Integrated care in patients with atrial fibrillation- a predictive heterogeneous treatment effect analysis of the ALL-IN trial.

INTRODUCTION: Integrated care is effective in reducing all-cause mortality in patients with atrial fibrillation (AF) in primary care, though time and resource intensive. The aim of the current study was to assess whether integrated care should be directed at all AF patients equally. METHODS: The ALL-IN trial (n = 1,240 patients, median age 77 years) was a cluster-randomized trial in which primary care practices were randomized to provide integrated care or usual care to AF patients aged 65 years and older. Integrated care comprised of (i) anticoagulation monitoring, (ii) quarterly checkups and (iii) easy-access consultation with cardiologists. For the current analysis, cox proportional hazard analysis with all clinical variables from the CHA2DS2-VASc score was used to predict all-cause mortality in the ALL-IN trial. Subsequently, the hazard ratio and absolute risk reduction were plotted as a function of this predicted mortality risk to explore treatment heterogeneity. RESULTS: Under usual care, after a median of 2 years follow-up the absolute risk of all-cause mortality in the highest-risk quarter was 31.0%, compared to 4.6% in the lowest-risk quarter. On the relative scale, there was no evidence of treatment heterogeneity (p for interaction = 0.90). However, there was substantial treatment heterogeneity on the absolute scale: risk reduction in the lowest risk- quarter of risk 3.3% (95% CI -0.4% - 7.0) compared to 12.0% (95% CI 2.7% - 22.0) in the highest risk quarter. CONCLUSION: While the relative degree of benefit from integrated AF care is similar in all patients, patients with a high all-cause mortality risk have a greater benefit on an absolute scale and should therefore be prioritized when implementing integrated care.

A Noninferiority Analysis of 3- vs 2-Incision Techniques for Hypoglossal Nerve Stimulator Implantation.

OBJECTIVE: The only hypoglossal nerve stimulation (HNS) device available for US clinical use is implanted through 3 incisions. A recently proposed 2-incision modification moved the respiratory sensing lead from the fifth to the second intercostal space to eliminate the third lower chest incision. This study compared perioperative data and therapeutic outcomes between the techniques. STUDY DESIGN: Noninferiority cohort analysis of a retrospective and prospective registry study. SETTING: Tertiary care and community surgical centers. METHODS: Patients with obstructive sleep apnea underwent HNS implantation via a modified 2-incision technique (I2). A cohort previously implanted via the standard 3-incision technique (I3) were 1:1 propensity score matched for a noninferiority analysis of postoperative outcomes. RESULTS: There were 404 I3 patients and 223 I2 patients across 6 participating centers. Operative time decreased from 128.7 minutes (95% CI, 124.5-132.9) in I3 patients to 86.6 minutes (95% CI, 83.7-97.6) in I2 patients (P < .001). Postoperative sleep study data were available for 76 I2 patients who were matched to I3 patients. The change in apnea-hypopnea index between the cohorts was statistically noninferior (a priori noninferiority margin: 7.5 events/h; mean difference, 1.51 [97.5% CI upper bound, 5.86]). There were no significant differences between the cohorts for baseline characteristics, perioperative adverse event rates, or change in Epworth Sleepiness Score (P > .05). CONCLUSION: In a multicenter registry, a 2-incision implant technique for a commercially available HNS device had a statistically noninferior therapeutic efficacy profile when compared with the standard 3-incision approach. The 2-incision technique is safe and effective for HNS implantation.

Impact of Body Mass Index and Discomfort on Upper Airway Stimulation: ADHERE Registry 2020 Update.

OBJECTIVES/HYPOTHESIS: To provide the ADHERE registry Upper Airway Stimulation (UAS) outcomes update, including analyses grouped by body mass index (BMI) and therapy discomfort. STUDY DESIGN: Prospective observational study. METHODS: ADHERE captures UAS outcomes including apnea-hypopnea index (AHI), Epworth sleepiness scale (ESS), therapy usage, patient satisfaction, clinician assessment, and safety over a 1-year period. BMI ≤32 kg/m2 (BMI32 ) and 32 < BMI ≤35 kg/m2 (BMI35 ) group outcomes were examined. RESULTS: One thousand eight hundred forty-nine patients enrolled in ADHERE, 1,019 reached final visit, 843 completed the visit. Significant changes in AHI (-20.9, P < .0001) and ESS (- 4.4, P < .0001) were demonstrated. Mean therapy usage was 5.6 ± 2.2 hr/day. Significant therapy use difference was present in patients with reported discomfort versus no discomfort (4.9 ± 2.5 vs. 5.7 ± 2.1 hr/day, P = .01). Patients with discomfort had higher final visit mean AHI versus without discomfort (18.9 ± 18.5 vs. 13.5 ± 13.7 events/hr, P = .01). Changes in AHI and ESS were not significantly different. Serious adverse events reported in 2.3% of patients. Device revision rate was 1.9%. Surgical success was less likely in BMI35 versus BMI32 patients (59.8% vs. 72.2%, P = .02). There was a significant therapy use difference: 5.8 ± 2.0 hr/day in BMI32 versus 5.2 ± 2.2 hr/day in BMI35 (P = .028). CONCLUSIONS: Data from ADHERE demonstrate high efficacy rates for UAS. Although surgical response rate differs between BMI32 and BMI35 patient groups, the AHI and ESS reduction is similar. Discomfort affects therapy adherence and efficacy. Thus, proper therapy settings adjustment to ensure comfort is imperative to improve outcomes. LEVEL OF EVIDENCE: 4 Laryngoscope, 131:2616-2624, 2021.

Referral of adults with obstructive sleep apnea for surgical consultation: an American Academy of Sleep Medicine systematic review, meta-analysis, and GRADE assessment.

INTRODUCTION: This systematic review provides supporting evidence for the accompanying clinical practice guideline on the referral of adults with obstructive sleep apnea (OSA) for surgical consultation. METHODS: The American Academy of Sleep Medicine commissioned a task force of experts in sleep medicine. A systematic review was conducted to identify studies that compared the use of upper airway sleep apnea surgery or bariatric surgery to no treatment as well as studies that reported on patient-important and physiologic outcomes pre- and postoperatively. Statistical analyses were performed to determine the clinical significance of using surgery to treat obstructive sleep apnea in adults. Finally, the Grading of Recommendations Assessment, Development and Evaluation (GRADE) process was used to assess the evidence for making recommendations. RESULTS: The literature search resulted in 274 studies that provided data suitable for statistical analyses. The analyses demonstrated that surgery as a rescue therapy results in a clinically significant reduction in excessive sleepiness, snoring, blood pressure (BP), apnea-hypopnea index (AHI), respiratory disturbance index (RDI), and oxygen desaturation index (ODI); an increase in lowest oxygen saturation (LSAT) and sleep quality; and an improvement in quality of life in adults with OSA who are intolerant or unaccepting of positive airway pressure (PAP) therapy. The analyses demonstrated that surgery as an adjunctive therapy results in a clinically significant reduction in optimal PAP pressure and improvement in PAP adherence in adults with OSA who are intolerant or unaccepting of PAP due to side effects associated with high pressure requirements. The analyses also demonstrated that surgery as an initial treatment results in a clinically significant reduction in AHI/RDI, sleepiness, snoring, BP, and ODI and an increase in LSAT in adults with OSA and major anatomical obstruction. Analysis of bariatric surgery data showed a clinically significant reduction in BP, AHI/RDI, sleepiness, snoring, optimal PAP level, BMI, and ODI and an increase in LSAT in adults with OSA and obesity. Analyses of very limited evidence suggested that upper airway surgery does not result in a clinically significant increase in risk of serious persistent adverse events and suggested that bariatric surgery may result in a clinically significant risk of iron malabsorption that may be managed with iron supplements. The task force provided a detailed summary of the evidence along with the quality of evidence, the balance of benefits and harms, patient values and preferences, and resource use considerations. CITATION: Kent D, Stanley J, Aurora RN, et al. Referral of adults with obstructive sleep apnea for surgical consultation: an American Academy of Sleep Medicine systematic review, meta-analysis, and GRADE assessment. J Clin Sleep Med. 2021;17(12):2507-2531.

Improving outcomes of hypoglossal nerve stimulation therapy: current practice, future directions, and research gaps. Proceedings of the 2019 International Sleep Surgery Society Research Forum.

Hypoglossal nerve stimulation (HGNS) has evolved as a novel and effective therapy for patients with moderate-to-severe obstructive sleep apnea. Despite positive published outcomes of HGNS, there exist uncertainties regarding proper patient selection, surgical technique, and the reporting of outcomes and individual factors that impact therapy effectiveness. According to current guidelines, this therapy is indicated for select patients, and recommendations are based on the Stimulation Therapy for Apnea Reduction or STAR trial. Ongoing research and physician experiences continuously improve methods to optimize the therapy. An understanding of the way in which airway anatomy, obstructive sleep apnea phenotypes, individual health status, psychological conditions, and comorbid sleep disorders influence the effectiveness of HGNS is essential to improve outcomes and expand therapy indications. This article presents discussions on current evidence, future directions, and research gaps for HGNS therapy from the 10th International Surgical Sleep Society expert research panel. CITATION: Suurna MV, Jacobowitz O, Chang J, et al. Improving outcomes of hypoglossal nerve stimulation therapy: current practice, future directions and research gaps. Proceedings of the 2019 International Sleep Surgery Society Research Forum. J Clin Sleep Med. 2021;17(12):2477-2487.

Efficacy and Safety of Simultaneous Application of HIFEM and Synchronized Radiofrequency for Abdominal Fat Reduction and Muscle Toning: A Multicenter Magnetic Resonance Imaging Evaluation Study.

BACKGROUND: Radiofrequency and high-Intensity Focused Electromagnetic (HIFEM) field procedure are well-known, stand-alone, body-shaping modalities, yet their simultaneous application has not been investigated. OBJECTIVE: The aim is to evaluate the efficacy of a novel device simultaneously delivering HIFEM and radiofrequency for subcutaneous fat reduction and muscle toning. MATERIALS AND METHODS: Forty-one subjects with an average age of 39.7 ± 11.5 years were recruited. The subjects received 3 abdominal treatments (one per week). Magnetic resonance imaging images of the treated area were evaluated at baseline and at 1-, 3-, and 6-month visits for changes in subcutaneous fat, muscle thickness, and abdominal separation (AS). Anthropometric data and digital photographs were collected. Subject satisfaction and therapy comfort were evaluated. RESULTS: The muscle mass increase peaked at 3 months, showing 26.1% thickening. The fat thickness reduction was most prominent at 3 months, showing a 30.8% reduction. The AS decreased by 18.8% at 3 months after treatment. The waist circumference reduced by 5.87 ± 3.64 cm at a 3-month follow-up. Six-month data showed maintenance of these outcomes. The treatment was considered as comfortable with high patient satisfaction. CONCLUSION: The analysis of magnetic resonance imaging images and waist measurements showed that the therapy combining HIFEM and radiofrequency is highly effective in reducing subcutaneous fat and muscle thickening.

Drug-Induced Sleep Endoscopy and Hypoglossal Nerve Stimulation Outcomes: A Multicenter Cohort Study.

OBJECTIVES/HYPOTHESIS: To determine the association between findings of blinded reviews of preoperative drug-induced sleep endoscopy (DISE) and outcomes of hypoglossal nerve stimulation (HNS) for obstructive sleep apnea (OSA). STUDY DESIGN: Cohort study. METHODS: A retrospective, multicenter cohort study of 343 adults who underwent treatment of OSA with HNS from 10 academic medical centers was performed. Preoperative DISE videos were scored by four blinded reviewers using the VOTE Classification and evaluation of a possible primary structure contributing to airway obstruction. Consensus DISE findings were examined for an association with surgical outcomes based on therapy titration polysomnogram (tPSG). Treatment response was defined by a decrease of ≥50% in the apnea-hypopnea index (AHI) to <15 events/hour. RESULTS: Study participants (76% male, 60.4 ± 11.0 years old) had a body mass index of 29.2 ± 3.6 kg/m2 . AHI decreased (35.6 ± 15.2 to 11.0 ± 14.1 events/hour; P < .001) on the tPSG, with a 72.6% response rate. Complete palate obstruction (vs. none) was associated with the greatest difference in AHI improvement (-26.8 ± 14.9 vs. -19.2 ± 12.8, P = .02). Complete (vs. partial/none) tongue-related obstruction was associated with increased odds of treatment response (78% vs. 68%, P = .043). Complete (vs. partial/none) oropharyngeal lateral wall-related obstruction was associated with lower odds of surgical response (58% vs. 74%, P = .042). CONCLUSIONS: The DISE finding of primary tongue contribution to airway obstruction was associated with better outcomes, whereas the opposite was true for the oropharyngeal lateral walls. This study suggests that the role for DISE in counseling candidates for HNS extends beyond solely for excluding complete concentric collapse related to the velum. LEVEL OF EVIDENCE: 3 Laryngoscope, 131:1676-1682, 2021.

Ultrasound Localization and Percutaneous Electrical Stimulation of the Hypoglossal Nerve and Ansa Cervicalis.

OBJECTIVE: Hypoglossal nerve stimulation for obstructive sleep apnea (OSA) can be effective for appropriately selected patients, but current patient selection criteria are complex and still result in a proportion of nonresponders. Ansa cervicalis stimulation of the infrahyoid cervical strap muscles has recently been proposed as a new form of respiratory neurostimulation (RNS) therapy for OSA treatment. We hypothesized that percutaneous stimulation of both nerves in humans with temporary electrodes would make testing of the physiologic response to different RNS strategies possible. STUDY DESIGN: Nonrandomized acute physiology study. SETTING: Tertiary care hospital. METHODS: Fifteen participants with OSA underwent ultrasonography and placement of percutaneous electrodes proximal to the medial division of the hypoglossal nerve and the branch of the ansa cervicalis innervating the sternothyroid muscle (ACST). Procedural success was documented in each participant, as were any failures or procedural complication. RESULTS: The hypoglossal nerve was successfully localized in 15 of 15 (100%) participants and successfully stimulated in 13 of 15 (86.7%). The ACST was successfully localized in 15 of 15 (100%) participants and successfully stimulated in 14 of 15 (93.3%). Stimulation failure of the hypoglossal nerve was due to suboptimal electrode placement in 1 participant and electrode displacement in the other 2 cases. No complications occurred. CONCLUSIONS: The hypoglossal nerve and ACST can be safely stimulated via percutaneous electrode placement. Larger trials of percutaneous stimulation may help to identify responders to different RNS therapies for OSA with temporary or permanent percutaneous electrodes. Techniques for electrode design, nerve localization, and electrode placement are described.

Ansa Cervicalis Stimulation: A New Direction in Neurostimulation for OSA.

BACKGROUND: Hypoglossal nerve stimulation (HNS) is an alternative treatment option for patients with OSA unable to tolerate positive airway pressure but implant criteria limit treatment candidacy. Previous research indicates that caudal tracheal traction plays an important role in stabilizing upper airway patency. RESEARCH QUESTION: Does contraction of the sternothyroid muscle with ansa cervicalis stimulation (ACS), which pulls the pharynx caudally via thyroid cartilage insertions, increase maximum inspiratory airflow (VImax)? STUDY DESIGN AND METHODS: Hook-wire percutaneous electrodes were used to stimulate the medial branch of the right hypoglossal nerve and right branch of the ansa cervicalis innervating the sternothyroid muscle during propofol sedation. VImax was assessed during flow-limited inspiration with a pneumotachometer. RESULTS: Eight participants with OSA were studied using ACS with and without HNS. Compared with baseline, the mean VImax increase with isolated ACS was 298%, or 473 mL/s (95% CI, 407-539). Isolated HNS increased mean VImax from baseline by 285%, or 260 mL/s (95% CI, 216-303). Adding ACS to HNS during flow-limited inspiration increased mean VImax by 151%, or 205 mL/s (95% CI, 174-236) over isolated HNS. Stimulation was significantly associated with increase in VImax in both experiments (P < .001). INTERPRETATION: ACS independently increased VImax during propofol sedation and drove further increases in VImax when combined with HNS. The branch of the ansa cervicalis innervating the sternothyroid muscle is easily accessed. Confirmation of the ansa cervicalis as a viable neurostimulation target may enable caudal pharyngeal traction as a novel respiratory neurostimulation strategy for treating OSA.

MRI and CT Assessment of Abdominal Tissue Composition in Patients After High-Intensity Focused Electromagnetic Therapy Treatments: One-Year Follow-Up.

BACKGROUND: Several studies investigating high-intensity focused electromagnetic (HIFEM) treatments have recently been published. However, due to the novelty of the procedure, long-term data are still missing. OBJECTIVES: The aim of this study was to evaluate changes in abdominal tissues on average 1 year after a series of HIFEM treatments, to determine the long-term durability of patients' original body responses. METHODS: Magnetic resonance imaging (MRI) or computed tomography (CT) scanning were performed on 21 patients a mean of 332.6 [88.5] days after their original HIFEM treatment series. The scans were evaluated by a blinded radiologist for abdominal muscle thickness, subcutaneous fat changes, and abdominal separation. The results were compared with the MRI/CT-assisted measurements taken at baseline and 6-week follow-up. Correlations between collected data sets were calculated and tested. The incidence of any adverse events related to earlier treatments was monitored. RESULTS: When comparing the 1-year follow-up measurements with the baseline, the MRI/CT-assisted calculations revealed mean reductions of 14.63% (2.97 [2.11] mm) in fat, 19.05% (1.89 [0.88] mm) in muscle thickening, and 10.46% (1.96 [1.71] mm) in diastasis recti. All changes were significant (P < 0.05) and not related to weight fluctuations (P > 0.05). The baseline width of diastasis positively correlated with the degree of improvement at follow-up. No adverse events were reported. CONCLUSION: The HIFEM-induced muscle hypertrophy, fat reduction, and reduction in abdominal separation were maintained 1-year posttreatment. This suggests long-term durability of the original bodily response, which needs to be verified by continuing follow-up of this group and by further studies.

Simultaneous Changes in Abdominal Adipose and Muscle Tissues Following Treatments by High-Intensity Focused Electromagnetic (HIFEM) Technology-Based Device: Computed Tomography Evaluation

Objective: This study investigates the effects of high-intensity focused electromagnetic technology for induction of changes in abdominal muscles and abdominal subcutaneous fat. Methods: 22 male and female subjects (aged 34 to 64, mean BMI, 23.5kg/m2) underwent 8 treatments of the abdomen (2 per week) with a high-intensity focused electromagnetic field device. Subjects were scanned by computed tomography (CT) at baseline and 1 month after the eighth treatment. Sub-umbilical and epi-umbilical slices were used to measure the thickness of subcutaneous fat and abdominal muscles and the abdominal separation. In addition, standardized photographs, weight, and circumference measurements were collected. Results: While comparing baseline to follow-up measurements, CT data showed on average 17.5% (-3.1±1.9mm) reduction in subcutaneous fat and simultaneous 14.8% (+1.5±0.8mm) thickening of the rectus abdominis muscle. Subjects lost on average 3.9±3.1cm in the waist circumference. Most of the waist reduction effect was achieved after the fourth treatment. The width of abdominal separation decreased by 9.5% (-2.0±1.7mm). All results were highly significant (P<0.01) while weight change was insignificant (P<0.05). Digital photographs showed aesthetic improvement in most subjects. The treatments were painless and without adverse events. Conclusion: Results suggest that the investigated device is effective for abdominal body sculpting. This technology produced rectus muscle hypertrophy and a reduction in subcutaneous abdominal fat. Data suggests 4 treatments as the ideal protocol delivering 86% of the observed improvement. J Drugs Dermatol. 2019;18(11):1098-1102.

Randomized, Controlled, Double-Masked, Multicenter, Pilot Study Evaluating Safety and Efficacy of Intranasal Neurostimulation for Dry Eye Disease.

Purpose: We assess the safety and effectiveness of intranasal neurostimulation to promote tear production via the nasolacrimal pathway in subjects with dry eye disease. Methods: A multicenter, randomized, controlled, double-masked pilot study was conducted in adults with dry eye diagnosis and at least one eye with corneal fluorescein staining ≥2 in at least one region or a sum of all regions ≥5 (National Eye Institute grading), basal Schirmer test score ≤10 mm, a cotton-swab stimulated Schirmer score ≥7 mm higher, and an Ocular Surface Disease Index score ≥23. Subjects were randomized to receive active intranasal neurostimulation or sham control intranasal stimulation 4 to 8 times per day. Assessments were scheduled before (unstimulated) and during (stimulated) device application at days 0, 7, 14, 30, and 90. The primary effectiveness endpoint was stimulation-induced change in Schirmer test (with anesthesia) score. Primary safety measure was incidence of device-related adverse events (AEs). Results: Fifty-eight subjects were randomized at nine sites in Australia and New Zealand; 56 completed the 90-day study. Stimulation-induced change in Schirmer score was significantly greater with active intranasal (mean ± SEM, 9.0 ± 2.0) than sham control intranasal stimulation (0.4 ± 0.6; P < 0.001) at day 90. Similar results were observed at days 0, 7, 14, and 30 (P < 0.001). No serious device-related AEs were observed. Mild nosebleed, the most common device-related AE, was reported in five (16.7%) subjects. Conclusions: Intranasal neurostimulation was effective in inducing acute tear production after 90 days of use and generally was well tolerated in subjects with dry eye disease.

Personalized evidence based medicine: predictive approaches to heterogeneous treatment effects.

The use of evidence from clinical trials to support decisions for individual patients is a form of "reference class forecasting": implicit predictions for an individual are made on the basis of outcomes in a reference class of "similar" patients treated with alternative therapies. Evidence based medicine has generally emphasized the broad reference class of patients qualifying for a trial. Yet patients in a trial (and in clinical practice) differ from one another in many ways that can affect the outcome of interest and the potential for benefit. The central goal of personalized medicine, in its various forms, is to narrow the reference class to yield more patient specific effect estimates to support more individualized clinical decision making. This article will review fundamental conceptual problems with the prediction of outcome risk and heterogeneity of treatment effect (HTE), as well as the limitations of conventional (one-variable-at-a-time) subgroup analysis. It will also discuss several regression based approaches to "predictive" heterogeneity of treatment effect analysis, including analyses based on "risk modeling" (such as stratifying trial populations by their risk of the primary outcome or their risk of serious treatment-related harms) and analysis based on "effect modeling" (which incorporates modifiers of relative effect). It will illustrate these approaches with clinical examples and discuss their respective strengths and vulnerabilities.

Bone Marrow-Derived Cell Recruitment to the Neurosensory Retina and Retinal Pigment Epithelial Cell Layer Following Subthreshold Retinal Phototherapy.

Purpose: We investigated whether subthreshold retinal phototherapy (SRPT) was associated with recruitment of bone marrow (BM)-derived cells to the neurosensory retina (NSR) and RPE layer. Methods: GFP chimeric mice and wild-type (WT) mice were subjected to SRPT using a slit-lamp infrared laser. Duty cycles of 5%, 10%, 15%, and 20% (0.1 seconds, 250 mW, spot size 50 µm) with 30 applications were placed 50 to 100 µm from the optic disc. In adoptive transfer studies, GFP+ cells were given intravenously immediately after WT mice received SRPT. Immunohistochemistry was done for ionized calcium-binding adapter molecule-1 (IBA-1+), CD45, Griffonia simplicifolia lectin isolectin B4, GFP or cytokeratin). Expression of Ccl2, Il1b, Il6, Hspa1a, Hsp90aa1, Cryab, Hif1a, Cxcl12, and Cxcr4 mRNA and flow cytometry of the NSR and RPE-choroid were performed. Results: Within 12 to 24 hours of SRPT, monocytes were detected in the NSR and RPE-choroid. Detection of reparative progenitors in the RPE occurred at 2 weeks using flow cytometry. Recruitment of GFP+ cells to the RPE layer occurred in a duty cycle-dependent manner in chimeric mice and in mice undergoing adoptive transfer. Hspa1a, Hsp90aa1, and Cryab mRNAs increased in the NSR at 2 hours post laser; Hif1a, Cxcl12, Hspa1a increased at 4 hours in the RPE-choroid; and Ccl2, Il1b, Ifng, and Il6 increased at 12 to 24 hours in the RPE-choroid. Conclusions: SRPT induces monocyte recruitment to the RPE followed by hematopoietic progenitor cell homing at 2 weeks. Recruitment occurs in a duty cycle-dependent manner and potentially could contribute to the therapeutic efficacy of SRPT.

Upper Airway Stimulation for OSA: Early Adherence and Outcome Results of One Center.

OBJECTIVE: To review outcome measures and objective adherence data for patients treated with hypoglossal nerve stimulation (HNS) therapy for moderate to severe obstructive sleep apnea (OSA). STUDY DESIGN: Case series with chart review. SETTING: Academic sleep medicine center. SUBJECTS AND METHODS: The first 20 implanted patients to complete postoperative sleep laboratory testing were assessed. All patients had moderate to severe OSA, were unable to adhere to positive pressure therapy, and met previously published inclusion criteria for the commercially available implantable HNS system. Data included demographics, body mass index (BMI), apnea-hypopnea index (AHI), Epworth Sleepiness Score (ESS), nightly hours of device usage, and procedure- and therapy-related complications. RESULTS: Mean age was 64.8 ± 12.0 years, with 50% female. Mean BMI was unchanged postoperatively (26.5 ± 4.2 to 26.8 ± 4.5 kg/m(2); P > .05). Mean AHI (33.3 ± 13.0 to 5.1 ± 4.3; P < .0001) and mean ESS (10.3 ± 5.2 to 6.0 ± 4.4; P < .01) decreased significantly. Seventy percent (14/20) of patients achieved a treatment AHI <5, 85% (17/20) an AHI <10, and 95% (19/20) an AHI <15. Average stimulation amplitude was 1.89 ± 0.50 V after titration. Adherence monitoring via device interrogation showed high rates of voluntary device use (mean 7.0 ± 2.2 h/night). CONCLUSION: For a clinical and anatomical subset of patients with OSA, HNS therapy is associated with good objective adherence, low morbidity, and improved OSA outcome measures. Early results at one institution suggest that HNS therapy can be implemented successfully into routine clinical practice, outside of a trial setting.

Comparative effectiveness of pharmacologic interventions for knee osteoarthritis: a systematic review and network meta-analysis.

BACKGROUND: The relative efficacy of available treatments of knee osteoarthritis (OA) must be determined for rational treatment algorithms to be formulated. PURPOSE: To examine the efficacy of treatments of primary knee OA using a network meta-analysis design, which estimates relative effects of all treatments against each other. DATA SOURCES: MEDLINE, EMBASE, Web of Science, Google Scholar, Cochrane Central Register of Controlled Trials from inception through 15 August 2014, and unpublished data. STUDY SELECTION: Randomized trials of adults with knee OA comparing 2 or more of the following: acetaminophen, diclofenac, ibuprofen, naproxen, celecoxib, intra-articular (IA) corticosteroids, IA hyaluronic acid, oral placebo, and IA placebo. DATA EXTRACTION: Two reviewers independently abstracted study data and assessed study quality. Standardized mean differences were calculated for pain, function, and stiffness at 3-month follow-up. DATA SYNTHESIS: Network meta-analysis was performed using a Bayesian random-effects model; 137 studies comprising 33,243 participants were identified. For pain, all interventions significantly outperformed oral placebo, with effect sizes from 0.63 (95% credible interval [CrI], 0.39 to 0.88) for the most efficacious treatment (hyaluronic acid) to 0.18 (CrI, 0.04 to 0.33) for the least efficacious treatment (acetaminophen). For function, all interventions except IA corticosteroids were significantly superior to oral placebo. For stiffness, most of the treatments did not significantly differ from one another. LIMITATION: Lack of long-term data, inadequate reporting of safety data, possible publication bias, and few head-to-head comparisons. CONCLUSION: This method allowed comparison of common treatments of knee OA according to their relative efficacy. Intra-articular treatments were superior to nonsteroidal anti-inflammatory drugs, possibly because of the integrated IA placebo effect. Small but robust differences were observed between active treatments. All treatments except acetaminophen showed clinically significant improvement from baseline pain. This information, along with the safety profiles and relative costs of included treatments, will be helpful for individualized patient care decisions. PRIMARY FUNDING SOURCE: Agency for Healthcare Research and Quality.