings of ambiguous faces after 8-IU OT treatment. These findings provide support for a direct nose-to-brain effect, independent of blood absorption, of low-dose OT delivered from a Breath Powered device.

Preliminary efficacy of fluticasone delivered by a novel device in recalcitrant chronic rhinosinusitis.

OBJECTIVE: To assess whether delivery of fluticasone propionate using a novel bi-directional delivery device (Opt-FP) offers therapeutic benefits in patients with chronic rhinosinusitis (CRS). METHODS: A prospective, single centre, randomized, double-blind, placebo (PBO)-controlled, parallel group study was conducted in adult subjects (n=20) with CRS without nasal polyps or only cobblestoned mucosa. Subjects received Opt-FP 400 µg or placebo twice daily for 12 weeks (n=10/group). Outcome measures included symptom scores, RSOM-31, CRS VAS, nasendoscopy, peak nasal inspiratory flow (PNIF) and magnetic resonance imaging (MRI). RESULTS: Endoscopy score for oedema showed a highly significant and progressive improvement (12 weeks (median scores): Opt-FP -4.0, PBO -1.0, p=0.015). PNIF increased significantly during Opt-FP treatment compared to placebo (4 weeks: p=0.006; 8 weeks: p=0.03). After 12 weeks MRI scores in the Opt-FP group improved against baseline (p=0.039) and a non-significant trend was seen versus placebo. The nasal RSOM-31 subscale was significantly improved with Opt-FP treatment (4 weeks: p<0.009, 8 weeks: p<0.016, 12 weeks: NS). Sense of smell, nasal discomfort and combined score were all significantly improved (p<0.05). The Opt-FP was well tolerated. CONCLUSIONS: The OptiNose breath-actuated bi-directional delivery device administering fluticasone propionate (400 µg b.i.d.) is an effective and well tolerated treatment for recalcitrant CRS.

Intranasal sumatriptan powder delivered by a novel breath-actuated bi-directional device for the acute treatment of migraine: A randomised, placebo-controlled study.

INTRODUCTION: Intranasal sumatriptan is an option for the treatment of migraine; however, nasal delivery using conventional spray pumps is suboptimal. METHODS: Adult subjects (n = 117) with migraine were enrolled in a multicentre, randomised, double-blind, parallel group, placebo-controlled study. A single migraine attack was treated in-clinic with sumatriptan 10 mg, sumatriptan 20 mg or placebo administered intranasally by a novel bi-directional powder delivery device when migraine was moderate or severe. RESULTS: A greater proportion of subjects who received sumatriptan were pain-free at 120 minutes compared with those who received placebo (10 mg/20 mg sumatriptan vs. placebo = 54%/57% vs. 25%, P < .05). Significant benefits were also observed for pain relief at 120 minutes (84%/80% vs. 44%, P < .001/.01) and as early as 60 minutes (73%/74% vs. 38%, P < .01) and for 48 hours sustained pain-free (P < .05). Treatment-related adverse events were rare, with a metallic taste being the most commonly reported (10%/13%). CONCLUSIONS: Sumatriptan nasal powder administered using the new device during a migraine attack was effective and well tolerated.

Oral spray immunization may be an alternative to intranasal vaccine delivery to induce systemic antibodies but not nasal mucosal or cellular immunity.

Sixty-five healthy adult volunteers were immunized four times at 1-week intervals with an inactivated whole-virus influenza vaccine based on the strain A/New Caledonia/20/99 (H1N1) without adjuvant. The vaccine was administered as nasal spray with a newly developed device to secure intranasal delivery (OptiMist, OptiNose AS, Oslo, Norway), as regular nasal spray, nasal drops or as an oral spray. Significant IgA-antibody responses in nasal secretions were induced in volunteers immunized intranasally but not after oral spray immunization. In saliva, IgA antibodies were only marginally amplified even after oral spray immunizations. At least 73% of the volunteers belonging to any group of vaccine delivery reached serum haemagglutination inhibition titres of 40 or higher, considered protective against influenza, after only two vaccine doses. Those who had the vaccine delivered intranasally also showed evidence from in vitro secretion of granzyme B that cytotoxic T cells had been stimulated. Although immunization with the breath-actuated OptiMist device and nasal drops were superior with respect to both mucosal and systemic immune responses, oral spray immunization might still be considered for studies of mucosal adjuvants that are not yet acceptable for intranasal use.

The effects of intervention with local electrostatic air cleaners on airborne dust and the health of office employees.

UNLABELLED: The aim of this intervention study was to identify any health improvements in the upper and lower airways of office workers after the installation of local electrostatic air cleaners. Eighty persons with airways symptoms were recruited and randomly assigned to an intervention or control group. Half of the air cleaners had a non-functioning electrostatic unit. Both participants and field researchers were blinded to the group status. Subjective symptoms were recorded using a questionnaire, and indexes calculated for general, irritation and skin symptoms. Objective respiratory health indicators were recorded, with acoustic rhinometry and peak expiratory flow (PEF) meters. In the intervention group there was a decrease in mean dust concentration from 65 to 35 microg/m(3), and a reduction from 57 to 47 microg/m(3) in the control group (P < 0.05 for difference in decline). The reduction was observed for all particles sizes. The irritation and general symptom indices decreased in both groups, but there was no improvement in the intervention group, compared with the control group. Median PEF increased 3 ml/s in the intervention group, and decreased 4 ml/s in the control group. The adjusted odds ratio for an increase above the 70th percentile was 5.7 (95% CI 1.0-32). PRACTICAL IMPLICATIONS: Electrostatic air cleaners can reduce the dust concentration effectively in the office environment. Small, medium and large sized particles can be reduced by approximately 50%, relatively most effectively for the respirable particles. However, the air cleaners tested in this study produced an annoying fan noise. Cleaning efficiency and noise data should be given consideration before installation. This experimental field study suggests that office workers with airways symptoms may benefit from installation of local electrostatic air cleaners.

Upper airway inflammation in waste handlers exposed to bioaerosols.

AIMS: To examine work associated upper airway inflammation in 31 waste handlers, and to correlate these findings with personally monitored exposure to different bioaerosol components. METHODS: Cell differentials, interleukin 8 (IL-8), myeloperoxidase (MPO), and eosinophilic cationic protein (ECP) were examined in NAL (nasal lavage), and swelling of the nasal mucosa was determined by acoustic rhinometry before work start on Monday and the following Thursday. Bioaerosol exposure was determined by personal full shift exposure measurements on Monday, Tuesday, and Wednesday and analysed for total bacteria, fungal spores, endotoxin, and beta(1-->3)-glucans. RESULTS: The increased percentage of neutrophils from Monday (28%) to Thursday (46%) correlated with increases in ECP (r(S) = 0.71, p < 0.001) and MPO (r(S) = 0.38, p < 0.05), and showed a close to significant correlation with nasal swelling (r(S) = -0.55, p = 0.07). The Thursday levels of neutrophils, MPO, and IL-8 were associated with the exposure to fungal spores (range 0-2.0 x 10(6)/m(3)) and endotoxin (range 4-183 EU/m(3)) measured the day before, and the median exposure to beta(1-->3)-glucans (range 3-217 ng/m(3)), respectively (r(S) = 0.47-0.54, p < 0.01). Swelling of the nasal mucosa was associated with the fungal spore and beta(1-->3)-glucan exposure (r(S) = 0.58-0.59, p < 0.05). CONCLUSION: These results are based on a relatively small population, and conclusions must be drawn with care. The results suggested that a moderate exposure to fungal spores, endotoxins, and beta(1-->3)-glucans during waste handling induced upper airway inflammation dominated by neutrophil infiltration and swelling of the nasal mucosa.

A new method for the remote collection of nasal and exhaled nitric oxide.

STUDY OBJECTIVES: The present study introduces a method that has been developed to improve the remote collection and transportation of gas samples from the nose and lungs. DESIGN: Assessment of agreement between two methods of clinical measurements. SETTING: Noninvasive exhaled gas measurement at a respiratory research laboratory. PARTICIPANTS: Ten nonsmoking adult volunteers (median age, 44 years; age range, 33 to 53 years; men, 6; women, 4) were recruited. MEASUREMENTS AND RESULTS: Exhaled nitric oxide (ENO) and nasal nitric oxide (NNO) outputs were measured directly (on-line) and remotely (off-line). With the velum closed, lung air was exhaled at fixed flows (ie, 6, 8, and 10 L/min) (ENO) or room-air was aspirated through the nose in series at one fixed flow (ie, 5 to 8 L/min) (NNO). The off-line nitric oxide (NO) measurements were achieved by a gas collection tube system, which consisted of a flow control unit, a tube reservoir with one-way valves at both ends, and an interrupter valve allowing the trapping of gas inside the tube and eliminating the inclusion of "dead space." After clamping, the reservoir may store and transport the gas samples for delayed analysis. The coefficient of variation of three consecutive NO measurements was < 3% for both on-line and off-line ENO and NNO. The correlations between on-line and off-line measurements in both ENO and NNO outputs were high (r = 0.99; R(2) = 0.99), and, unlike previous studies using bag-collection, the ENO outputs for on-line and off-line measurements were in good agreement (Bland-Altman test) at all flows tested. CONCLUSIONS: The tube gas collection system eliminates the dead space and contamination during the gas sampling and permits the cost-effective and reliable off-line collection of both nasal and exhaled gas samples.

Gas and dust exposure in underground construction is associated with signs of airway inflammation.

Exposure to gases and dust may induce airway inflammation. It was hypothesized that heavy construction workers who had been exposed to dust and gases in underground construction work for 1 yr, would have early signs of upper and lower airway inflammation, as compared to outdoor workers. A study group comprising 29 nonsmoking underground concrete workers (mean +/- SD age 44+/-12 yrs), and a reference group of 26 outdoor concrete workers (39+/-12 yrs) were examined by acoustic rhinometry, nasal and exhaled nitric oxide spirometry and a questionnaire on respiratory symptoms. Exposure measurements were carried out. The underground workers had higher exposure to total and respirable dust, alpha-quartz and nitrogen dioxide than the references (p<0.001). The occurrence of respiratory symptoms was higher in the underground workers than in the references (p<0.05). Exhaled nitric oxide (NO) (geometric mean+/-SEM) was higher in the underground workers than in the references (8.4+/-1.09 versus 5.6+/-1.07 parts per billion (ppb), p = 0.001), whereas spirometric values were comparable. The underground workers had smaller nasal cross-sectional area and volume than the references, and more pronounced increases after decongestion (p<0.001). To conclude the exposure in underground construction may cause nasal mucosal swelling and increased levels of exhaled nitric oxide, indicating signs of upper and lower airway inflammation.

Accuracy of acoustic rhinometry.

OBJECTIVES: The objective of this study was to evaluate the ability of acoustic rhinometry (AR) (Rhin2100, Rhinometrics, Lynge, Denmark) to accurately determine the dimensions (cross-sectional areas and volumes) of the curved and complex slit-like geometry of the nasal airway. MATERIALS AND METHODS: A plastic model representing the replicate of a decongested nasal airway was produced by stereolithographic techniques from a 3-D MRI-scan. The exact dimensions of this model was determined from a high resolution CT-scan. Dimensions perpendicular to the curved course of the acoustic pathway were compared with dimensions inferred from parallel sections. The impact of sound loss to the paranasal sinuses and the ability to detect posterior volume changes was tested in the same model. RESULTS: The error in volume determination was < 14% for the MCA and < 8% for the volumes, whereas the error reached 52% for dimensions calculated from parallel sections in the coronal plane. The influence of the simulated maxillary sinuses depend primarily on the size of the ostia and may represent an important source of error for posterior measurements, in particular after decongestion. CONCLUSIONS: The accuracy of acoustically derived dimensions of the 3-D model depend on the orientation of the planes used to calculate the dimensions of the model. Volume estimates based on the smallest cross-sectional areas in points along the acoustic pathway correlate well with acoustically derived volumes, whereas single cross-sectional areas are more susceptible to error. Sound leakage to patent sinus ostia reduce the accuracy of posterior measurements.

Dichotomous physiological effects of nocturnal external nasal dilation in heavy snorers: the answer to a rhinologic controversy?

The purpose of this article was to study the impact of external dilation on nasal airway dimensions, sleep architecture, and snoring. Eighteen heavy snorers without severe obstructive sleep apnea syndrome (mean apnea-hypopnea index (AHI) 9.3) reporting nocturnal nasal obstruction were enrolled in a randomized (controlled) cross-over study, evaluating subjective and objective effects of external nasal dilation (Breathe Right, 3M). The active dilator was also worn during a one-week pretrial run-in period. Polysomnography, recording of snoring sounds, and repeated acoustic rhinometry were performed on two consecutive nights, one with the active dilator and one with a placebo strip. The significant subjective improvement reported during the run-in period compared to the preceding period without dilator (p < 0.01), remained only for nasal patency (p < 0.05) when comparing the two nights in the sleep laboratory. The nasal dimensions increased significantly (p < 0.001) with the active dilator compared to placebo, both in the evening and the next morning. In a subgroup (n = 6) of habitual snorers (AHI < 10) with severe morning obstruction (combined minimal cross-sectional area < 0.6 cm2), external dilation significantly improved the mean sleep PaSO2 (92.4 --> 96.7) and the percentage of sleep with a PaSO2 < 95% (49.9% --> 4.9%) (p < 0.05). In this subgroup there was a trend toward reduction in (7.4 --> 5.4) (p = 0.06), whereas the AHI increased significantly in the group of 12 with larger nocturnal nasal dimensions (p < 0.05). Duration and intensity of snoring remained unchanged regardless of the subgrouping. Objective beneficial effects were restricted to nocturnal oxygen saturation and AHI in a subgroup of habitual heavy snorers identified by repeated acoustic rhinometry, in whom external dilation objectively relieved marked nocturnal nasal obstruction. This finding may provide a logical explanation for the conflicting results of medical, surgical, and mechanical expansion of the nasal dimensions on snoring and sleep disturbances. (American

Evaluation of a new method for assessing symptoms.

BACKGROUND: Many studies in rhinology are based on results from symptom scoring. Numerous methods are used to estimate symptoms. With some of them the patients choose between various alternatives for estimating the severity of their symptoms, but the commonest method is the visual analogue scale (VAS), which is regarded as reliable. METHODS: In this study, we evaluate a new method for assessing symptoms, with which the patient uses the telephone to call a computer. We compare the results using the new method with those using symptoms estimation with VAS. RESULTS: The results are based on 487 observations in patients with birch pollen allergic rhinitis in the pollen season. A high correlation was found between the results using the new method and those using the VAS. In a questionnaire, the patients answered questions concerning the two methods. Most patients preferred the new telephone method. They found it easier to estimate their symptoms properly and easier to perform. CONCLUSION: We conclude that telephone scoring of symptoms is a reliable and adequate method when symptom scoring is used as hard data in a study.

Nitric oxide in the nasal airway: a new dimension in otorhinolaryngology.

The discovery that the gas nitric oxide (NO) is an important signaling molecule in the cardiovascular system earned its Nobel prize in 1998. NO has since been found to play important roles in a variety of physiologic and pathophysiologic processes in the body including vasoregulation, hemostasis, neurotransmission, immune defense, and respiration. The surprisingly high concentrations of NO in the nasal airway and paranasal sinuses has important implications for the field of otorhinolaryngology. NO provides a first-line defense against micro-organisms through its antiviral and antimicrobial activity and by its upregulation of ciliary motility. Nasal treatments such as polypectomy, sinus surgery, removal of hypertrophic adenoids and tonsils, and treatment of allergic rhinitis may alter NO output and, therefore, the microbial colonization of the upper airways. Nasal surgery aimed at relieving nasal obstruction may do the same but would also be expected to improve pulmonary function in patients with asthma and upper airway obstruction. NO output rises in a number of conditions associated with chronic airway inflammation, but not all of them. Concentrations are increased in asthma, allergic rhinitis, and viral respiratory infections, but reduced in sinusitis, cystic fibrosis, primary ciliary dysfunction, chronic cough, and after exposure to tobacco and alcohol. Therefore, NO, similar to several other inflammatory mediators, probably subserves different functions as local conditions dictate. At present, it seems that the measurement of NO in the upper airway may prove valuable as a simple, noninvasive diagnostic marker of airway pathologies. The objective of this review is to highlight some aspects of the origin, physiology, and functions of upper airway NO, and to discuss the particular methodological problems that result from the complex anatomy.

Unilateral nasal nitric oxide measurement after nasal surgery.

This study was designed to validate and standardize a method for unilateral nasal nitric oxide (NO) measurement. Fourteen healthy volunteers and 11 patients who had undergone unilateral medial maxillectomy were enrolled. Nasal NO was measured unilaterally by means of a dual pump system, and bilateral nasal NO was measured by aspirating air through the nasal airway in series. The median unilateral NO output was 195 nL/min on the surgical side and 291 nL/min on the contralateral, surgically untreated side (p = .006). The NO output was not significantly different between nostrils in the control group (p = .82). With the bilateral technique, there was no significant difference between the surgery group and the healthy-subjects group (p = .72). The unilateral nasal NO technique is sensitive in determining unilateral differences in nasal NO production. The NO outputs from the nostrils were similar in normal subjects regardless of the nasal cycle, but were significantly lower on the operated side in the unilateral nasal surgery group.

Is homeopathic 'immunotherapy' effective? A double-blind, placebo-controlled trial with the isopathic remedy Betula 30c for patients with birch pollen allergy.

The objective of the study was to examine the effect of the homeopathic remedy Betula 30c vs. placebo for patients with birch pollen allergy. A double-blind, randomized, placebo-controlled trial was carried out. Tablets were given for 4 weeks during the birch pollen season. The setting was Oslo, Norway, May 1995. Patients were aged between 18 and 50 y; 32 patients received Betula 30c tablets and 34 patients received placebo tablets. The main outcome measure was the total score of 17 different allergy symptoms. Daily total scores were calculated, as well as differences and ratios between the run-in and the following time periods. Point estimates of the median difference between the experimental and placebo groups, with their 95% confidence intervals, were the main measure of effect. No statistically significant difference between the groups was found during the first and last period of May. However, from 8 to 18 May, a clinically interesting difference was revealed between the groups, those receiving Betula 30c having fewer and less serious symptoms. For some days these differences were statistically significant. Surprisingly, this group reported more aggravation from the tablets than did the placebo group. With a statistical power of 70% for a defined clinically interesting difference (25%), the present results indicate that treatment with Betula 30c during the pollen season deserves further attention.

Is homeopathic 'immunotherapy' effective? A double-blind, placebo-controlled trial with the isopathic remedy Betula 30c for patients with birch pollen allergy

The objective of the study was to examine the effect of the homeopathic remedy Betula 30c vs placebo for patients with birch pollen allergy. A double-blind, randomized, placebo-controlled trial was carried out. Tablets were given for 4 weeks during the birch pollen season. The setting... (AU)

Computational simulation of accumulation of expired air in the infant cot.

Accumulation and re-breathing of CO2 in expired air has been suggested as one possible explanation for the strong association between prone sleeping position and sudden infant death syndrome (SIDS). This preliminary study applying a modern computational fluid dynamics (CFD) program to simulate the aerodynamics in an infant cot supports the idea that accumulation of expired air may occur in the prone position. The literature dealing with the potential association between re-breathing of accumulated CO2 and SIDS is briefly reviewed.