[Short-term quality of life assessment after sinus surgery for chronic rhinosinusitis]. / Kurzfristige Lebensqualitätsbewertung nach Nasennebenhöhlenoperation bei chronischer Rhinosinusitis.

BACKGROUND: Chronic rhinosinusitis (CRS) has a negative impact on health-related quality of life (HRQoL). Functional endoscopic sinus surgery (FESS) is the treatment of choice for those not responding to medical treatments. To date, the short-term effects of FESS on HRQoL are still unclear. OBJECTIVE: Evaluation of the short-term effects of FESS on HRQoL in CRS patients using the SNOT-22 questionnaire. METHODS: The results of the validated German version of the Sino-Nasal Outcome Test-22 (SNOT-22) questionnaire were analysed from 89 patients with CRS before surgery and 10-14 days (n = 77), four (n = 77), six weeks (n = 76) and 6 months (n = 71) after FESS, and compared with those of 1,000 healthy controls selected using a non-probability quota sample in accordance to the distribution of the German Microcensus. RESULTS: Compared to the preoperative mean SNOT-22 score (47.35), CRS patients significantly improved in HRQoL 10-14 days (31.75, p < 0.01), 4 weeks (25.84, p < 0.01), 6 weeks (24.16, p < 0.01) and 6 months after FESS (27.16, p < 0.01). Pre- and 6 months postoperatively, the five most important SNOT-22 items were nasal obstruction, smell and taste reduction, thick, mucous nasal secretions, need to blow the nose and postnasal drip. At the 2, 4 and 6-week follow-up, the reduction in smell and taste was most frequently perceived as limiting the HRQoL. CONCLUSIONS: This follow-up study shows for the first time that the reduction in smell and taste should be treated and controlled concervatively in the short term after FESS.

Can patient-reported outcomes and inflammatory markers define endotype 2 in chronic rhinosinusitis without nasal polyps?

BACKGROUND: Chronic rhinosinusitis (CRS) is a heterogeneous disease at the clinical phenotype level (without nasal polyp [CRSsNP] vs with nasal polyp [CRSwNP]) and at the underlying inflammatory endotype level (type 2 vs non-type 2). Whether the endotype is associated with clinical presentation in patients with CRSsNP has yet to be explored in detail. OBJECTIVE: To identify associations between endotypes and their clinical significance in patients with CRSsNP based on tissue interleukin-5 levels. METHODS: A total of 104 patients with CRSsNP who underwent functional endoscopic sinus surgery between 2013 and 2017 were endotyped. We collected immunologic and clinical parameters and evaluated whether there were associations between the endotype and clinical features using Visual Analog Scale (VAS), Sino-Nasal Outcome Test-22 (SNOT-22), Sniffin' Sticks test, Lund-Mackay CT score, and nasal endoscopy. RESULTS: Mean tissue interleukin-5 levels were used to identify type 2 inflammation (non-type 2: 3.37 vs type 2: 191.98 pg/g tissue; P < .001). There were no significant clinical differences measured by patient-reported outcome measures between patients with type 2 CRSsNP and those with non-type 2 CRSsNP preoperatively. Type 2 and non-type 2 CRSsNP did not differentiate in CT score, Sniffin' Sticks test, and nasal endoscopy. Postoperative SNOT-22 and VAS scores correlated well with each other (r = 0.75; P < .01). Postoperative VAS scores were in both groups significantly lower than before the operation (type 2: 5.07 vs 2.99; P < .01; non-type 2: 5.74 vs 3.22; P < .01), but not associated to the inflammatory subtype. CONCLUSION: The type of inflammation does not affect the symptoms, the computed tomography scan, or the postoperative results in CRSsNP in contrast to former findings in CRSwNP. TRIAL REGISTRATION: Belgian registration number (B.U.N.) No. B6702020000097.

Does a tonsillectomy indicated according to the German S2k guideline affect short-term quality of life in adults?

BACKGROUND: Tonsillectomy (TE) for recurrent tonsillitis (RT) is one of the most common surgical interventions. Since 2015, the indication criteria for TE have become much stricter (German S2k guideline). Patient-reported outcome measures (PROMs) of short-term quality of life (QoL) after TE have not yet been investigated. PURPOSE: To clarify if stringent indication for TE will better identify patients worthy of surgery and patients' QoL. METHODS: We prospectively studied the Tonsillectomy Outcome Inventory 14 (TOI-14) responses of 38 RT-patients recruited according to the S2k guideline in 2020 and compared their TOI-14 scores with those of a historical RT cohort from 2006 to 2008 and with a healthy middle-European cohort. New RT patients were assessed before, 2, 4, and 14 days and 6 months after TE. TOI-14 was measured as total and as disease-specific score. RESULTS: From pre- to 6-month postoperative, patients' QoL was significantly different, measured by TOI-14 (49.92 vs. 6.35; p < 0.001) and disease-specific score (60.35 vs. 9.9; p < 0.001). Preoperative disease-specific score was not different from that of the 2nd and 4th postoperative days but from the 14th postoperative day (60.35 vs. 29.26; p < 0.001). The historical cohort had significantly less RT complaints than the new cohort beforehand, but more dissatisfaction in QoL after TE. New TE patients had worse QoL pre- (49.92 vs. 11.78; p < 0.001) but more QoL postoperatively (6.34 vs. 11.78; p = 0.004) than healthy individuals. CONCLUSIONS: Our results show that the tightening of the indication criteria for TE was justified and that TE patients significantly benefit from this surgery from day 14.

Long-term analysis of prognostic risk factors impacting surgical outcomes in patients with external auditory canal carcinoma.

BACKGROUND: Malignant neoplasms of the external auditory canal (EAC) are rare. No consensus on management has emerged. OBJECTIVE: To determine possible risk factors influencing tumorgenesis and prognosis of EAC carcinoma. MATERIALS AND METHODS: 108 patients (87 men/21 women) with an average age of 74 ± 13.8 years were recruited from 2005 to 2019 at Department of Otorhinolaryngology, Head and Neck Surgery Heidelberg. The follow-up interval was 43.62 ± 55.39 months. Partial and (sub)total ablative otis, supplementary surgery (petrosectomy, parotidectomy, neck dissection, mastoidectomy) and adjuvant radio(chemo)therapy belonged to treatment options. TNM status was determined at time of diagnosis using the AJCC staging system. RESULTS: 63.9% of patients underwent a total ablative otis. Tumor recurrence was seen in 24.1%. The 1-year survival rate was 87%, the 5-year survival rate was 52%, the mean overall survival (OS) was 3.82 ± 4.6 years. Male EAC carcinoma patients had a better OS (p < 0.001), PFS (p < 0.001) and DSS (p = 0.02) than females. T1 patients had a better OS (p = 0.01), PFS (p = 0.01) and DSS (p < 0.001) than T4 patients. Lymph node but not distant metastasis, tumor grading, perineural, venous and lymphatic invasion, histology, age and tumor localization influenced the OS in EAC carcinoma patients (p = 0.04). The more radical the ablative otis, the worse the OS (p = 0.002), PFS (p = 0.02) and DSS (p < 0.001). Radio(chemo)therapy did not improve the OS. CONCLUSIONS: EAC carcinoma are difficult to treat and benefit from early diagnosis so that a radical combined treatment approach does not need to be used.

[Validity of the German Menière's Disease Patient-Oriented Symptom Severity Index]. / Validierung des deutschsprachigen Menière's Disease Patient-Oriented Symptom Severity Index.

BACKGROUND: The MD POSI is a disease-specific questionnaire to determine the health-related quality of life (HRQoL) of patients with Menière's disease (MD). OBJECTIVES: Validity and reliability of the German translation of the MD POSI. MATERIAL AND METHODS: Prospective data analysis of a patient group with vertigo (n = 162), which was treated in the otorhinolaryngology of a University Hospital from 2005-2019. A clinical selection was made according to the new Bárány classification in a "definite" and "probable" Menière's disease. HRQoL was assessed using the German translation of the MD POSI, the Vertigo Symptom Score (VSS) and the Short Form (SF-36). Reliability was measured by Cronbach's α and test-retesting after 12 months and again 2 weeks later. Content and agreement validity were examined. RESULTS: Cronbach α values greater than 0.9 indicated good internal consistency. There was no statistically significant difference from baseline to 12 months, except for the subscore "during the attack". There were significant positive correlations between the VSS overall/VER/AA and the overall index of the MD POSI and negative significant correlations with the SF-36 domains physical functioning, physical role functioning, social functioning, emotional role functioning, mental well-being. There were low SRM (standardized response mean) values below 0.5. CONCLUSIONS: The German translation of the MD POSI is a valid and reliable instrument to evaluate the impact of MD on patients' disease-specific quality of life.

Statistical Analysis in the German National Cohort (NAKO) - Specific Aspects and General Recommendations.

The German National Cohort (NAKO) is an ongoing, prospective multicenter cohort study, which started recruitment in 2014 and includes more than 205,000 women and men aged 19-74 years. The study data will be available to the global research community for analyses. Although the ultimate decision about the analytic methods will be made by the respective investigator, in this paper we provide the basis for a harmonized approach to the statistical analyses in the NAKO. We discuss specific aspects of the study (e.g., data collection, weighting to account for the sampling design), but also give general recommendations which may apply to other large cohort studies as well.

Prospective study on health-related quality of life in patients before and after cochlear implantation.

PURPOSE: Assessing cochlear implant (CI)-associated patient outcomes is a focus of implant research. Most studies have analyzed outcomes retrospectively with low patient numbers and few measurement time points. In addition, standardized CI-specific health-related quality of life (HRQoL) instruments have not been used. To address this, we prospectively assessed HRQoL in patients before and after implantation. METHODS: We assessed HRQoL using the Nijmegen Cochlear Implant Questionnaire (NCIQ), Abbreviated Profile of Hearing Aid Benefit (APHAB), Hearing Participation Scale (HPS), and the Visual Analogue Scale (VAS) in 100 deaf or severely hearing-impaired patients (57 unilaterally deaf and 43 bilaterally deaf) before and 3, 6, and 12 months after cochlear implantation. We compared the results of unilaterally and bilaterally hearing-impaired patients and patients with or without a hearing aid. Principal component (PCA) and exploratory factor analyses (EFA) were also conducted. RESULTS: The NCIQ measured improvements in all 6 domains after CI and correlated well with other QoL instruments. The PCA revealed that the NCIQ can be better explained by physical, physical advanced, and socio-psychological components. The APHAB score ameliorated over time, except for the background noise domain. The overall HPS score improved over time, but the hearing handicap subscore significantly decreased. Sociodemographic influences on the questionnaire scores were relatively weak. CONCLUSION: Assessing HRQoL is essential for quantifying the patient outcome after CI. NCIQ scores in our patient cohort showed improved HRQoL in all domains and we recommend that the NCIQ be used as a first-line questionnaire for assessing QoL in hearing-impaired patients after CI.

[Validity and reliability of the Nijmegen Cochlear Implant Questionnaire in German]. / Validierung und Reliabilitätsprüfung des Nijmegen Cochlear Implant Questionnaire in deutscher Sprache.

BACKGROUND: The Nijmegen Cochlear Implant Questionnaire (NCIQ) is a disease-specific questionnaire to determine the health-related quality of life (HRQoL) of patients before and after cochlear implantation. OBJECTIVE: This study aimed to assess the validity and reliability of the German translation of the NCIQ. MATERIALS AND METHODS: A prospective study was performed in 100 postlingually deaf or severely hearing-impaired patients. HRQoL was assessed using the NCIQ, the Abbreviated Profile of Hearing Aid Benefit (APHAB), and the Hearing Participation Scale (HPS) before as well as 3 and 6 months after cochlear implantation. An untreated group of postlingually deaf or severely hearing-impaired patients (n = 54) served as a control. Cronbach's α and test-retest reliability were measured. The content, discrimination, and agreement validity were tested. The evaluation of construct validity was based on recently published data. Sensitivity and receiver operating curve (ROC) analysis, including consideration of the area under the curve (AUC), were used as quality criteria. RESULTS: The test-retest analysis showed stable NCIQ values 3 and 6 months postoperatively. The Cronbach's α values indicated good internal consistency. The NCIQ validly discriminated between treated and untreated patient groups. There were statistically significant albeit weak correlations between the NCIQ and the APHAB (r = -0.22; p = 0.04) and the HPS (r = 0.30; p = 0.01). Sensitivity and ROC analyses showed good measurement quality of the German-speaking NCIQ. CONCLUSION: The German translation of the NCIQ reliably and validly measures HRQoL before and after cochlear implantation and can be used for clinical monitoring after treatment with cochlear implants.

Normative tonsillectomy outcome inventory 14 values as a decision-making tool for tonsillectomy.

PURPOSE: The study aimed to determine normative values for the Tonsillectomy Outcome Inventory 14 (TOI-14) in a healthy middle-European cohort. We also compared these generated values with TOI-14 scores from a patient population with recurrent tonsillitis (RT) and explored the factorial structure of the TOI-14. METHODS: We systematically studied the responses of healthy individuals (reference cohort) and patients with RT (clinical cohort) to the TOI-14 survey. The reference cohort contained 1000 participants, who were recruited using the Respondi panel for market and social science research. This subsample was quoted to the population distribution of the German Microcensus and selected from a non-probability panel. Tonsillitis patients were assessed before and 6 and 12 months after tonsillectomy. Data were analysed using principal component and exploratory factor analyses. RESULTS: The PCA revealed three TOI-14 domains (physiological, psychological and socio-economic), which explained 73% of the total variance. The reference cohort perceived a good quality of life (QOL) with a TOI-14 total score of 11.8 (physiological: 8.0, psychological: 5.8, and socio-economic subscale score: 13.9). TOI-14 scores were higher in the patient cohort, indicating that the TOI-14 discriminates between patients with RT and healthy individuals with no RT. Age and female gender significantly influenced the total TOI-14 score, especially in the psychological (age) and socio-economic (gender) subscales. CONCLUSION: We have developed a set of normative values that, together with the TOI-14, can determine the disease burden indicating tonsillectomy.

Correction: Comparison of Four Active SARS-CoV-2 Surveillance Strategies in Representative Population Sample Points: Two-Factor Factorial Randomized Controlled Trial.

[This corrects the article DOI: 10.2196/44204.].

Normative data for interpreting the SNOT-22.

Objectives: The Sino-Nasal Outcome Test 22 (SNOT-22) is a validated patient-reported outcome instrument to evaluate the health-related quality of life (HRQoL) in patients with chronic rhinosinusitis (CRS). There are no published normative SNOT-22 scores, limiting its interpretation. Methods: Symptom scores from 1,000 SNOT-22 questionnaires were analysed by principal component analysis (PCA) and exploratory factor analyses. Data were derived from a survey with 1,000 healthy Europeans (reference cohort) who were recruited using the Respondi panel for market and social science research. This subsample was quoted to the population distribution of the German Microcensus and selected from a non-probability panel. Results: The overall normative SNOT-22 score can be detected to be 20.2 ± 19.44. Male (18.49 ± 19.15) and older (> 50 years old; 18.3 ± 17.49) participants had overall lower SNOT-22 mean results than females (21.8 ± 19.6) and younger (21.4 ± 20.55) participants, indicating higher levels of satisfaction. PCA proposed two SNOT-22 domains ("physiological well-being" and "psychological well-being"), which explained 65% of the variance. Conclusions: These are the first published (German) normative scores for the SNOT-22 and provide a clinical reference point for the interpretation of data.

Human papillomavirus prevalence and vaccine effectiveness in young women in Germany, 2017/2018: results from a nationwide study.

Background: Infections with human papillomaviruses (HPV) are sexually transmitted and can cause cancer. In Germany, vaccination against HPV is recommended for girls and boys aged 9-17 years. We aimed to investigate HPV DNA prevalence, genotype distribution and vaccine effectiveness (VE) in women aged 20-25 years 10 years after the introduction of HPV vaccination in Germany (2018-2019), and compared these data to an equally designed study from 2010-2012. Methods: Seventy six geographical clusters were randomly selected, followed by random selection of 61 women aged 20-25 years per cluster. Participants performed cervicovaginal self-sampling and answered questions on demographics, sexual behaviour and HPV vaccination. Samples were tested for 18 high risk and nine low risk HPV genotypes. We performed chi-square tests, Fisher's exact test, unpaired Student's t-test and proportion t-test, and calculated crude and adjusted prevalence ratios (PR) and 95% CIs. Results: Of 7,858 contacted women a total of 1,226 agreed to participate. Of these, 94 women were positive for HPV types 16 and/or 18. HPV16 prevalence was 7.0% (95% CI 5.6-8.6) and HPV18 prevalence was 0.8% (95% CI 0.4-1.5). HPV6 and HPV11 were rare with only five (0.4%; 0.1-0.9) and one (0%; 95% CI 0.0-0.5) positive tests. Seven hundred fifty-seven women (62%) had received at least one HPV vaccine dose and 348 (28%) were vaccinated as currently recommended. Confounder-adjusted VE was 46.4% (95% CI 4.2-70.1) against HPV16/18 infection and 49.1% (95% CI 8.2-71.8) against infection with at least one HPV genotype covered by the quadrivalent HPV vaccine. Compared with the 2010-2012 study results, HPV16/18 prevalence dropped from 22.5% (95% CI 19.0-26.3) to 10.3% (95% CI 7.5-13.9; p < 0.0001) in unvaccinated participants. Conclusion: Vaccine-covered HPV genotypes were rare among 20-25 years old women in Germany and decreased compared to the time point shortly after the start of the HPV vaccination program. HPV prevalence of almost all vaccine-covered genotypes was strongly reduced in vaccinated participants. A decrease of HPV16 and HPV18 was even observed in unvaccinated participants, compared to 2010-2012 data, suggesting indirect protection of unvaccinated women. Low VE against HPV16/18 and HPV6/11/16/18 in our study might be attributable to study design in combination with the endpoint selection of (mainly transient) HPV DNA positivity.

Comparison of Four Active SARS-CoV-2 Surveillance Strategies in Representative Population Sample Points: Two-Factor Factorial Randomized Controlled Trial.

BACKGROUND: The COVID-19 pandemic is characterized by rapid increases in infection burden owing to the emergence of new variants with higher transmissibility and immune escape. To date, monitoring the COVID-19 pandemic has mainly relied on passive surveillance, yielding biased epidemiological measures owing to the disproportionate number of undetected asymptomatic cases. Active surveillance could provide accurate estimates of the true prevalence to forecast the evolution of the pandemic, enabling evidence-based decision-making. OBJECTIVE: This study compared 4 different approaches of active SARS-CoV-2 surveillance focusing on feasibility and epidemiological outcomes. METHODS: A 2-factor factorial randomized controlled trial was conducted in 2020 in a German district with 700,000 inhabitants. The epidemiological outcome comprised SARS-CoV-2 prevalence and its precision. The 4 study arms combined 2 factors: individuals versus households and direct testing versus testing conditioned on symptom prescreening. Individuals aged ≥7 years were eligible. Altogether, 27,908 addresses from 51 municipalities were randomly allocated to the arms and 15 consecutive recruitment weekdays. Data collection and logistics were highly digitized, and a website in 5 languages enabled low-barrier registration and tracking of results. Gargle sample collection kits were sent by post. Participants collected a gargle sample at home and mailed it to the laboratory. Samples were analyzed with reverse transcription loop-mediated isothermal amplification (RT-LAMP); positive and weak results were confirmed with real-time reverse transcription-polymerase chain reaction (RT-PCR). RESULTS: Recruitment was conducted between November 18 and December 11, 2020. The response rates in the 4 arms varied between 34.31% (2340/6821) and 41.17% (2043/4962). The prescreening classified 16.61% (1207/7266) of the patients as COVID-19 symptomatic. Altogether, 4232 persons without prescreening and 7623 participating in the prescreening provided 5351 gargle samples, of which 5319 (99.4%) could be analyzed. This yielded 17 confirmed SARS-CoV-2 infections and a combined prevalence of 0.36% (95% CI 0.14%-0.59%) in the arms without prescreening and 0.05% (95% CI 0.00%-0.108%) in the arms with prescreening (initial contacts only). Specifically, we found a prevalence of 0.31% (95% CI 0.06%-0.58%) for individuals and 0.35% (95% CI 0.09%-0.61%) for households, and lower estimates with prescreening (0.07%, 95% CI 0.0%-0.15% for individuals and 0.02%, 95% CI 0.0%-0.06% for households). Asymptomatic infections occurred in 27% (3/11) of the positive cases with symptom data. The 2 arms without prescreening performed the best regarding effectiveness and accuracy. CONCLUSIONS: This study showed that postal mailing of gargle sample kits and returning home-based self-collected liquid gargle samples followed by high-sensitivity RT-LAMP analysis is a feasible way to conduct active SARS-CoV-2 population surveillance without burdening routine diagnostic testing. Efforts to improve participation rates and integration into the public health system may increase the potential to monitor the course of the pandemic. TRIAL REGISTRATION: Deutsches Register Klinischer Studien (DRKS) DRKS00023271; https://tinyurl.com/3xenz68a. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR2-10.1186/s13063-021-05619-5.

Long-term outcomes and quality of life following parotidectomy for benign disease.

Objective: Parotidectomy worsens quality of life (QoL) in the short-term, but the long-term impact is unknown. In this study, we analysed the long-term effects of parotidectomy on QoL. Methods: In this prospective long-term follow-up study, participants were divided into three groups: short-term (ST) follow-up of six weeks, long-term (LT) follow-up of 13 years and short- and long-term (SLT) follow-up. QoL was assessed using the Parotidectomy Outcome Inventory (POI-8). Parotidectomies were classified based on whether the great auricular nerve (GAN) had been preserved or sacrificed. Results: In total, 164 observations were analysed, 74 in the LT group, 57 in the ST group and 33 in the SLT group. Hypoaesthesia was a major problem and facial palsy was a minor problem. Pain (p < 0.01) and hypoaesthesia (p < 0.001) were significantly lower after 13 years compared with after six weeks, and QoL was higher after 13 years compared with after six weeks (p = 0.04). The disease-specific impairment rate decreased from 70% at short-term follow-up to 30% at long-term follow-up. Removal of the GAN was associated with hypoaesthesia in the ST group (p = 0.028). Conclusions: Hypoaesthesia has a long-term impact on the QoL, and this should be emphasised during preoperative discussions.

Monitoring the health and healthcare provision for refugees in collective accommodation centres: Results of the population-based survey RESPOND.

To date, the integration of refugees in German health surveys is insufficient. The survey RESPOND (Improving regional health system responses to the challenges of forced migration) aimed to collect valid epidemiological data on refugee health status and healthcare provision. The core elements of the survey consisted of a population-based sampling procedure in Baden-Württemberg, multilingual questionnaires and a face-to-face approach of recruitment and data collection in collective accommodation centres with multilingual field teams. In addition, data on the geographical locations of accommodation centres and their structural quality were obtained. The results indicate a high overall health burden. The prevalence of depression (44.3%) and anxiety symptoms (43.0%) was high. At the same time, high unmet needs were reported for primary (30.5%) and specialist (30.9%) care. Despite sufficient geographical accessibility of primary care services, frequent ambulatory care sensitive hospitalisations, i.e. hospitalisations that could potentially have been avoided through primary care (25.3%), as well as subjective deficits in the quality of care, suggest barriers to accessing healthcare services. Almost half of all refugees (45.3%) live in accommodation facilities of poor structural quality. Collecting valid data on the health situation of refugees is possible through a combination of targeted sampling, multilingual recruitment and survey instruments as well as personal recruitment. The presented approach could complement established procedures for conducting health surveys and be extended to other federal states.

How to predict the outcome of septorhinoplasty? A normative study of ROE and FROI-17 scores.

OBJECTIVE: Normative values of patient-reported outcome instruments are needed to identify good candidates for rhinoplasty. Rhinoplasty Outcome Evaluation (ROE) and Functional Rhinoplasty Outcome Inventory-17 (FROI-17) are disease-specific questionnaires that evaluate quality of life in patients undergoing rhinoplasty. METHODS: The reference cohort contained 1,000 participants, selected from a non-probability panel. Normative ROE and FROI-17 scores from this reference cohort were compared with ROE and FROI-17 scores from a patient cohort before (n = 104) and 6 (n = 55) and 12 months (n = 32) after septorhinoplasty. RESULTS: Mean FROI-17 scores (± SD) were: overall score, 20.8 ± 17; nasal symptoms, 16.8 ± 7; general symptoms, 24.8 ± 22; and self-confidence, 16.4 ± 21. The ROE total score was 73.1 ± 16. Normative values differed significantly from the preoperative ROE and FROI-17 scores of septorhinoplasty patients (p < 0.01). Except for the FROI-17 general score at 12 months postoperatively (p = 0.004), there were no significant differences between normative ROE/FROI-17 and septorhinoplasty scores postoperatively, indicating that they returned to normalcy. CONCLUSIONS: Normative scores for ROE and FROI-17 provide a reference point from which to identify patients who are most likely to benefit from rhinoplasty.

Effectiveness and cost-effectiveness of four different strategies for SARS-CoV-2 surveillance in the general population (CoV-Surv Study): study protocol for a two-factorial randomized controlled multi-arm trial with cluster sampling.

BACKGROUND: To achieve higher effectiveness in population-based SARS-CoV-2 surveillance and to reliably predict the course of an outbreak, screening, and monitoring of infected individuals without major symptoms (about 40% of the population) will be necessary. While current testing capacities are also used to identify such asymptomatic cases, this rather passive approach is not suitable in generating reliable population-based estimates of the prevalence of asymptomatic carriers to allow any dependable predictions on the course of the pandemic. METHODS: This trial implements a two-factorial, randomized, controlled, multi-arm, prospective, interventional, single-blinded design with cluster sampling and four study arms, each representing a different SARS-CoV-2 testing and surveillance strategy based on individuals' self-collection of saliva samples which are then sent to and analyzed by a laboratory. The targeted sample size for the trial is 10,000 saliva samples equally allocated to the four study arms (2500 participants per arm). Strategies differ with respect to tested population groups (individuals vs. all household members) and testing approach (without vs. with pre-screening survey). The trial is complemented by an economic evaluation and qualitative assessment of user experiences. Primary outcomes include costs per completely screened person, costs per positive case, positive detection rate, and precision of positive detection rate. DISCUSSION: Systems for active surveillance of the general population will gain more importance in the context of pandemics and related disease prevention efforts. The pandemic parameters derived from such active surveillance with routine population monitoring therefore not only enable a prospective assessment of the short-term course of a pandemic, but also a more targeted and thus more effective use of local and short-term countermeasures. TRIAL REGISTRATION: ClinicalTrials.gov DRKS00023271 . Registered November 30, 2020, with the German Clinical Trials Register (Deutsches Register Klinischer Studien).

Effectiveness and cost-effectiveness of four different strategies for SARS-CoV-2 surveillance in the general population (CoV-Surv Study): a structured summary of a study protocol for a cluster-randomised, two-factorial controlled trial.

OBJECTIVES: In this cluster-randomised controlled study (CoV-Surv Study), four different "active" SARS-CoV-2 testing strategies for general population surveillance are evaluated for their effectiveness in determining and predicting the prevalence of SARS-CoV-2 infections in a given population. In addition, the costs and cost-effectiveness of the four surveillance strategies will be assessed. Further, this trial is supplemented by a qualitative component to determine the acceptability of each strategy. Findings will inform the choice of the most effective, acceptable and affordable strategy for SARS-CoV-2 surveillance, with the most effective and cost-effective strategy becoming part of the local public health department's current routine health surveillance activities. Investigating its everyday performance will allow us to examine the strategy's applicability to real time prevalence prediction and the usefulness of the resulting information for local policy makers to implement countermeasures that effectively prevent future nationwide lockdowns. The authors would like to emphasize the importance and relevance of this study and its expected findings in the context of population-based disease surveillance, especially in respect to the current SARS-CoV-2 pandemic. In Germany, but also in many other countries, COVID-19 surveillance has so far largely relied on passive surveillance strategies that identify individuals with clinical symptoms, monitor those cases who then tested positive for the virus, followed by tracing of individuals in close contact to those positive cases. To achieve higher effectiveness in population surveillance and to reliably predict the course of an outbreak, screening and monitoring of infected individuals without major symptoms (about 40% of the population) will be necessary. While current testing capacities are also used to identify such asymptomatic cases, this rather passive approach is not suitable in generating reliable population-based estimates of the prevalence of asymptomatic carriers to allow any dependable predictions on the course of the pandemic. To better control and manage the SARS-CoV-2 pandemic, current strategies therefore need to be complemented by an active surveillance of the wider population, i.e. routinely conducted testing and monitoring activities to identify and isolate infected individuals regardless of their clinical symptoms. Such active surveillance strategies will enable more effective prevention of the spread of the virus as they can generate more precise population-based parameters during a pandemic. This essential information will be required in order to determine the best strategic and targeted short-term countermeasures to limit infection spread locally. TRIAL DESIGN: This trial implements a cluster-randomised, two-factorial controlled, prospective, interventional, single-blinded design with four study arms, each representing a different SARS-CoV-2 testing and surveillance strategy. PARTICIPANTS: Eligible are individuals age 7 years or older living in Germany's Rhein-Neckar Region who consent to provide a saliva sample (all four arms) after completion of a brief questionnaire (two arms only). For the qualitative component, different samples of study participants and non-participants (i.e. eligible for study, but refuse to participate) will be identified for additional interviews. For these interviews, only individuals age 18 years or older are eligible. INTERVENTION AND COMPARATOR: Of the four surveillance strategies to be assessed and compared, Strategy A1 is considered the gold standard for prevalence estimation and used to determine bias in other arms. To determine the cost-effectiveness, each strategy is compared to status quo, defined as the currently practiced passive surveillance approach. Strategy A1: Individuals (one per household) receive information and study material by mail with instructions on how to produce a saliva sample and how to return the sample by mail. Once received by the laboratory, the sample is tested for SARS-CoV-2 using Reverse Transcription Loop-mediated Isothermal Amplification (RT-LAMP). Strategy A2: Individuals (one per household) receive information and study material by mail with instructions on how to produce their own as well as saliva samples from each household member and how to return these samples by mail. Once received by the laboratory, the samples are tested for SARS-CoV-2 using RT-LAMP. Strategy B1: Individuals (one per household) receive information by mail on how to complete a brief pre-screening questionnaire which asks about COVID-19 related clinical symptoms and risk exposures. Only individuals whose pre-screening score crosses a defined threshold, will then receive additional study material by mail with instructions on how to produce a saliva sample and how to return the sample by mail. Once received by the laboratory, the saliva sample is tested for SARS-CoV-2 using RT-LAMP. Strategy B2: Individuals (one per household) receive information by mail on how to complete a brief pre-screening questionnaire which asks about COVID-19 related clinical symptoms. Only individuals whose pre-screening score crosses a defined threshold, will then receive additional study material by mail with instructions how to produce their own as well as saliva samples from each household member and how to return these samples by mail. Once received by the laboratory, the samples are tested for SARS-CoV-2 using RT-LAMP. In each strategy, RT-LAMP positive samples are additionally analyzed with qPCR in order to minimize the number of false positives. MAIN OUTCOMES: The identification of the one best strategy will be determined by a set of parameters. Primary outcomes include costs per correctly screened person, costs per positive case, positive detection rate, and precision of positive detection rate. Secondary outcomes include participation rate, costs per asymptomatic case, prevalence estimates, number of asymptomatic cases per study arm, ratio of symptomatic to asymptomatic cases per study arm, participant satisfaction. Additional study components (not part of the trial) include cost effectiveness of each of the four surveillance strategies compared to passive monitoring (i.e. status quo), development of a prognostic model to predict hospital utilization caused by SARS-CoV-2, time from test shipment to test application and time from test shipment to test result, and perception and preferences of the persons to be tested with regard to test strategies. RANDOMISATION: Samples are drawn in three batches of three continuous weeks. Randomisation follows a two-stage process. First, a total of 220 sampling points have been allocated to the three different batches. To obtain an integer solution, the Cox-algorithm for controlled rounding has been used. Afterwards, sample points have been drawn separately per batch, following a probability proportional to size (PPS) random sample. Second, for each cluster the same number of residential addresses is randomly sampled from the municipal registries (self-weighted sample of individuals). The 28,125 addresses drawn per municipality are then randomly allocated to the four study arms A1, A2, B1, and B2 in the ratio 5 to 2.5 to 14 to 7 based on the expected response rates in each arm and the sensitivity and specificity of the pre-screening tool as applied in strategy B1 and B2. Based on the assumptions, this allocation should yield 2500 saliva samples in each strategy. Although a municipality can be sampled by multiple batches and the overall number of addresses per municipality might vary, the number of addresses contacted in each arm is kept constant. BLINDING (MASKING): The design is single-blinded, meaning the staff conducting the SARS-CoV-2 tests are unaware of the study arm assignment of each single participant and test sample. SAMPLE SIZES: Total sample size for the trial is 10,000 saliva samples equally allocated to the four study arms (i.e. 2,500 participants per arm). For the qualitative component, up to 60 in-depth interviews will be conducted with about 30 study participants (up to 15 in each arm A and B) and 30 participation refusers (up to 15 in each arm A and B) purposefully selected from the quantitative study sample to represent a variety of gender and ages to explore experiences with admission or rejection of study participation. Up to 25 asymptomatic SARS-CoV-2 positive study participants will be purposefully selected to explore the way in which asymptomatic men and women diagnosed with SARS-CoV-2 give meaning to their diagnosis and to the dialectic between feeling concurrently healthy and yet also being at risk for transmitting COVID-19. In addition, 100 randomly selected study participants will be included to explore participants' perspective on testing processes and implementation. TRIAL STATUS: Final protocol version is "Surveillance_Studienprotokoll_03Nov2020_v1_2" from November 3, 2020. Recruitment started November 18, 2020 and is expected to end by or before December 31, 2020. TRIAL REGISTRATION: The trial is currently being registered with the German Clinical Trials Register (Deutsches Register Klinischer Studien), DRKS00023271 ( https://www.drks.de/drks_web/navigate.do?navigationId=trial . HTML&TRIAL_ID=DRKS00023271). Retrospectively registered 30 November 2020. FULL PROTOCOL: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol.