Bilateral Alar Hanging Correction with Modified Arrow Tip Technique: 4 Years Experience.

Prognostic Value of Resting Heart Rate in a Broad Population of Patients With Stable Coronary Artery Disease: Prospective Single-Center Cohort Study

This study had two main objectives: 1. To enable patients with amyotrophic lateral sclerosis (ALS) who had not participated in previous riluzole trials to receive riluzole therapy, and 2. To expand safety experience with the drug in a broad patient population. This was a Phase IIIb multicentre, multinational, open-label, uncontrolled single treatment study of riluzole. Patients with diagnosed possible or probable ALS were administered 100 mg of riluzole/day (50 mg b.i.d.). Clinical and laboratory adverse events were recorded every month for the first 3 months and thereafter at 3-monthly intervals. 8383 patients from 44 countries were entered into the study; 7916 of these patients with recorded data were administered the study drug. The mean duration of riluzole treatment was 202.1 days, with a range of 1-630 days. The most frequently reported serious and non-serious adverse events were common symptoms of ALS (respiratory symptoms and dysphagia), and only 1.9% of serious adverse events were considered to be related to the study drug. The safety results with this broad population (over 10% of the estimated ALS population worldwide) were consistent with those previously reported from placebo-controlled trials. No increase in adverse events and no unexpected adverse events were observed.

Treatment of infraorbital dark circles and under-eye puffiness is challenging due to its multifactorial nature and lack of broadly applicable, effective treatments. A daily skincare treatment option that is multimodal, effective, and tolerable across a broad patient population is an unmet need. A multicorrective topical eye cream (MTEC) formulated with Tetrahexyldecyl (THD) ascorbate (vitamin C), prebiotic Inula Helenium, bioavailable peptides, botanical extracts, chrysin, and caffeine is hypothesized to improve the appearance of infraorbital dark circles and under-eye puffiness by targeting microvasculature congestion and permeability, melanin accumulation and hemoglobin degradation-related pigmentation, and skin health. An IRB approved, open-label, 12-week clinical study set out to evaluate the efficacy and tolerability of the MTEC across a broad patient population including varying ethnicities and Fitzpatrick Skin Types (FST). Female subjects (n = 40) ages 35-60 years old, with moderate-to-severe under-eye dark circles, moderate under-eye puffiness, and mild-to-moderate fine lines were enrolled into the study. Objective (Chromameter, VISIA® imaging, and Laser Doppler) and subjective assessments (clinical grading and self-assessment questionnaire) were conducted at baseline and post-baseline timepoints. Thirty-seven subjects completed the study, and the MTEC efficaciously demonstrated short-term and long-term improvements in objective and subjective assessments across a broad patient population. Specifically, the MTEC demonstrated significant improvement of infraorbital dark circles, mainly by the reduction in microvasculature congestion and permeability, melanin, and hemoglobin degradation-related pigmentation. Topical application of the MTEC may offer an effective and tolerable treatment option for infraorbital dark circles and puffiness.

The objective of the study is to assess effectiveness and safety of minimally invasive lumbar interbody fusion (MILIF) for degenerative lumbar disorders (DLD) in daily surgical practice and follow up with patients for one year after surgery.A prospective, multicenter, pragmatic, monitored, international outcome study in patients with DLD causing back/leg pain was conducted (19 centers). Two hundred fifty-two patients received standard of care available in the centers. Patients were included if they were aged >18 years, required one- or two-level lumbar fusion for DLD, and met the criteria for approved device indications. Primary endpoints: time to first ambulation (TFA) and time to surgery recovery (TSR). Secondary endpoints: patient-reported outcomes (PROs)--back and leg pain (visual analog scale), disability (Oswestry Disability Index (ODI)), health status (EQ-5D), fusion rates, reoperation rates, change in pain medication, rehabilitation, return to work, patient satisfaction, and adverse events (AEs). Experienced surgeons (≥30 surgeries pre-study) treated patients with DLD by one- or two-level MILIF and patients were evaluated for one year (NCT01143324).At one year, 92% (233/252) of patients remained in the study. Primary outcomes: TFA, 1.3 ±0.5 days and TSR, 3.2 ±2.0 days. Secondary outcomes: Most patients (83.3%) received one level MILIF; one (two-level) MILIF mean surgery duration, 128 (182) min; fluoroscopy time, 115 (154) sec; blood loss, 164 (233) mL; at one year statistically significant (P<.0001) and clinically meaningful changes from baseline were reported in all PROs--reduced back pain (2.9 ±2.5 vs. 6.2 ±2.3 at intake), reduced leg pain (2.2 ±2.6 vs. 5.9 ±2.8), and ODI (22.4% ± 18.6 vs. 45.3% ± 15.3), as well as health-related quality of life (EQ-5D index: 0.71 ±0.28 vs. 0.34 ±0.32). More of the professional workers were working at one year than those prior to surgery (70.3% vs. 55.2%). Three AEs and one serious AE were considered procedure-related; there were no deep site infections or deaths.This is the first study evaluating MILIF for treatment of DLD in daily clinical practice. Clinically significant improvements were observed in all endpoints. Short-term post-surgery improvements (four weeks) were maintained through one year with minimal complications. Our results suggest that MILIF has good-to-excellent outcomes for the treatment of DLD in a broad patient population under different clinical conditions and healthcare delivery systems.

A Head-to-Head Comparison of the Safety and Efficacy of Ferumoxytol to Iron Sucrose for the Treatment of Iron Deficiency Anemia

ABSTRACTObjective: To evaluate intraocular pressure (IOP)-lowering efficacy, tolerability, and safety of the fixed combination of bimatoprost 0.03% and timolol 0.5% (Ganfort) among German patients.† Ganfort is a registered tradename of Allergan, Inc., Irvine, CA, USAMethods: Multicenter, observational, open-label study of patients with primary open angle glaucoma or ocular hypertension (n = 606). As determined by participating physicians, patients had insufficient IOP control and required a medication change. They were switched to once-daily fixed-combination bimatoprost/timolol with no wash-out period. IOP was recorded at treated baseline, 4–6 weeks and 12 weeks after switching. Tolerability was measured using a 4-step scale (excellent, good, moderate, poor) and all adverse events were recorded.Results: A total of 405 patients switched from monotherapy, 97 switched from other fixed combinations, and 104 switched from non-fixed combinations. Among all patients, 32.5% had used prostaglandin analog (PGA) monotherapy, 8.7% had been using a fixed combination that included a PGA, and 6.9% had been using an adjunctive combination of a PGA and a β-blocker. Mean treated baseline IOP (±SD) for all patients was 20.7 ± 3.5 mmHg. Overall, changing medication to fixed-combination bimatoprost/timolol lowered IOP to 16.6 ± 2.7 mmHg (p < 0.001 vs. baseline) after 4–6 weeks and to 16.1 ± 2.6 mmHg (p < 0.001) after 12 weeks; reductions of 19.8% and 22.2%, respectively. Combined bimatoprost/timolol provided an additional IOP reduction versus baseline in most subgroups based on prior treatment. At week 12, patients who had previously used a β-blocker achieved an additional 25.8% decrease from baseline and IOP was reduced by 22.6% in former PGA monotherapy patients. At week 12, 84.6% of all eyes reached a target pressure less than or equal to 18 mmHg. Tolerability of bimatoprost/timolol was rated excellent or good by the physicians for 98.7% of patients and by 96.7% of the patients themselves. Few adverse events occurred during the treatment period.Conclusions: Although this study was limited by its observational design, our results show that the fixed combination of bimatoprost 0.03%/timolol 0.5% was effective, well tolerated, and safe in a broad patient population.

It is widely known that the optimization of imaging systems based on objective, task-based measures of image quality via computer-simulation requires the use of a stochastic object model (SOM). However, the development of computationally tractable SOMs that can accurately model the statistical variations in human anatomy within a specified ensemble of patients remains a challenging task. Previously reported numerical anatomic models lack the ability to accurately model inter-patient and inter-organ variations in human anatomy among a broad patient population, mainly because they are established on image data corresponding to a few of patients and individual anatomic organs. This may introduce phantom-specific bias into computer-simulation studies, where the study result is heavily dependent on which phantom is used. In certain applications, however, databases of high-quality volumetric images and organ contours are available that can facilitate this SOM development. In this work, a novel and tractable methodology for learning a SOM and generating numerical phantoms from a set of volumetric training images is developed. The proposed methodology learns geometric attribute distributions (GAD) of human anatomic organs from a broad patient population, which characterize both centroid relationships between neighboring organs and anatomic shape similarity of individual organs among patients. By randomly sampling the learned centroid and shape GADs with the constraints of the respective principal attribute variations learned from the training data, an ensemble of stochastic objects can be created. The randomness in organ shape and position reflects the learned variability of human anatomy. To demonstrate the methodology, a SOM of an adult male pelvis is computed and examples of corresponding numerical phantoms are created.

Comparison of ticagrelor, the first reversible oral P2Y 12 receptor antagonist, with clopidogrel in patients with acute coronary syndromes: Rationale, design, and baseline characteristics of the PLATelet inhibition and patient Outcomes (PLATO) trial

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Eosinophilic Esophagitis: A Prevalent Disease in the United States That Affects All Age Groups

To determine whether carotid stenting with embolic protection is equivalent to carotid endarterectomy (CEA) in a broad risk population of patients with symptomatic and asymptomatic carotid stenosis. A prospective, multicenter Phase I trial was conducted comparing standard CEA to carotid stenting systems (CSS) in patients with symptomatic (> or =50%) and asymptomatic (> or =75%) carotid stenosis. Patients were enrolled using selection criteria reflective of broad clinical practice. The enrollment ratio at each clinical site was designed to be 2:1 (CEA to CSS) to achieve a planned enrollment of 450 patients: 300 in the CEA arm and 150 in the CSS cohort, which would ensure adequate precision with a coefficient of variation < or =0.35. The primary endpoint for comparison was 30-day all-cause mortality and nonfatal stroke. Between April 2001 and December 2002, 14 clinical sites enrolled 439 patients, of which 397 (247 men; mean age 71 years, range 44-89) were treated: 254 with CEA and 143 patients with CSS (ratio 1.8 to 1.0). More than 90% of patients had >75% stenosis; approximately 68% of patients were asymptomatic. There were no significant differences in baseline patient characteristics between the treatment groups with the exception of a more frequent history of prior CEA (30% CSS versus 11% for CEA, p<0.0001) and prior carotid stent placement in the CSS group (6% versus 0% for CEA, p=0.0002). There was no significant difference in the 30-day combined all-cause mortality and stroke rate by Kaplan-Meier estimate between CEA (2%) and CSS (2%). There was no significant difference in the secondary endpoint of combined 30-day all-cause mortality, stroke, and myocardial infarction between CEA (3%) and CSS (2%). This study suggests that the 30-day risk of stroke or death following carotid stenting with cerebral protection is equivalent to standard carotid endarterectomy in a broad risk population of patients with carotid stenosis.

l Purpose: To determine whether carotid stenting with embolic protection is equivalent to carotid endarterectomy (CEA) in a broad risk population of patients with symptomatic and asymptomatic carotid stenosis. Methods: A prospective, multicenter Phase I trial was conducted comparing standard CEA to carotid stenting systems (CSS) in patients with symptomatic ($50%) and asymptomatic ($75%) carotid stenosis. Patients were enrolled using selection criteria reflective of broad clinical practice. The enrollment ratio at each clinical site was designed to be 2:1 (CEA to CSS) to achieve a planned enrollment of 450 patients: 300 in the CEA arm and 150 in the CSS cohort, which would ensure adequate precision with a coefficient of variation #0.35. The primary endpoint for comparison was 30-day all-cause mortality and nonfatal stroke. Results: Between April 2001 and December 2002, 14 clinical sites enrolled 439 patients, of which 397 (247 men; mean age 71 years, range 44-89) were treated: 254 with CEA and 143 patients with CSS (ratio 1.8 to 1.0). More than 90% of patients had .75% stenosis; ;68% of patients were asymptomatic. There were no significant differences in baseline patient characteristics between the treatment groups with the exception of a more frequent history of prior CEA (30% CSS versus 11% for CEA, p,0.0001) and prior carotid stent placement in the CSS group (6% versus 0% for CEA, p50.0002). There was no significant difference in the 30-day combined all-cause mortality and stroke rate by Kaplan-Meier estimate between CEA (2%) and CSS (2%). There was no significant difference in the sec- ondary endpoint of combined 30-day all-cause mortality, stroke, and myocardial infarction between CEA (3%) and CSS (2%). Conclusions: This study suggests that the 30-day risk of stroke or death following carotid stenting with cerebral protection is equivalent to standard carotid endarterectomy in a broad risk population of patients with carotid stenosis. J Endovasc Ther 2003;10:1021-1030 l

Where Are We Now? Much like with sports teams, politics, or religion, human nature often dictates that we follow or believe in something even when data may be lacking. Surgeons may approach the decision about which surgical approach to use for THA in a similar way. While there now is good evidence suggesting short-term functional benefits of the direct anterior approach (arguably at the expense of higher risk of periprosthetic fracture, aseptic loosening, or failure of osseous integration, but with a lower risk of dislocation) we still lack long-term comparative data [1, 2, 6, 10]. Enter Nambiar et al. [7] in this issue of Clinical Orthopaedics and Related Research®, who provide mid-term follow-up data on a previously published randomized trial comparing the outcomes of direct anterior and posterior approaches for primary THA. The initial study, which analyzed early postoperative outcomes out to 1 year, compared the direct anterior and posterior approaches to implant a cementless THA. The direct anterior approaches were performed using the assistance of a specialized operating table and fluoroscopic guidance, and the posterior approach employed an enhanced posterior capsular repair. The two participating surgeons were experienced with both surgical approaches. They found improved hip flexion activities at 6 weeks in the direct anterior group, but no other differences in various outcome measures, nor any between-group differences by 12 weeks [3]. This current study provides 5-year follow-up on the same series of patients [7]. The authors found no difference between approaches as measured by a variety of functional outcome measures, radiographic parameters, or complications. They conclude that both direct anterior and posterior approaches provide equal outcomes, and the choice of approach should be based on individual patient factors (though specific factors are not discussed) and surgeon experience [7]. Where Do We Need To Go? We still need short-term and especially long-term data to help us determine whether differences exist between approaches for a broader group of patients as well as for specific subsets of patients who may benefit from one approach versus another. One size or one approach may not fit all patients. With additional data on broader groups of patients, but with appropriate subgroup analysis, we may find that patient selection is key to the surgical approach, with some patients benefiting from one approach and others from a different one. Surgeons should be trained and experienced in doing the approach that gives the greatest benefit to the patient and results in the most predictable outcome. This may be an anterior approach for some patients and a posterior approach for others. While the difference in functional outcomes between approaches may be small, when applied to a broad patient population, they may be important, but difficult to measure, for a subset of patients. Why wouldn’t you want to recover faster if all other things were equal; with “if” being the key word? We also need to know whether the potential downsides of a direct anterior approach, such as a potentially higher risk of failure of osseous integration or periprosthetic fracture, persist over time. Just as the posterior approach evolved to include an enhanced posterior capsular repair to reduce the risk of dislocation [8, 12], similar nuances for the direct anterior approach will be discovered as a new generation of surgeons puts the approach to broader use and subjects it to more study. Finally, we need to be aware that patients undergoing THA vary widely in terms of their preoperative function and surgical goals. Outcomes tools now in use do not do a good job of distinguishing results at the high end of the activity scale. We need to recognize that it is OK—in fact, desirable—to have different metrics for patients with different functional goals. Some patients may be pleased if THA helps them to decrease pain and return to simple activities of daily living; others wish to return to competitive sports. While the WOMAC or Oxford Hip Score are handy in the first group, they’re ineffective in measuring degrees of surgical success in the latter. We need outcomes tools that help us to resolve differences among our most-functional and active patients. How Do We Get There? Despite convincing data that a direct anterior approach provides improved early function compared to other surgical approaches, these benefits come at a potential cost. Indeed, the direct anterior approach has been associated in some studies with an increased risk of periprosthetic fracture, failure of osseus integration of the femoral component, but generally a lower dislocation rate [1, 2, 9, 11]. We need more studies that compare surgical approaches to see if the potential downsides of a particular approach persist as those approaches see wider use. Much like studies on a posterior approach have demonstrated a reduction in dislocation compared to historical controls, future study is needed to see if the drawbacks of a direct anterior approach change over time. Ideally, these studies should be large, randomized trials that also allow for adequately powered subgroup analysis. But while large, randomized controlled trials would be ideal, they are difficult to perform. Smaller randomized trials studying specific groups of patients or retrospective case series of unselected patients should help give us answers to these questions. Large total joint registry studies that include the detailed information required to analyze subsets of patients would also provide answers to these questions. With time, further knowledge, and experience, outcomes may change. Additionally, studies on this topic that compare functional outcomes should also categorize patients functionally and use metrics that can differentiate subtle differences. For example, the UCLA activity score, which is a 10-point scoring system based on various activity levels, may differentiate across a broad population but unlikely differentiates when applied to a population of patients with no other medical or joint comorbidities. By today’s standards, one can argue that someone who golfs or bowls regularly does not warrant a score of 8. That leaves only two higher scores for patients who are more active. Rather, a scoring system that starts with a baseline of golf or bowling at the low end and graduates activities to a high end of expert skiing, high-level mountain cycling, or competitive tennis may be a better way to differentiate patients functioning at a high activity level. A per hour step or calorie count, which is easily calculated with today’s wearables, may be another method to stratify activity at the high end. These types of metrics may help us show important difference for this subset of patients. Finally, we cannot forget that THA is one of the most predictable, successful, and cost-effective procedures in orthopaedics and perhaps in all of medicine for improving quality of life [4, 5]. Thus, one should not risk a predictable outcome for a very small incremental improvement in a small subset of patients. As is so often said, do what you do well; the data support it.

AimsThis study investigated the effect of clopidogrel treatment on inflammatory activity as evidenced by the change in high-sensitivity C-reactive protein (hsCRP) levels in a broad population of patients who are...

We created a Dutch version of the Paris Arousal Disorders Severity Scale (PADSS), which assesses non-rapid eye movement (NREM) parasomnia symptoms over the past year (PADSS-year). This questionnaire was previously validated in patients with sleep walking and/or sleep terrors (SW/ST). We validated the questionnaire in SW/ST patients, and in a broader population, including patients with confusional arousals, comorbidities, and medication users ("other NREM parasomnias"). Furthermore, we introduced a version covering the past month (PADSS-month), with the potential purpose of evaluating symptom evolution and treatment response. We compared PADSS scores among 54 SW/ST patients, 34 age-matched controls, and 23 patients with other NREM parasomnias. We evaluated discriminative capacity, internal consistency, and construct validity. Furthermore, we assessed the test-retest reliability and treatment response of PADSS-month. Healthy controls scored significantly lower than both patient groups. We found an excellent diagnostic accuracy (area under the curve PADSS-year 0.990, PADSS-month 0.987) and an acceptable internal consistency. Exploratory factor analysis identified 3 components: "behaviors outside the bed," "behaviors in/around the bed," and "violent behaviors," with the former 2 factors reflecting the distinction between SW and ST. PADSS-month showed an acceptable test-retest reliability (0.75). Additionally, PADSS-month significantly decreased after pharmaceutical and/or behavioral treatment. This change was correlated with the clinical impression of the caregiver, implying that PADSS-month is sensitive to treatment effects. The Dutch PADSS questionnaire can be used as a screening tool in a broad population of patients with NREM parasomnia, not only SW/ST. Furthermore, we validated a PADSS-month version to assess the evolution of symptoms and treatment effect. van Mierlo P, Hermans L, Arnulf I, Pijpers A, Overeem S, van Gilst M. Validation of the Dutch translation of the Paris Arousal Disorders Severity Scale for non-REM parasomnias in a 1-year and 1-month version. J Clin Sleep Med. 2022;18(4):1135-1143.