Diagnostic prediction models for CT-confirmed and bacterial rhinosinusitis in primary care: individual participant data meta-analysis.

BACKGROUND: Antibiotics are overused in patients with acute rhinosinusitis (ARS) as it is difficult to identify those who benefit from antibiotic treatment. AIM: To develop prediction models for computed tomography (CT)-confirmed ARS and culture-confirmed acute bacterial rhinosinusitis (ABRS) in adults presenting to primary care with symptoms suggestive of ARS. DESIGN AND SETTING: This was a systematic review and individual participant data meta-analysis. METHOD: CT-confirmed ARS was defined as the presence of fluid level or total opacification in any maxillary sinuses, whereas culture-confirmed ABRS was defined by culture of fluid from antral puncture. Prediction models were derived using logistic regression modelling. RESULTS: Among 426 patients from three studies, 140 patients (32.9%) had CT-confirmed ARS. A model consisting of seven variables: previous diagnosis of ARS, preceding upper respiratory tract infection, anosmia, double sickening, purulent nasal discharge on examination, need for antibiotics as judged by a physician, and C-reactive protein (CRP) showed an optimism-corrected c-statistic of 0.73 (95% confidence interval [CI] = 0.69 to 0.78) and a calibration slope of 0.99 (95% CI = 0.72 to 1.19). Among 225 patients from two studies, 68 patients (30.2%) had culture-confirmed ABRS. A model consisting of three variables: pain in teeth, purulent nasal discharge, and CRP showed an optimism-corrected c-statistic of 0.70 (95% CI = 0.63 to 0.77) and a calibration slope of 1.00 (95% CI = 0.66 to 1.52). Clinical utility analysis showed that both models could be useful to rule out the target condition. CONCLUSION: Simple prediction models for CT-confirmed ARS and culture-confirmed ABRS can be useful to safely reduce antibiotic use in adults with ARS in high-prescribing countries.

Endoscopic sinus surgery (ESS) to change quality of life for adults with recurrent rhinosinusitis: study protocol for a randomized controlled trial.

BACKGROUND: Endoscopic sinus surgery (ESS) has been used for decades to treat recurrent acute rhinosinusitis episodes (RARS) in adults. RARS results in infectious symptoms, antibiotic courses, sick leaves, and impaired quality of life. Theoretically, the ESS procedure, through improving the drainage of the paranasal sinuses, decreases the symptoms and enhances the quality of life of the RARS patients. Whether this is true has not been reported in a randomized trial yet. METHODS: We conduct a single-center, non-blinded, randomized, 6-month, parallel group superiority clinical study including 80 adult participants referred to surgical treatment for RARS. The participants will either have ESS or conservative medical treatment (control group). The primary outcome will be the difference between the mean disease-specific Sinonasal Outcome Test 22 (quality of life questionnaire) change scores (from baseline to 6 months) of ESS and control group. DISCUSSION: This study will add significant new information to the effect and harms of ESS procedure in the treatment of adults with RARS. TRIAL REGISTRATION: ClinicalTrials.gov NCT04241016 . Registered on 17 January 2020.

Total or partial tonsillar resection (tonsillectomy or tonsillotomy) to change the quality of life for adults with recurrent or chronic tonsillitis: study protocol for a randomised controlled trial.

BACKGROUND: Tonsillar surgery has been used for decades to treat recurrent and chronic tonsillitis in adults. Recurrent and chronic tonsillitis result in disturbing symptoms, treatment costs, sick leave, and impaired quality of life (QoL). Theoretically, removing all or part of the altered pathological palatal lymphoid tissue alleviates the symptoms and enhances the QoL. Whether this is true with total or partial tonsillar resection (tonsillectomy (TE) and tonsillotomy (TT), respectively) has not been reported in a randomised trial yet. METHODS: We conduct a multicentre, partly blinded, randomised, 6-month, parallel-group clinical study including 285 adult participants referred to surgical treatment for chronic or recurrent tonsillitis. The participants will either have TE, TT or watchful waiting (WW). The primary outcome will be the difference between the mean disease-specific Tonsillectomy Outcome Inventory-14 (QoL questionnaire) scores at 6 months. Comparison is made firstly between the combined TE+TT and WW groups (superiority analysis), and secondly between the TE and TT groups (non-inferiority analysis). DISCUSSION: This study will add significant new information to the effects and harms of TE and TT procedures in the treatment of adults with chronic or recurrent tonsillitis. TRIAL REGISTRATION: ClinicalTrials.gov: NCT04657549.

Interpretation of Tonsillectomy Outcome Inventory-14 scores: a prospective matched cohort study.

PURPOSE: Knowledge of disease-specific instruments enables the evaluation of health- related quality-of-life (QoL) change associated with chronic and recurrent tonsillitis in adults. The main objective was to explore the interpretation of scores according to the throat-related QoL instrument, Tonsillectomy Outcome Inventory-14 (TOI-14), by determining the typical scores in healthy subjects and patients and define the minimum important change (MIC). METHODS: We performed a prospective matched cohort study in a secondary care area of Oulu University Hospital. The surgical cohort consisted of 42 patients referred to tonsillectomy due to recurrent or chronic tonsillitis. The control cohort consisted of 42 age- and sex-matched healthy controls obtained from the escorts of patients in the same hospital. We translated and validated the Finnish TOI-14 instrument and collected TOI-14 scores at entry and at 6 months and compared results to the anchor question. RESULTS: At entry, the mean TOI-14 scores were significantly higher in the surgical cohort than in the control cohort [mean (95% confidence interval)] 33.0 (27.0-39.1) vs. 5.0 (3.6-6.4), respectively. At 6 months follow-up, the mean TOI-14 scores had improved markedly after tonsillectomy to the level of the control cohort. In the healthy population, the score was in most cases under 15.0 points. In patients, a score of about 20.0 indicated mild symptoms, 30.0 moderate symptoms and 40.0 or higher intense symptoms. The MIC value was 10.0 points. CONCLUSIONS: These results enable the more accurate interpretation of the scores of the only disease-specific QoL instrument for adult throat-related diseases.

Predictive factors of a beneficial quality of life outcome in patients undergoing primary sinonasal surgery: a population-based prospective cohort study.

PURPOSE: To assess predictive factors of a beneficial quality of life (QoL) outcome after primary sinonasal surgery. METHODS: A population-based prospective cohort study among 160 adult patients undergoing primary sinonasal surgery (76 septoplasties, SP; 84 endoscopic sinus surgeries, ESS) was conducted. We collected QoL data using the Sinonasal Outcome Test-22 (SNOT-22) before and after surgery. A beneficial QoL outcome was defined as a SNOT-22 score change ≥ 9 points 12 months after surgery. Various demographic, clinical and symptom-related factors predicting a beneficial QoL outcome were sought using binary logistic regression analysis. RESULTS: The mean age of the patients was 39 years (range 18-61) and 82 (51%) were males. The SNOT-22 score change varied markedly after SP (range - 17 to + 80) and ESS (range - 20 to + 58), but on average it improved (median + 15 after SP and + 16 after ESS). 41 patients (64%) achieved beneficial QoL outcome after SP and 46 (66%) after ESS. In a multivariate analysis, poor QoL before surgery (preoperative SNOT-22 ≥ 20 points) predicted a beneficial QoL outcome after SP and ESS (adjusted odds ratio 10; 95% confidence interval 1.6-64 and 12; 2.5-55, respectively) and a senior surgeon operating after SP (9.9; 1.5-67). On receiver operating characteristic curve analysis, the integer threshold value for the preoperative SNOT-22 score that gave the highest sensitivity (74%) and specificity (70%) was 30. CONCLUSIONS: QoL change after primary SP and ESS varies. A preoperative SNOT-22 score of at least 30 best predicted a beneficial QoL outcome after both procedures.

Cause-specific mortality in patients with head and neck cancer: Long-term follow-up of a population-based cohort from 1986 to 2012 accounting for competing risks.

OBJECTIVES: Recent recommendations for treating head and neck cancer (HNC) patients favor an individualized approach. Expected long-term survival - together with short-term survival - after diagnosis is the primary focus in assessing the treatment modality and follow-up scheme. "Disease-specific" survival up to five years is often used for measuring the prognosis and for assessing treatment methods. However, especially long-term survival is strongly affected by competing causes of death among HNC patients. MATERIALS AND METHODS: The long-term prognosis of patients with HNC in terms of mortality from both cancer and competing causes was analyzed according to recent methodological guidelines by examining cumulative incidence functions and models for cause-specific hazards and sub-distribution hazards in a population based cohort of 220 patients treated in a tertiary care center in Northern Finland. RESULTS: In addition to well-known tumor-related factors, mortality from HNC was associated with older age. The mortality from other causes of death was strongly dependent on age and Charlson's Comorbidity Index, but less on gender. When demonstrating the importance of individualized approach in simulated patients, the mortality was highly variable across patients with similar cancer status, but with different comorbidities or age. CONCLUSION: The overall survival pattern of HNC patients depends not only on their cancer characteristics, but also varies greatly according to their age and comorbidities. Our findings support the need for individualized treatment and follow-up protocols, and active management of comorbid diseases. Appropriate methods for analyzing competing risks should be used when presenting survival estimates of cancer patients.

Inflammatory Biomarkers During Bacterial Acute Rhinosinusitis.

PURPOSE OF REVIEW: Diagnosis of bacterial acute rhinosinusitis is difficult. Several attempts have been made to clarify the diagnostic criteria. Inflammatory biomarkers are easily obtainable variables that could shed light on both the pathophysiology and diagnosis of bacterial acute rhinosinusitis. The purpose of this review article is to assess literature concerning the course of inflammatory biomarkers during acute rhinosinusitis and the use of inflammatory biomarkers in diagnosing bacterial acute rhinosinusitis. RECENT FINDINGS: We included C-reactive protein, erythrocyte sedimentation rate, white blood cell counts, procalcitonin, and nasal nitric oxide in this review and found that especially elevated C-reactive protein and erythrocyte sedimentation rate are related to a higher probability of a bacterial cause of acute rhinosinusitis. Still, normal levels of these two biomarkers are quite common as well, or the levels can be heightened even during viral respiratory infection without suspicion of bacterial involvement. Elevated levels of C-reactive protein or erythrocyte sedimentation rate support diagnosis of bacterial acute rhinosinusitis, but due to a lack of sensitivity, they should not be used to screen patients for bacterial acute rhinosinusitis.

Quality of life before and after sinonasal surgery: a population-based matched cohort study.

A population-based matched cohort study was conducted to explore how the quality of life (QoL) changes in patients with septal deviation or recurrent/chronic rhinosinusitis after septoplasty (SP) and endoscopic sinus surgery (ESS). We also compared the QoL of the surgical cohort with that of a concurrently collected healthy cohort. We collected data on QoL in a population-based surgical cohort of 160 patients residing in one health care district (population 405,000) in Northern Finland, and in a control cohort comprised of 206 age- and sex-matched randomly selected subjects residing in Finland (population 5,470,000). QoL was assessed at entry and 12 months later with the Sino-Nasal Outcome Test-22 (SNOT-22) and the RAND-36 generic instruments. Seventy-six SP and 84 ESS patients and 206 controls were enrolled. At entry, the mean SNOT-22 scores of the SP and ESS groups were similar (34.9 and 35.1, respectively) and both were significantly worse than the control group (17.7). At 12 months, the mean SNOT-22 score had improved after SP [change 15.7, 95 % confidence interval (CI) 11.4-19.9] and ESS (change 18.0, 95 % CI 12.4-20.9) and almost reached that of the control group, which remained unchanged. The benefit was similar regardless of the surgical indication. At 12 months, mean RAND-36 scores had improved in most domains in both patient groups and remained unchanged in the controls. After appropriate surgical criteria, both SP and ESS are effective in enhancing QoL on the population level, and postoperative QoL almost reaches the level of the control population.

Predictive factors and treatment outcome of laryngeal carcinoma recurrence.

BACKGROUND: Up to 30% of patients with laryngeal squamous cell carcinoma (SCC) present with recurrence after treatment. We analyzed factors associated with the risk of cancer recurrence and prognosis after recurrence. METHODS: A nationwide laryngeal SCC cohort from Finnish university hospitals during 2001 to 2005 with initial successful therapy (n = 316) was analyzed. RESULTS: Laryngeal SCC recurred in 22% of patients. The median time to recurrence was 9 months, with 90% occurring within 36 months after treatment. The World Health Organization (WHO) performance status >0, neck metastasis at presentation, and nonsurgical treatment were independent prognostic factors for recurrence. Patients with local recurrence had a 5-year overall survival (OS) of 53% compared with 5% in patients with regional/distant recurrences. OS for glottic and nonglottic laryngeal SCC recurrence was 45% and 0%, respectively. CONCLUSION: The type of treatment affected the risk of recurrence in this retrospective series. Local recurrences carried a chance for successful salvage treatment. Routine follow-up beyond 36 months remains controversial. © 2016 Wiley Periodicals, Inc. Head Neck 39: 555-563, 2017.

Longitudinal analysis of inflammatory biomarkers during acute rhinosinusitis.

OBJECTIVE: To illuminate the pathophysiology of acute rhinosinusitis (ARS) with sequential monitoring of inflammatory biomarkers during an ARS episode and to clarify their diagnostic usability in bacterial ARS. STUDY DESIGN: Inception cohort study with 50 conscripts with ARS. METHODS: We collected peripheral blood high-sensitive C-reactive protein (hs-CRP), white blood cell (WBC), procalcitonin, and nasal nitric oxide (nNO) counts at 2 to 3 and 9 to 10 days of symptoms during an ARS episode. We simultaneously gathered various clinical parameters and microbiological samples. Bacterial ARS was confirmed with a positive culture of sinus aspirate. RESULTS: Reciprocal correlations and a significant change in biomarker levels between the two visits suggest that ARS involves a local and systemic inflammatory response that was strongest at 2 to 3 days. High-sensitive CRP and nNO reflected responses best (52% had increased CRP levels at 2-3 days; 66% had decreased nNO levels). White blood cell and procalcitonin counts rarely exceeded the reference range. Increased local and systemic inflammatory response were linked to multiple, adenoviral, or influenza A viral etiology or the detection of bacterial ARS. Local response correlated with imaging findings of wide paranasal sinus involvement and ostiomeatal complex occlusion. At 9 to 10 days, elevated (≥ 11 mg/L) and moderately elevated (≥ 49 mg/L) hs-CRP predicted bacterial ARS well (likelihood ratio [LR]+ 3.3 and LR+ 15.8, respectively), but the sensitivity for both findings remained low. CONCLUSION: Acute rhinosinusitis (particularly bacterial ARS) involves a local and systemic inflammatory response that is strongest at the beginning of symptoms. Elevated hs-CRP supports the diagnosis of bacterial ARS. LEVEL OF EVIDENCE: 4. Laryngoscope, 2016 127:E55-E61, 2017.

Competing risks analysis of cause-specific mortality in patients with oral squamous cell carcinoma.

BACKGROUND: Survival studies on head and neck cancers are frequently reported with inadequate account for competing causes of death. Realistic descriptions and predictions of postdiagnosis mortality should be based on proper competing risks methodology. METHODS: Prognosis of patients with oral squamous cell carcinoma (OSCC) in terms of mortality from OSCC and from other causes, respectively, was analyzed according to recent methodological recommendations using cumulative incidence functions and models for cause-specific hazards and subdistribution hazards in 306 patients treated in a tertiary care center in Northern Finland. RESULTS: More coherent and informative descriptions and predictions of mortality by cause were obtained with state-of-the-art statistical methods for competing risks than using the prevalent but questionable practice to graph "disease-specific survival." CONCLUSION: From the patients' perspective, proper competing risks analysis offers more relevant prognostic scenarios than naïve analyses of "disease-specific survival"; therefore, it should be used in prognostic studies of head and neck cancers. © 2016 Wiley Periodicals, Head Neck 39: 56-62, 2017.

Imaging follow-up study of acute rhinosinusitis.

OBJECTIVES/HYPOTHESIS: To evaluate with imaging the course of acute rhinosinusitis (ARS) and the associations between paranasal imaging results, symptoms, bony anatomic variations, and culture-proven bacterial ARS. STUDY DESIGN: Inception cohort study with 50 conscripts with ARS. METHODS: During a single ARS episode, we collected symptoms daily and took sequential cone-beam computed tomography (CBCT) scans of the paranasal sinuses of the same patients 2 to 3, 5 to 6 and 9 to 10 days after the onset of symptoms. Culture-proven bacterial ARS was verified with maxillary sinus aspiration and bacterial culture at 9 to 10 days. RESULTS: At 2 to 3 days, 38% of the patients had major abnormalities, 42% had minor abnormalities in their paranasal sinuses, and 68% had an occluded ostiomeatal complex (OMC). At 5 to 6 days and 9 to 10 days, these proportions remained essentially the same. At 2 to 3 days, patients with bacterial ARS had slightly higher CBCT scores than those without bacterial ARS. Later, the CBCT and symptom scores gradually increased in patients with bacterial ARS and decreased in those without bacterial ARS. The CBCT and symptom scores had only a weak correlation (rs = 0.36), and anatomic variations were not related to development of bacterial ARS. CONCLUSIONS: Paranasal mucosal abnormalities and occlusion of the OMC do not develop gradually during ARS, but are present when symptoms begin and remain fairly constant in most patients both with and without bacterial ARS. This indicates that the spread of the disease process to the paranasal sinuses and obstruction of the OMC may not be etiological factors in the development of bacterial ARS. LEVEL OF EVIDENCE: 4 Laryngoscope, 126:1965-1970, 2016.

Dynamic Changes in Heart Rate Variability and Nasal Airflow Resistance during Nasal Allergen Provocation Test.

Allergic rhinitis is a major chronic respiratory disease and an immunoneuronal disorder. We aimed at providing further knowledge on the function of the neural system in nasal allergic reaction. Here, a method to assess simultaneously the nasal airflow resistance and the underlying function of autonomic nervous system (ANS) is presented and used during the nasal provocation of allergic and nonallergic subjects. Continuous nasal airflow resistance and spectral heart rate variability parameters show in detail the timing and intensity differences in subjects' reactions. After the provocation, the nasal airflow resistance of allergic subjects showed a positive trend, whereas LF/HF (Low Frequency/High Frequency) ratio and LF power showed a negative trend. This could imply a gradual sympathetic withdrawal in allergic subjects after the allergen provocation. The groups differed significantly by these physiological descriptors. The proposed method opens entirely new opportunities to research accurately concomitant changes in nasal breathing function and ANS.

Diagnostic accuracy of history and physical examination in bacterial acute rhinosinusitis.

OBJECTIVES/HYPOTHESIS: To evaluate the diagnostic accuracy of symptoms, the symptom progression pattern, and clinical signs in identifying bacterial acute rhinosinusitis (ARS). STUDY DESIGN: We conducted an inception cohort study among 50 military recruits with ARS. METHODS: We collected symptoms daily from the onset of symptoms to approximately 10 days. At 9 to 10 days, standardized data on symptoms and physical findings were gathered. A positive culture of maxillary sinus aspirate was considered to be the reference standard for bacterial ARS. RESULTS: At 9 to 10 days, the presence or deterioration after 5 days of any of the symptoms could not be used to diagnose bacterial ARS. Toothache had an adequate positive likelihood ratio (positive likelihood ratio [LR+] 4.4) but was too rare to be used for screening. In contrast, several physical findings at 9 to 10 days were of more diagnostic use and frequent enough for screening. Moderate or profuse (vs. none/minimal) amount of secretion in nasal passage seen in anterior rhinoscopy satisfactorily either ruled in, if present (LR+ 3.2), or ruled out, if absent (negative likelihood ratio 0.2), bacterial ARS. If any secretion was seen in the posterior pharynx or middle meatus, the probability of bacterial ARS increased markedly (LR+ 5.3 and LR+ 11.0, respectively). CONCLUSION: We found symptoms or their change to be of little use in identifying bacterial ARS. In contrast, we observed several clinical findings after 9 to 10 days of symptoms to predict bacterial ARS quite accurately.

Concomitant dynamic changes in autonomic nervous system function and nasal airflow resistance during allergen provocation.

Allergic rhinitis is a major chronic respiratory disease which more than 500 million people suffer from around the world. It is considered to be an immuno-neuronal disorder, but little is known about the part played by the neural system in nasal allergic reaction. This is due mainly to the lack of objective measurement techniques producing accurate, reliable and continuous measurement data about the dynamic changes in nasal respiratory function. Here, a method to assess the association of nasal airflow resistance and the underlying function of autonomic nervous system (ANS) is presented and used during the birch pollen provocation test. Ten allergic volunteers were challenged with allergen. Continuous nasal airflow resistance and spectral heart rate variability parameters were computed and analyzed for the dynamic changes. The derived signals show in detail the timing and intensity differences in subjects' reactions. After the provocation, the nasal airflow resistance rose gradually, whereas LF power and LF/HF ratio decreased gradually for all subjects. This implies gradually increasing sympathetic withdrawal in allergic patients during the provocation with allergen. The proposed method opens entirely new possibilities to assess accurately the dynamic and short-term changes in non-stationary nasal function and could increase the accuracy and reliability of diagnostics and assessment of the effect of nasal treatments.

Accurate measurement of respiratory airflow waveforms using depth data.

Respiratory disorders are a very common and growing health problem. Signal waveforms of respiratory airflow and volume may indicate pathological signs of several diseases and, thus, it would be important to measure them accurately. Currently, devices used in respiration measurements are mostly obtrusive in nature interfering with the natural respiration patterns. We used a depth camera for the continuous measurement of respiratory function without contact on a subject. We propose a novel calibration method which enables accurate estimates of the respiratory airflow waveforms from the depth camera data. Eight subjects were measured with the depth camera and spirometer at the same time using different breathing styles. Results show that not only the respiratory volume and respiratory rate (RR) can be computed precisely from the estimated respiratory airflow, but also the respiratory airflow waveforms are very accurate. This offers interesting opportunities, e.g. in pulmonary and critical care medicine, when objective measurements are required.

The role of microbes in the pathogenesis of acute rhinosinusitis in young adults.

OBJECTIVES/HYPOTHESIS: To provide information on the course of acute rhinosinusitis (ARS) with sequential nasal and paranasal microbiological data and their correlation with clinical outcomes. STUDY DESIGN: We conducted a prospective cohort study among 50 Finnish military recruits with clinically diagnosed ARS in spring 2012. METHODS: We collected symptom, nasal endoscopy, and cone-beam CT (CBCT) scores during the early (2-3 days from onset) and later phases (9-10 days). We took viral samples from the nasopharynx (multiplex respiratory virus polymerase chain reaction [PCR]), bacterial culture from the middle meatus during both phases, and both viral and bacterial samples from the maxillary sinus aspirate (respiratory virus PCR, bacterial culture, broad-range bacterial PCR) during the later phase. Cilia destruction and microbial biofilms were sought from a nasal mucosal biopsy sample. RESULTS: We found that 42 (84%) of the subjects had viral nucleic acid in the nasopharynx during ARS. During the early phase, 28 (56%) of the subjects had nontypeable H. influenzae (NTHi) in the middle meatus, which was associated with wider paranasal mucosal changes in CBCT scans and increased symptoms during the study period. After 9 to 10 days from the onset, NTHi was found in the maxillary sinus in eight subjects (40%, 8/20) and led to prolonged symptoms. Bacterial biofilm was ruled out in 39 (78%) cases, and cilia destruction did not correlate with microbiological or clinical outcomes. CONCLUSION: Nasal and paranasal H. influenzae coinfection during viral infection may modify the symptoms and the extent of sinonasal mucosal disease observed in CBCT scans already from the beginning of the ARS episode.

Characteristics and medical-care-seeking of head and neck cancer patients: a population-based cross-sectional survey.

OBJECTIVES: Well-known risk factors, such as smoking and alcohol consumption, easily denounce head and neck cancer patients as smokers, alcohol abusers, and persons who are socially excluded and have low socioeconomic status. To diagnose these patients as early as possible, we should not have a prejudiced assumption of their characteristics. MATERIALS AND METHODS: We collected detailed data on patient characteristics and health behavior and explored whether these traits had any effect on seeking medical advice in a population-based cross-sectional study involving 85 patients with head and neck cancer diagnosed between January 2003 and December 2007, residing in two health care districts (population 1,600,000) in Finland. The data were gathered from patient charts and questionnaires. The questionnaire data were compared with the general population in Finland. RESULTS: We found these patients to be ordinary elderly people whose demographic and social features resembled those of the general population. They smoked more often, but otherwise had a rather healthy lifestyle. Only half were aware that smoking and alcohol consumption were risk factors of head and neck cancer. In a multivariate analysis, fear of physicians (adjusted odds ratio 11.0; 95% confidence interval 1.2-103), medical-care-seeking for symptoms other than pain (18.5; 2.2-156), and not suspecting cancer (11.2; 1.7-75.1) were independent risk factors for delayed consultation (combined appraisal and help-seeking interval over 3 months). CONCLUSION: Head and neck cancer patients deviated from the same-aged general population only in excessive smoking. Fear of doctors, having no pain, and no suspicion of cancer resulted in delayed medical-care-seeking.

Effect of antimicrobial treatment of acute otitis media on the daily disappearance of middle ear effusion: a placebo-controlled trial.

IMPORTANCE: Antimicrobial treatment reduces the symptoms of acute otitis media (AOM). The effect of antimicrobial treatment on the duration of middle ear effusion (MEE) and concomitant hearing impairment is not known. OBJECTIVE: To determine whether the antimicrobial treatment of AOM reduces the duration of MEE. DESIGN, SETTING, AND PARTICIPANTS: This randomized, double-blind, placebo-controlled trial involved a total of 84 children with AOM between 6 months and 15 years of age. Participants were recruited from September 14, 1999, to January 4, 2000; October 10, 2005, to December 16, 2005; and September 22, 2009, to June 4, 2012, from among children attending an AOM prevention trial and children visiting local outpatient clinics in Oulu, Finland. INTERVENTIONS: Children were randomly allocated to receive either 40 mg/kg of amoxicillin-clavulanate or a placebo mixture per day for 7 days. MAIN OUTCOMES AND MEASURES: The primary outcome measure was the time to the disappearance of MEE as defined by a normal tympanogram finding (A curve) from both ears on 2 consecutive measurement days. Parents performed daily tympanometry at home. The study physician performed tympanometry and otoscopy at study entry, after 3 and 7 days, and then weekly until both ears were healthy. The main secondary outcome measures were the time to normal otoscopy findings and the proportion of children without persistent MEE at 14 days and 2 months. RESULTS: Middle ear effusion disappeared 2.0 weeks (13.7 days) earlier (P = .02) in the antimicrobial group (mean time, 2.7 weeks; 95% CI, 1.7-3.7) than in the placebo group (4.7 weeks; 95% CI, 3.6-5.7). Normal otoscopy findings were observed 1.4 weeks sooner in the antimicrobial group than in the placebo group (P = .02). On day 14, 69% of children in the antimicrobial group and 38% in the placebo group had normal tympanometry findings (number needed to treat, 3.2; 95% CI, 2.0-10.5). On day 60, 2 children (5%) in the antimicrobial group and 10 children (24%) in the placebo group had persistent MEE (P = .01). CONCLUSIONS AND RELEVANCE: Antimicrobial treatment effectively reduced the duration of MEE and possible concomitant hearing impairment in children with AOM. Antimicrobial treatment also reduced the risk for persistent MEE. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01244581.