Team Approach: Hip Preservation Surgery.

The evaluation and treatment of adolescents and young adults with hip pain has seen tremendous growth over the past 20 years. Labral tears are well established as a common cause of hip pain but often occur because of underlying bony abnormalities. Femoroacetabular impingement (FAI) and acetabular dysplasia are now well-established causes of hip osteoarthritis and are increasingly treated in the prearthritic stage in hopes of improving symptoms and prolonging the longevity of the native hip. Beyond FAI and acetabular dysplasia, this patient population can present with a complex and variable group of underlying conditions that need to be taken into account. Expertise in the conservative management of this population, including physical therapy, is valuable to maximize the success. Preoperative, surgical, and postoperative decision-making and care in this population is complex and evolving. A comprehensive, multidisciplinary approach to the care of this patient population has been used for over 20 years by our institution with great success. The purpose of this article is to review the "team-based approach" necessary for successful management of the spectrum of adolescent and young adult hip disorders.

Is combined surgical dislocation and proximal femoral osteotomy a safe procedure for correction of complex hip deformities?

Complex deformities of the hip requiring intra-articular and proximal femoral correction are challenging with regard to surgical access and complication risk. Combined surgical dislocation and proximal femoral osteotomy (SD/PFO) is a surgical strategy that provides unrestricted access to the joint with the capability for adjunctive PFO. Although providing excellent surgical access, concerns over a potentially high risk of postoperative complications remain, and published information on the safety of this technique remain scarce. In this study, we defined the early complication profile of combined surgery across 48 hips with a variety of complex deformities using a standardized, validated complication grading scheme for hip preservation surgery. Patients were mean age 19.1 years 13-33 years and 60% had previous surgery. At the early mean follow-up of 2.9 years, considerable improvement was seen across all outcome scores. Major complications (Grade III or higher) occurred at a rate of 4.2% (n = 2). Both were osteotomy non-unions, and both were treated successfully with revision PFO and bone grafting at mean 1.1 years. To our knowledge, the current series of combined SD-PFO surgeries represents the largest to date for which detailed complication data have been reported. Given the complexity of these disorders, a major complication rate of 4.2% is acceptable. Our complication rates were comparable to those reported for isolated SD and PFO procedures. These rates did not vary significantly across morphologic variants or patient-specific characteristics. Additionally, our complication risk profile is consistent with previous, smaller reports, which supports the generalizability of these results among appropriately experienced surgeons.

Combined Surgical Dislocation and Periacetabular Osteotomy for Complex Residual Legg-Calvé-Perthes Deformities: Intermediate-Term Outcomes.

BACKGROUND: Residual Legg-Calvé-Perthes (LCP) deformities represent one of the most challenging disorders in hip reconstructive surgery. In complex cases, both instability (acetabular dysplasia) and multifocal femoroacetabular impingement (FAI) (proximal femoral deformities) require correction. We assessed intermediate-term patient-reported outcome measures, radiographic correction, complications, and survivorship for combined surgical dislocation (SD) and periacetabular osteotomy (PAO) for the treatment of complex LCP deformities. METHODS: A retrospective cohort study was performed on 31 hips with complex LCP deformities undergoing combined SD and PAO for concurrent instability and FAI. Treatment included femoral head reshaping, trochanteric advancement and relative femoral neck lengthening, management of intra-articular lesions, and PAO. Twenty-seven hips (87%) had a minimum follow-up of 5 years. The mean age was 19.8 years, 56% of patients were female, and 44% of patients had undergone a previous surgical procedure. RESULTS: At a mean of 8.4 years, 85% of hips (23 of 27) remained preserved (no conversion to total hip arthroplasty). The survivorship estimates were 93% at 5 years and 85% at 10 years. The median (and interquartile range) increased from 64 points (55, 67 points) to 92 points (70, 97 points) (p < 0.001) for the modified Harris hip score (mHHS) and from 60 points (45, 75 points) to 86 points (75, 100 points) (p = 0.001) for the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain score. Symptoms (mHHS < 70 points) were reported for an additional 19% of hips (n = 5) at the final follow-up. The University of California Los Angeles (UCLA) activity score increased from a median of 8 points (6, 10 points) to 9 points (7, 10 points) (p = 0.207). Structural correction included mean improvement (and standard deviation) of 15.3° ± 7.6° for acetabular inclination, 20.7° ± 10.8° for the lateral center-edge angle, 23.4° ± 16.3° for the anterior center-edge angle, and 18 ± 10 mm for trochanteric height (p < 0.001 for all). Complications occurred in 2 hips (7%), including 1 deep wound infection and 1 superficial wound infection. There was 1 reoperation due to complication, but there were no nerve palsies, thromboembolic events, fractures, or nonunions. CONCLUSIONS: At an intermediate follow-up of combined SD and PAO for complex LCP deformities, 85% of hips were preserved. This procedure provides reliable deformity correction, major pain relief, improved function, and acceptable complication and failure rates. LEVEL OF EVIDENCE: Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.

Nanotechnology Driven Cancer Chemoradiation: Exploiting the Full Potential of Radiotherapy with a Unique Combination of Gold Nanoparticles and Bleomycin.

One of the major issues in current radiotherapy (RT) is the associated normal tissue toxicity. Enhancement of the RT effect with novel radiosensitizers can address this need. In this study, gold nanoparticles (GNPs) and bleomycin (BLM) were used as a unique combination of radiosensitizers. GNPs offer a two-fold promise as a delivery vehicle for BLM and as a radiosensitizing agent. In this study, GNPs were functionalized and complexed with BLM using a gold-thiol bond (denoted GNP-BLM). Our results show that there was a 40% and 10% decrease in cell growth with GNP-BLM vs. free BLM for the MIA PaCa-2 and PC-3 cell lines, respectively. Testing the GNP-BLM platform with RT showed an 84% and 13% reduction in cell growth in MIA PaCa-2 cells treated with GNP-BLM and GNPs, respectively. Similar results were seen with PC-3 cells. The efficacy of this approach was verified by mapping DNA double-strand breaks (DSBs) as well. Therefore, this proposed incorporation of nanomedicine with RT is promising in achieving a significantly higher therapeutic ratio which is necessary to make a paradigm change to the current clinical approach.

Docetaxel-Mediated Uptake and Retention of Gold Nanoparticles in Tumor Cells and in Cancer-Associated Fibroblasts.

Due to recent advances in nanotechnology, the application of nanoparticles (NPs) in cancer therapy has become a leading area in cancer research. Despite the importance of cancer-associated fibroblasts (CAFs) in creating an optimal niche for tumor cells to grow extensively, most of the work has been focused on tumor cells. Therefore, to effectively use NPs for therapeutic purposes, it is important to elucidate the extent of NP uptake and retention in tumor cells and CAFs. Three tumor cell lines and three CAF cell lines were studied using gold NPs (GNPs) as a model NP system. We found a seven-fold increase in NP uptake in CAFs compared to tumor cells. The retention percentage of NPs was three-fold higher in tumor cells as compared to CAFs. Furthermore, NP uptake and retention were significantly enhanced using a 50 nM concentration of docetaxel (DTX). NP uptake was improved by a factor of three in tumor cells and a factor of two in CAFs, while the retention of NPs was two-fold higher in tumor cells compared to CAFs, 72 h post-treatment with DTX. However, the quantity of NPs in CAFs was still three-fold higher compared to tumor cells. Our quantitative data were supported by qualitative imaging data. We believe that targeting of NPs in the presence of DTX is a very promising approach to accumulate a higher percentage of NPs and maintain a longer retention in both tumor cells and CAFs for achieving the full therapeutic potential of cancer nanotechnology.

Patients With Symptomatic Sequelae of Slipped Capital Femoral Epiphysis Have Advanced Cartilage Wear at the Time of Surgical Intervention.

BACKGROUND: Slipped capital femoral epiphysis (SCFE) is a common hip problem in children. The resulting deformity can cause impingement similar to cam-type idiopathic femoroacetabular impingement (FAI). Although there are similarities between FAI and SCFE, deformity patterns, severity, and time of onset of symptoms varies, which may impact management. The purpose of this study was to describe patterns of articular cartilage damage in patients undergoing surgical hip dislocation for sequelae of SCFE in comparison to patients undergoing arthroscopic surgery for primary FAI. METHODS: Patients were identified who underwent surgical treatment for hip pain due to primary FAI (cam type) or sequelae of SCFE. Clinical data and radiographic measurements were recorded. Cartilage was assessed intraoperatively. Severity was classified using the modified Beck classification, while location was classified into 6 sectors. Statistical analysis was performed to test for differences in demographic and radiographic characteristics between the SCFE and FAI patients. χ2 or Fisher exact tests were used to evaluate trends in patterns of acetabular and femoral cartilage wear between SCFE and FAI groups. RESULTS: The SCFE group had 28 hips compared with 304 in the FAI group. SCFE patients were younger (19 vs. 32, P<0.001), had higher body mass index (30±5.9 vs. 24±4.8, P<0.001), and were more often male (61% vs. 27%, P<0.001). Deformity severity based on α-angle was higher in the SCFE group [AP 74 vs. 55 (P=0.001) and Dunn 72 vs. 58 (P<0.001)]. There were no significant differences with regards to lateral center edge angle, anterior center edge angle, or Tonnis angle. In both groups the most common locations for cartilage lesions in both groups were the anterior peripheral and superolateral peripheral regions with fewer but more widely distributed femoral head lesions. The SCFE group had higher rates of femoral head and superolateral central cartilage lesions compared with the FAI group. There was no statistical difference between high-grade femoral or acetabular cartilage lesions between groups. CONCLUSIONS: Patients with SCFE were younger at the time of surgery and presented with more severe deformity based on radiographic α-angle compared to patients with FAI. Our results suggest higher prevalence of femoral head lesions and more diffuse cartilage injury in patients with SCFE. This study can be used to support early surgical intervention in patients with symptomatic sequelae of SCFE due to risk of premature joint damage. LEVEL OF EVIDENCE: Level III-prognostic study.

Severe Hip Dysplasia in Skeletally Mature Patients With Spastic Cerebral Palsy: The Technique and Early Outcome of Comprehensive Surgical Correction (Including the Bernese PAO).

BACKGROUND: Treatment of symptomatic hip dysplasia in skeletally mature patients with spastic cerebral palsy (CP) can be challenging. This study examines our technical experience with the Bernese periacetabular osteotomy (PAO) in combination with adjunctive procedures in the treatment of this complex hip deformity. METHODS: Sixteen consecutive patients (18 hips) with symptomatic CP hip dysplasia were treated with a PAO and variable adjunctive procedures and retrospectively reviewed. Two patient (2 hips) were excluded due to insufficient follow-up. The average age at the time of surgery was 17.7 years (range: 13 to 28 y). We compared the preoperative to postoperative changes in radiographic parameters as well as early outcomes as measured by patient assessment of hip pain and function using the modified Harris Hip Score (mHHS). RESULTS: The average time of follow-up was 3.3 years (range: 2.0 to 6.3 y). Tönnis angles decreased from a median of 30 degrees (range: 18 to 45 degrees) preoperatively to a median of 6 degrees (range: -9 to 21 degrees) postoperatively. Lateral center-edge angles increased from a median of -8 degrees (range: -28 to 15 degrees) to a median of 32 degrees (range: 19 to 38 degrees). Anterior center-edge angles increased from a median of 2 degrees (range: -22 to 39 degrees) to a median of 35 degrees (range: 22 to 47 degrees). The extrusion index decreased from a median of 57% preoperatively (range: 35% to 73%) to a median of 21% (range: 11% to 36%) postoperatively.The median mHHS was 62 (range: 37 to 81) preoperatively and 85 (range: 65 to 100) postoperatively. Notably, the pain component of the mHHS improved from 20 (range: 0 to 44) to 42 (range: 30 to 44). Tönnis osteoarthritis grade preoperatively was either 0 (11 hips) or 1 (5 hips) and remained unchanged in 11 hips and increased by 1 grade in 5 hips. CONCLUSIONS: It has been our experience that the Bernese PAO in combination with appropriate adjunctive treatments has provided a very satisfactory surgical approach in the treatment of CP hip dysplasia. In the adolescent and young adult with spastic CP, utilizing the Bernese PAO technique makes it possible to obtain redirection of often a very severe acetabular dysplasia. Adjunctive soft tissue procedures and a proximal femoral osteotomy are frequently necessary to maintain postoperative stability. A notable improvement in the quality of life and function directly attributable to our surgical treatment of their pre-existing problematic hip dysplasia has been consistently noted in early follow-up for our patients. LEVEL OF EVIDENCE: Level IV-therapeutic.

A retrospective histologic study of 140 cases of clinically significant equine ocular disorders.

Ocular diseases are an important category in equine medicine; however, most articles regarding histologic ocular lesions in horses are exclusive to a specific condition and do not provide a complete review of clinically significant ocular disease frequency in a diagnostic laboratory. We reviewed sections of equine eyes from 140 cases (98 enucleations [biopsies] and 42 autopsies) with clinically relevant ocular alterations at 2 diagnostic centers in the United States. The most common primary conditions were non-traumatic keratitis (36), equine recurrent uveitis (ERU; 31), traumatic injuries (22), ocular and periocular neoplasms (19), and uveitis and/or endophthalmitis resulting from sepsis (18). Congenital anomalies (3) and retinal atrophy and detachment alone (3) were infrequent. Non-traumatic keratitis was frequently accompanied by anterior uveitis (22), corneal rupture (16), pre-iridal fibrovascular membrane formation (13), and secondary mycotic infection (11). ERU was the second and third most prevalent disease in autopsies and enucleations, respectively. This condition was commonly associated with glaucoma (15). Glaucoma (25) and cataract (20) were the most prevalent secondary alterations in the evaluated cases. Keratitis (20) and corneal rupture (16) were among the most prevalent consequences of trauma. Information presented herein may guide clinicians and pathologists, contributing to the early diagnosis of potentially vision-impairing conditions and raising the chances of successful treatment and cure.

Open Reduction and Internal Fixation for the Treatment of Symptomatic Osteochondritis Dissecans of the Femoral Head in Patients With Sequelae of Legg-Calvé-Perthes Disease.

BACKGROUND: Osteochondritis dissecans (OCD) is estimated to occur in 2% to 7% of patients with Legg-Calvé-Perthes disease (LCPD). Unstable osteochondral fragments secondary to LCPD may produce mechanical symptoms requiring surgical intervention. Reattachment of the fragment with open reduction and internal fixation (ORIF) may provide good clinical outcomes. The purpose of this study is to report short-term clinical and radiographic results of ORIF for the treatment of symptomatic osteochondral lesions resulting from LCPD. METHODS: Clinical data including patient demographics and patient-reported outcome scores were collected prospectively. All patients underwent preoperative radiographs and magnetic resonance imaging confirming an unstable OCD fragment as well as postoperative radiographs at regular intervals. Indications for ORIF of the OCD fragment were hip pain and mechanical symptoms with radiographic evidence of LCPD and a magnetic resonance imaging demonstrating an OCD fragment of the femoral head. Osteochondral fragment instability was confirmed intraoperatively. Preoperative and postoperative physical examination findings were documented. All patients failed a course of nonsurgical treatment (activity modification, anti-inflammatories, and physical therapy). RESULTS: From a total of 64 consecutive patients treated with hip preservation surgery for LCPD, 7 patients with symptomatic OCD secondary to LCPD were treated with surgical hip dislocation and ORIF of the femoral head osteochondral fragment. OCD size lesion ranged from 200 to 625 mm. All patients reported marked clinical improvement, with resolution of both pain and mechanical symptoms. Radiographs at final follow-up demonstrated complete osteochondral fragment healing without implant failure. Mean follow-up was 4.6 years (range, 1.1 to 7.4 y). There was a significant postoperative improvement in measured internal rotation in flexion (5.0±5.0 to 16.4±9.8; P=0.02). Modified Harris Hip Score markedly improved from baseline to final follow-up (47.8 to 82.7; [INCREMENT]34.9; minimal clinically important difference, 11; P=0.002), with all patients meeting minimal clinically important difference for modified Harris Hip Score. There were no complications and no progression of osteoarthritis in all patients at final follow-up. CONCLUSIONS: We have demonstrated both predictable radiographic healing and marked clinical improvement following ORIF of symptomatic post-Perthes OCD lesions. We advocate ORIF for symptomatic osteochondral lesions as a first-line surgical treatment for these patients due to the advantages of native osteochondral tissue preservation, predictable healing, and marked clinical improvement. LEVEL OF EVIDENCE: Level IV-case series.

Parachute geckos free fall into synonymy: Gekko phylogeny, and a new subgeneric classification, inferred from thousands of ultraconserved elements.

Recent phylogenetic studies of gekkonid lizards have revealed unexpected, widespread paraphyly and polyphyly among genera, unclear generic boundaries, and a tendency towards the nesting of taxa exhibiting specialized, apomorphic morphologies within geographically widespread "generalist" clades. This is especially true in Australasia, where monophyly of Gekko proper has been questioned with respect to phenotypically ornate flap-legged geckos of the genus Luperosaurus, the Philippine false geckos of the genus Pseudogekko, and even the elaborately "derived" parachute geckos of the genus Ptychozoon. Here we employ sequence capture targeting 5060 ultraconserved elements (UCEs) to infer phylogenomic relationships among 42 representative ingroup gekkonine lizard taxa. We analyze multiple datasets of varying degrees of completeness (10, 50, 75, 95, and 100 percent complete with 4715, 4051, 3376, 2366, and 772 UCEs, respectively) using concatenated maximum likelihood and multispecies coalescent methods. Our sampling scheme addresses four persistent systematic questions in this group: (1) Are Luperosaurus and Ptychozoon monophyletic, and are any of these named species truly nested within Gekko? (2) Are prior phylogenetic estimates of Sulawesi's L. iskandari as the sister taxon to Melanesian G. vittatus supported by our genome-scale dataset? (3) Is the high-elevation L. gulat of Palawan Island correctly placed within Gekko? (4) And, finally, where do the enigmatic taxa P. rhacophorus and L. browni fall in a higher-level gekkonid phylogeny? We resolve these issues; confirm with strong support some previously inferred findings (placement of Ptychozoon taxa within Gekko; the sister taxon relationship between L. iskandari and G. vittatus); resolve the systematic position of unplaced taxa (L. gulat, and L. browni); and transfer L. iskandari, L. gulat, L. browni, and all members of the genus Ptychozoon to the genus Gekko. Our unexpected and novel systematic inference of the placement of Ptychozoon rhacophorus suggests that this species is not grouped with Ptychozoon or even Luperosaurus (as previously expected) but may, in fact, be most closely related to several Indochinese species of Gekko. With our resolved and strongly supported phylogeny, we present a new classification emphasizing the most inclusive, original generic name (Gekko) for these ~60 taxa, arranged into seven subgenera.

Toxicity and Efficacy Evaluation of an Adeno-Associated Virus Vector Expressing Codon-Optimized RPGR Delivered by Subretinal Injection in a Canine Model of X-linked Retinitis Pigmentosa.

Applied Genetic Technologies Corporation (AGTC) is developing a recombinant adeno-associated virus (rAAV) vector AGTC-501, also designated rAAV2tYF-GRK1-hRPGRco, to treat X-linked retinitis pigmentosa (XLRP) in patients with mutations in the retinitis pigmentosa GTPase regulator (RPGR) gene. The vector contains a codon-optimized human RPGR cDNA (hRPGRco) driven by a photoreceptor-specific promoter (G protein-coupled receptor kinase 1 [GRK1]), and is packaged in an AAV2 capsid variant with three surface tyrosine residues changed to phenylalanine (AAV2tYF). We conducted a toxicity and efficacy study of this vector administered by subretinal injection in the naturally occurring RPGR mutant (X-linked progressive retinal atrophy 2 [XLPRA2]) dog model. Sixteen RPGR mutant dogs divided into four groups of three to five animals each received either a subretinal injection of 0.07 mL of AGTC-501 at low (1.2 × 1011 vector genome [vg]/mL), mid (6 × 1011 vg/mL), or high dose (3 × 1012 vg/mL), or of vehicle control in the right eye at early-stage disease. The left eye remained untreated. Subretinal injections were well tolerated and were not associated with systemic toxicity. Electroretinography, in vivo retinal imaging, and histological analysis showed rescue of photoreceptor function and structure in the absence of ocular toxicity in the low- and mid-dose treatment groups when compared with the vehicle-treated group. The high-dose group showed evidence of both photoreceptor rescue and posterior segment toxicity. These results support the use of AGTC-501 in clinical studies with patients affected with XLRP caused by RPGR mutations and define the no-observed-adverse-effect level at 6 × 1011 vg/mL.

Late Effects of Clubfoot Deformity in Adolescent and Young Adult Patients Whose Initial Treatment Was an Extensive Soft-tissue Release: Topic Review and Clinical Case Series.

Children with congenital clubfoot often have residual deformity, pain, and limited function in adolescence and young adulthood. These patients represent a heterogeneous group that often requires an individualized management strategy. This article reviews the available literature on this topic while proposing a descriptive classification system based on a review of patients at our institution who underwent surgery for problems related to previous clubfoot deformity during the period between January 1999 and January 2012. Seventy-two patients (93 feet) underwent surgical treatment for the late effects of clubfoot deformity at an average age of 13 years (range 9 to 19 years). All patients had been treated at a young age with serial casting, and most had at least one previous surgery on the affected foot or feet. Five common patterns of pathology identified were as follows: undercorrection, overcorrection, dorsal bunion, anterior ankle impingement, and lateral hindfoot impingement. Management pathways for each group of the presenting problems is described. To our knowledge, this topic review represents the largest report of adolescent and young adult patients with residual clubfoot deformity in the literature.

Activity Level Maintenance at Midterm Follow-up Among Active Patients Undergoing Periacetabular Osteotomy.

BACKGROUND: For active patients undergoing periacetabular osteotomy (PAO), returning to and maintaining a high level of activity postoperatively is a priority. PURPOSE: To evaluate the maintenance of activity levels at midterm follow-up in active patients treated with PAO for symptomatic acetabular dysplasia. STUDY DESIGN: Case series; Level of evidence, 4. METHODS: Patients who underwent PAO for symptomatic acetabular dysplasia between June 2006 and August 2013 were identified by a retrospective review of our prospective longitudinal institutional Hip Preservation Database. All patients with a preoperative University of California, Los Angeles (UCLA) score of ≥7 and a potential minimum 5 years of follow-up were included in the study. Functional outcome measures were the UCLA score, modified Harris Hip Score (mHHS), and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC). The maintenance of high activity levels was defined as a UCLA score of ≥7 at final follow-up. Radiographic parameters were measured. Statistical significance was defined as a P value <.05. RESULTS: A total of 66 hips (58 patients) were included. The mean age was 25.3 years (range, 14-47 years), the mean body mass index was 23.9 kg/m2 (range, 19-32 kg/m2), and 72% were female. The mean follow-up was 6.8 years (range, 5-11 years). There were 67% of patients who maintained a UCLA score of ≥7. Patient-reported outcomes improved postoperatively from preoperatively for the mHHS (88 ± 14 vs 67 ± 17, respectively; P < .001) and WOMAC (89 ± 15 vs 73 ± 20, respectively; P < .001). The lateral center-edge angle, anterior center-edge angle, and acetabular inclination were significantly improved at final follow-up (P < .001). Only 4 patients (7%) cited postoperative activity limitations as being caused by hip pain. There were no conversions to total hip arthroplasty. CONCLUSION: The majority (67%) of active patients returned to preoperative or higher activity levels after PAO at midterm follow-up.

Complications associated with combined surgical hip dislocation and periacetabular osteotomy for complex hip deformities.

Surgical hip dislocation (SD) and periacetabular osteotomy (PAO) are well-described treatments for femoroacetabular impingement (FAI) and acetabular dysplasia, respectively. Occasionally, complex deformities require a combined SD/PAO; the morbidity of performing both procedures in a single stage has not been fully investigated. We performed a retrospective review of a consecutive group of patients undergoing combined SD/PAO to investigate the incidence and character of perioperative complications. Forty-five patients (46 hips) were identified. Perioperative complications were graded by the modified Clindo-Davien complication scheme. Mean follow-up was 36 months (range 12-128), and no patients were lost to follow-up. Six complications occurred in six hips (13%). Four (8.7%) complications were minor (Grades I or II): one Brooker Grade III heterotopic ossification requiring no treatment, one superior pubic ramus nonunion requiring no treatment and two superficial wound infections requiring antibiotics. Two (4.3%) complications were major (Grades III or IV): one coxa saltans interna and labral tear requiring hip arthroscopy with labral repair and iliopsoas lengthening, and one deep surgical site infection requiring irrigation and debridement followed by development of arthritis requiring conversion to arthroplasty. The average Harris hip score improved from 62 ± 13 preoperatively to 80 ± 19 at final follow-up. Except for the single joint replacement, there were no long-term disabilities. There were no major neurovascular injuries, osteonecrosis, fractures or trochanteric nonunions. Combined SD/PAO for the treatment of complex, concomitant deformities of the proximal femur and acetabulum is associated with an acceptable risk of complications. The vast majority of complications that occurred were managed without permanent disability. Level of Evidence: IV.

A comparative pilot-scale evaluation of gas-sparged and granular activated carbon-fluidized anaerobic membrane bioreactors for domestic wastewater treatment.

Two significantly different pilot-scale AnMBRs were used to treat screened domestic wastewater for over one year. Both systems similarly reduced BOD5 and COD by 86-90% within a 13-32 °C temperature range and at comparable COD loading rates of 1.3-1.4 kg-COD m-3 d-1 and membrane fluxes of 7.6-7.9 L m-2 h-1 (LMH). However, the GAC-fluidized AnMBR achieved these results at a 65% shorter hydraulic retention time than the gas-sparged AnMBR. The gas-sparged AnMBR was able to operate at a similar operating permeability with greater reactor concentrations of suspended solids and colloidal organics than the GAC-fluidized AnMBR. Also, the membranes were damaged more in the GAC-fluidized system. To better capture the relative advantages of each system a hybrid AnMBR comprised of a GAC-fluidized bioreactor connected to a separate gas-sparged ultrafiltration membrane system is proposed. This will likely be more effective, efficient, robust, resilient, and cost-effective.

Pain intensity and pain self-management strategies following discharge after surgery: An Australian prospective observational study.

WHAT IS KNOWN AND OBJECTIVE: Up to 80% of patients experience acute pain following surgery. This study aimed to improve the current understanding about the strategies individuals use to self-manage pain following discharge after surgery, stratified by pain intensity. METHODS: A prospective observational study conducted at the Royal Hobart Hospital, Australia, between November 2014 and March 2015. Eligible participants were 18 years or older and had undergone surgery requiring an incision. Patients who had undergone surgery related to cancer, childbirth or multitrauma or those with dementia were excluded. Participants were identified through hospital records and mailed a survey within 1 week of discharge. This survey asked about post-discharge pain, management strategies utilized and advice on self-management of pain provided during their inpatient stay. RESULTS: Five hundred surveys were mailed, with 169 (33.8%) being returned. The median age of the respondents was 57 years (range: 18-92 years); 53% were female. The majority (89.3%) of participants recalled receiving information about pain self-management. Analgesic use was reported by 95.4% of participants in the week following discharge. Moderate-severe pain was reported by 80 participants (47.3%); 63.7% and 11.3% of patients reported underuse and overuse of analgesics compared to what was recommended, respectively. WHAT IS NEW AND CONCLUSION: A high proportion of patients underused analgesics despite experiencing moderate-severe pain. Although the vast majority of participants reported receiving advice regarding pain self-management, this did not appear to translate into optimal pain management after discharge. Different approaches to the provision of advice appear to be required.

Effect of the Tool to Reduce Inappropriate Medications on Medication Communication and Deprescribing.

OBJECTIVES: To examine the effect of the Tool to Reduce Inappropriate Medications (TRIM), a web tool linking an electronic health record (EHR) to a clinical decision support system, on medication communication and prescribing. DESIGN: Randomized clinical trial. SETTING: Primary care clinics at a Veterans Affairs Medical Center. PARTICIPANTS: Veterans aged 65 and older prescribed seven or more medications randomized to receipt of TRIM or usual care (N = 128). INTERVENTION: TRIM extracts information on medications and chronic conditions from the EHR and contains data entry screens for information obtained from brief chart review and telephonic patient assessment. These data serve as input for automated algorithms identifying medication reconciliation discrepancies, potentially inappropriate medications (PIMs), and potentially inappropriate regimens. Clinician feedback reports summarize discrepancies and provide recommendations for deprescribing. Patient feedback reports summarize discrepancies and self-reported medication problems. MEASUREMENTS: Primary: subscales of the Patient Assessment of Care for Chronic Conditions (PACIC) related to shared decision-making; clinician and patient communication. Secondary: changes in medications. RESULTS: 29.7% of TRIM participants and 15.6% of control participants provided the highest PACIC ratings; this difference was not significant. Adjusting for covariates and clustering of patients within clinicians, TRIM was associated with significantly more-active patient communication and facilitative clinician communication and with more medication-related communication among patients and clinicians. TRIM was significantly associated with correction of medication discrepancies but had no effect on number of medications or reduction in PIMs. CONCLUSION: TRIM improved communication about medications and accuracy of documentation. Although there was no association with prescribing, the small sample size provided limited power to examine medication-related outcomes.

The effect of PD-L1 testing on the cost-effectiveness and economic impact of immune checkpoint inhibitors for the second-line treatment of NSCLC.

BACKGROUND: Immune checkpoint inhibitors improve outcomes compared with chemotherapy in lung cancer. Tumor PD-L1 receptor expression is being studied as a predictive biomarker. The objective of this study was to assess the cost-effectiveness and economic impact of second-line treatment with nivolumab, pembrolizumab, and atezolizumab with and without the use of PD-L1 testing for patient selection. DESIGN: We developed a decision-analytic model to determine the cost-effectiveness of PD-L1 assessment and second-line immunotherapy versus docetaxel. The model used outcomes data from randomized clinical trials (RCTs) and drug acquisition costs from the United States. Thereafter, we used epidemiologic data to estimate the economic impact of the treatment. RESULTS: We included four RCTs (2 with nivolumab, 1 with pembrolizumab, and 1 with atezolizumab). The incremental quality-adjusted life year (QALY) for nivolumab was 0.417 among squamous tumors and 0.287 among non-squamous tumors and the incremental cost-effectiveness ratio (ICER) were $155 605 and $187 685, respectively. The QALY gain in the base case for atezolizumab was 0.354 and the ICER was $215 802. Compared with treating all patients, the selection of patients by PD-L1 expression improved incremental QALY by up to 183% and decreased the ICER by up to 65%. Pembrolizumab was studied only in patients whose tumors expressed PD-L1. The QALY gain was 0.346 and the ICER was $98 421. Patient selection also reduced the budget impact of immunotherapy. CONCLUSION: The use of PD-L1 expression as a biomarker increases cost-effectiveness of immunotherapy but also diminishes the number of potential life-years saved.

Achieving Health Equity Through Community Engagement in Translating Evidence to Policy: The San Francisco Health Improvement Partnership, 2010-2016.

BACKGROUND: The San Francisco Health Improvement Partnership (SFHIP) promotes health equity by using a novel collective impact model that blends community engagement with evidence-to-policy translational science. The model involves diverse stakeholders, including ethnic-based community health equity coalitions, the local public health department, hospitals and health systems, a health sciences university, a school district, the faith community, and others sectors. COMMUNITY CONTEXT: We report on 3 SFHIP prevention initiatives: reducing consumption of sugar sweetened beverages (SSBs), regulating retail alcohol sales, and eliminating disparities in children's oral health. METHODS: SFHIP is governed by a steering committee. Partnership working groups for each initiative collaborate to 1) develop and implement action plans emphasizing feasible, scalable, translational-science-informed interventions and 2) consider sustainability early in the planning process by including policy and structural interventions. OUTCOME: Through SFHIP's efforts, San Francisco enacted ordinances regulating sale and advertising of SSBs and a ballot measure establishing a soda tax. Most San Francisco hospitals implemented or committed to implementing healthy-beverage policies that prohibited serving or selling SSBs. SFHIP helped prevent Starbucks and Taco Bell from receiving alcohol licenses in San Francisco and helped prevent state authorization of sale of powdered alcohol. SFHIP increased the number of primary care clinics providing fluoride varnish at routine well-child visits from 3 to 14 and acquired a state waiver to allow dental clinics to be paid for dental services delivered in schools. INTERPRETATION: The SFHIP model of collective impact emphasizing community engagement and policy change accomplished many of its intermediate goals to create an environment promoting health and health equity.