The therapeutic monoclonal antibody market.

Since the commercialization of the first therapeutic monoclonal antibody product in 1986, this class of biopharmaceutical products has grown significantly so that, as of November 10, 2014, forty-seven monoclonal antibody products have been approved in the US or Europe for the treatment of a variety of diseases, and many of these products have also been approved for other global markets. At the current approval rate of ∼ four new products per year, ∼ 70 monoclonal antibody products will be on the market by 2020, and combined world-wide sales will be nearly $125 billion.

The impact of balloon catheter dilation on frequency of sinus surgery in the United States.

PURPOSE: Endoscopic sinus surgery for patients with chronic rhinosinusitis (CRS) unresponsive to medical therapy has traditionally been performed under general anesthesia and in the operating room. Balloons for catheter dilation of paranasal sinuses were introduced in 2005, allowing sinus surgery to be safely performed either in the operating room or the office care setting, under local anesthesia. This change in care setting has raised concerns of overuse or expanded indications for sinus surgery. This study was thus designed to evaluate changes in surgical volumes in the United States, for the period 2006-2011, and to evaluate the impact of the sinus balloons on surgical practice. METHODS: The MarketScan(®) Commercial Claims and Encounter Database was queried for the period 2006 to 2011 using CRS International Classification of Diseases, Ninth Revision codes (473.X) and sinus surgery US-based Common Procedural Terminology (CPT) codes (endoscopic sinus surgery: CPT codes 31254-31294 and 31299; balloon catheter dilation: CPT codes 31295-31297). MarketScan's projection methodology was applied to estimate the nationwide prevalence of CRS and the incidence of sinus surgery. Procedural case mix and total average payment per surgery were analyzed. RESULTS: From 2006 to 2011, the yearly prevalence of CRS and sinus surgery volume remained flat with ~430 patients with CRS per 100,000 in the employer-sponsored insured population, of which ~117/100,000 underwent surgery. In 2006, 2.69 paranasal sinuses (95% confidence interval [95% CI]: 2.65-2.71) were treated during each individual sinus surgery, with an additional 1.11 nasal procedures (95% CI: 1.08-1.13) performed concurrently. By 2011, the procedural case mix had expanded to 2.90 sinus (95% CI: 2.87-2.93) and 1.16 nasal procedures (95% CI: 1.14-1.85) per surgery. Payments increased from $7,011.06 (α=$6,378.30; ß=3.1490) in 2006 to $9,090.11 (α=$8,350.20; ß=2.9535) in 2011, in line with US medical inflation. CONCLUSION: In the study population, approximately 1 in 3.7 patients diagnosed with CRS underwent sinus surgery. This ratio remained constant from 2006 to 2011. There was no evidence that the number of distinct sinus surgeries per 100,000 people increased despite the introduction and utilization of balloon catheter dilation tools that enabled migration of sinus surgery to the office.

Surgeon radiation exposure in ESS with balloon catheters.

OBJECTIVE: Less invasive instruments such as balloon catheters are available for sino-ostial dilation during endoscopic sinus surgery (ESS). Currently, balloon catheter position is confirmed under fluoroscopic visualization. Radiation exposure has been an area of concern. This study was initiated to determine surgeon radiation exposure when fluoroscopy is used during ESS with balloon catheters. STUDY DESIGN: A multi-center, prospective evaluation of surgeon radiation exposure was conducted. SUBJECTS AND METHODS: For three months, 14 sinus surgeons wore dosimeters to record radiation exposure while using C-arm fluoroscopy during balloon catheter-aided sinus surgery. One dosimeter was placed at collar level (chest), outside the lead apron and another dosimeter was placed on a finger (extremity). These dosimeters were sent for readings. Deep, eye, and shallow radiation dose for each surgeon was calculated. RESULTS: Thirteen chest badges recorded annualized averages of 191.08, 193.54, and 187.69 mrems for deep, eye, and shallow exposure respectively. Eleven ring badges recorded 584.00 mrems. CONCLUSIONS: A recent publication reported low levels of surgeon radiation exposure during ESS with balloon catheters. This study validates radiation exposure among experienced surgeons is well below the annual occupational radiation exposure limit of 50,000 mrem. With vigilant technique and education, fluoroscopy reliance can be minimized.

Balloon catheter sinusotomy: one-year follow-up--outcomes and role in functional endoscopic sinus surgery.

OBJECTIVE: The primary objective was to assess the long-term effectiveness of balloon catheter sinusotomy. METHODS: Patients who had sinus ostia dilated with balloon catheters were prospectively evaluated 1 year after surgery with nasal endoscopy, a CT scan, and the Sino-Nasal Outcome Test (SNOT-20). RESULTS: Sixty-six patients (202 sinuses) were examined. One hundred seventy-two of 202 sinus ostia (85%) were endoscopically patent, 1 percent (2/202) were nonpatent, and ostial patency could not be determined by endoscopy in 28 of 202 (14%). In these "indeterminate" sinuses, the CT scans were normal in 13, implying functional patency in 91.6 percent of sinuses (185/202). Sinus CT scan scores were 1.95 at 1 year versus 8.89 at baseline (P < 0.001), and 1-year SNOT-20 scores (0.91) were significantly improved from baseline (2.14, P < 0.0001). CONCLUSION: Balloon catheter sinusotomy results were durable over the study period, showing long-term effectiveness.

Long-term outcome analysis of balloon catheter sinusotomy: two-year follow-up.

OBJECTIVE: Assess two-year postoperative clinical outcomes for patients receiving balloon catheter sinusotomy. METHODS: Patients who had sinus ostia dilated with balloon catheters were prospectively evaluated two years after surgery by Sinonasal Outcome Test (SNOT-20) and computed tomographic (CT) scan. RESULTS: Sixty-five patients (195 ballooned sinuses) were followed for two years after surgery, including 34 "balloon-only" patients and 31 "hybrid" patients. SNOT-20 symptom scores were significantly improved from baseline (0.87 vs 2.17 baseline, P < 0.001) and stable compared to six months and one year; this was the case for both balloon-only (1.09 vs 2.09, P < 0.001) and hybrid (0.64 vs 2.26, P < 0.001) patients. Lund-MacKay CT scores were significantly improved from baseline (2.69 vs 9.66, P < 0.001) and stable compared to one year, confirmed for both balloon-only (1.75 vs 5.67, P < 0.015) and hybrid (3.25 vs 12.05, P < 0.001) subsets of patients. A total of 85% of patients reported improvement of their sinus symptoms, with 15% same and 0% worsened. Revision treatment was required in seven of 195 sinuses (3.6%) in six of 65 patients (9.2%). CONCLUSION: Patients who receive balloon catheter sinusotomy in endoscopic sinus surgery have significant improvement in symptoms two years after surgery. Radiographic evidence also confirms resolution of disease after two years. This demonstrates durability of clinical results previously reported at 24 weeks and one year after surgery.

Multicenter registry of balloon catheter sinusotomy outcomes for 1,036 patients.

OBJECTIVES: This study assesses the safety and effectiveness of balloon catheters used as instruments in sinus surgery in a "real-world" multicenter registry of 1,036 patients across 27 US otolaryngology practices. METHODS: Data were collected by standardized chart review with centralized database administration for all consecutive functional endoscopic sinus surgeries that included the use of balloon catheters across the 18-month time period from December 2005 to May 2007. RESULTS: Balloon catheters were used in 3,276 peripheral (maxillary, frontal, and sphenoid) sinuses, for an average of 3.2 sinuses per patient. There were no major adverse events related to the use of balloon catheter instruments. The revision rate was 1.3% of sinuses treated with a balloon catheter after an average follow-up of 40.2 weeks. Sinus symptoms were improved in 95.2%, unchanged in 3.8%, and worse in 1.0% of patients. Postoperative sinus infections were significantly less frequent and less severe compared to infections before surgery. The results were consistent across all patient categories, including balloon-only patients and revision patients. CONCLUSIONS: Use of balloon catheters as instruments in sinus surgery appears to be relatively safe and effective and to improve the patient's quality of life. The results are consistent and generalizable across a wide range of sinusitis patients and physician practices. The complication rates, revision rates, and patient symptom improvement rates all compare favorably with previously reported results of functional endoscopic sinus surgery.

Chronic daily headache: when to suspect sinus disease.

Migraine may be responsible for many headaches thought to be caused by the sinuses. Patients complaining of "sinus headache" must have a complete ear, nose, and throat examination. Occasionally, chronic headaches may arise from the sinuses; a thorough history is important to search for symptoms of facial pain and pressure along with other nasal sinus symptoms.

Extended follow-up of palatal implants for OSA treatment.

OBJECTIVE: Evaluate long-term safety and outcomes of palatal implants for patients with mild to moderate obstructive sleep apnea (OSA). STUDY DESIGN AND SETTING: Continuation of a prospective case series of patients with palatal implants. Polysomnography, daytime sleepiness, and snoring intensity were measured at baseline, 90 days, and extended follow-up. RESULTS: Twenty-two (42%) patients from the previous study were followed for a median of 435.5 days. Thirteen were classified as responders, based on their 90-day evaluation. 76.9% of initial responders maintained improvements in apnea-hypopnea index (AHI), daytime sleepiness, and snoring at extended follow-up. Nine patients were initial nonresponders for AHI and daytime sleepiness and remained unchanged at extended follow-up. However, snoring for these nine patients initially improved, and the improvement continued through extended follow-up. CONCLUSION: Initial response or nonresponse to palatal implants remains stable over an extended period. The generalizability of these results is unknown because of significant loss to follow-up. SIGNIFICANCE: Study results report safety and beneficial long-term outcomes of palatal implants for mild to moderate OSA treatment in selected patients.

Safety and outcomes of balloon catheter sinusotomy: a multicenter 24-week analysis in 115 patients.

OBJECTIVE: The aim of this study was to further evaluate the safety and effectiveness of balloon catheter devices to dilate obstructed sinus ostia/perform sinusotomy. METHODS: Through a prospective, multicenter evaluation, safety was assessed by rate of adverse events, patency was determined by endoscopic examination, and sinus symptoms were determined by the Sino-Nasal Outcome Test (SNOT 20). RESULTS: At the conclusion of the 24-week analysis, endoscopy determined that the sinusotomy was patent in 80.5% (247 of 307) sinuses and nonpatent in 1.6% (5 of 307), and could not determine ostial patency status in 17.9% (55 of 307). Of the ostia visualized on endoscopy, 98% were patent (247 of 252), while 2% (5 of 252) were considered nonpatent. SNOT 20 scores showed consistent symptomatic improvement over baseline. Revision treatment was required in 3 sinuses (3 of 307 sinuses, 0.98%) in 3 patients (3 of 109 patients, 2.75%). CONCLUSION: Balloon catheter technology appears safe and effective in relieving ostial obstruction. Patients were pleased and indicated that they experienced symptomatic improvement.

Palatal implants: a new approach for the treatment of obstructive sleep apnea.

OBJECTIVE: To evaluate the short-term safety and efficacy of palatal implants in patients with mild and moderate obstructive sleep apnea (OSA). STUDY DESIGN AND SETTING: A prospective, non-randomized study conducted at 5 clinical sites. Three polyester implants were placed in the soft palate under local anesthesia during a single-stage office procedure. Polysomnography was conducted at baseline and 90 days post-procedure. Subjective quality of life data were collected. RESULTS: Fifty-three patients were evaluated; the apnea hypopnea index (AHI) decreased from 25.0 +/- 13.9 to 22.0 +/- 14.8 events/hour (P = 0.05). The Epworth Sleepiness Scale (ESS) decreased from 11.0 +/- 5.1 to 6.9 +/- 4.5 (P < 0.001), and the snore score decreased from 7.9 +/- 2.1 to 4.0 +/- 3.0 (P < 0.001). No serious complications occurred during the study. CONCLUSION: Palatal implants can be an effective initial low morbidity treatment option for patients diagnosed with mild to moderate OSA.

Endonasal laser surgery: an update.

Although surgical lasers were introduced more than 30 years ago,their use and popularity in nasal and sinus disease have been limited. Even so, there are many practitioners who find the laser a valuable surgical tool for nasal and sinus disease, either alone or in combination with other treatment modalities. Those who do not use lasers probably do not because of a lack of skill, knowledge,or understanding of the role and availability of the technology. This article reviews the history and current role of lasers in nasal and sinus surgery.

An otolaryngology, neurology, allergy, and primary care consensus on diagnosis and treatment of sinus headache.

While "sinus" headache is a widely accepted clinical diagnosis, many medical specialists consider it to be an uncommon cause of recurrent headaches. Unnecessary diagnostic studies, surgical interventions, and medical treatments are often the result of the inappropriate diagnosis of sinus headache. Both the International Headache Society and the American Academy of Otolaryngology-Head and Neck Surgery have attempted to characterize conditions leading to headaches of rhinogenic origin. However, they have done so from different perspectives and in isolation from the other specialty groups. An interdisciplinary ad hoc committee recently convened to discuss the role of sinus disease and the nose in the etiology of headache and to review recent epidemiologic studies suggesting that sinus headache (headache of rhinogenic origin) and migraine are frequently confused with one another. Clinical trial data are presented which clearly indicate that the majority of sinus headaches can actually be classified as migraines. This committee reviewed scientific evidence available from multiple disciplines and concludes that considerable research and clinical study are needed to further understand and explain the role of nasal pathology and autonomic activation in migraine and headaches of rhinogenic origin. However, there was a consensus from this group that greater diagnostic and therapeutic attention needs to be given to patients complaining of sinus headache that may indeed be due to the nose.

Sinus headache: a neurology, otolaryngology, allergy, and primary care consensus on diagnosis and treatment.

Sinus headache is a widely accepted clinical diagnosis, although many medical specialists consider it an uncommon cause of recurrent headaches. The inappropriate diagnosis of sinus headache can lead to unnecessary diagnostic studies, surgical interventions, and medical treatments. Both the International Headache Society and the American Academy of Otolaryngology-Head and Neck Surgery have attempted to define conditions that lead to headaches of rhinogenic origin but have done so from different perspectives and in isolation of each other. An interdisciplinary ad hoc committee convened to discuss the role of sinus disease as a cause of headache and to review recent epidemiological studies that suggest sinus headache (headache of rhinogenic origin) and migraine are frequently confused with one another. This committee reviewed available scientific evidence from multiple disciplines and concluded that considerable research and clinical study are required to further understand and delineate the role of nasal pathology and autonomic activation in migraine and headaches of rhinogenic origin. However, this group agreed that greater diagnostic and therapeutic attention needs to be given to patients with sinus headaches.

New testosterone buccal system (Striant) delivers physiological testosterone levels: pharmacokinetics study in hypogonadal men.

A new mucoadhesive testosterone buccal system (Striant), 30 mg testosterone (T), was applied twice daily in 82 hypogonadal men for 3 months. Serum T, free T, and 5alpha-dihydrotestosterone were measured during this period. T pharmacokinetics were determined from the data obtained during a 24-h sampling at wk 12. Physiological mean serum T concentrations were steady and consistently maintained. The mean percentage of time over a 24-h period that total serum T concentrations were above the lower limit of adult male range was 80.1%. During treatment, mean serum 5alpha-dihydrotestosterone, free T, and estradiol concentrations paralleled serum T. T pharmacokinetics were not significantly affected by body mass index, age, food or beverage, gum abnormalities, or medications known to cause dry mouth. Gum-related adverse events occurred in 16.3% of subjects. Except for three subjects, the gum adverse effects occurred early during treatment, did not cause interruption of treatment, and resolved rapidly and completely. The T buccal system is a novel T formulation that offers a safe, effective, and convenient alternative to existing formulations for physiological T replacement therapy in hypogonadal men.