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PubMed2004

[A case-control study on risk factors of hypospadias].

OBJECTIVE: Hypospadias is one of the most commonly seen urogenital congenital malformations in males and to identify its etiological factors. METHODS: A hospital-based case-control study was conducted, with 107 hypospadias cases. Two matched controls per case were randomly selected. Both cases and controls were face to face interviewed with a uniformed questionnaire. Conditional logistic regression model was used for univariable and multivariate analysis on SAS 6.12 to estimate odds ratios (OR) and 95 per cent confidence internals (95% CI). RESULTS: Data from multiple conditional logistic regression analysis showed that hypospadias was positively associated with maternal history of spontaneous abortion (OR = 3.87, 95% CI: 1.60 - 9.39), with threatened abortion in the first or second trimester (OR = 3.57, 95% CI: 1.31 - 9.64), with common cold accompanied fever in the first trimester (OR = 7.63, 95% CI: 2.50 - 23.24), with maternal drug (antibiotic, analgesiscs) exposure during the second trimester (OR = 16.46, 95% CI: 3.46 - 78.21), with paternal exposure to pesticides occupationally (OR = 3.70,95% CI: 1.49 - 9.16), with neonatal low birth weight (OR = 12.62, 95% CI: 2.97 - 53.67), but was negatively associated with maternal diet supplemented with protein in the first trimester (OR = 0.33, 95% CI: 0.15 - 0.74). CONCLUSIONS: The risk factors of hypospadias seemed to include maternal history of spontaneous abortion, threatened abortion in the first or second trimester, maternal common cold accompanied fever in the first trimester, maternal drug exposure during the second trimester, paternal occupational exposure to pesticides, neonatal low birth weight. However, maternal diet supplemented with protein probably acted as the protective factor for neonatal hypospadias in the first trimester.

Adolescent↗
PubMed1988

Comparison between the weekly returns service and the Oxford regional sentinel practice scheme for monitoring communicable diseases.

Weekly data for seven conditions reported to the weekly returns service of the Royal College of General Practitioners' Birmingham research unit over a 52-week period have been compared with those reported to the Oxford regional sentinel practice scheme. The mean weekly recorded rates for otitis media, asthma and intestinal infectious disease were similar in both systems; in the weekly returns service, mean weekly rates for common cold, acute bronchitis and influenza/influenza-like illness were approximately twice and for sore throat/tonsillitis slightly higher than rates in the Oxford scheme.In the weekly returns service no recommendations are made about criteria for diagnosis but in the Oxford scheme diagnostic criteria agreed by the participants are used. Where rates in both monitoring systems are the same, agreed criteria are likely to be conventional clinical practice and therefore superfluous. Where rates are different, the use of criteria enhances specificity of the information content but results in an underestimation of the total incidence of - respiratory disease presented to general practitioners.For common cold, acute bronchitis, otitis media and influenza/ influenza-like illness the associations between the rates in the two systems were high (R>/=O. 79), as might be expected, but these high values cross validate both recording systems in their monitoring of trends. For the remaining (non-epidemic) conditions the associations were low. There were no significant associations between the rates for asthma and the upper respiratory infectious diseases in either recording system, which suggests there was effective discrimination of asthma.

Communicable Disease Control↗
PubMed2005

Population-based case-control study of isolated congenital cataract.

BACKGROUND: The aim of this study was to detect possible etiological factors in the origin of isolated congenital cataracts. METHODS: The data set of the Hungarian Case-Control Surveillance of Congenital Abnormalities, 1980-2002, contains 111 cases of isolated congenital cataract and 111 matched control pairs without the defect, 37,837 population controls without any defects, and 22,744 malformed controls with other nonocular abnormalities. Exposure data and family history are based on prospective medical records, retrospective maternal information, and information obtained by regional nurses during a home visit with nonrespondent mothers. RESULTS: A positive family history indicated an autosomal-dominant origin in 10% of cases. Rubella infections occurred more frequently in case mothers than in control mothers before vaccination against rubella virus was instituted. A higher prevalence of influenza or common cold during pregnancy was found in the case group (55.9%) than in the population control group (18.5%; adjusted odds ratios [ORs], 5.8; 95% confidence interval (CI), 4.0-8.4) or in the malformed control group (21.7%; adjusted OR, 4.7; 95% CI, 3.2-6.9). The prevalence of acute infectious diseases of the respiratory system during pregnancy was also higher in the case group (26.1%) than in the population control group (9.1%; adjusted OR, 3.8; 95% CI, 2.5-5.8), or the malformed control group (9.3%; adjusted OR, 3.4; 95% CI, 2.3-5.3). The higher risk for isolated congenital cataract in cases of mothers with influenza or common cold and acute infectious diseases of the respiratory system during pregnancy was not found after administration of antifever therapy. CONCLUSIONS: Some isolated congenital cataracts are preventable by rubella vaccination and probably by influenza vaccination in the epidemic period. In addition, our results suggest that using antifever therapy for fever-related respiratory diseases may restrict the teratogenic risk of hyperthermia.

Adult↗
PubMed1987

Nasal disorders and anticholinergic therapy.

Treatment of patients with perennial rhinitis, common cold and watery nasal hypersecretion, is still unsatisfactory. As the glands are innervated by parasympathetic nerves we examined the effect of intranasal application of a parasympatholytic drug, ipratropium bromide. In the laboratory we have studied the effect, dosage and duration of ipratropium in normal subjects. These investigations showed a strong inhibition of the secretion from the nasal glands for more than 6 hours in a dosage regimen with no local or systemic adverse effects. We continued in a placebo-controlled clinical short term study and an open long term study on patients with perennial rhinitis. Furthermore we conducted a clinical trial in patients with common cold. We found an effect on watery hypersecretion in all these patient groups. Several laboratory and clinical studies have since confirmed our results. Ipratropium inhibits the reflectory watery secretion from the nasal glands, but does not change the basal secretion rate. The onset of action is rapid and the effect is prolonged. Long term treatment is safe and may possibly have a curative effect in some patients.

Airway Resistance↗
PubMed1987

Intranasally administered atropine methonitrate treatment of experimental rhinovirus colds.

The role of parasympathetic/cholinergic mechanisms in the syndrome of the common cold is not clear. Under double-blind, randomized, placebo-controlled conditions, we intranasally administered the anticholinergic atropine methonitrate (AM) to assess its tolerance in uninfected adults and therapeutic efficacy in volunteers with experimental rhinovirus (RV) colds. Healthy adults given sprays of AM intranasally 250 or 500 micrograms 4 times a day for 5 days developed nasal dryness and systemic side effects more often than did placebo (P) recipients. In 2 separate challenge studies, treatments were begun with AM 125 micrograms 3 times a day (AM = 8, P = 7) or AM 250 micrograms 4 times a day (AM = 9, P = 7) for 5 days, 24 h after intranasal inoculation of RV type 39. The low AM dose was well tolerated but had no effect on nasal mucus weights or nasal symptom scores in persons with RV colds. The higher dose of AM was associated with subjective drying and a reduction in nasal mucus production. These findings suggest that cholinergic mechanisms have a role in the pathogenesis of RV colds but that more work is necessary to determine if anticholinergic compounds will be of practical value in their treatment.

Administration, Intranasal↗
PubMedDate not supplied

[Community-acquired respiratory infections].

BACKGROUND: Respiratory infections are the most frequent reason for primary health care consultation. Although generally not severe, they are responsible for a large number of days of laboral and scholar absenteeism and an excessive use of antibiotics. METHODS: The clinical and epidemiologic data of extrahospitalary infections in primary health care centers throughout Spain were collected according to the one day cut off system repeated trimestrally over one year. RESULTS: Data of 3,732 days of consultation were collected in which a total of 144,608 patients were attended. Of these, 20,614 had respiratory infections and 11,684 extrarespiratory infections. The most frequent processes were pharyngitis (33.7%), common cold (31.7%) followed by bronchitis (18.7%), otitis (11%), influenza (4.6%), laryngitis (4%), sinusitis (3.6%) and pneumonia (1.8%). Antibiotic treatment was prescribed in 13,488 patients (65%). The type of antibiotic was analyzed in the 11,977 patients treated for only one infection. Penicillins were the antibiotics most used followed by cephalosporins. The antibiotic prescribed was considered adequate in 70% of the 8,484 patients treated for potentially bacterial infection. A total of 3,493 patients had infection considered to be of viral etiology. CONCLUSIONS: Twenty-two percent of the patients attending a primary health care center presented infection and of these two out of three cases had respiratory infection. Pharyngitis and common cold were the most frequent processes observed. Two thirds of the patients consulting for respiratory infection received antibiotic treatment, with 29.2% being diagnosed with infections considered to be of viral etiology. The empiric treatment chosen for the two thirds of the potentially bacterial infections was considered as adequate.

Adolescent↗
PubMed1990

Bacterial expression of antibody fragments that block human rhinovirus infection of cultured cells.

Human rhinoviruses are the major causative agents of the common cold in humans and have been divided into major and minor groups based on receptor specificity. cDNAs encoding the light and heavy chains of a murine monoclonal antibody that recognizes the major group receptor were cloned, abundantly expressed in Escherichia coli, and renatured into Fab fragments that blocked virus binding and protected HeLa cell monolayers from rhinovirus infection. Elimination of the cysteines normally bridging the heavy and light chains yielded molecules indistinguishable from wild-type Fab fragments in virus binding assays. Single-chain antibodies with covalently linked light and heavy variable domains were also expressed and showed receptor binding and cell protection activities. These recombinant antibody fragments are potentially useful in preventing or treating common colds in humans.

Amino Acid Sequence↗
PubMedDate not supplied

Primary and secondary ciliary dyskinesia.

It has recently been shown that patients with Kartagener's triad and also some subjects with similar symptoms, but without situs inversus, have a congenital abnormality of cilia as an explanation for their chronic airway symptoms; this disease has been named "the immotile-cilia syndrome" or more correctly "primary ciliary dyskinesia". Studying 27 such patients, we have found daily nose blowings since birth, chronic-recurrent sinusitis, and chronic secretory otitis media highly characteristic features. The frequency of common colds was not increased, and most patients did not suffer from repeated episodes of acute purulent otitis media. The number of ciliated cells with immotile cilia was increased, but only a single patient had completely immotile cilia; also the degree of asynchrony within the single ciliated cell was increased. Electron microscopy showed a decreased number of dynein arms in some patients, and abnormal arrangement of microtubules in others. Some patients, however, had normal ultrastructure, and this appeared to be associated with a hyperfrequent beating pattern. At least three subgroups of patients with primary ciliary dyskinesia can be delineated based on the motility-ultrastructure studies. Bacterial infection tends to reduce the number of ciliated cells with motile cilia, and viral infection (common cold) gives a very marked and long-lasting reduction in the number of ciliated cells. This may account for some otherwise unexplainable subchronic symptoms from nose and throat.

Adolescent↗
PubMed2004

Comparative controlled study of Andrographis paniculata fixed combination, Kan Jang and an Echinacea preparation as adjuvant, in the treatment of uncomplicated respiratory disease in children.

A three-arm study comparing the efficacy of Kan Jang, a fixed herbal combination containing standardized Andrographis paniculata (N.) SHA-10 extract, with Immunal, a preparation containing Echinacea purpurea (L.) extract, in uncomplicated common colds was carried out in 130 children aged between 4 and 11 years over a period of 10 days. The study was designed as an adjuvant treatment of Kan Jang and Immunal with a standard treatment. The patients were assigned to one of the three groups. In control group C; 39 patients received only standard treatment. Kan Jang and Immunal were used as an adjuvant to this therapy in the other two groups. Adjuvant group A; 53 patients treated with Kan Jang tablets concomitant to standard treatment, and adjuvant control group B; 41 patients treated with concomitant Immunal. It was found that the adjuvant treatment with Kan Jang, was significantly more effective than Immunal, when started at an early stage of uncomplicated common colds. The symptoms of the disease were less severe in the Kan Jang group. The effect of Kan Jang was particularly pronounced in two objective parameters, amount of nasal secretion g/day and nasal congestion. Kan Jang also accelerated the recovery time, whereas Immunal did not show the same efficacy. The use of standard medication was significantly less in the Kan Jang adjuvant group than in either the Immunal or standard treatment group. Kan Jang treatment was well tolerated and no side effects or adverse reactions were reported.

Adjuvants, Immunologic↗
PubMedDate not supplied

Viral illnesses and sports performance.

Viruses are ubiquitous and cause numerous infections in humans. These may vary from asymptomatic infection to severe debilitating illness. Viruses enter the host cells to replicate, using host synthetic mechanisms, and, thus, are resistant to conventional antibiotics. The human body responds to viral infection by synthesising specific antibody which can be used to aid diagnosis. Infectious mononucleosis (glandular fever) commonly affects the 15 to 30 years age group. It may produce severe debility which may last a month or more. Coxsackie virus infection can produce symptoms of the common cold but may also invade heart muscle and produce myocarditis, a potentially serious disease. Other viruses also produce a wide spectrum of disease. Recent evidence has shown that people undergoing severe mental or physical stress may have reduced immunity to viral infections. There are risks associated with strenuous physical activity during the acute phase of viral infection, and there are reports of sudden death and serious complications occurring in previously fit young adults who undertake vigorous exercise when in the acute phase of a viral illness. Abnormalities of skeletal muscle have been demonstrated in patients with viral infection and this may explain the loss of performance experienced by athletes after upper respiratory tract infection. As a general rule, for all but mild common colds, it is advised that the athlete avoids hard training for the first month after infection.

Coxsackievirus Infections↗
PubMed2003

Rhinovirus increases human beta-defensin-2 and -3 mRNA expression in cultured bronchial epithelial cells.

Human beta-defensins (hBDs) are antimicrobial peptides that play important roles in host defense against infection, inflammation and immunity. Previous studies showed that micro-organisms and proinflammatory mediators regulate the expression of these peptides in airway epithelial cells. The aim of the present study was to investigate the modulation of expression of hBDs in cultured primary bronchial epithelial cells (PBEC) by rhinovirus-16 (RV16), a respiratory virus responsible for the common cold and associated with asthma exacerbations. RV16 was found to induce expression of hBD-2 and -3 mRNA in PBEC, but did not affect hBD-1 mRNA. Viral replication appeared essential for rhinovirus-induced beta-defensin mRNA expression, since UV-inactivated rhinovirus did not increase expression of hBD-2 and hBD-3 mRNA. Exposure to synthetic double-stranded RNA (dsRNA) molecule polyinosinic:polycytidylic acid had a similar effect as RV16 on mRNA expression of these peptides in PBEC. In line with this, PBEC were found to express TLR3, a Toll-like receptor involved in recognition of dsRNA. This study shows that rhinovirus infection of PBEC leads to increased hBD-2 and hBD-3 mRNA expression, which may play a role in both the uncomplicated common cold and in virus-associated exacerbations of asthma.

Bronchi↗
PubMed1999

[Local injection of dexamethasone acetate suspension into the nasal mucosa in cases of olfactory disturbance].

Local injections of suspended steroid solution into the nasal mucosa were performed for 102 patients with olfactory disturbances. Dexamethasone acetate suspension in a concentration of 4 mg/0.5 ml was injected into the mucosa of the nasal septum on each side every 2 weeks for a total of 8 times. Mecobalamin and ATP were also administrated in a daily dose of 750 micrograms and 300 mg, respectively. Of the 102 olfactory disturbance patients, 32 patients had chronic sinusitis, 24 patients had common cold, 14 patients had allergic rhinitis, 9 patients had head trauma and the remaining 23 patients the reason for the disturbance was unknown. Using a visual analogue scale, improvements were found in 63.7%. We assessed the effect of this therapy on the threshold of olfactory sensation and perception using a T & T olfactogram. The overall mean values of olfactory sensation and perception were significantly improved; from 4.75 +/- 1.44 (SD) to 3.01 +/- 2.13 (SD) and from 5.30 +/- 0.88 (SD) to 4.19 +/- 1.60 (SD), respectively. All but the cases of head trauma showed significant improvement. Overall, 44 (43.1%) of the 102 patients were defined as having had a positive olfactory response to this treatment (an improvement in the average perception olfactory score of > = 1.0). In cases of chronic sinusitis, 15 (46.9%) of the 32 patients were positive. 12 (50.0%) of the common cold 24 patients, 7 (50.0%) of the 14 allergic rhinitis patients, 2 (22.2%) of the 9 head trauma patients and 11 (47.8%) of the 23 unknown etiology patients were positive for this treatment. Patients with severe olfactory dysfunction and anosmia showed a lower response than the patients who were mildly to moderately affected. Patients showing no response in the Alinamin intravenous test showed also lower improvement rates than those showing a normal response. Interestingly, 8 (27.6%) of 29 patients with a normal appearance of the olfactory clefts and no response for the Alinamin test responded positively to this treatment. This meant that the olfactory disturbance might be due to the existence of edema surrounding the olfactory nerve, not of the olfactory cleft. The improvement rate of patients treated within one year from the onset of these olfactory disturbance was better than the rate of those over one year. The present new therapeutic modality is very useful as a treatment which showed only be performed by otolaryngologists.

Adenosine Triphosphate↗
PubMed2005

Experimental surveillance using data on sales of over-the-counter medications--Japan, November 2003-April 2004.

OBJECTIVES: This report describes a study to explore the possibility of using data on sales of over-the- counter (OTC) medications as part of a routine syndromic surveillance system aimed at early detection of infections of public health concern. A retrospective evaluation was conducted of sales of OTC medications used to treat the common cold. This report discusses the correlation of these data to influenza activity in Japan during the 2003-04 influenza season and evaluates the potential of using such data to predict influenza epidemics. METHODS: Data from approximately 1,100 pharmacies throughout Japan collected during November 2003-April 2004 were analyzed. OTC sales data were compared with influenza incidence data (one weekly and two daily data sets) to determine correlations and predictability. Adjusted R-square was used as an index of goodness of-fit in the estimation. Data reflecting daily influenza activity were obtained from the National Surveillance of Daily Influenza Outpatients and the Mailing List-Based Influenza Epidemic Database. National sentinel surveillance data for influenza from approximately 5,000 sites nationwide also were analyzed. RESULTS: Although a correlation was demonstrated between sales of OTC medications used to treat the common cold and concurrent influenza activity, analysis of sales data alone was not sufficient to determine influenza activity in advance even when sales promotion effects were excluded from the analysis. CONCLUSION: Because visiting a health-care provider costs more than purchasing OTC medications, the hypothesis was formed that an ill person will purchase OTC medications first and visit a physician only if the condition does not resolve or worsens. The results of this study do not provide any clear evidence to support this hypothesis. For this reason, OTC sales do not appear to be a good candidate for a national real-time detection system for influenza epidemics in Japan.

Commerce↗
PubMed2003

[Acquired inhibitor against coagulation factor V with severe hematuria].

A 42-year-old man was admitted with hematuria after a common cold. No purpura could be observed but there was oozing on the site of the forearm where blood had been taken in a previous hospital. Platelet count was 292 x 10(3)/microliter, examination of coagulation system showed abnormalities; prolonged prothrombin time: PT (99.7 sec) and activated partial thromboplastin time: APTT (more than 200 sec), which suggested deficiency of coagulation factor II (FII), factor V (FV) or factor X (FX). In fact, the FV activity was only 2% of the pooled normal plasma. Mixing test of patient's plasma with normal pooled plasma revealed the existence of an FV inhibitor (FVI), which was IgA with an activity levels of 3 Bethesda unit/ml. Although hematuria stopped soon after beginning treatment with steroids (PSL), the abnormalities in PT and APTT improved very slowly and incompletely. At the time of writing, FVI is still observed ten months after onset. The patient had no underlying disease, and in this case FVI appeared following a common cold. Previous reports have said that FVI can cause mild bleeding, and it disappear in a short time. This case showed the possibility of the hidden presence of FVI in patients with hematuria.

Adult↗
PubMed1998

[Acetaminophen-induced pneumonitis].

We report a case of drug-induced pneumonitis caused by acetaminophen taken for headache. The patient was a 49-year-old woman who had been taking a common cold drug (Benza BlockSP) containing acetaminophen and an anti-gastritis drug for headache. Seven days after she began taking acetaminophen, fever, dry cough, and dyspnea developed. The patient was admitted to our hospital on December 6,1996. Chest X-ray films and computed tomography scans revealed ground-glass and reticulonodular opacities. All chemotherapy was discontinued under a presumptive diagnosis of drug-induced pneumonitis. Transbronchial lung biopsy specimens revealed infiltration of lymphocytes and eosinophils into the alveolar walls and interstitum, with granulomotous lesions and macrophages in the alveolar spaces. The patient's chest X-ray findings improved and her symptoms subsided after the medications were stopped. However, she was given oral prednisolone (30 mg/day) because shadows were still evident on chest X-ray films. Prednisolone was effective in removing those shadows. A lymphocyte stimulation test was positive for acetaminophen. Based on the above findings, acetaminophen-induced pneumonitis was diagnosed. To our knowledge, acetaminophen-induced pneumonitis is rare. However, when drug-induced pneumonitis is suspended, common cold drugs containing acetaminophen should be kept in mind.

Acetaminophen↗
PubMed1998

Rhinovirus infection induces mucus hypersecretion.

Rhinorrhea is a prominent symptom of the common cold. Although increases in vascular permeability and serous cell secretion have been demonstrated in human nasal mucus during active rhinovirus infections, changes in mucin constituents have not been quantified. Nonallergic (n = 48) and asymptomatic allergic rhinitis (n = 32) subjects were inoculated with rhinovirus type hanks before the spring allergy season. Nasal lavages were performed before inoculation (day 0), then daily for 5 days afterward. The subjects were divided into infected and noninfected groups on the basis of evidence of successful rhinovirus infection (nasal shedding of virus or fourfold increases in specific serum antibodies). Concentrations of interleukin (IL)-8, markers of vascular leak (IgG), seromucous cells (lysozyme), and mucoglycoprotein exocytosis [7F10-immunoreactive mucin (7F10-irm) and Alcian blue staining of acidic mucoglycoproteins] were measured in lavage fluids. The infected subgroup had maximal increases in nasal lavage fluid concentrations of IL-8 (sevenfold), IgG (fourfold), total protein (twofold), and gel-phase 7F10-irm (twofold) on day 3. There were no differences between infected allergic and nonallergic subjects. IL-8 and gel-phase 7F10-irm were significantly higher in infected than in noninfected subjects. In addition to promoting plasma exudation, rhinovirus hanks infection increases IL-8 and gel-phase mucin secretion. These processes may contribute to a progression from watery rhinorrhea to mucoid discharge, with mild neutrophilic infiltration during the common cold.

Adolescent↗
PubMed2006

Rhinovirus chemotherapy.

Human rhinoviruses (HRV), members of the Picornaviridae family, are comprised of over 100 different virus serotypes. HRV represent the single most important etiological agents of the common cold [Arruda, E., Pitkaranta, A., Witek Jr., T.J., Doyle, C.A., Hayden, F.G., 1997. Frequency and natural history of rhinovirus infections in adults during autumn. J. Clin. Microbiol. 35, 2864-2868; Couch, R.B., 1990. Rhinoviruses. In: Fields, B.N., Knipe, D.M. (Eds.), Virology. Raven Press, New York, pp. 607-629; Turner, R.B., 2001. The treatment of rhinovirus infections: progress and potential. Antivir. Res. 49 (1), 1-14]. Although HRV-induced upper respiratory illness is often mild and self-limiting, the socioeconomic impact caused by missed school or work is enormous and the degree of inappropriate antibiotic use is significant. It has been estimated that upper respiratory disease accounts for at least 25 million absences from work and 23 million absences of school annually in the United States [Anzueto, A., Niederman, M.S., 2003. Diagnosis and treatment of rhinovirus respiratory infections. Chest 123 (5), 1664-1672; Rotbart, H.A., 2002. Treatment of picornavirus infections. Antivir. Res. 53, 83-98]. Increasing evidences also describe the link between HRV infection and more serious medical complications. HRV-induced colds are the important predisposing factors to acute otitis media, sinusitis, and are the major factors in the induction of exacerbations of asthma in adults and children. HRV infections are also associated with lower respiratory tract syndromes in individuals with cystic fibrosis, bronchitis, and other underlying respiratory disorders [Anzueto, A., Niederman, M.S., 2003. Diagnosis and treatment of rhinovirus respiratory infections. Chest 123 (5), 1664-1672; Gern, J.E., Busse, W.W., 1999. Association of rhinovirus infections with asthma. Clin. Microbiol. Rev. 12 (1), 9-18; Pitkaranta, A., Arruda, E., Malmberg, H., Hayden, F.G., 1997. Detection of rhinovirus in sinus brushings of patients with acute community-acquired sinusitis by reverse transcription-PCR. J. Clin. Microbiol. 35, 1791-1793; Pitkaranta, A., Virolainen, A., Jero, J., Arruda, E., Hayden, F.G., 1998. Detection of rhinovirus, respiratory syncytial virus, and coronavirus infections in acute otitis media by reverse transcriptase polymerase chain reaction. Pediatrics 102, 291-295; Rotbart, H.A., 2002. Treatment of picornavirus infections. Antivir. Res. 53, 83-98]. To date, no effective antiviral therapies have been approved for either the prevention or treatment of diseases caused by HRV infection. Thus, there still exists a significant unmet medical need to find agents that can shorten the duration of HRV-induced illness, lessen the severity of symptoms, minimize secondary bacterial infections and exacerbations of underlying disease and reduce virus transmission. Although effective over-the-counter products have been described that alleviate symptoms associated with the common cold [Anzueto, A., Niederman, M.S., 2003. Diagnosis and treatment of rhinovirus respiratory infections. Chest 123 (5), 1664-1672; Gwaltney, J.M., 2002a. Viral respiratory infection therapy: historical perspectives and current trials. Am. J. Med. 22 (112 Suppl. 6A), 33S-41S; Turner, R.B., 2001. The treatment of rhinovirus infections: progress and potential. Antivir. Res. 49 (1), 1-14; Sperber, S.J., Hayden, F.G., 1988. Chemotherapy of rhinovirus colds. Antimicrob. Agents Chemother. 32, 409-419], this review will primarily focus on the discovery and development of those agents that directly or indirectly impact virus replication specifically highlighting new advances and/or specific challenges with their development.

Antiviral Agents↗
PubMed2004

Delayed antibiotics for symptoms and complications of respiratory infections.

BACKGROUND: The use of antibiotics for upper respiratory tract infections is controversial. Any benefits have to be weighed against common adverse reactions (including rash, abdominal pain, diarrhoea and vomiting), cost and antibacterial resistance. There has been interest in ways to reduce antibiotic prescribing for acute respiratory infections. One is delaying the use of prescribed antibiotics by more than 48 hours for acute upper respiratory tract infections. Such methods have been shown to reduce prescribing. This review asks what effect this practice has on the clinical course of the illness. OBJECTIVES: To evaluate the clinical effect of delayed antibiotic use in acute upper respiratory tract infections compared to immediate use of antibiotics SEARCH STRATEGY: The following electronic databases were searched: the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library Issue 1, 2004) which includes the Acute Respiratory Infection Groups' specialised register; MEDLINE (January 1966 to January Week 1 2004), EMBASE (1990 to September 2003) and Current Contents (1998 to 2003). The search was carried out by an expert librarian. Abstracts of identified articles were used to determine which studies were trials. SELECTION CRITERIA: Randomised controlled trials involving patients of all ages defined as having acute otitis media, acute pharyngitis, sore throat, common cold, a viral upper respiratory tract infection, acute sinusitis, and acute bronchitis were included in which delayed antibiotics are compared to antibiotics used immediately. Delayed antibiotic use was defined as the use of or advice to use antibiotics more than 48 hours after the initial consultation. 'Immediate antibiotic use' was defined as the immediate use of oral antibiotics given at the initial consultation. Clinical outcomes measured included: the presence or absence of fever, cough, pain, duration and severity of illness, complications of the disease, adverse effects from the antibiotics. Trial quality was assessed independently by two reviewers who were blinded to the author, journal and results of each study. DATA COLLECTION AND ANALYSIS: Data was collected by two reviewers who were blinded to the author and journal. Data were analysed and reported using RevMan. MAIN RESULTS: Seven trials were eligible on the basis of design and all reported patient-centred outcomes. Methodological quality of included trials was generally high. There was no difference between immediate and delayed antibiotic groups for symptoms on day one and day seven. For most symptom measures there was no significant difference between the immediate and delayed antibiotic groups. Missing data and marked heterogeneity between study outcomes prevented pooling of results as a meta-analysis. Three studies out of six reporting fever, all involving patients with sore throat, indicated that there was more fever in the delayed antibiotic group. The remaining three studies showed no difference. There was no significant symptom difference for patients with cough or the common cold between the two intervention groups. Pain and malaise severity scores at day three significantly favoured the immediate antibiotic group in children with acute otitis media (Little 2001). In this study by Little 2001 of children with otitis media proxies for other malaise related outcomes were reported, including 'last day of crying' which favoured the immediate antibiotic group by approximately 16 hours (0.69 days; 95% CI 0.31 to 1.07). In the same study, just over half a spoon of paracetamol a day less was used in the immediate antibiotic group (0.59; 95% CI 0.25 to 0.93). There was no significant difference between the intervention groups for the adverse outcome of rash. Two studies reported the outcome of vomiting which was reduced in the immediate antibiotic group in children with suspected streptococcal pharyngitis in El-Daher 1991 but there was no difference in children with sore throat in Little 1997. Diarrhoea was reported by three studies of which two showed no difference Little 1997; Arroll 2002a while Little 2001 reported less diarrhoea in the delayed antibiotic group in children with otitis media. REVIEWERS' CONCLUSIONS: When considering treatment options for upper respiratory tract infections, the option of delayed antibiotics has been used in an attempt to reduce the use of antibiotic prescriptions. This review shows that for all symptom scores the evidence varies between trials. Most symptom outcomes show no difference between immediate and delayed antibiotic groups. Three of the six studies, all involving patients with sore throat, indicated that patients in the delayed antibiotic group had significantly more fever that their counterparts in the immediate antibiotic group. The other three showed no difference for the outcome of fever. There is evidence indicating that for children with otitis media, pain and malaise scores are worse in the delayed antibiotic group compared to the immediate antibiotic group. This price must be weighed up against the benefits of reduced antibiotic prescribing. Future randomised controlled trials of delaying antibiotics as an intervention should fully report symptoms as well as changes of prescription rates.

Anti-Bacterial Agents↗