***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: Adults and children in the United States experience two to six colds per year ( 1 , 2 ) . The morbidity and loss of working hours due to the common cold are substantial ( 1 - 3 ) , and treatment remains elusive . Ten controlled trials of treatment of the common cold with zinc lozenges have been published ( 4 - 13 ) . Five studies reported that zinc lozenges reduced the duration of cold symptoms ( 4 - 8 ) . The other five studies , however , showed no effect of zinc on cold symptoms ( 9 - 13 ) . It has been argued that some studies did not find zinc to be effective because inadequate doses or incorrect formulations of zinc were used ( 13 , 14 ) . No studies have eluci date d the biochemical , immunologic , or virologic basis for zinc action . The most frequent cause of the common cold is rhinovirus infection ; however , as many as 200 other viruses may be responsible for this condition ( 1 , 2 , 7 ) . Korant and Butterworth ( 15 ) showed that zinc prevents the formation of viral capsid proteins and thus inhibits in vitro replication of several viruses , including rhinovirus . It has also been hypothesized that zinc prevents the virus from binding with intracellular adhesion molecule 1 and thus from entering cells ( 16 , 17 ) . Two r and omized , controlled trials examined viral shedding in volunteers who were inoculated with rhinovirus and were treated with zinc ;  the investigators concluded that zinc had no effect on this infection ( 9 ) . We determined the duration of cold symptoms in zinc-treated and placebo-treated participants . We also assayed plasma zinc and proinflammatory cytokine levels on the day 1 of the study and at the end of the resolution of cold symptoms in both groups . Methods Participants We recruited 50 volunteers from Detroit Medical Center , Detroit , Michigan , to participate in a r and omized , placebo-controlled trial of the efficacy of zinc acetate lozenges in treating the common cold . Two participants in the placebo group dropped out on day 2 . We therefore had complete data on 48 participants . Participants were medical students , graduate and undergraduate students , staff , and employees at Wayne State University who were older than 18 years of age . Recruitment took place throughout 1998 . Each volunteer was paid $ 10 for participation and transportation costs . Participants were informed of the placebo-controlled , double-blind nature of the study , and the study protocol was approved by the Human and Animal Investigation Committee of Wayne State University . Volunteers were recruited if they had had cold symptoms for 24 hours or less and had at least 2 of the following 10 symptoms :  cough , headache , hoarseness , muscle ache , nasal drainage , nasal congestion , scratchy throat , sore throat , sneezing , and fever . We excluded persons who were pregnant , had a known immunodeficiency disorder , had a chronic illness , had had symptoms of the common cold for more than 24 hours , or had previously used zinc lozenges to treat the common cold . We chose a sample size of 50 so that we could detect a difference in the mean number of days of symptoms from 8 days in the placebo group to 4 days in the zinc group with a st and ard deviation of 2 days , a two-sided P value of 0.05 , and an approximate power of 80 % or more . In view of Mossad and colleagues ' findings ( 7 ) , a 50 % reduction in the duration of symptoms of the common cold in the treatment group was considered a reasonable end point . Intervention Each zinc lozenge consisted of 42.96 mg of zinc acetate dihydrate ( USP ) ( Heico Chemicals , Delaware Water Gap , Pennsylvania ) , 6.0 mg of peppermint oil ( National Formulary ) ( Bell Flavors , North Brook , Illinois ) , 16.0 mg of silica gel ( National Formulary ) ( Siloid 244 FP , Davidson Chemical , Baltimore , Maryl and ) , 4.0 mg of stevia extract powder ( 90 % pure steviodside ) , 3835.04 mg of directly compressible dextrose ( USP ) ( Unidex 2034 ) , and 100 mg of glycerol monostearate ( Myvaplex TM 600 P , Eastman Chemical , Kingsport , Tennessee ) . Each lozenge contained 12.8 mg of zinc . Each placebo lozenge contained 0.25 mg of sucrose octa acetate , 6.0 mg of peppermint oil , 16.0 mg of silica gel , 3877.75 mg of dextrose DC , and 100 mg of glycerol monostearate . The placebo and zinc lozenges were identical in weight ( 4000 mg ) , appearance , flavor , and texture . A research consultant prepared the r and omization code and the packages of medication ( 18 ) . The packages were identical in appearance except for the r and omization numbers . A research assistant who was blinded to treatment assignments distributed the study medication . Participants were given 50 lozenges and were asked to dissolve one lozenge in their mouths every 2 to 3 hours while awake for as long as they had cold symptoms . They were instructed to take no other cold preparations during the study period . Outcome Measures Our primary end point was the average duration of cold symptoms . Secondary end points were plasma levels of zinc and proinflammatory cytokines . Participants were asked to complete a daily log documenting the severity of symptoms and the medications taken throughout the duration of the cold . Every day , the participants grade d each symptom as 0 for none , 1 for mild , 2 for moderate , and 3 for severe . Total symptom scores were calculated by summing the scores of the 10 symptoms for each day . Resolution of cold symptoms was defined as resolution of all symptoms ( a total symptom score of 0 ) or resolution of all but one mild symptom ( a total symptom score of 1 ) . The participants were not asked to rate their overall illness in terms of severity . We obtained plasma sample s for assay of zinc and proinflammatory cytokines . Zinc was assayed by using methods established in our laboratory that are based on atomic absorption spectrophotometry ( 19 ) . Every pre caution was taken to avoid contamination during collection , preparation , and analysis . We measured levels of three proinflammatory cytokines before and after treatment : soluble interleukin-1 receptor antagonist , soluble tumor necrosis factor receptor , and neopterin . We also recruited 17 healthy adult volunteers with no symptoms of cold for a comparison assay of plasma proinflammatory cytokines and zinc . Cytokines were analyzed by using enzyme-linked immunosorbent assay . Quantikine assay kits for soluble tumor necrosis factor receptor and soluble interleukin-1 receptor antagonist were obtained from R and D Systems , Minneapolis , Minnesota , and kits for analysis of neopterin were obtained from American Laboratory Products Company Ltd. , Windham , New Hampshire . All cytokine assays were run on the same day . To assess side effects of the treatment , participants were given a question naire to be filled out at the end of the trial . Participants provided yes or no answers to questions about nausea , vomiting , abdominal pain , diarrhea , constipation , dry mouth , bad taste , and mouth irritation . Participants returned to the clinic for the final visit within 1 day of resolution of cold symptoms . At this time , they returned unused lozenges . This was done to check adherence and confirm that cold symptoms had resolved . Maintenance of Blinding Comparability in taste between zinc and placebo was tested in healthy volunteers . Ten participants were given a zinc lozenge and 10 received a placebo lozenge . One week later , the participants who received zinc were given placebo and those who received placebo were given zinc . At each visit , the participants filled out a question naire in which they were asked to guess whether they received a zinc or placebo lozenge . They had seven choices : certainly placebo , certainly zinc , do not know , possibly placebo , possibly zinc , probably placebo , and probably zinc .  Volunteers who selected certainly , probably , or possibly and were correct about the type of lozenge they received were considered correct . We therefore categorized participants as correct , incorrect , or do not know . We assessed the adequacy of blinding among study participants by administering the question naire used to assess comparability of taste in healthy volunteers . Participants filled out the question naire at the beginning and at the end of the trial . Statistical Analysis We compared the change in outcomes before and after intervention in the zinc and placebo groups . When changes in both groups were normally distributed , as determined by using the ShapiroWilk W test , we used the t-test to compare mean changes . When they were not normally distributed , the differences between changes were compared by using the nonparametric Wilcoxon rank-sum test . Multivariate analysis of variance with repeated measures was used to determine the effect of treatment time on severity scores over the study period . The Fisher exact test were used to determine group differences in side effects . Chi-square analyses were performed to determine group differences in correctly identifying lozenges at baseline and after treatment . The t-test was used to compare plasma zinc and cytokine levels before group assignment with levels in healthy controls . This was done to determine whether participants with colds  differed from controls . All statistical analyses were done by using JMP version 3.2.2 on a Macintosh computer ( SAS Institute , Inc. , Cary , North Carolina ) . Role of the Funding Source The George and Patsy Eby Research Foundation , Austin , Texas , donated unrestricted research funds to Wayne State University for partial support of this study . The research foundation had no role in the collection , analysis , or interpretation of the data or in the decision to publish the study . George Eby holds U.S. patent rights for zinc lozenges and donated funds earned from his patent rights to the research foundation . George Eby supplied zinc and placebo lozenges for this study . The authors have neither industry connections nor personal financial conflicts of interest related to the study . Results Table 1 shows the demographic characteristics of the study participants . Table 1 . Demographic Characteristics of Study Participants  Duration and Severity of Cold Symptoms The Objective : To investigate bacterial nasopharyngitis as a cause of adult upper respiratory infection . Design : Prospect i ve case series . Setting : Walk-in medical clinic of a university hospital . Patients : 507 patients with cold or flu symptoms , sore throat , or recent cough ; 21 control subjects without symptoms of upper respiratory infection . Measurements and main results : After thorough history and physical examination , the patients underwent nasopharyngeal aspiration and throat culture . Nasopharyngeal specimens were cultured for both bacteria and viruses ; antigens for influenza , parainfluenza , and respiratory syncytial virus were sought by enzyme-linked immunosorbent assay ( ELISA ) ; serum antibodies to viral respiratory pathogens were determined . Group A beta-hemolytic streptococci grew from the throat specimens of 39 of the 507 patients ( 8 % ) or 38 of 3 34 patients ( 11 % ) who had clinical diagnoses of pharyngitis . Thirty-three cases of influenza A , 20 cases of influenza B , and seven cases of parainfluenza infections were diagnosed . Bacteria were cultured from the nasopharyngeal secretions of 284 patients ( 56 % ) . In contrast to pharyngeal culture , commensal mixed flora were rarely found in nasopharyngeal culture . Nasopharyngeal culture of bacteria usually considered to be respiratory pathogens was significantly associated with the presence of leukocytes . Streptococcus pneumoniae ( odds ratio 6.0 , 95 % confidence interval 2.6–14.2),Moraxella catarrbalis ( odds ratio 12.9 , 95 % confidence interval 3.1–79.5 ) , and Hemophilus influenzae ( odds ratio 3.0 , 95 % confidence interval 1.2–7.4 ) were all associated with the presence of leukocytes . In contrast , nasophaiyngeal culture of coagulase-negative staphylococci , mixed flora , and the documentation of a viral infection were not associated with the presence of leukocytes . For none of 21 control subjects were “ pathogenic ” bacteria found . Conclusions : These data suggest that potentially pathogenic bacteria may have a causal role in adult nasopharyngitis , although further data are needed to confirm this hypothesis Background The Need To Improve Antibiotic Prescription for Acute Respiratory Infections 1 . The epidemic increase in antibiotic-resistant Streptococcus pneumoniae is an ambulatory care problem . Excessive use of antibiotics in ambulatory practice has contributed to the emergence and spread of antibiotic-resistant bacteria in the community ( 1 - 4 ) . Penicillin resistance in S. pneumoniae has increased in an epidemic manner in the past 10 years ( 5 , 6 ) . Resistance to macrolides , doxycycline , trimethoprimsulfamethoxazole , and second- and third-generation cephalosporins has also increased . Special attention to antibiotic-resistance profiles of S. pneumoniae is warranted , since this pathogen is the leading cause of community-acquired bacterial pneumonia , bacterial meningitis , bacterial sinusitis , and otitis media in the United States ( 7 ) . 2 . Previous antibiotic use is an important risk factor for carriage of and infection with antibiotic-resistant Streptococcus pneumoniae . The major 
    Output:
    
Sinusitis usually develops after an upper respiratory tract infection because of obstruction of the sinus ostia , whereas bacterial pneumonia in adults with influenza infection usually results from the effects of influenza on host immunity .
As described below , antibiotic treatment of upper respiratory tract infection has not been shown to alter the rates of these uncommon complications .
Although physicians often rely on the presence of purulent nasal discharge and purulent sputum to assign more specific diagnoses , such as acute rhinosinusitis or acute bronchitis , in patients with acute respiratory illness , these symptoms