Nasal decongestants in monotherapy for the common cold

Background : Many treatments for the common cold exist and are sold over-the-counter. Nevertheless, evidence on the effectiveness and safety of nasal decongestants is limited. Objectives : To assess the efficacy, and short-and long-termsafety, of nasal decongestants used inmonotherapy to alleviate symptoms of the common cold in adults and children. Search methods : We searched the Cochrane Central Register of Controlled Trials (CENTRAL, Issue 6, June 2016), which contains the Cochrane Acute Respiratory Infections (ARI) Specialised Register, MEDLINE (1946 to July 2016), Embase (2010 to 15 July 2016), CINAHL (1981 to 15 July 2016), LILACS (1982 to July 2016), Web of Science (1955 to July 2016) and clinical trials registers. Selection criteria : Randomised controlled trials (RCTs) and cluster-RCTs investigating the effectiveness and adverse effects of nasal decongestants compared with placebo for treating the common cold in adults and children. We excluded quasi-RCTs. Data collection and analysis : Three review authors independently extracted and summarised data on subjective measures of nasal congestion, overall patient wellbeing score, objective measures of nasal airway resistance, adverse effects and general recovery. One review author acted as arbiter in cases of disagreement. We categorised trials as single and multi-dose and analysed data both separately and together. We also analysed studies using an oral or topical nasal decongestant separately and together. Main results : We included 15 trials with 1838 participants. Fourteen studies included adult participants only (aged 18 years and over). In six studies the intervention was a single dose and in nine studies multiple doses were used. Nine studies used pseudoephedrine and three studies used oxymetazoline. Other decongestants included phenylpropanolamine, norephedrine and xylometazoline. Phenylpropanolamine (or norephedrine) is no longer available on the market therefore we did not include the results of these studies in the meta-analyses. Eleven studies used oral decongestants; four studies used topical decongestants. Participants were included after contracting the common cold. The duration of symptoms differed among studies; in 10 studies participants had symptoms for less than three days, in three studies symptoms were present for less than five days, one study counted the number of colds over one year, and one study experimentally induced the common cold. In the single-dose studies, the effectiveness of a nasal decongestant was measured on the same day, whereas the follow-up in multi-dose studies ranged between one and 10 days. Most studies were conducted in university settings (N = eight), six at a specific university common cold centre. Three studies were conducted at a university in collaboration with a hospital and two in a hospital only setting. In two studies the setting was unclear. There were large differences in the reporting of outcomes and the reporting of methods in most studies was limited. Therefore, we judged most studies to be at low or unclear risk of bias. Pooling was possible for a limited number of studies only; measures of effect are expressed as standardised mean differences (SMDs). A positive SMD represents an improvement in congestion. There is no defined minimal clinically important difference for measures of subjective improvement in nasal congestion, therefore we used the SMDs as a guide to assess whether an effect was small (0.2 to 0.49), moderate (0.5 to 0.79) or large (>= 0.8). Single-dose decongestant versus placebo: 10 studies compared a single dose of nasal decongestant with placebo and their effectiveness was tested between 15 minutes and 10 hours after dosing. Seven of 10 studies reported subjective symptom scores for nasal congestion; none reported overall patient well-being. However, pooling was not possible due to the large diversity in the measurement and reporting of symptoms of congestion. Two studies recorded adverse events. Both studies used an oral decongestant and each of them showed that there was no statistical difference between the number of adverse events in the treatment group versus the placebo group. Multi-dose decongestant versus placebo: nine studies compared multiple doses of nasal decongestants with placebo, but only five reported on the primary outcome, subjective symptom scores for nasal congestion. Only one study used a topical decongestant; none reported overall patient well-being. Subjective measures of congestion were significantly better for the treatment group compared with placebo approximately three hours after the last dose (SMD 0.49, 95% confidence interval (CI) 0.07 to 0.92; P = 0.02; GRADE: low-quality evidence). However, the SMD of 0.49 only indicates a small clinical effect. Pooling was based on two studies, one oral and one topical, therefore we were unable to assess the effects of oral and topical decongestants separately. Seven studies reported adverse events (six oral and one topical decongestant); meta-analysis showed that there was no statistical difference between the number of adverse events in the treatment group (125 per 1000) compared to the placebo group (126 per 1000). The odds ratio (OR) for adverse events in the treatment group was 0.98 (95% CI 0.68 to 1.40; P = 0.90; GRADE: low-quality evidence). The results remained the same when we only considered studies using an oral decongestant (OR 0.95, 95% CI 0.65 to 1.39; P = 0.80; GRADE: low-quality evidence). Authors' conclusions : We were unable to draw conclusions on the effectiveness of single-dose nasal decongestants due to the limited evidence available. For multiple doses of nasal decongestants, the current evidence suggests that these may have a small positive effect on subjective measures of nasal congestion in adults with the common cold. However, the clinical relevance of this small effect is unknown and there is insufficient good-quality evidence to draw any firm conclusions. Due to the small number of studies that used a topical nasal decongestant, we were also unable to draw conclusions on the effectiveness of oral versus topical decongestants. Nasal decongestants do not seem to increase the risk of adverse events in adults in the short term. The effectiveness and safety of nasal decongestants in children and the clinical relevance of their small effect in adults is yet to be determined

GP trainees’ perceptions on learning EBM using conversations in the workplace : a video-stimulated interview study

Background To be able to practice evidence-based medicine (EBM) when making decisions for individual patients, it is important to learn how to combine the best available evidence with the patient's preferences and the physician's clinical expertise. In general practice training, these skills can be learned at the workplace using learning conversations: meetings between the supervising general practitioner (GP) and GP trainee to discuss medical practice, selected topics or professional performance. This study aimed to give insight into the perceptions of GP trainees on their EBM learning processes during learning conversations. Methods We held semi-structured video-stimulated elicitation interviews (n = 22) with GP trainees affiliated to GP training institutes in the Netherlands and Belgium. GP trainees were shown fragments of their learning conversations, enabling reflection during the interview. Taking an inductive approach, interview recordings were transcribed verbatim and analysed with NVivo software. Results GP trainees perceived learning conversations as useful for learning and discussing EBM. Multiple EBM learning activities were identified, such as discussing evidence together, relating evidence to cases in daily practice and discussing the supervisor's experience and the specific local context in the light of what the evidence recommends. However, for learning to occur, trainees need and expect specific behaviour, both from their supervisors and themselves. Supervisors should supply well-substantiated answers that are applicable in practice and give the trainee confirmation. In turn, the trainee needs to prepare well in order to ask focused, in-depth questions. A safe space allowing equal and open discussion between trainee and supervisor is perceived as an essential context for optimal EBM learning. Conclusions Our findings show that trainees find learning conversations useful for EBM learning in general practice. To bring EBM learning to its full potential, attention should be paid to optimising the behavioural and contextual factors found relevant to enhancing EBM learning

Mice Transgenic for the Human Carcinoembryonic Antigen Gene Maintain Its Spatiotemporal Expression Pattern

The tumor marker carcinoembryonic antigen (CEA) is predominantly expressed in epithelial cells along the gastrointestinal tract and in a variety of adenocarcinomas. As a basis for investigating its in vivo regulation and for establishing an animal model for tumor immunotherapy, transgenic mice were generated with a 33-kilobase cosmid clone insert containing the complete human CEA gene and flanking sequences. CEA was found in the tongue, esophagus, stomach, small intestine, cecum, colon, and trachea and at low levels in the lung, testis, and uterus of adult mice of independent transgenic strains. CEA was first detected at day 10.5 of embryonic development (embryonic day 10.5) in primary trophoblast giant cells and was found in the developing gut, urethra, trachea, lung, and nucleus pulposus of the vertebral column from embryonic day 14.5 onwards. From embryonic day 16.5 CEA was also visible in the nasal mucosa and tongue. Because this spatiotemporal expression pattern correlates well with that known for humans, it follows that the transferred genomic region contains all of the regulatory elements required for the correct expression of CEA. Furthermore, although mice apparently lack an endogenous CEA gene, the entire repertoire of transcription factors necessary for correct expression of the CEA transgene is conserved between mice and humans. After tumor induction, these immunocompetent mice will serve as a model for optimizing various forms of immunotherapy, using CEA as a target antigen

Ubiquity of optical activity in planar metamaterial scatterers

Recently it was discovered that periodic lattices of metamaterial scatterers show optical activity, even if the scatterers or lattice show no 2D or 3D chirality, if the illumination breaks symmetry. In this Letter we demonstrate that such `pseudo-chirality' is intrinsic to any single planar metamaterial scatterer and in fact has a well-defined value at a universal bound. We argue that in any circuit model, a nonzero electric and magnetic polarizability derived from a single resonance automatically imply strong bianisotropy, i.e., magneto-electric cross polarizability at the universal bound set by energy conservation. We confirm our claim by extracting polarizability tensors and cross sections for handed excitation from transmission measurements on near-infrared split ring arrays, and electrodynamic simulations for diverse metamaterial scatterers.Comment: 5 pages, 4 figure

Applying evidence-based medicine in general practice : a video-stimulated interview study on workplace-based observation

BACKGROUND: Evidence-based medicine (EBM) in general practice involves applying a complex combination of best-available evidence, the patient's preferences and the general practitioner's (GP) clinical expertise in decision-making. GPs and GP trainees learn how to apply EBM informally by observing each other's consultations, as well as through more deliberative forms of workplace-based learning. This study aims to gain insight into workplace-based EBM learning by investigating the extent to which GP supervisors and trainees recognise each other's EBM behaviour through observation, and by identifying aspects that influence their recognition. METHODS: We conducted a qualitative multicentre study based on video-stimulated recall interviews (VSI) of paired GP supervisors and GP trainees affiliated with GP training institutes in Belgium and the Netherlands. The GP pairs (n = 22) were shown fragments of their own and their partner's consultations and were asked to elucidate their own EBM considerations and the ones they recognised in their partner's actions. The interview recordings were transcribed verbatim and analysed with NVivo. By comparing pairs who recognised each other's considerations well with those who did not, we developed a model describing the aspects that influence the observer's recognition of an actor's EBM behaviour. RESULTS: Overall, there was moderate similarity between an actor's EBM behaviour and the observer's recognition of it. Aspects that negatively influence recognition are often observer-related. Observers tend to be judgemental, give unsolicited comments on how they would act themselves and are more concerned with the trainee-supervisor relationship than objective observation. There was less recognition when actors used implicit reasoning, such as mindlines (internalised, collectively reinforced tacit guidelines). Pair-related aspects also played a role: previous discussion of a specific topic or EBM decision-making generally enhanced recognition. Consultation-specific aspects played only a marginal role. CONCLUSIONS: GP trainees and supervisors do not fully recognise EBM behaviour through observing each other's consultations. To improve recognition of EBM behaviour and thus benefit from informal observational learning, observers need to be aware of automatic judgements that they make. Creating explicit learning moments in which EBM decision-making is discussed, can improve shared knowledge and can also be useful to unveil tacit knowledge derived from mindlines

Earthquake modelling at the country level using aggregated spatio-temporal point processes

The goal of this paper is to derive a risk map for earthquake occurrences in Pakistan from a catalogue that contains spatial coordinates of shallow earthquakes of magnitude 4.5 or larger aggregated over calendar years. We test relative temporal stationarity and use the inhomogeneous J-function to test for inter-point interactions. We then formulate a cluster model, and deconvolve in order to calculate the risk map. The model is validated using the leave-one-out principle

Earthquake modelling at the country level using aggregated spatio-temporal point processes

The goal of this paper is to derive a hazard map for earthquake occurrences in Pakistan from a catalogue that contains spatial coordinates of shallow earthquakes of magnitude $4.5$ or larger aggregated over calendar years. We test relative temporal stationarity by the KPSS statistic and use the inhomogeneous J--function to test for inter-point interactions. We then formulate a cluster model, and deconvolve in order to calculate the hazard map, and verify that no particular year has an undue influence on the map. Within the borders of the single country, the KPSS test did not show any deviation from homogeneity in the spatial intensities. The inhomogeneous J-function indicated clustering that could not be attributed to inhomogeneity, and the analysis of aftershocks showed some evidence of two major shocks instead of one during the 2005 Kashmir earthquake disaster. Thus, the spatial point pattern analysis carried out for these data was insightful in various aspects and the hazard map that was obtained may lead to improved measures to protect the population against the disastrous effects of earthquakes

Simultaneous Robotic Manipulation and Functional Magnetic Resonance Imaging: Feasibility in Children with Autism Spectrum Disorders

An unanswered question concerning the neural basis of autism spectrum disorders (ASD) is how sensorimotor deficits in individuals with ASD are related to abnormalities of brain function. We previously described a robotic joystick and video game system that allows us to record functional magnetic resonance images (FMRI) while adult humans make goal- directed wrist motions. We anticipated several challenges in extending this approach to studying goal-directed behaviors in children with ASD and in typically developing (TYP) children. In particular we were concerned that children with autism may express increased levels of anxiety as compared to typically developing children due to the loud sounds and small enclosed space of the MRI scanner. We also were concerned that both groups of children might become restless during testing, leading to an unacceptable amount of head movement. Here we performed a pilot study evaluating the extent to which autistic and typically developing children exhibit anxiety during our experimental protocol as well as their ability to comply with task instructions. Our experimental controls were successful in minimizing group differences in drop-out due to anxiety. Kinematic performance and head motion also were similar across groups. Both groups of children engaged cortical regions (frontal, parietal, temporal, occipital) while making goal- directed movements. In addition, the ASD group exhibited task- related correlations in subcortical regions (cerebellum, thalamus), whereas correlations in the TYP group did not reach statistical significance in subcortical regions. Four distinct regions in frontal cortex showed a significant group difference such that TYP children exhibited positive correlations between the hemodynamic response and movement, whereas children with ASD exhibited negative correlations. These findings demonstrate feasibility of simultaneous application of robotic manipulation and functional imaging to study goal-directed motor behaviors in autistic and typically developing children. The findings also suggest the presence of marked changes in neural activation during a sensorimotor task requiring goal- directed movement