Second international guidelines for the diagnosis and management of hereditary hemorrhagic telangiectasia

Hereditary hemorrhagic telangiectasia (HHT) is an autosomal dominant disease with an estimated prevalence of 1 in 5000 that is characterized by the presence of vascular malformations (VMs). These result in chronic bleeding, acute hemorrhage, and complications from shunting through VMs. The goal of the Second International HHT Guidelines process was to develop evidence-based consensus guidelines for the management and prevention of HHT-related symptoms and complications. The guidelines were developed using the AGREE II (Appraisal of Guidelines for Research and Evaluation II) framework and GRADE (Grading of Recommendations Assessment, Development and Evaluation) methodology. The guidelines expert panel included expert physicians (clinical and genetic) in HHT from 15 countries, guidelines methodologists, health care workers, health care administrators, patient advocacy representatives, and persons with HHT. During the preconference process, the expert panel generated clinically relevant questions in 6 priority topic areas. A systematic literature search was done in June 2019, and articles meeting a priori criteria were included to generate evidence tables, which were used as the basis for recommendation development. The expert panel subsequently convened during a guidelines conference to conduct a structured consensus process, during which recommendations reaching at least 80% consensus were discussed and approved. The expert panel generated and approved 6 new recommendations for each of the following 6 priority topic areas: epistaxis, gastrointestinal bleeding, anemia and iron deficiency, liver VMs, pediatric care, and pregnancy and delivery (36 total). The recommendations highlight new evidence in existing topics from the first International HHT Guidelines and provide guidance in 3 new areas: anemia, pediatrics, and pregnancy and delivery. These recommendations should facilitate implementation of key components of HHT care into clinical practice.

Pathology-based staging for HPV-positive squamous carcinoma of the oropharynx.

OBJECTIVE: The rapid worldwide rise in incidence of human papillomavirus (HPV)-positive oropharyngeal squamous cell carcinoma (OPSCC) has generated studies confirming this disease as an entity distinct from traditional OPSCC. Based on pathology, surgical studies have revealed prognosticators specific to HPV-positive OPSCC. The current AJCC/UICC staging and pathologic nodal (pN)-classification do not differentiate for survival, demonstrating the need for new, HPV-specific OPSCC staging. The objective of this study was to define a pathologic staging system specific to HPV-positive OPSCC. METHODS: Data were assembled from a surgically-managed, p16-positive OPSCC cohort (any T, any N, M0) of 704 patients from five cancer centers. Analysis was performed for (a) the AJCC/UICC pathologic staging, (b) newly published clinical staging for non-surgically managed HPV-positive OPSCC, and (c) a novel, pathology-based, "HPVpath" staging system that combines features of the primary tumor and nodal metastases. RESULTS: A combination of AJCC/UICC pT-classification and pathology-confirmed metastatic node count (⩽4 versus ⩾5) yielded three groups: stages I (pT1-T2, ⩽4 nodes), II (pT1-T2, ⩾5 nodes; pT3-T4, ⩽4 nodes), and III (pT3-T4, ⩾5 nodes), with incrementally worse prognosis (Kaplan-Meier overall survival of 90%, 84% and 48% respectively). Existing AJCC/UICC pathologic staging lacked prognostic definition. Newly published HPV-specific clinical stagings from non-surgically managed patients, although prognostic, showed lower precision for this surgically managed cohort. CONCLUSIONS: Three loco-regional "HPVpath" stages are identifiable for HPV-positive OPSCC, based on a combination of AJCC/UICC primary tumor pT-classification and metastatic node count. A workable, pathologic staging system is feasible to establish prognosis and guide adjuvant therapy decisions in surgically-managed HPV-positive OPSCC.

International guidelines for the diagnosis and management of hereditary haemorrhagic telangiectasia.

BACKGROUND: HHT is an autosomal dominant disease with an estimated prevalence of at least 1/5000 which can frequently be complicated by the presence of clinically significant arteriovenous malformations in the brain, lung, gastrointestinal tract and liver. HHT is under-diagnosed and families may be unaware of the available screening and treatment, leading to unnecessary stroke and life-threatening hemorrhage in children and adults. OBJECTIVE: The goal of this international HHT guidelines process was to develop evidence-informed consensus guidelines regarding the diagnosis of HHT and the prevention of HHT-related complications and treatment of symptomatic disease. METHODS: The overall guidelines process was developed using the AGREE framework, using a systematic search strategy and literature retrieval with incorporation of expert evidence in a structured consensus process where published literature was lacking. The Guidelines Working Group included experts (clinical and genetic) from eleven countries, in all aspects of HHT, guidelines methodologists, health care workers, health care administrators, HHT clinic staff, medical trainees, patient advocacy representatives and patients with HHT. The Working Group determined clinically relevant questions during the pre-conference process. The literature search was conducted using the OVID MEDLINE database, from 1966 to October 2006. The Working Group subsequently convened at the Guidelines Conference to partake in a structured consensus process using the evidence tables generated from the systematic searches. RESULTS: The outcome of the conference was the generation of 33 recommendations for the diagnosis and management of HHT, with at least 80% agreement amongst the expert panel for 30 of the 33 recommendations.

[Development of the Sino-Nasal Outcome Test-20 Chinese version (SNOT-20 CV)].

OBJECTIVE: To develop the Sino-Nasal Outcome Test-20 Chinese Version (SNOT-20 CV). METHODS: By introducing, translating, pretesting, adjusting, and performance testing of SNOT-20 inventory, a Chinese draft scale came into being. On the basis of the clinical applications and feedbacks from ten domestic hospitals, the scale was further modified and was more strictly tested in sixty patients with chronic rhinosinusitis, and then its psychometric properties were compared with that of the original edition. RESULTS: The SNOT-20 CV showed the following psychometric properties: The scale was easily accepted and answered in patients, showing a satisfactory feasibility. The split-half reliability, Cronbach' alpha and intraclass correlation coefficient were 0.95, 0.88, and 0.98, respectively. The content validity was approved by experts of working group. The criteria validity calculated between SNOT-20 and SF-36 was -0.67. Factor analysis of construct validity showed that the comparative fit index was 0.93 and the 20 items were classified into 4 domains which were accorded with the designed constructs. The category rating system was of reasonable additivity and comparability. Every domain was of sensitivity to effectively discriminate between patient population and healthy population (P < 0.01). The standardized response mean of twenty items and five important items at three months postoperatively was respectively 0.48 and 0.57, suggesting moderate responsibility to clinical change. SNOT-20 CV passed the tests of feasibility, reliability, validity, scalability, sensitivity, and responsibility, showing good properties comparable to that of the original edition. CONCLUSIONS: SNOT-20 CV passes the psychometric and clinimetric tests and can be used for measuring rhinosinusitis-specific quality of life in China.

[Quality of life in patients with chronic rhinosinusitis: validation of the Sino-Nasal Outcome Test-20 German Adapted Version]. / Lebensqualität bei Patienten mit chronischer Rhinosinusitis: Validierung des Sino-Nasal Outcome Test-20 German Adapted Version.

BACKGROUND: No validated German instrument for measuring health-related quality of life (QOL) in patients with chronic rhinosinusitis (CRS) has been available to date. METHODS: The Sino-Nasal Outcome Test-20 German Adapted Version (SNOT-20 GAV) is a translated and adapted version of SNOT-20. To validate this instrument, we evaluated its reliability, validity and sensitivity. SNOT-20 GAV was completed by 163, 123, and 82 patients at the initial visit and at 3 months and 1 year after treatment commencement, respectively. RESULTS: Cronbach's alpha indicated good internal consistency. Test-retest scores in 38 patients were highly correlated. Discrimination validity was demonstrated by a comparison with healthy controls. Sensitivity to change showed medium to large effects. CONCLUSIONS: SNOT-20 GAV is the first reliable, validated and sensitive German instrument for measuring health-related QOL in patients with CRS.

[Patients with chronic rhinosinusitis: disease-specific and general health-related quality of life]. / Patienten mit chronischer Rhinosinusitis : Krankheitsspezifische und allgemeine gesundheitsbezogene Lebensqualität.

BACKGROUND: The negative effect of chronic rhinosinusitis on patient quality of life has been generally underappreciated and undervalued. So far, only a few studies have examined health-related quality of life at German language patient collectives with validated measuring instruments. PATIENTS AND METHODS: Preoperatively, 163 patients were included into the study. Three months and 1 year after functional endonasal sinus surgery 123 and 82 patients, respectively, participated in the questioning. To measure health-related quality of life, we used version 20 of the German Adapted Version of the Sinonasal Outcome Test and the Short Form 36 Health Survey (SF-36). The German normative values of the SF-36 were used for analysis. RESULTS: Postoperatively, a significant improvement in health-related quality of life was determined on all scales of both measuring instruments. Comparing our data with the German normative values of the SF-36, we found a lasting approximation of the average assessment levels in seven of eight scales. CONCLUSION: Functional endonasal sinus surgery leads to significant improvements in disease-specific and general quality of life in patients with chronic rhinosinusitis.

Evaluation of co-morbidity indices in patients admitted for chronic obstructive pulmonary disease.

BACKGROUND: There is limited and conflicting information on the use of co-morbidity instruments to predict mortality in patients with chronic obstructive pulmonary disease (COPD). METHODS: We sought to test the validity of the Charlson Index and another co-morbidity instrument, the Adult co-morbidity evaluation 27 (ACE-27), in patients admitted with COPD exacerbations. Co-morbidity scores were obtained by chart review. Information on mortality was retrieved from the Social Security Death Index. We examined the predictive validity of the Charlson and the ACE-27 using survival analysis. RESULTS: There were 112 patients eligible for the study. The ACE-27 but not the Charlson predicted survival, after adjusting for age, gender, and smoking history in Cox regression, hazard ratio (95% CI) of 1.99 (1.17-3.39). CONCLUSIONS: This study confirms earlier findings that the Charlson Index is not a reliable predictor of mortality in patients with COPD. However, the ACE-27 appears to be useful for predicting survival in this study.

Impact of first-line vs second-line antibiotics for the treatment of acute uncomplicated sinusitis.

CONTEXT: Studies suggest little benefit in relief of acute sinusitis symptoms from the use of newer and more expensive (second-line) antibiotics instead of older and less expensive (first-line) antibiotics. However, researchers have failed to include development of complications and cost of care in their analyses. OBJECTIVE: To compare the effectiveness and cost of first-line with second-line antibiotics for the treatment of acute uncomplicated sinusitis in adults. DESIGN, SETTING, AND PATIENTS: Retrospective cohort study using a pharmaceutical database containing demographic, clinical (International Classification of Diseases, Ninth Revision), treatment, and charge information for 29 102 adults with a diagnosis of acute sinusitis receiving initial antibiotic treatment between July 1, 1996, and June 30, 1997. MAIN OUTCOME MEASURES: Absence of additional claim for an antibiotic in the 28 days after the initial antibiotic, presence of a claim for a second antibiotic, serious complications of sinusitis, and direct charges and use for the acute sinusitis treatment. RESULTS: There were 17 different antibiotics prescribed in this study. The majority (59.5%) of patients received 1 of the first-line antibiotics. The overall success rate was 90.4% (95% confidence interval [CI], 90.0%-90.8%). The success rate for the 17 329 patients who received a first-line antibiotic was 90.1% and for the 11 773 patients who received a second-line antibiotic was 90.8%, a difference of 0.7% (95% CI, 0.01%-1.40%; P<.05). There were 2 cases of periorbital cellulitis, one in each treatment group. The average total direct charge for patients receiving a first-line antibiotic was $68.98 and a second-line antibiotic was $135.17, a difference of $66.19 (95% CI, $64.95-$67.43; P<.001). This difference was due entirely to the difference in charge of antibiotics and not other charges, such as professional fees, laboratory tests, or emergency department visits. CONCLUSIONS: Patients treated with a first-line antibiotic for acute uncomplicated sinusitis did not have clinically significant differences in outcomes vs those treated with a second-line antibiotic. However, cost of care was significantly higher for patients treated with a second-line antibiotic.

Chemoradiation for metastatic SCCA: role of comorbidity.

OBJECTIVES: A previous study of 371 patients with extracapsular spread (ECS) of cervical metastases from squamous cell carcinoma (SCCA) of the head and neck revealed a survival advantage for patients treated with adjuvant chemoradiation, compared with those treated with surgery and radiation or surgery alone. While all patients in the study were offered adjuvant chemotherapy, only 35% selected this option. Comorbidity was identified as a reason for declining chemotherapy. Recently, Piccirillo demonstrated that the Modified Medical Comorbidity Index (MMCI) is a valid instrument to classify and quantify severity of comorbidity. We applied this instrument to previously reported patients with ECS to determine 1) how comorbidity affected treatment selection, 2) whether the survival advantage of adjuvant chemoradiation persisted after controlling for comorbidity, and 3) the impact of comorbidity on outcome. STUDY DESIGN: This was a nonrandomized, retrospective study. METHODS: Patients in the initial study underwent resection of the primary tumor and neck dissection. Eligible patients elected to receive chemoradiation, radiation, or no further treatment. Comorbidity scores were assigned according to the MMCI. Data were analyzed according to disease-specific survival and overall survival. RESULTS: The study population consisted of 330 patients. More severe comorbidity was related to higher overall mortality rates after controlling for treatment. Adjuvant chemoradiation resulted in improved disease-specific and overall survival compared with adjuvant radiation after adjusting for severity of comorbidity. CONCLUSIONS: These results substantiate the benefits of adjuvant chemoradiation for patients with SCCA of the head and neck. Furthermore, these results reinforce the importance of comorbidity as a prognostic indicator for this population of patients.

Factors related to outcome of salvage therapy for isolated cervical recurrence of squamous cell carcinoma in the previously treated neck: a multi-institutional study.

OBJECTIVE: The goal was to identify factors associated with the outcome of salvage therapy for patients with isolated cervical recurrences of squamous cell carcinoma in the previously treated neck (ICR-PTN). STUDY DESIGN AND SETTINGS: A tumor registry search for ICR-PTN patients was performed at 7 participating institutions, and the charts were reviewed. Kaplan-Meier plots for survival and time until re-recurrence were used to evaluate the significance of associated variables. RESULTS: Median survival and time until re-recurrence were both 11 months. Survival was better in patients with the following characteristics: nonsurgical initial neck treatment, negative initial disease resection margins, no history of prior recurrence, ipsilateral location of the ICR-PTN relative to the primary, and use of surgical salvage. CONCLUSIONS: By pooling the experience of 7 US tertiary care medical centers, we have identified 5 factors that are associated with outcome of salvage therapy for ICR-PTN. SIGNIFICANCE: Consideration of these factors, as well as the reviewed literature, should facilitate patient selection for salvage protocols.

Student Research Award 1999: comparative contrast of voice measurements.

Currently, a variety of objective and subjective measures are available to describe voice and voice function. Despite these various tools, there is no standard measure of voice function that incorporates both objective and subjective measures. The goal of this research was to study the relationship between objective, subjective, and patient-based measures of voice function. Objective voice function was measured with 4 laboratory-based parameters (subglottic pressure, airflow at the lips, maximum phonation time, and vocal efficiency), subjective function with the GRBAS (grade, rough, breathy, asthenic, strained) scale, and patient-based function according to an overall global rating of quality. The objective and subjective measures were significantly related to each other (P < 0.05); the objective and patient-based measures were also related (P = 0.019), but the subjective and patient-based measures were not related. We demonstrate a significant relationship between some but not all measures of voice function. We believe that subjective measures provide additional valuable information not obtained from objective measures alone.

Importance of comorbidity in head and neck cancer.

OBJECTIVES/HYPOTHESIS: Patients with head and neck cancer are staged according to the morphology of the tumor with little or no attention given to the importance of the other diseases, illnesses, or conditions. These other conditions are generally referred to as comorbidities. Although not a feature of the cancer itself, comorbidity is an important attribute of the patient with cancer. Comorbidity has direct impact on the care of patients, selection of initial treatment, and evaluation of treatment effectiveness. The objective of this thesis is to demonstrate the importance of comorbidity in head and neck cancer. Specifically, the aims are 1) to demonstrate the burden of comorbidity among head and neck cancer patients by comparing the incidence of none, mild, moderate, and severe comorbidity among patients with head and neck cancer to patients with cancers of the colorectum, lung, breast, gynecological sites, or prostate, 2) to demonstrate the independent impact of comorbidity on overall survival, and 3) to demonstrate the importance of comorbidity in the assessment of initial treatment effectiveness. STUDY DESIGN: This was a prospective cohort study of the impact of comorbidity on head and neck cancer patients presenting for treatment between January 1995 and December 1996. METHODS: In 1994, the author trained cancer registrars at an academic teaching hospital to code comorbidity from the medical record of new patients using a standard comorbidity index. Standard statistical techniques, including multivariable analysis, were used to compare and contrast the burden of comorbidity for patients with different cancers. Life survival techniques and multivariable logistic regression analysis were used to assess the independent prognostic impact of comorbidity. Further, the technique of conjunctive consolidation was used to augment the TNM system with comorbidity information, to more completely assess the impact of different initial treatments for patients with head and neck cancers. RESULTS: The cohort consisted of 3,378 patients with cancers of the head and neck (341), colorectum (307), lung (655), breast (483), gynecological sites (482), and prostate (1,110). The percentage of head and neck cancer patients with moderate to severe comorbidity was 21%; this degree of comorbidity burden was second only to patients with lung (40%) and colorectal (25%) cancer. There was a significant relationship between severity of comorbidity and overall survival (log-rank test, chi2 = 15.75; P < .0013). For cancers of the head and neck, lung, breast, and prostate the prognostic significance of comorbidity remained even after controlling for other factors, such as age and TNM stage. CONCLUSIONS: The results of this study show that comorbidity is an important feature of patients with head and neck cancer. Valid instruments exist to measure and classify the overall severity of comorbidity. The scientific evaluation of treatment and the care of patients are impeded by a rigid adherence to a staging system based solely on morphological descriptions of the cancer while ignoring suitable descriptions of the patient. The author believes that the addition of comorbidity information will improve the value of cancer statistics and the care of cancer patients.

Outcomes research and obstructive sleep apnea.

Sleep disorders in general and obstructive sleep apnea syndrome in particular are prevalent health problems. This report describe the methodology and findings from a prospective multicenter outcomes research study on obstructive sleep apnea syndrome that was conducted by the American Academy of Otolaryngology-Head and Neck Surgery. Other outcome measures available for outcomes research in obstructive sleep apnea syndrome are also summarized.

Head and neck squamous cell carcinoma: better to be young.

Most head and neck squamous cell carcinoma patients are elderly, with few younger than 40 years. Controversy exists in the literature regarding outcomes for younger patients. The goal of this research project was to compare baseline features and outcomes for young patients (/=65 years). To investigate the relationship between age and important presenting features and outcomes, 1160 recently diagnosed patients first treated at Washington University between 1980 and 1991 were identified from an existing database. Full 5-year survival information was available for 1030 patients (89%). Overall, the 5-year survival rate was 46% (478/1030); young patients (65%, 26/40) had a significantly better survival rate than middle-aged (52%, 292/566) or old patients (38%, 160/424) (chi(2) = 24.5; P = 0. 001). Survival was also related to smoking, comorbidity, primary site, TNM stage, and nodal disease. Age remained a significant factor even after we controlled for these other factors. Young patients developed fewer recurrent and new primary tumors. We conclude that young patients have a much better overall prognosis than older patients. The reasons for this difference are unclear, but it appears that the impact of age goes beyond an actuarial effect.

Conscious sedation: a new approach for peritonsillar abscess drainage in the pediatric population.

OBJECTIVE: To assess the safety and efficacy of conscious sedation (CS) in children undergoing emergency department incision and drainage (I&D) of peritonsillar abscesses (PTAs). DESIGN: A 33-month retrospective chart review of all children presenting to the emergency department with the diagnosis of a PTA or peritonsillar cellulitis. Children who underwent CS prior to I&D were compared with children without CS for complications and efficacy. SETTING: St Louis Children's Hospital, an academic tertiary care pediatric hospital. PATIENTS: Fifty-two children were enrolled; 30 PTAs were drained with CS in 27 children (3 underwent I&D twice), and 25 PTAs were drained in 25 children without CS. INTERVENTIONS: The CS team included an otolaryngologist, a pediatric emergency department physician, and a registered nurse. A standardized CS protocol assessing vital signs and level of consciousness was employed during each procedure. A combination of midazolam, ketamine hydrochloride, and glycopyrrolate was used in appropriately weighted calculated doses. Patients were assessed for major and minor airway complications. MAIN OUTCOME MEASURES: Airway complications related to CS were reviewed. Patients who underwent I&D with and without CS were compared with regard to purulent drainage. RESULTS: There were no major airway complications in patients undergoing I&D with CS. There was 1 minor complication in this group, oxygen desaturation to 88%, which resolved with stimulation. Of the 55 procedures, 45 (82%) yielded purulence: 29 (97%) of 30 in the CS group and 16 (64%) of 25 in the non-CS group (chi2 = 9.8; P = .002). Of those children undergoing CS, 3 (10%) of 30 were admitted to the hospital from the emergency department as compared with 6 (24%) of 25 without CS (chi2 = 1.95; P = .16). In the CS group, PTAs had a low recurrence rate of 1 (3.3%) of 30 compared with 2 (8%) of 25 in the non-CS group (chi2 = 0.57; P = .45). No one in the CS group required a secondary procedure under general anesthesia. CONCLUSIONS: This preliminary study demonstrates CS to be a potentially safe and efficacious approach to drainage of PTAs in children. Given its efficacy and its associated lower levels of anxiety and pain for the patient, CS seems to be a promising new approach to caring for children with PTAs.

Development of a new staging system for recurrent oral cavity and oropharyngeal squamous cell carcinoma.

BACKGROUND: Approximately 33% of patients with squamous cell carcinoma of the oral cavity and oropharynx develop a recurrence. The management of recurrent tumors can be challenging to both physician and patient, at least in part due to the lack of an accurate and clinically applicable staging system for these patients. The purposes of this study were to examine the survival patterns of patients presenting with recurrent oral cavity and oropharyngeal tumors, to identify key factors affecting prognosis, and to combine these factors to create a new staging system to predict survival and aid in planning therapy. METHODS: The methods included a retrospective chart review of 641 patients with oral cavity and oropharyngeal squamous cell carcinoma who underwent their initial treatment at Washington University between 1980 and 1992. From this population, 249 patients (39%) developed a recurrence. RESULTS: The overall 2-year survival rate was 20% (50 of 249 patients). Six variables affected survival significantly: histologic differentiation, initial (prior to first therapy) TNM stage, initial treatment, time to recurrence, extent of recurrence, and treatment of recurrence. These six variables were entered into a logistic model to determine the individual prognostic significance of each variable. Two variables were found to be statistically significant: initial TNM stage (chi-square test = 7.67; P = 0.0056) and extent of recurrence (chi-square test = 11.75; P = 0.0006). Using the process of conjunctive consolidation, these two variables were combined to create a new staging system for recurrent tumors of the oral cavity and oropharynx. CONCLUSIONS: This staging system provides accurate estimates of prognosis, involves no new technology to implement, demonstrates statistically significant differences in survival by stage, and may aid both the physician and the patient in planning therapy.