Shifting institutional culture to develop climate solutions with Open Science.

To address our climate emergency, "we must rapidly, radically reshape society"-Johnson & Wilkinson, All We Can Save. In science, reshaping requires formidable technical (cloud, coding, reproducibility) and cultural shifts (mindsets, hybrid collaboration, inclusion). We are a group of cross-government and academic scientists that are exploring better ways of working and not being too entrenched in our bureaucracies to do better science, support colleagues, and change the culture at our organizations. We share much-needed success stories and action for what we can all do to reshape science as part of the Open Science movement and 2023 Year of Open Science.

Arthroplasty for femoral neck fractures is at risk for under restoration of lateral femoral offset.

PURPOSE: The aim of the study was to determine the restoration of hip biomechanics through lateral offset, leg length, and acetabular component position when comparing non-arthroplasty surgeons (NAS) to elective arthroplasty surgeons (EAS). METHODS: 131 patients, with a femoral neck fracture treated with a THA by 7 EAS and 20 NAS, were retrospectively reviewed. 2 blinded observers measured leg-length discrepancy, femoral offset, and acetabular component position. Multivariate logistic regression models examined the association between the surgeon groups and restoration of lateral femoral, acetabular offset, leg length discrepancy, acetabular anteversion, acetabular position, and component size, while adjusting for surgical approach and spinal pathology. RESULTS: NAS under-restored 4.8 mm of lateral femoral offset (43.9 ± 8.7 mm) after THA when compared to the uninjured side (48.7 ± 7.1 mm, p = 0.044). NAS were at risk for under-restoring lateral femoral offset when compared to EAS (p = 0.040). There was no association between lateral acetabular offset, leg length, acetabular position, or component size and surgeon type. CONCLUSIONS: Lateral femoral offset is at risk for under-restoration after THA for femoral neck fractures, when performed by surgeons that do not regularly perform elective THA. This indicates that lateral femoral offset is an under-appreciated contributor to hip instability when performing THA for a femoral neck fracture. Lateral femoral offset deserves as much attention and awareness as acetabular component position since a secondary analysis of our data reveal that preoperative templating and intraoperative imaging did not prevent under-restoration.

Investigation of monoclonal antibody CSX-1004 for fentanyl overdose.

The opioid crisis in the United States is primarily driven by the highly potent synthetic opioid fentanyl leading to >70,000 overdose deaths annually; thus, new therapies for fentanyl overdose are urgently needed. Here, we present the first clinic-ready, fully human monoclonal antibody CSX-1004 with picomolar affinity for fentanyl and related analogs. In mice CSX-1004 reverses fentanyl antinociception and the intractable respiratory depression caused by the ultrapotent opioid carfentanil. Moreover, toxicokinetic evaluation in a repeat-dose rat study and human tissue cross-reactivity study reveals a favorable pharmacokinetic profile of CSX-1004 with no safety-related issues. Using a highly translational non-human primate (NHP) model of respiratory depression, we demonstrate CSX-1004-mediated protection from repeated fentanyl challenges for 3-4 weeks. Furthermore, treatment with CSX-1004 produces up to a 15-fold potency reduction of fentanyl in NHP respiration, antinociception and operant responding assays without affecting non-fentanyl opioids like oxycodone. Taken together, our data establish the feasibility of CSX-1004 as a promising candidate medication for preventing and reversing fentanyl-induced overdose.

Lack of alignment between orthopaedic surgeon priorities and patient expectations in total joint arthroplasty.

BACKGROUND: Healthcare systems are shifting toward "patient-centered" care often without assessing the values important to patients. Analogously, the interests of the patient may be disparate with physician interests, as pay-for-performance models become common. The purpose of the study was to determine which medical preferences are essential for patients during their surgical care. METHODS: This prospective, observational study surveyed 102 patients who had undergone a primary knee replacement and/or hip replacement surgery about hypothetical scenarios regarding their surgical experience. Data analysis included categorical variables presented as a number and percent, while continuous variables presented as mean and standard deviation. Statistical analysis for anticoagulation data included the Pearson chi-square test and one-way ANOVA test. RESULTS: A large majority, 73 patients (72%), would not pay to have a four-centimeter or smaller incision. The remaining 29 patients (28%) would prefer to have a four-centimeter or smaller incision and would pay a mean of $1,328 ± 1,629 for that day. A significant number of patients preferred not to use anticoagulation (p = 0.019); however, the value attributed to avoiding a specific method of anticoagulation was found not to be significant (p = 0.507). CONCLUSIONS: The study determined the metrics prioritized by hospitals and surgeons are not important to the majority of patients when they evaluate their own care. These disconnects in the entitlements patients expect and receive can be solved by including patients in discussions with physicians and hospital systems.

Comparison of histopathological turnaround times for mandibulectomies, glossectomies, and incisional biopsies of the tongue.

Diagnostic histopathology plays a key role in the management of oral cancer and timely reports are essential. The aim of this study was to retrospectively compare the time interval between receipt of the specimen and issue of the histopathology report (the 'turnaround time', TT) of two types of oral cancer resections (mandibulectomies and glossectomies) and incisional biopsies from the tongue (n = 100 of each). The information documented included the number of days from receipt of the specimen until the sample was ready for reporting, and the number of subsequent days until the report was authorised by the pathologist. The number of days mandibulectomies required decalcification, the number of blocks processed per sample, and pathological TNM stage were also recorded. Results showed that mandibulectomies had statistically significantly longer TT than glossectomies. Incisional biopsies had the shortest TT with 87% reported in seven days and 95% in ten. There were also statistically significantly longer TT for pT3/pT4 than for pT1/pT2 glossectomies, and between the number of blocks processed for the three main groups. Decalcification and the interval whilst the slides awaited the pathologists' attention were identified as 'bottlenecks'. Dentate mandibulectomies had the longest TT of all; extraction of teeth at operation and detachment of the lower border of the mandible at macroscopic sampling are thus potential means by which the decalcification delay might be reduced. Expectations of the multidisciplinary team managing the patient should be realistic when scheduling postoperative discussion.

Supine Knee Positioning Does Not Interfere with Mobile-Bearing Unicompartmental Knee Arthroplasty Performance.

The Food and Drug Administration has only approved mobile-bearing unicompartmental knee arthroplasty (MB-UKA) to be performed with a hanging leg holder. The purpose of this study is to evaluate the impact of a supine knee position on MB-UKA performance.In total, 16 cadavers were randomized so that either the right or left knee was placed in the flexed or supine positions. One board-certified orthopaedic surgeon and three adult reconstruction fellows that attended the required Oxford partial knee instructional course performed four operations in each position. The primary outcome was final knee balance. Secondary outcomes included procedure duration, timing of individual surgical steps, implant sizes, range of motion, implant alignment, and fracture. A Students t-test was used to examine differences between positions with significance set at p < 0.05. Secondary analyses using two one-sided tests were conducted to explore equivalence between the two positions.There was no significant difference in mean final balance between supine (1.7 mm ± standard deviation [SD] = 1.5 mm) and flexed (1.3 ± 1.3 mm) positions (p = 0.390). There were also no significant differences between positions for procedure time (p = 0.497), tibia coronal alignment (p = 0.614), tibial slope (p = 0.194), femoral component sagittal alignment (p = 0.091), and fractures (n = 0). Exploratory equivalence analyses indicated that the positions were equivalent for final balance (p = 0.002).MB-UKA performed in the supine position is not significantly different from the flexed position in terms of ligament balance, overall procedure time, and radiographic appearance. These initial safety data warrant further clinical investigations and support the expansion of the surgical technique to include performing MB-UKAs in the supine position.

Enhanced simulated early 21st century Arctic sea ice loss due to CMIP6 biomass burning emissions.

The mechanisms underlying decadal variability in Arctic sea ice remain actively debated. Here, we show that variability in boreal biomass burning (BB) emissions strongly influences simulated Arctic sea ice on multidecadal time scales. In particular, we find that a strong acceleration in sea ice decline in the early 21st century in the Community Earth System Model version 2 (CESM2) is related to increased variability in prescribed BB emissions in the sixth phase of the Coupled Model Intercomparison Project (CMIP6) through summertime aerosol-cloud interactions. Furthermore, we find that more than half of the reported improvement in sea ice sensitivity to CO2 emissions and global warming from CMIP5 to CMIP6 can be attributed to the increased BB variability, at least in the CESM. These results highlight a new kind of uncertainty that needs to be considered when incorporating new observational data into model forcing while also raising questions about the role of BB emissions on the observed Arctic sea ice loss.

Dose Proportionality and Steady-State Pharmacokinetics of Serdexmethylphenidate/Dexmethylphenidate, a Novel Prodrug Combination to Treat Attention-Deficit/Hyperactivity Disorder.

Objective: The study was designed to determine (1) the pharmacokinetic (PK) profile of dexmethylphenidate (d-MPH) after oral administration of three dosage strengths of a new treatment containing d-MPH and a novel prodrug, serdexmethylphenidate (SDX); (2) the dose proportionality of the different SDX/d-MPH dosages; and (3) the steady-state PK profile of d-MPH and SDX after multiple dosing of SDX/d-MPH. Methods: Twenty-three healthy volunteers (aged 18-55 years) under fasted conditions received in a crossover design SDX/d-MPH 26.1/5.2 mg (Treatment A), 39.2/7.8 mg (Treatment B), and 52.3/10.4 mg (Treatment C) for a total d-MPH hydrochloride equivalent dose of 20, 30, and 40 mg, respectively. After a 96-hour washout period, all participants received four consecutive daily doses of SDX/d-MPH 52.3/10.4 mg. Blood samples were collected for measurement of plasma d-MPH and SDX and for PK analysis. Results: Administration of all three doses of SDX/d-MPH resulted in a rapid rise and slow decline in the plasma concentration of d-MPH. For Treatments A, B, and C, mean (± standard deviation) maximum concentrations (Cmax) were 7.1 ± 2.1, 9.8 ± 2.8, and 13.8 ± 3.8 ng/mL, and overall exposures (AUC0-last) were 97.2 ± 28.8, 142.5 ± 41.2, and 199.8 ± 57.2 h*ng/mL, respectively. Dose-normalized Cmax, AUC0-last, and AUC0-inf for d-MPH were similar when comparing the high and low doses versus the middle dose. Power model regression analysis revealed that Cmax and AUC0-inf proportionally increased with an increase in SDX/d-MPH dose. In the multiple-dose study, d-MPH reached steady state before the third dose, and SDX after the first dose. Conclusion: The PK profile of SDX/d-MPH is characterized by a rapid rise and a gradual decline in d-MPH concentration, with proportional Cmax and AUC0-inf across doses. The PK attributes of SDX/d-MPH may optimize symptom control from early morning to early evening, while the demonstrated dose proportionality may facilitate initial dose titration and ongoing dose adjustment.

Rational and practical considerations to guide a target product profile for patient-centric drug product development with measurable patient outcomes - A proposed roadmap.

The increasing awareness of acceptability and usability of pharmaceutical drug products by the patient as a key quality requirement continues to drive need for integrating patient centric drug product design into the pharmaceutical development process. The complex matrix of multiple drug product related decisions during the early drug development process often limits patient-centric drug product (PCDP) design options in the final commercial drug product development phase. To integrate the specific needs and perspectives of patients into drug development and product design process, a rational approach integrated into the complex development matrix is required from the start and weighs product development decision options accordingly. The aim of this work was to develop a roadmap for PCDP design in a multidisciplinary approach that leads to better usability, adherence and acceptance of the drug by patients via early integration into the development matrix. The proposed rational approach is based upon regulatory requirements and lessons learned from pediatric and geriatric drug development.

Oral, intranasal, and intravenous abuse potential of serdexmethylphenidate, a novel prodrug of d-methylphenidate.

OBJECTIVES: Serdexmethylphenidate (SDX) chloride (Cl) is a novel prodrug of d-methylphenidate (d-MPH). These studies evaluated the abuse potential of SDX Cl when administered orally, intranasally (IN), and intravenously (IV). METHODS: Three randomized, double-blind, placebo- and active-controlled crossover studies were conducted in recreational drug users to evaluate the abuse-related effects of oral SDX (120 and 240 mg) vs. extended-release (ER) d-MPH (80 mg) and phentermine (60 mg); IN SDX (80 mg) vs. d-MPH (40 mg), and IV SDX (30 mg) vs. d-MPH (15 mg). Abuse-related subjective measures, pharmacokinetics, and safety were assessed. RESULTS: The primary endpoint of maximum (Emax) Drug Liking (DL) (0-100-point scale) was significantly higher following d-MPH vs. placebo, validating the studies. In the oral study, DL Emax was significantly higher following 80 mg ER d-MPH (Emax = 81.5) than 120 mg SDX (Emax = 62.8, p < .001) and 240 mg SDX (Emax = 63.8, p = .006); and following 60 mg phentermine (Emax = 80.2) than 120 mg SDX (p = .0195), but not 240 mg SDX (p = .0665). DL Emax scores were significantly higher following IN d-MPH vs SDX (Emax = 93.2 vs. 71.0, p < .0001) and following IV d-MPH vs. SDX (Emax = 84.3 vs. 56.6, p = .001). Intravenous SDX was non-inferior to placebo (p = .001) for DL Emax. Secondary endpoints (e.g. Take Drug Again) were generally consistent with the primary endpoint. Maximal and overall d-MPH exposure was lower for SDX than d-MPH for all routes. Adverse events typical of stimulants were more frequent with d-MPH than SDX. CONCLUSIONS: These findings indicate that the novel d-MPH prodrug, SDX, has lower abuse potential than d-MPH and support its classification as a C-IV controlled substance.

A Randomized, Controlled Laboratory Classroom Study of Serdexmethylphenidate and d-Methylphenidate Capsules in Children with Attention-Deficit/Hyperactivity Disorder.

Objectives: To evaluate the efficacy and safety of once-daily serdexmethylphenidate/dexmethylphenidate (SDX/d-MPH) capsules (Azstarys™) compared with placebo in children with attention-deficit/hyperactivity disorder (ADHD) in a randomized, double-blind, dose-optimized laboratory classroom study. Methods: Children ages 6-12 with ADHD were enrolled. During a 3-week, open-label, Dose Optimization Phase, subjects initiated treatment with 39.2 mg/7.8 mg/day of SDX/d-MPH and were titrated weekly to an optimal dose (maximum dose of 52.3/10.4 mg). During the double-blind Treatment Phase, subjects were randomized to receive their optimal dose of SDX/d-MPH or placebo for 7 days. On day 7, efficacy was assessed in the laboratory classroom using the Swanson, Kotkin, Agler, M-Flynn, and Pelham (SKAMP) Rating Scale and Permanent Product Measure of Performance (PERMP). To evaluate safety, adverse events (AEs), vital signs, and electrocardiograms were assessed, and suicide risk was assessed. Results: A total of 149 subjects completed the study. In the primary efficacy analysis, the mean postdose change from baseline in SKAMP-Combined scores averaged over the laboratory classroom day was significantly improved with SDX/d-MPH versus placebo (least-squares mean treatment difference [95% confidence interval]: -5.41 [-7.10 to -3.71]; p < 0.001). A significant treatment effect for SDX/d-MPH compared with placebo was observed from 1 to 10 hours postdose. A post hoc analysis more comparable with that conducted in similar studies indicated a 0.5- to 13-hour onset and duration of efficacy. Both average postdose PERMP-Attempted and PERMP-Correct score changes from baseline were significantly improved among those treated with SDX/d-MPH versus placebo (p < 0.001 for both). No serious AEs were reported. During the Dose Optimization Phase, two-thirds of subjects reported AEs; the most common being insomnia and decreased appetite. Conclusions: SDX/d-MPH showed significant improvement in ADHD symptoms compared with placebo in children 6-12 years of age, with a rapid onset and extended duration of treatment effect. SDX/d-MPH was safe, with AEs comparable with those observed with other stimulant treatments.

Medial Unicompartmental Knee Arthroplasty with a Mobile-Bearing Implant.

BACKGROUND: For patients with isolated medial knee arthritis, unicompartmental knee arthroplasty (UKA) is an appealing surgical option. Compared with total knee arthroplasty (TKA), UKA is less invasive, preserves more native bone stock, has lower perioperative morbidity and mortality1,2, allows for quicker recovery1,2, and has higher patient satisfaction2,3. It also allows for more dynamic proprioception and postural control, allowing for function more similar to a native knee4. Proper surgical technique and patient selection are critical to the growing success of UKA. DESCRIPTION: The general principles of UKA are to remove and replace the diseased femoral and tibial joint surfaces while restoring limb alignment. The key steps of this procedure are demonstrated in the video article: (1) patient evaluation, (2) patient positioning, (3) surgical exposure, (4) tibial guide placement and resection, (5) femoral guide placement and resection, (6) knee balancing and implant trialing, (7) preventing impingement, (8) final tibial preparation, (9) final component placement, and (10) closure and postoperative course. ALTERNATIVES: Patients should first exhaust all nonoperative treatments before considering UKA. For those patients who do not meet the appropriate indications for UKA, TKA is the most acceptable alternative treatment. In active patients <55 years old without bone-on-bone osteoarthritis, a high tibial osteotomy may be considered. When considering UKA, options include both mobile-bearing and fixed-bearing designs. RATIONALE: The potential advantages of UKA over TKA make it an attractive option for the appropriate patient. Recently, indications for UKA have expanded to include (1) isolated noninflammatory bone-on-bone arthritis in the medial compartment; (2) retained full-thickness cartilage in the lateral compartment, best visualized on valgus-stress radiographs; (3) a functionally normal medial collateral ligament; and (4) a functionally normal anterior cruciate ligament5. Mobile-bearing UKA designs consist of a dual articulation between the concave polyethylene insert and the metallic tibial and spherical femoral components, which allows for distribution of contact forces over a large surface area6. In contrast, fixed-bearing designs have a flat polyethylene insert that does not conform to the femur. Current data do not demonstrate a clear difference in clinical performance between the 2 bearings. However, a recent systematic review has shown lower polyethylene wear rates in mobile-bearing implants7. EXPECTED OUTCOMES: The survivorship of mobile-bearing UKA ranges from 85% to 98% at 10 years8-12 and from 79% to 94% at 15 years8,13,14. The most common indications for revision include aseptic loosening (36%), progression of osteoarthritis (20%), and unexplained pain (11%)7. Bearing dislocation is a unique complication for mobile-bearing UKAs, with reported rates between 0.3% to 4.2%6,10,12. IMPORTANT TIPS: Always inspect all compartments of the knee for evidence of substantial degenerative changes prior to proceeding with UKA. If there is advanced arthritis in other compartments, the decision should be made to proceed with TKA instead. Therefore, preoperatively, all patients indicated for UKA should also sign a consent form for TKA, and TKA implants should be available in case they are needed.When assessing bearing size, it is important that there is no axial loading through the heel to properly assess the flexion gap. Intraoperatively, this can be done by elevating the thigh so that the foot hangs freely. The trial spoon should fit into the joint without substantial resistance or effort.Spigots do not reference the end of the bone. Rather, they reference the end of the spigot hole that was drilled using the initial 0 spigot.Spigot number represents the total thickness of additional bone that will be removed from the first mill cut.Confirm the amount of bone that was resected by inspecting the small rim of bone that remains around the spigot hole after milling.

Recurrence and malignant transformation rates of high grade oral epithelial dysplasia over a 10 year follow up period and the influence of surgical intervention, size of excision biopsy and marginal clearance in a UK regional maxillofacial surgery unit.

OBJECTIVES: To determine the overall recurrence rate (RR) and malignant transformation rate (MTR) of high grade oral mucosal epithelial dysplasias (HGOED). MATERIALS & METHODS: A clinicopathological review of records of patients diagnosed with a unifocal HGOED between 2004 and 2016 on incisional biopsy who then underwent excision. The mean duration of follow-up was 47.7 months (±29.9 SD). RESULTS: Full demographic, historical and histopathological data were available for 120 patients. Six were lost to follow-up after excisional biopsy. Invasive squamous cell carcinoma (SCC) was present in 19 (18.3%) excisions. HGOED affected the lateral and ventral tongue in 58% of patients. Fourteen (11.7%) were not treated surgically but kept under surveillance. The overall RR was 34.7% (33 patients) and MTR 17.8% (17 patients). Four of the 14 (28.6%) patients who had not had the HGOED excised developed SCC, by contrast to the 13 of the 106 (12.3%) who had been treated. RR was significantly associated with positive excision margins (p = 0.007; OR = 3.6) and a clinical presentation of erythroplakia (p = 0.023; OR = 1.5). MTR was significantly associated with age (p = 0.034), clinical appearance (p = 0.030), site (p = 0.007), treatment received (p = 0.012) and positive excision margins (p = 0.007). The mean time for recurrence to develop was 62 months (±31.5 SD) (range 22-144 months), that for malignant transformation was 50 months (±32.5 SD) (range 8-97 months). CONCLUSION: Patients with HGOED require follow-up for at least 10 years after treatment. Younger age, homogeneous clinical appearance, complete excision, a larger excision specimen and clear margins all improve prognosis.

Perineural and lymphovascular invasion in squamous cell carcinoma of the tongue.

BACKGROUND: Perineural invasion (PNI) and lymphovascular invasion (LVI) may be adverse prognostic indicators in squamous cell carcinoma (SCC) of the tongue. METHODS: The percentages of histological PNI and LVI were determined in 335 patients with tongue SCC. Sixty tumours originally reported as negative for these features were tested to determine how many more were positive with "immunohistochemical enhancement." RESULTS: PNI was found in 141 (42.1%) and LVI in 51 (15.2%) patients. 79.4% of the 141 patients who had PNI and 72.6% of the 51 with LVI had a T3 or T4 tumour. Lymph node metastasis was identified in 145 (51.2%) of the 280 patients who had undergone neck dissection; 58.2% of the 141 patients with PNI and 80.4% of the 51 patients with LVI had lymph node metastasis. There was a highly statistically significant correlation between PNI with increasing pT (P < .00001) and pN (P < .0001) stage, and a statistically significant correlation between LVI and pT stage (P < .001), the association of LVI with pN status could not be reliably tested statistically. Immunohistochemistry for S100 identified five further cases of PNI, but review of the original H&E showed the feature was present in four and had been missed at original reporting. CD31 identified three further possible cases of LVI and D2-40 none. The endothelium of some vascular channels was positive for both CD31 and D2-40 and cross-reactivity with other cells compromised interpretation. CONCLUSIONS: Histological identification of PNI and LVI per se remains of uncertain prognostic significance. "Immunohistochemical enhancement" offered little benefit.

A Small Amount of Retraction Force Results in Inadvertent Piriformis Muscle Damage During a Piriformis-Sparing Approach to the Hip.

BACKGROUND: Piriformis-sparing approaches to the hip allow surgeons to avoid releasing the piriformis tendon during total hip arthroplasty; however, the consequences of retracting an intact piriformis tendon during such an approach remain ill-defined. The present study aimed to determine the upper limit of force that can be applied during retraction of the piriformis tendon to expose the hip, and to quantify the resultant damage to the piriformis musculotendinous complex. METHODS: A patent-pending instrumented retractor was designed to record the applied force, duration, and angle of retraction during a piriformis-sparing posterior approach to the hip. In addition to the data collected with use of the instrumented retractor, damage to the piriformis muscle and tendon was quantified by a blinded observer. RESULTS: There was no damage to the piriformis tendon in 22 (96%) of 23 hips during piriformis retraction for visualization of the hip capsule; however, there was complete or partial damage to the piriformis muscle at the sacral origin, belly, or musculotendinous junction (i.e., outside the surgical field) noted in 21 (91%) of 23 hips. The mean peak force to failure of the piriformis muscle was exceedingly small (29.0 ± 9.4 N; range, 10.1 to 44.9 N). CONCLUSIONS: The mean peak force applied to the piriformis retractor is much less than the force required for several common daily activities, such as opening a door or crushing an empty aluminum can. Soft-tissue damage that occurs outside the surgical field during the retraction of unreleased muscles, like the piriformis muscle, is common and remains an uncontrolled surgical variable. This inadvertent soft-tissue damage is not routinely accounted for when accessing the invasiveness of a procedure. Hence, it is no longer adequate to define a minimally invasive surgical procedure simply as an approach that involves the limited release of anatomical structures. CLINICAL RELEVANCE: The use of instrumented retractors may redefine surgical invasiveness by providing data that could alter our understanding of the soft-tissue damage caused by retraction and open the possibility of robot-assisted or damage-limiting retractor systems.

Challenges and opportunities to include patient-centric product design in industrial medicines development to improve therapeutic goals.

In the past, drug developers in industry chose approaches mainly focusing on the drug product's efficacy, safety and quality according to the level required by regulatory expectations stipulated in guidelines, pharmacopoeia and other regulatory provisions. By putting more focus on the patient perspective, regulatory authorities are currently raising their requirements regarding successful product submissions. The increasing involvement of patients in the product development process (e.g. conduction of human factor use tests, integration of feedback from patient and patient advisory groups into clinical programmes) requires adaptations to the existing and established industrial drug development processes without compromising fast patient access to innovative therapies. This review provides an expert opinion on the emerging challenges and opportunities to implement a patient-centric approach into new drug development programmes. The aim is to better understand the challenge of finding the right balance between bringing innovative drugs fast to the patients and to develop these in parallel in a patient-centric product form as well as why this is an opportunity and how stakeholder parties (e.g. patients, clinicians, pharmacists, caregivers, regulators) can provide support to achieve desired outcomes.

Learning Curve for the Direct Superior Approach to Total Hip Arthroplasty.

Surgical learning curves are a representation of the number of cases required for a surgeon to reach a stable rate of outcomes and complications. In this study, the authors present the learning curve for the direct superior (DS) approach to total hip arthroplasty, which is a muscle-sparing modification to the mini-posterior technique. This was a retrospective analysis of the first 40 primary DS cases done by a single surgeon. These cases were divided into 2 groups of 20 and compared for intra- and postoperative complications, acetabular component positioning, and Harris Hip Score at 90 days after surgery. As a control, the first 20 primary mini-posterior cases were analyzed as the baseline performance of the surgeon and the DS approach. There was no statistically significant difference between the first and second sets of DS patients regarding Harris Hip Score, intraoperative complications, dislocations, estimated blood loss, length of hospital stay, and components positioned within the Lewinnek safe zone. The only statistically significant difference between the first and second sets of DS cases was a decrease in operating time (P<.001). This suggests that the learning curve is less than 20 patients. The results also indicate that the first 20 DS cases ambulated farther (P=.007) and had a shorter length of stay (P=.007), outperforming the mini-posterior approach. This study suggests that the DS learning curve is short for surgeons trained in the posterior approach. The data could be especially pertinent as 90-day results and safety are becoming increasingly important in evaluating performance for bundled-payment models. [Orthopedics. 2020;43(4):e237-e243.].