Variability in Cochlear Implantation Outcomes in a Large German Cohort With a Genetic Etiology of Hearing Loss.

OBJECTIVES: The variability in outcomes of cochlear implantation is largely unexplained, and clinical factors are not sufficient for predicting performance. Genetic factors have been suggested to impact outcomes, but the clinical and genetic heterogeneity of hereditary hearing loss makes it difficult to determine and interpret postoperative performance. It is hypothesized that genetic mutations that affect the neuronal components of the cochlea and auditory pathway, targeted by the cochlear implant (CI), may lead to poor performance. A large cohort of CI recipients was studied to verify this hypothesis. DESIGN: This study included a large German cohort of CI recipients (n = 123 implanted ears; n = 76 probands) with a definitive genetic etiology of hearing loss according to the American College of Medical Genetics (ACMG)/Association for Molecular Pathology (AMP) guidelines and documented postoperative audiological outcomes. All patients underwent preoperative clinical and audiological examinations. Postoperative CI outcome measures were based on at least 1 year of postoperative audiological follow-up for patients with postlingual hearing loss onset (>6 years) and 5 years for children with congenital or pre/perilingual hearing loss onset (≤6 years). Genetic analysis was performed based on three different methods that included single-gene screening, custom-designed hearing loss gene panel sequencing, targeting known syndromic and nonsyndromic hearing loss genes, and whole-genome sequencing. RESULTS: The genetic diagnosis of the 76 probands in the genetic cohort involved 35 genes and 61 different clinically relevant (pathogenic, likely pathogenic) variants. With regard to implanted ears (n = 123), the six most frequently affected genes affecting nearly one-half of implanted ears were GJB2 (21%; n = 26), TMPRSS3 (7%; n = 9), MYO15A (7%; n = 8), SLC26A4 (5%; n = 6), and LOXHD1 and USH2A (each 4%; n = 5). CI recipients with pathogenic variants that influence the sensory nonneural structures performed at or above the median level of speech performance of all ears at 70% [monosyllable word recognition score in quiet at 65 decibels sound pressure level (SPL)]. When gene expression categories were compared to demographic and clinical categories (total number of compared categories: n = 30), mutations in genes expressed in the spiral ganglion emerged as a significant factor more negatively affecting cochlear implantation outcomes than all clinical parameters. An ANOVA of a reduced set of genetic and clinical categories (n = 10) identified five detrimental factors leading to poorer performance with highly significant effects ( p < 0.001), accounting for a total of 11.8% of the observed variance. The single strongest category was neural gene expression accounting for 3.1% of the variance. CONCLUSIONS: The analysis of the relationship between the molecular genetic diagnoses of a hereditary etiology of hearing loss and cochlear implantation outcomes in a large German cohort of CI recipients revealed significant variabilities. Poor performance was observed with genetic mutations that affected the neural components of the cochlea, supporting the "spiral ganglion hypothesis."

The potential of eHealth for cancer patients-does COVID-19 pandemic change the attitude towards use of telemedicine services?

BACKGROUND: Internet penetration worldwide has increased rapidly over the recent years. With this growth, modern information and communication technologies (ICT) have become increasingly important. They do not only change daily life but also patient-physician interaction and health related information search, which can be summarized as electronic Health (eHealth). eHealth was already known before the emergence of the coronavirus disease 2019 (COVID-19), but this pandemic substantially challenged health systems, physicians and hospitals so profoundly that new services and methods of patient-physician interaction had to be implemented rapidly. This study investigates the attitude of cancer patients towards eHealth and the potential impact of COVID-19 on its use. METHODS AND FINDINGS: The study was a multicentered study carried out at the university hospitals Bonn and Aachen. Patients were asked to answer a structured questionnaire in the time span between September 2019 and February 2021. Due to the COVID-19 pandemic, no patients were addressed between March 2020 and July 2020. The questionnaire focused on socio-demographic data, the dissemination of internet-enabled devices, the patients' attitude towards eHealth and the use of modern ICT in daily life and for health-related information search. In total, 280 patients have filled the questionnaire of which 48% were female and 52% were male. Men have a slightly more positive attitude towards the overall potential of eHealth than women which was shown by a significant influence for receiving medical information via e-mail. Hematological-oncological patients with a higher education level reported a significantly higher willingness to send personal health information to their physician and health insurance. A frequency of medical consultation of more than 5 times during the previous year has a significantly positive impact regarding the use of online communication, online video consultation and treatment quality. Younger patients have more concerns about data security than older patients. The study shows a different attitude towards the influence of eHealth on the patient-physician relationship in different therapy situations. While there were no significant changes in patients' attitude towards eHealth after the start of the COVID-19 pandemic, there was a trend towards an increasingly embracing attitude in patients, who answered the questionnaire during COVID-19 pandemic situation. CONCLUSIONS: Overall, cancer patients had a positive attitude towards eHealth and the dissemination of internet-enabled devices was high. The study shows that the potential of eHealth is high among hematological-oncological patients. Further eHealth technologies and especially telemedically supported care processes should be implemented to improve patient-physician interaction and cross-sectoral care. COVID-19 pandemic led to a fast initiation and acceleration of new structures and routines for physicians, hospitals and patients. These new processes should be used to promote digitalization in hematological and oncological telemedicine. To successfully implement new eHealth technologies, future research should focus on patients' concerns about data privacy and data availability especially in the context of exchange of medical information in cross sectoral and interdisciplinary care processes.

Diagnostic Yield of Targeted Hearing Loss Gene Panel Sequencing in a Large German Cohort With a Balanced Age Distribution from a Single Diagnostic Center: An Eight-year Study.

OBJECTIVES: Hereditary hearing loss exhibits high degrees of genetic and clinical heterogeneity. To elucidate the population-specific and age-related genetic and clinical spectra of hereditary hearing loss, we investigated the sequencing data of causally associated hearing loss genes in a large cohort of hearing-impaired probands with a balanced age distribution from a single center in Southwest Germany. DESIGN: Genetic testing was applied to 305 hearing-impaired probands/families with a suspected genetic hearing loss etiology and a balanced age distribution over a period of 8 years (2011-2018). These individuals were representative of the regional population according to age and sex distributions. The genetic testing workflow consisted of single-gene screening (n = 21) and custom-designed hearing loss gene panel sequencing (n = 284) targeting known nonsyndromic and syndromic hearing loss genes in a diagnostic setup. Retrospective reanalysis of sequencing data was conducted by applying the current American College of Medical Genetics and Genomics/Association for Molecular Pathology guidelines. RESULTS: A genetic diagnosis was established for 75 (25%) of the probands that involved 75 causal variants in 35 genes, including 16 novel causal variants and 9 medically significant variant reclassifications. Nearly half of the solved cases (47%; n = 35) were related to variants in the five most frequently affected genes: GJB2 (25%), MYO15A, WFS1, SLC26A4, and COL11A1 (all 5%). Nearly one-quarter of the cases (23%; n = 17) were associated with variants in seven additional genes (TMPRSS3, COL4A3, LOXHD1, EDNRB, MYO6, TECTA, and USH2A). The remaining one-third of single cases (33%; n = 25) were linked to variants in 25 distinct genes. Diagnostic rates and gene distribution were highly dependent on phenotypic characteristics. A positive family history of autosomal-recessive inheritance in combination with early onset and higher grades of hearing loss significantly increased the solve rate up to 60%, while late onset and lower grades of hearing loss yielded significantly fewer diagnoses. Regarding genetic diagnoses, autosomal-dominant genes accounted for 37%, autosomal-recessive genes for 60%, and X-linked genes for 3% of the solved cases. Syndromic/nonsyndromic hearing loss mimic genes were affected in 27% of the genetic diagnoses. CONCLUSIONS: The genetic epidemiology of the largest German cohort subjected to comprehensive targeted sequencing for hereditary hearing loss to date revealed broad causal gene and variant spectra in this population. Targeted hearing loss gene panel analysis proved to be an effective tool for ensuring an appropriate diagnostic yield in a routine clinical setting including the identification of novel variants and medically significant reclassifications. Solve rates were highly sensitive to phenotypic characteristics. The unique population-adapted and balanced age distribution of the cohort favoring late hearing loss onset uncovered a markedly large contribution of autosomal-dominant genes to the diagnoses which may be a representative for other age balanced cohorts in other populations.

ENT Residents Benefit from a Structured Operation Planning Approach in the Training of Functional Endoscopic Sinus Surgery.

Background and Objectives: Preoperative planning utilizing computed tomographies (CT) is of utmost importance in functional endoscopic sinus surgery (FESS). Frequently, no uniform documentation and planning structures are available to residents in training. Consequently, overall completeness and quality of operation planning may vary greatly. The objective of the present study was to evaluate the impact of a structured operation planning (SOP) approach on the report quality and user convenience during a 4-day sinus surgery course. Materials and Methods: Fifteen participant were requested to plan a FESS procedure based on a CT scan of the paranasal sinuses that exhibited common pathological features, in a conventional manner, using a free text. Afterwards, the participants reevaluated the same scans by means of a specifically designed structured reporting template. Two experienced ENT surgeons assessed the collected conventional operation planning (COP) and SOP methods independently with regard to time requirements, overall quality, and legibility. User convenience data were collected by utilizing visual analogue scales. Results: A significantly greater time expenditure was associated with SOPs (183 s vs. 297 s, p = 0.0003). Yet, legibility (100% vs. 72%, p < 0.0001) and overall completeness (61.3% vs. 22.7%, p < 0.0001) of SOPs was significantly superior to COPs. Additionally, description of highly relevant variants in anatomy and pathologies were outlined in greater detail. User convenience data delineated a significant preference for SOPs (VAS 7.9 vs. 6.9, p = 0.0185). Conclusions: CT-based planning of FESS procedures by residents in training using a structured approach is more time-consuming while producing a superior report quality in terms of detailedness and readability. Consequently, SOP can be considered as a valuable tool in the process of preoperative evaluations, especially within residency.

Reduced Rate of Inpatient Hospital Admissions in 18 German University Hospitals During the COVID-19 Lockdown.

The COVID-19 pandemic has caused strains on health systems worldwide disrupting routine hospital services for all non-COVID patients. Within this retrospective study, we analyzed inpatient hospital admissions across 18 German university hospitals during the 2020 lockdown period compared to 2018. Patients admitted to hospital between January 1 and May 31, 2020 and the corresponding periods in 2018 and 2019 were included in this study. Data derived from electronic health records were collected and analyzed using the data integration center infrastructure implemented in the university hospitals that are part of the four consortia funded by the German Medical Informatics Initiative. Admissions were grouped and counted by ICD 10 chapters and specific reasons for treatment at each site. Pooled aggregated data were centrally analyzed with descriptive statistics to compare absolute and relative differences between time periods of different years. The results illustrate how care process adoptions depended on the COVID-19 epidemiological situation and the criticality of the disease. Overall inpatient hospital admissions decreased by 35% in weeks 1 to 4 and by 30.3% in weeks 5 to 8 after the lockdown announcement compared to 2018. Even hospital admissions for critical care conditions such as malignant cancer treatments were reduced. We also noted a high reduction of emergency admissions such as myocardial infarction (38.7%), whereas the reduction in stroke admissions was smaller (19.6%). In contrast, we observed a considerable reduction in admissions for non-critical clinical situations, such as hysterectomies for benign tumors (78.8%) and hip replacements due to arthrosis (82.4%). In summary, our study shows that the university hospital admission rates in Germany were substantially reduced following the national COVID-19 lockdown. These included critical care or emergency conditions in which deferral is expected to impair clinical outcomes. Future studies are needed to delineate how appropriate medical care of critically ill patients can be maintained during a pandemic.

[Chances and Risks of Telemedicine in Orthopaedics and Trauma Surgery]. / Chancen und Risiken der Telemedizin in der Orthopädie und Unfallchirurgie.

BACKGROUND: The use of information technology (IT) in health care has continuously increased. This includes software solutions for digitalisation, data storage and innovative approaches in diagnostics. The facilitation of the access to specific information, even by the patient, has changed daily clinical work. Patients inform themselves about symptoms, diagnostic methods and treatment options. This urge for information and the wish for the best treatment is summarised in the expression "patient empowerment". In some countries, the gap between do-it-yourself diagnosis and telemedicine via the telephone has already been closed. A sophisticated telemedical hotline may help to improve consultation and treatment of patients living in remote regions or rural communities. Traumatology telemedicine may also be used in trauma environments, such as disasters or mass casualties. Therefore, the purpose of this study was to assess the demand for e-health solutions among patients seeking the help of the emergency department in a trauma hospital. METHODS: A total of 255 patients (age range 18 - 75 years) were included in the study and were surveyed with the use of a questionnaire. As regards personal data, the questionnaire asked the patient about their Internet habits and about interesting topics they had researched in the world wide web. However, the questionnaire was specifically designed to ask for potential benefits and the patient's expectations for e-health solutions. Expected weaknesses and procedures for telemedical services were also included in a subsection. RESULTS: 43.5% of the patient cohort were woman and 56.5% men. The average distance to the hospital was 39.86 km. 223 patients were insured by the governmental health service providers and 32 had private insurance coverage. Aside from online shopping and online banking, the search for health topics was most frequent. The greatest fear was the lack of personal contact to the doctor (71.2%). Patients were also concerned about the safety of individual health data in privately run databanks (54.3%). On the other hand, patients were neutral towards the web-based scheduling of medical appointments. Automatic reminders for such appointments were desired via e-mail (68.8%) or SMS (66.5%). CONCLUSION: Patients are demanding mobile solutions for scheduling medical appointments, including reminders of these. Patients are keen to be involved in the communications and would like to receive overall information about their health status. Online chats or video calls with physicians are not their first choice but might be a possibility until personal presentation.

The potential of eHealth in otorhinolaryngology-head and neck surgery: patients' perspectives.

The use of modern information and communication technologies (ICT) in daily life has significantly increased during the last several years. These essential online technologies have also found their way into the healthcare system. The use of modern ICT for health reasons can be summarized by the term 'eHealth'. Despite the potential importance of eHealth in the field of otorhinolaryngology (ORL), there is little understanding of patients' attitudes towards the deeper integration of these technologies into intersectoral care. The aim of this study was to gain a better understanding of patients' attitudes towards the use of modern ICT for intersectoral communication and information transfer in the field of ORL. Therefore, a structured interview was developed by an interdisciplinary team of otorhinolaryngologists, public health researchers, and information technology (IT) specialists. Overall, 211 ORL patients were interviewed at the Department of Otorhinolaryngology-Head and Neck Surgery, Tuebingen University Hospital, Germany, and 203 of these patients completed the interview. This study revealed ORL patients' perspectives on the potential of eHealth, especially for appointment scheduling, appointment reminders, and intersectoral communication of personal medical information. Furthermore, this study provides evidence that data security and the impacts of eHealth on the physician-patient relationship and on treatment quality warrant special attention in future research.

Compliance of Clinical Pathways in Elective Laparoscopic Cholecystectomy: Evaluation of Different Implementation Methods.

BACKGROUND: Clinical pathways aim to standardize perioperative and postoperative care of surgical procedures and are shown to result in a significant optimization associated with cost reduction. The aim of this study was to establish the impact of two different implementations forms of clinical pathways on the pathway compliance and resulting costs. METHODS: Data of patients undergoing elective cholecystectomy for symptomatic cholecystolithiasis were collected over two different periods: using a clinical pathway in the form of a paper-based checklist, or a clinical pathway integrated into the paper-based medical treatment and nursing documentation. Outcome measures were compliance of the clinical pathway and total costs per case. RESULTS: The compliance was significantly higher using integrated pathways compared to paper-based checklists (n = 117 of 123, 95 % vs 54 of 118, 46 %; p < 0.001). Mean total costs (€2206 vs €2458, p = 0.027) and length of hospital stay (2.13 vs 2.77 days, p < 0.001) were significantly reduced by the integrated clinical pathway compared to checklists. Further, the variation of costs per case and variation of length of hospital stay were significantly smaller with integrated clinical pathway (±€440 vs ±€538, p = 0.039 and ±0.53 vs ±0.68 days, p < 0.001, respectively). No difference regarding postoperative complication was observed (n = 3 vs. 4 events; p = 0.67). CONCLUSION: Integrated clinical pathways display a significant higher compliance compared to checklists resulting in reduced total costs, shorter hospital stay and a smaller variation of cost, making it a useful tool in process controlling and planning.

A case of recurrent respiratory papillomatosis with malignant transformation, HPV11 DNAemia, high L1 antibody titre and a fatal papillary endocardial lesion.

BACKGROUND: Recurrent respiratory papillomatosis (RRP) is a rare disease, which is characterised by the growth of papillomavirus-induced papillomas within the respiratory tract. Malignant transformation occurs in less than 1% of the cases. CASE PRESENTATION: We report a case of human papillomavirus (HPV) type 11-associated juvenile-onset RRP (JORRP) initially diagnosed at the age of two years. Remarkably high copy numbers of HPV11 DNA and antibody titres targeting the capsid protein L1 were detected in the patient's serum. The patient developed squamous cell carcinomas in both lungs and extraordinarily an HPV11 DNA-positive papillary endocardial lesion in the left atrium of the heart, which caused thromboembolic events leading to the patient's death at 19 years old. CONCLUSION: We here report a severe case of JORRP hallmarked by HPV11 DNAemia and very high antibody titres directed against the major viral capsid protein L1. Furthermore, the extent of malignant transformation and the discovery of a very rare fatal endocardial lesion highlight the unpredictability of JORRP and the complexity of its clinical management.

New shift models for doctors in a large German University Neurosurgery Department: how they comply with the European Working Time Directive 3 years after implementation.

BACKGROUND: Due to the European Working Time Directive (EWTD) and a new collective agreement for doctors working at University hospitals in 2006 new shift models had to be designed in the Department of Neurosurgery of the University Hospital Tübingen, Germany. The aim of the study was to show the fit of the models regarding the average weekly working time limits (aWTL), the daily maximum of 10-h working time (10-h dWT), and the staff expenditures 3 years after implementation. METHODS: The new shift model was implemented in 2008, and hence planning and documentation were done electronically. Adherence to the work schedules was measured, and aWTL adherence rates were compared. The relative number of 10-h dWT violations in 2009 and 2010 was analysed. Staff costs relative to performance before and after implementation were calculated and tested using analysis of variance (ANOVA). Four other departments without alteration of shift models served as a control group in cost trend analysis. RESULTS: In 2010 all doctors in the Department of Neurosurgery were able to stay within the limit of 54 h/week; one doctor without opt-out exceeded the 48 h/week limit (50.1 h/week). The median per capita rate of 10-h dWT violations in 2009 was 20.3 % of all eligible working days and further declined to 10.7 % in 2010 (p < 0.001). Staff costs per case-weight point did not change significantly (2007: 339.88€, 2009: 307.99€, 2010: 322.54€; p = 0.22) in neurosurgery or in the control group (2007: 633.72€, 2009: 637.06€, 2010: 690.30€; p = 0.67). CONCLUSIONS: After implementation of the new shift model, current monitoring and properly matching modifications led to long-term stability in complying with the EWTD regulations without increasing costs for staff expenditures.