Medication use in patients with chronic rhinosinusitis in Germany - a large retrospective patient-based study.

BACKGROUND: The aim of the present study was to provide an insight into medical treatment practices among patients with chronic rhinosinusitis (CRS) in Germany. An investigation of ICD codes and ATC classes of CRS patients in general and otolaryngology offices in Germany should reveal the prevalent treatment behaviors of German physicians. METHODS: The present study used data from the Disease Analyzer database (IQVIA). The study sample included patients from 940 general (GP) and 106 otolaryngology (ENT) practices who were coded as having chronic sinusitis (ICD-10: J32) or nasal polyps (ICD-10: J33) in 2015 (index date). The primary outcome measures were the number of patients with these diagnoses per practice as well as the proportion of patients with prescriptions for topical corticosteroids, systemic corticosteroids, antibiotics, antihistamines, and local decongestants within 365 days after the first diagnosis. RESULTS: This retrospective study included 26,768 patients with coding for chronic sinusitis (ICD-10: J32) and 516 patients for nasal polyps (ICD-10: J33) in 940 GP practices and 19,826 patients with coding for chronic sinusitis (ICD-10: J32) and 1,773 patients for nasal polyps (ICD-10: J33) in 106 ENT practices. In patients coded as having chronic sinusitis (ICD-10: J32), topical corticosteroids were prescribed at a low rate (GP: 12.3%, ENT: 34.3%). In patients coded as having nasal polyps (ICD-10: J33), topical corticosteroid usage was higher in GP practices (27.3%) and in ENT practices (71.2%). CONCLUSIONS: Topical corticosteroid usage in CRS patients in GP practices in Germany is as low as in other Western countries. Increased usage of topical corticosteroids in CRS patients with polyposis should be encouraged in GP and ENT practices.

Impact of TP53 mutation status on systemic treatment outcome in ALK-rearranged non-small-cell lung cancer.

Background: We analyzed whether co-occurring mutations influence the outcome of systemic therapy in ALK-rearranged non-small-cell lung cancer (NSCLC). Patients and methods: ALK-rearranged stage IIIB/IV NSCLC patients were analyzed with next-generation sequencing and fluorescence in situ hybridization analyses on a centralized diagnostic platform. Median progression-free survival (PFS) and overall survival (OS) were determined in the total cohort and in treatment-related sub-cohorts. Cox regression analyses were carried out to exclude confounders. Results: Among 216 patients with ALK-rearranged NSCLC, the frequency of pathogenic TP53 mutations was 23.8%, while other co-occurring mutations were rare events. In ALK/TP53 co-mutated patients, median PFS and OS were significantly lower compared with TP53 wildtype patients [PFS 3.9 months (95% CI: 2.4-5.6) versus 10.3 months (95% CI: 8.6-12.0), P < 0.001; OS 15.0 months (95% CI: 5.0-24.9) versus 50.0 months (95% CI: 22.9-77.1), P = 0.002]. This difference was confirmed in all treatment-related subgroups including chemotherapy only [PFS first-line chemotherapy 2.6 months (95% CI: 1.3-4.1) versus 6.2 months (95% CI: 1.8-10.5), P = 0.021; OS 2.0 months (95% CI: 0.0-4.6) versus 9.0 months (95% CI: 6.1-11.9), P = 0.035], crizotinib plus chemotherapy [PFS crizotinib 5.0 months (95% CI: 2.9-7.2) versus 14.0 months (95% CI: 8.0-20.1), P < 0.001; OS 17.0 months (95% CI: 6.7-27.3) versus not reached, P = 0.049] and crizotinib followed by next-generation ALK-inhibitor [PFS next-generation inhibitor 5.4 months (95% CI: 0.1-10.7) versus 9.9 months (95% CI: 6.4-13.5), P = 0.039; OS 7.0 months versus 50.0 months (95% CI: not reached), P = 0.001). Conclusions: In ALK-rearranged NSCLC co-occurring TP53 mutations predict an unfavorable outcome of systemic therapy. Our observations encourage future research to understand the underlying molecular mechanisms and to improve treatment outcome of the ALK/TP53 co-mutated subgroup.

[What is new in symptomatic MS treatment: Part 3-bladder dysfunction]. / Neues zur symptomatischen MS-Therapie: Teil 3 ­ Blasenfunktionsstörungen.

The symptomatic treatment of multiple sclerosis (MS) nowadays is of similar importance as immunotherapy within a comprehensive concept of therapy of this chronic disease, since it contributes considerably to the reduction of disabilities in activities of daily living as well as social and occupational life. Moreover, symptomatic treatment is of great importance for amelioration of quality of life. Since our last survey of symptomatic MS treatment in 2004 and publication of the guidelines of the German Neurological Society and the Klinisches Kompetenznetz Multiple Sklerose (KKNMS) in 2014 several developments within the topics of mobility, bladder and sexual function, vision, fatigue, cognition and rehabilitation took place. These new findings together with further aspects of disease measures and overall treatment strategies of the respective symptoms, as well as treatment goals are introduced in a series of six individual contributions. Here, the symptoms of bladder dysfunction will be discussed.

[New aspects of symptomatic MS treatment: Part 4-sexual dysfunction and eye movement disorders]. / Neues zur symptomatischen MS-Therapie: Teil 4 ­ Störungen der Sexualfunktion und der Augenbewegungen.

The symptomatic treatment of multiple sclerosis (MS) is nowadays of similar importance as immunotherapy within a comprehensive treatment concept of this chronic disease. It makes a considerable contribution to the reduction of disabilities in activities of daily living as well as social and occupational life. Moreover, symptomatic treatment is of great importance for amelioration of the quality of life. Since our last survey of symptomatic MS treatment in 2004 and publication of the guidelines of the German Neurological Society and the Clinical Competence Network Multiple Sclerosis (Klinisches Kompetenznetz Multiple Sklerose, KKNMS) in 2014, several developments within the topics of mobility, bladder and sexual function, vision, fatigue, cognition and rehabilitation have taken place. These new findings together with further aspects of disease measurement methods and overall treatment strategies of the respective symptoms as well as treatment goals are introduced in several individual contributions. In this article the symptoms of sexual dysfunction and eye movement disorders are discussed.

[New aspects of symptomatic MS treatment: Part 6 - cognitive dysfunction and rehabilitation]. / Neues zur symptomatischen MS-Therapie: Teil 6 ­ kognitive Störungen und Rehabilitation.

The symptomatic treatment of multiple sclerosis (MS) is nowadays of similar importance as immunotherapy within a comprehensive treatment concept of this chronic disease. It makes a considerable contribution to the reduction of disabilities in activities of daily living as well as social and occupational life. Moreover, symptomatic treatment is of great importance for amelioration of the quality of life. Since our last survey of symptomatic MS treatment in 2004 and publication of the guidelines of the German Neurological Society and the Clinical Competence Network Multiple Sclerosis ("Klinisches Kompetenznetz Multiple Sklerose", KKN-MS) in 2014 several developments within the topics of mobility, bladder and sexual function, vision, fatigue, cognition and rehabilitation have taken place. These new findings together with further aspects of disease measurement methods and overall treatment strategies of the respective symptoms, as well as treatment goals are introduced in several individual contributions. In this article the symptoms of cognitive disorders and the growing impact of rehabilitation are discussed.

[New aspects of symptomatic MS treatment: Part 5 - fatigue]. / Neues zur symptomatischen MS-Therapie: Teil 5 ­ Fatigue.

The symptomatic treatment of multiple sclerosis (MS) is nowadays of similar importance as immunotherapy within a comprehensive treatment concept of this chronic disease. It makes a considerable contribution to the reduction of disabilities in activities of daily living as well as social and occupational life. Moreover, symptomatic treatment is of great importance for amelioration of the quality of life. Since our last survey of symptomatic MS treatment in 2004 and publication of the guidelines of the German Neurological Society and the Clinical Competence Network Multiple Sclerosis (Klinisches Kompetenznetz Multiple Sklerose, KKN-MS) in 2014 several developments within the topics of mobility, bladder and sexual function, vision, fatigue, cognition and rehabilitation have taken place. These new findings together with further aspects of disease measurement methods and overall treatment strategies of the respective symptoms as well as treatment goals are introduced in a series of 6 individual contributions. In this article the symptom of fatigue is discussed.

[Diagnoses of thyroid disorders in ENT and general practices in Germany between 2008 and 2016]. / Diagnosen von Schilddrüsenerkrankungen in HNO-Praxen und Hausarztpraxen in Deutschland 2008­2016.

OBJECTIVE: The aim of this study was to investigate thyroid disorder diagnoses in otorhinolaryngologic (ENT) practices in Germany compared to general (GP) practices using data from a representative Germany-wide practice database. METHODS: The database was retrospectively searched for diagnoses of thyroid disorders made in ENT and GP practices between January 2008 and December 2016. Data were collected on the most common three-character disease classes (categories) from the "Disorders of thyroid gland" (E00-E07) group as well as the "Benign neoplasm of thyroid gland" (D34) and "Malignant neoplasm of thyroid gland" (C73) categories. The periods 2008-2010, 2011-2013, and 2014-2016 were evaluated. RESULTS: The database included 71 ENT and 506 GP practices with continuous participation from 2008 to 2016. The relative frequency (patients/practice) of diagnoses from the "Disorders of thyroid gland" group was 4.4-times higher in GP than in ENT practices. The relative frequency of benign neoplasms of the thyroid gland was 5­times higher in GP than in ENT practices. The relative frequency of malignant neoplasms of the thyroid gland was almost identical in GP and ENT practices. The most frequent diagnoses in both ENT and GP practices were found in the categories "Other nontoxic goiter" (E04) and "Other hypothyroidism" (E03). Diagnoses in the categories "Hyperthyroidism" (E05) and "Thyroiditis" (E06) were less frequent. Diagnoses of thyroid neoplasms were the least frequent, with benign neoplasms diagnosed more frequently in GP practices and malignant neoplasms diagnosed more frequently in ENT practices. During the study period, the diagnostic frequency of thyroid diseases decreased in ENT practices, whereas it increased in GP practices. CONCLUSION: Despite the increasing interest in establishing thyroid surgery in ENT clinics in Germany in recent years, thyroid diagnoses in ENT practices in Germany have been continuously declining, whereas they have considerably increased in GP practices. The reason for this may be health insurance provider-related differences in reimbursement practices for GPs and specialists.

Risk factors for epistaxis in patients followed in general practices in Germany.

BACKGROUND: The goal of the present study was to analyze the risk factors for epistaxis in patients followed in general practices in Germany. METHODS: The current study sample included patients aged 18 years or older who received a first epistaxis diagnosis between January 2012 and December 2016 (index date). Epistaxis patients and controls without epistaxis were matched (1:1) on the basis of age, gender, insurance status and physician. RESULTS: A total of 16,801 patients with epistaxis and 16,801 control subjects were included in this study. Of the subjects, 53.2% were men, and the mean age was 59.6 years (SD=21.2 years). Epistaxis was found to be positively associated with hypertension, obesity, chronic sinusitis, other disorders of the nose and nasal sinuses, anxiety disorder, and adjustment disorder (ORs ranging from 1.13 to 1.44). Epistaxis was also associated with the prescription of vitamin K antagonists, preparations from the heparin group, platelet aggregation inhibitors excluding heparin, direct thrombin inhibitors, direct factor Xa inhibitors, other antithrombotic agents, selective serotonin reuptake inhibitors and nasal steroids (ORs ranging from 1.15 to 3.55). CONCLUSIONS: Overall, epistaxis risk is increased by multiple medical and psychiatric disorders. Several antithrombotic and nasal steroid therapies are also associated with this risk.

[What is new in symptomatic MS treatment: Part 2-gait disorder and spasticity]. / Neues zur symptomatischen MS­Therapie: Teil 2 ­ Gangstörung und Spastik.

The symptomatic treatment of multiple sclerosis (MS) nowadays is of similar importance as immunotherapy within a comprehensive concept of therapy of this chronic disease, since it contributes considerably to the reduction of disabilities in activities of daily living as well as social and occupational life. Moreover, symptomatic treatment is of great importance for amelioration of quality of life. Since our last survey of symptomatic MS treatment in 2004 and publication of the guidelines of the German Neurological Society and the Klinisches Kompetenznetz Multiple Sklerose (KKN­MS) in 2014 several developments within the topics of mobility, bladder and sexual function, vision, fatigue, cognition and rehabilitation took place. These new findings together with further aspects of disease measures and overall treatment strategies of the respective symptoms, as well as treatment goals are introduced in a series of six individual contributions. Here, the symptoms of gait disorders and spasticity will be discussed.

[What is new in symptomatic MS treatment: Part 1-introduction and methodical approach, ataxia and tremor]. / Neues zur symptomatischen MS­Therapie: Teil 1 ­ Einleitung und methodisches Vorgehen, Ataxie und Tremor.

The symptomatic treatment of multiple sclerosis (MS) nowadays is of similar importance as immunotherapy within a comprehensive concept of therapy of this chronic disease, since it contributes considerably to the reduction of disabilities in activities of daily living as well as social and occupational life. Moreover, symptomatic treatment is of great importance for amelioration of quality of life. Since our last survey of symptomatic MS treatment in 2004 and publication of the guidelines of the German Neurological Society and the Klinisches Kompetenznetz Multiple Sklerose (KKN­MS) in 2014 several developments within the topics of mobility, bladder and sexual function, vision, fatigue, cognition and rehabilitation took place. These new findings together with further aspects of disease measures and overall treatment strategies of the respective symptoms, as well as treatment goals are introduced in a series of six individual contributions. Here, the topic will be introduced, the methodical approach will be explained, and the treatment of ataxia and tremor will be discussed.

A multicentre, randomized, single-blind, parallel-group study comparing the efficacy and tolerability of benzoyl peroxide 3%/clindamycin 1% with azelaic acid 20% in the topical treatment of mild-to-moderate acne vulgaris.

BACKGROUND: Mild-to-moderate acne vulgaris is treated with a range of mono- and combination therapies; however, clinical evidence is still required to optimize treatment recommendations. OBJECTIVE: To compare the efficacy, tolerability and safety of a combination of benzoyl peroxide 3% and clindamycin 1% (BPO + CLN) with azelaic acid 20% (AzA) for the topical treatment of mild-to-moderate acne vulgaris. METHOD: This was a randomized, assessor-blinded, parallel-group, multicentre study conducted in Germany. Patients with a confirmed diagnosis of acne vulgaris, aged 12-45 years, were randomized 1 : 1 to once-daily BPO + CLN gel or twice-daily AzA cream for up to 12 weeks. The primary endpoint was the percentage change in inflammatory lesions from baseline at Week 4. Secondary endpoints included total and inflammatory lesion counts and tolerability assessments. For selected secondary endpoints, inductive statistical analysis was performed post hoc. Patient safety was assessed by adverse event (AE) monitoring. RESULTS: Efficacy was assessed in the modified intent-to-treat (mITT) population [patients using ≥1 dose of study medication (ITT), plus baseline and ≥1 post-baseline lesion count (n = 215)]. There was a statistically significant difference in the primary endpoint, with a median decrease of -52.6% for BPO + CLN (n = 107) vs.-38.8% for AzA (n = 108; P = 0.0004). There was also a greater difference in secondary lesion endpoints at Week 12, with a median decrease in inflammatory lesions of -78.8% and -65.3% and total lesions of -69.0% and -53.9% with BPO + CLN and AzA, respectively (both P < 0.0001). Tolerability was acceptable for both treatments. Overall, 55.6% (BPO + CLN) and 69.7% (AzA) of patients reported treatment-emergent AEs, and 15.7% and 35.8% of patients experienced application site reactions with BPO + CLN (24 events; 17 patients) and AzA (60 events; 39 patients) treatment, respectively (ITT population). CONCLUSION: BPO + CLN demonstrated greater efficacy than AzA in the treatment of mild-to-moderate acne vulgaris and has a positive tolerability and safety profile.

Superselective microcoil embolization in severe intractable epistaxis: an analysis of 12 consecutive cases from an otorhinolaryngologic and an interventional neuroradiologic point of view.

From 2006 to 2013, 12 patients with severe epistaxis refractory to prior conservative and surgical therapy were treated by superselective embolization of nasal arteries. Supersoft platinum microcoils with smallest diameters were used as the sole embolic agent in all cases. Coils were applied far distally in a stretched position for obtaining ideal target vessel superselectivity. The objective of this study is to evaluate efficacy and complications of superselective coil embolization for treatment of severe intractable epistaxis and to discuss results from an otorhinolaryngologic and an interventional neuroradiologic point of view. Retrospectively, all epistaxis inpatients between 2006 and 2013 were identified and subdivided by form of treatment: conservative, surgical and interventional therapy. Medical records of interventionally treated patients were reviewed for demographics, medical history, risk factors, clinical data, complications and short-term success, and patients were followed up for long-term success. Mean follow-up was 37 months. In 12 patients, 14 embolizations were carried out, with short-term success in 9 patients (75%), while early post-interventional rebleeding occurred in 3 patients (25%). Of 9 patients with short-term success, 1 died during stay, 1 was lost to follow-up and 1 had minor re-bleeding after 30 months. Six patients had short-term and long-term success. Before the first embolization, 3 ± 1 conservative and/or surgical procedures had been undertaken. Length of stay was 12.8 ± 3.6 days. 8 patients (67%) received red cell concentrates. Most frequent complications were mucosal damage and nasal pain, but these were related to repeated packing and surgery. Typical embolic complications as neurological or visual impairment or soft tissue necrosis were not observed in any patient. From the otorhinolaryngologic point of view, surgery is the treatment of choice in severe refractory epistaxis, but in case of repeated failure, superselective microcoil embolization is a valuable addition to the therapeutic spectrum. From the interventional neuroradiologic point of view, superselective microcoil embolization is an effective, well tolerable and safe procedure and complications may be reduced in comparison to microparticle embolization. Modern supersoft microcoils with smallest diameters enable ideal superselectivity of the target vessels.

[Reconstruction of isolated orbital floor fractures with a prefabricated titanium mesh]. / Versorgung isolierter Orbitabodenfrakturen - Rekonstruktion mit präfabriziertem Titanmesh.

PURPOSE: Concerning safety and efficiency in surgery of isolated orbital floor fractures, several treatment modalities are being discussed. It is a matter of recent interest that prefabricated titanium meshes provide significant advantages. The purpose of this study was to review the usability of the MatrixORBITAL® plate. MATERIAL AND METHODS: In a prospective study we evaluated 10 patients (June 2011 to November 2013) with an isolated orbital floor fracture. All patients in the study group had undergone reconstruction with the MatrixORBITAL® plate. For purposes of analysis were recorded: age, gender, fracture category according to Jaquiéry et al. (2007), duration of surgery, complications, globe motility (Harms wall), exophthalmometry, function of the infraorbital nerve, evaluation of facial symmetry and aesthetic as well as personal contentment of the patient. A reference group received a PDS® sheet, an antral balloon or other materials. RESULTS: In the study group (2 women and 8 men aged between 26 and 83 years) all cases presented a large disruption of the orbital floor (> 2 cm2 bony defect; category II-III). Volume changes were universally associated with diplopia, but only in two cases with an entrapment of the inferior rectus muscle. The mean duration of the operation was 110 minutes (minimum 50, maximum 135 minutes). Postoperatively diplopia was decreasing in all cases. None of the patients had a significant impairment of visus and no reoperation was necessary. The analysis of functional outcomes between the groups mesh, PDS sheet and antral balloon revealed no significant differences. CONCLUSIONS: Based on this experience and due to good intraoperative handling, the authors recommend the prefabricated titanium plate in the treatment of isolated orbital wall fractures or in combination with the medial wall despite the material costs.

[Total laryngopharyngectomy and reconstruction with a jejunum speech siphon : A case report]. / Totale Laryngopharyngektomie und Rekonstruktion mit Jejunumsprechsiphon : Fallbericht.

Advanced laryngeal and hypopharyngeal carcinomas are associated with a poor prognosis and a pronounced loss of quality of life due to impairment of the swallowing and voice function. The fundamental therapeutic challenge is successful tumor control with concomitant rehabilitation of swallowing and voice functions. Further objectives are a low complications rate (fistula, aspiration) and prompt transfer to the adjuvant radio-oncologic therapy. With these factors in mind, the microvascular anastomosed jejunum speech siphon with a biventer rein has proven to be an effective method of reconstruction following extensive circular laryngopharyngeal resections. In this case report, a typical operative and postoperative course is presented, as are the functional results.

Stabilization of a Kerr frequency comb oscillator.

We study stability and spectral purity of a microresonator-based Kerr frequency comb oscillator experimentally and observe a correlation between the frequency of the continuous wave laser pumping the nonlinear resonator and the repetition frequency of the comb. This correlation is used in a proof-of-principle demonstration of a Kerr frequency comb stabilized with an optical transition of 87Rb.

Kerr frequency comb generation in overmoded resonators.

We show that scattering-based interaction among nearly degenerate optical modes is the key factor in low threshold generation of Kerr frequency combs in nonlinear optical resonators with small group velocity dispersion (GVD). Mode interaction is capable of producing drastic changes in the local GVD, resulting in either a significant reduction, or an increase, in the oscillation threshold. Furthermore, we show that mode interaction is also responsible for majority of observed optical frequency combs in resonators characterized with large normal GVD. We present results of our numerical simulations together with supporting experimental data.

Randomised, controlled pilot to compare collagen and foam in stagnating pressure ulcers.

OBJECTIVE: To compare the clinical efficacy of a collagen dressing covered with a foam dressing with the same foam used as a primary dressing in stagnating granulating pressure ulcer patients. METHOD: Patients were randomised to receive either a foam dressing (Suprasorb P; Lohmann & Rauscher) as a primary dressing (group A), or a combination of a collagen dressing (Suprasorb C; Lohmann & Rauscher) covered with the same foam dressing (group B).Wound fluid was collected and evaluated prior to treatment (day 0), and on days 3,7, 14 and 21 .The level and expression of matrix metalloproteinases (MMPs) MMP-2 and MMP-9, and tissue inhibitors of metalloproteinases (TIMPs) TIMP- I and TIMP-2,as well as elastase content in wound fluid and angiogenesis,were evaluated, comparing results on day 0 and day 2 I.Time to ulcer healing, reduction in ulcer area, safety of treatment, patient-reported ulcer pain and comfort of the dressing regimen were evaluated as secondary outcomes. Patients received standard preventive measures, in line with the pressure ulcer prevention guidelines. RESULTS: Ten patients were included in the pilot; five were treated with the foam dressing (group A) and five patients received the collagen dressing, using the foam as a secondary dressing (group B).Wound fluid from group B displayed a significant positive effect on angiogenesis (p < 0.05) compared with group A. In the collagen and foam groupTIMP- I and -2 increased faster and levels were higher than in group A. Furthermore, MMP-2, MMP-9 (p < 0.04) and elastase in group B showed faster and greater decrease in levels, compared with group A, indicating a faster and superior reduction of inflammation. In both groups the ulcers started to heal, with a faster onset of healing for group B. CONCLUSION: The results of this pilot support published data on the use of collagen dressings compared with foam for stagnating wounds, shown in clinical studies. DECLARATION OF INTEREST: This study was supported with an educational grant by Lohmann & Rauscher GmbH.Apart from DrAbel, the sponsors had no role in the design or conduct of the study, in the collection, analysis and interpretation of the data, or in the preparation, review or approval of the manuscript. DrAbel gave input to the study design from a scientific perspective. None of the authors received administrative, technical or material support for the conduct of this study.The authors have no other relevant financial interests to declare.

Generation of near-infrared frequency combs from a MgF2 whispering gallery mode resonator.

We report on generation of a 20 nm wide, 35 GHz repetition rate optical frequency comb in a magnesium fluoride whispering gallery mode resonator pumped with 2 mW of 1543 nm light. The high efficiency of comb generation is associated with the small anomalous group velocity dispersion of the resonator. Growth dynamics of the comb is studied and compared with earlier theoretical predictions.

Surface acoustic wave opto-mechanical oscillator and frequency comb generator.

We report on realization of an efficient triply resonant coupling between two long lived optical modes and a high frequency surface acoustic wave (SAW) mode of the same monolithic crystalline whispering gallery mode resonator. The coupling results in an opto-mechanical oscillation and generation of a monochromatic SAW. A strong nonlinear interaction of this mechanical mode with other equidistant SAW modes leads to mechanical hyperparametric oscillation and generation of a SAW pulse train and associated frequency comb in the resonator. We visualized the comb by observing the modulation of the light escaping the resonator.

Mode-locked Kerr frequency combs.

We analyze a mode-locked regime in Kerr frequency combs generated in nonlinear microresonators. Using damped driven nonlinear Schrödinger equations we show that the combs can produce subpicosecond optical pulses when the resonators are characterized with a small enough anomalous group velocity dispersion. We provide an analytical solution of the problem for the case of small damping.