A descriptive analysis of real-world oncology biosimilar use in Japan.

Aim: To describe patient and treatment characteristics associated with bevacizumab BS-Pfizer, rituximab BS-Pfizer and trastuzumab BS-Pfizer and their reference products in Japan. Methods: This retrospective observational study used an administrative claims database to identify patients with ≥1 biosimilar or reference product prescription from 2019 to 2022 for approved indications. Descriptive statistics were calculated. Results: Overall, 14-39% of biosimilar-prescribed patients initiated therapy with reference products. Biosimilar utilization significantly increased from 2019 to 2022. The most-commonly prescribed concomitant class of therapy with biosimilars was antineoplastic therapy. Conclusion: Reference products were most frequently prescribed among the Japanese cohorts, but substantial and increasing proportions received biosimilars over time. Future studies should extend our initial insights to assess biosimilar clinical outcomes in Japanese settings.

This study examines the adoption of cancer biosimilar therapies in Japan from 2019 to 2022. Cancer biosimilars are complex treatments that closely resemble established cancer therapies already available in Japan. We looked into the characteristics of patients receiving three specific biosimilars ­ bevacizumab BS-Pfizer, rituximab BS-Pfizer and trastuzumab BS-Pfizer. We also investigated where patients received biosimilar treatment, other therapies they received alongside biosimilars and the proportion of patients using these therapies each year during the study. Our analysis utilized data from the 'Medical Data Vision' database, which records care provided in hospitals across Japan. We analyzed patient demographics and treatment patterns, and compared different groups using statistics to identify significant differences. Notably, we observed that between 14 and 39% of patients initially started treatment with the original version of the drug on the market, known as the 'reference product,' before switching to the biosimilar. Furthermore, our findings revealed a significant increase in the use of biosimilars each year during the study period. Biosimilars were most-commonly used alongside chemotherapy drugs. These initial findings shed light on the patient population using cancer biosimilars in Japan and the treatment contexts in which they are utilized. Future research should delve deeper into aspects such as cost of care, patient survival, side effects and other pertinent factors related to the use of biosimilars in cancer care in Japan.

An Apparatus for Measuring Combined Shear-Tensile Loading in Fibrous Tissues Ex Vivo.

Soft tissues such as tendon and ligament undergo a combination of shear and tensile loading in vivo due to their boundary conditions at muscle and/or bone. Current experimental protocols are limited to pure tensile loading, biaxial loading, or simple shear, and thus may not fully characterize the mechanics of these tissues under physiological loading scenarios. Our objective was to create an experimental protocol to determine the shear modulus of fibrous tissues at different tensile loads. We assembled a four-actuator experimental system that facilitated shear deformation to be superimposed on a tissue subjected to an axial preload. We measured shear modulus in axially loaded electrospun nanofiber scaffolds with either randomly oriented or aligned fibers. We found that shear modulus in the nanofiber phantoms was shear-strain stiffening and dependent on both the axial load (p < 0.001) and fiber alignment (p < 0.001) of the scaffold. The proposed system can enhance our understanding of microstructure and functional mechanics in soft tissues, while also providing a platform to investigate the behavior of electrospun scaffolds for tissue regeneration. Our experimental protocol for determining loaded shear modulus would be further useful as a method to gauge tissue mechanics under loading conditions that are more representative of physiological loads applied to tendon and ligament.

Solo and Partnered Sexual Behavior Among an International Sample of Adults With Spina Bifida.

BACKGROUND: Spina bifida (SB) may differentially impact adults' participation in solo and partnered sexual behaviors, but little research investigates this topic. AIM: Describe solo and partnered sexual behaviors among an international sample of adult men and women with SB. MAIN OUTCOME MEASURES: Ever participated (no/yes) and recent participation (>1 year ago/within last year) in solo masturbation, cuddled with a partner, held hands with a partner, kissed a partner, touched a partner's genital, had genitals touched by a partner, gave a partner oral sex, received oral sex from a partner, vaginal sex, anal sex, and sex toy use. METHODS: Data were drawn from a larger cross-sectional, internet-based survey assessing the sexual behaviors of an international sample of men and women with SB. We used logistic regression to examine the impact of background (gender, age, independent living, and relationship status) and health (shunt status, ambulation, and genital sensation) factors on each outcome. RESULTS: The sample consisted of 345 respondents aged 18-73 years from 26 nations. Very few (<3%) had no lifetime experience with any solo or partnered behaviors; 25.0% reported participating in all behaviors at some point in their lives. The median number of past year sexual behaviors (of 16 total) was 7. Lifetime and recent participation were associated with demographic and health factors. CLINICAL IMPLICATIONS: Despite impairment, adults with spina bifida do participate in solo and partnered sexual behaviors. Medical personnel who work with this population should include discussions about sexuality as part of routine care. STRENGTHS & LIMITATIONS: Although this research measured solo and partnered sexual behavior in large international sample of adults with spina bifida, it is limited by its cross-sectional retrospective design and non-clinical convenience sample. CONCLUSION: Despite disability, many adults with SB participate in solo and partnered sexual behavior. Medical and psychosocial supports are needed to help adults in this population enjoy sexuality in a healthy and safe manner. Hensel DJ, Misseri R, Wiener JS, et al. Solo and Partnered Sexual Behavior Among an International Sample of Adults With Spina Bifida. J Sex Med 2022;19:1766-1777.

Health State Utilities for Sickle Cell Disease: A Catalog Prepared From a Systematic Review.

OBJECTIVES: Sickle cell disease (SCD) is a complex, chronic condition that impairs health-related quality of life of affected individuals and their caregivers. As curative therapies emerge, comprehensive cost-effectiveness models will inform their value. These models will require descriptions of health states and their corresponding utility values that accurately reflect health-related quality of life over the disease trajectory. The objectives of this systematic review were to develop a catalog of health state utility (HSU) values for SCD, identify research gaps, and provide future directions for preference elicitation. METHODS: Records were identified through searches of PubMed and Embase, Tufts Medical Center Cost-Effectiveness Analysis Registry, reference lists of relevant articles, and consultation with SCD experts (2008-2020). We removed duplicate records and excluded ineligible studies. For included studies, we summarized the study characteristics, methods used for eliciting HSUs, and HSU values. RESULTS: Five studies empirically elicited utilities using indirect methods (EQ-5D) (n = 3) and Short Form-6 Dimension (n = 2); these represent health states associated with general SCD (n = 1), SCD complications (n = 2), and SCD treatments (n = 3). Additionally, we extracted HSUs from 7 quality-adjusted life-years-based outcome research studies. The HSU among patients with general SCD without specifying complications ranged from 0.64 to 0.887. Only 36% of the HSUs used in the quality-adjusted life-year-based outcomes research studies were derived from individuals with SCD. No study estimated HSUs in caregivers. CONCLUSIONS: There is a dearth of literature of HSUs for use in SCD models. Future empirical studies should elicit a comprehensive set of HSUs from individuals with SCD and their caregivers.

Potential Cost-Effectiveness of Risk-Based Pancreatic Cancer Screening in Patients With New-Onset Diabetes.

BACKGROUND: There are no established methods for pancreatic cancer (PAC) screening, but the NCI and the Pancreatic Cancer Action Network (PanCAN) are investigating risk-based screening strategies in patients with new-onset diabetes (NOD), a group with elevated PAC risk. Preliminary estimates of the cost-effectiveness of these strategies can provide insights about potential value and inform supplemental data collection. Using data from the Enriching New-Onset Diabetes for Pancreatic Cancer (END-PAC) risk model validation study, we assessed the potential value of CT screening for PAC in those determined to be at elevated risk, as is being done in a planned PanCAN Early Detection Initiative trial. METHODS: We created an integrated decision tree and Markov state-transition model to assess the cost-effectiveness of PAC screening in patients aged ≥50 years with NOD using CT imaging versus no screening. PAC prevalence, sensitivity, and specificity were derived from the END-PAC validation study. PAC stage distribution in the no-screening strategy and PAC survival were derived from the SEER program. Background mortality for patients with diabetes, screening and cancer care expenditure, and health state utilities were derived from the literature. Life-years (LYs), quality-adjusted LYs (QALYs), and costs were tracked over a lifetime horizon and discounted at 3% per year. Results are presented in 2020 US dollars, and we took a limited US healthcare perspective. RESULTS: In the base case, screening resulted in 0.0055 more LYs, 0.0045 more QALYs, and $293 in additional expenditures for a cost per QALY gained of $65,076. In probabilistic analyses, screening resulted in a cost per QALY gained of <$50,000 and <$100,000 in 34% and 99% of simulations, respectively. In the threshold analysis, >25% of screen-detected PAC cases needed to be resectable for the cost per QALY gained with screening to be <$100,000. CONCLUSIONS: We found that risk-based PAC screening in patients with NOD is likely to be cost-effective in the United States if even a modest fraction (>25%) of screen-detected patients with PAC are resectable. Future studies should reassess the value of this intervention once clinical trial data become available.

Fertility and sexuality issues in congenital lifelong urology patients: female aspects.

PURPOSE: With advances in treatment modalities and medical knowledge, girls with congenital urologic disorders are living well into adulthood. Although, sexual and reproductive function in this population is still poorly understood. The aim is to review existing literature about fertility and sexuality in women with congenital genitourinary disorders, including spina bifida (SB), bladder exstrophy-epispadias complex (BEEC) and congenital adrenal hyperplasia (CAH). METHODS: This review represents the joint SIU-ICUD (Société Internationale d'Urologie-International Consultation on Urological Disease) consultation on congenital lifelong urology. The results of this analysis were first presented at a joint consultation of the SIU and ICUD at the 2018 SIU annual conference in Seoul, South Korea. Appropriate experts were asked to write specific sections regarding sexuality and reproductive function in female patients with these complex congenital urogenital disorders. Each expert performed their own literature review which was reviewed by GDW, AFS, Hadley M. Wood and Dan Wood. Expert opinion was obtained where data are non-existent. RESULTS: Only about half of the individuals with SB express a satisfactory sex life. In women with BEEC, cosmetic concerns surrounding genital appearance and function may increase psychological distress, including severe depression, suicide and sexual dysfunction. Professional health care is key for improving self-esteem and to interact in the biopsychosocial model of the quality of life. Patients with SB and BEEC should be informed about all the potential risks and difficulties before, during and after pregnancy. Screening for pelvic organ prolapse is important as it can exacerbate their already existing sexual dysfunction, difficulties achieving pregnancy and challenges with clean intermittent catheterization. CONCLUSIONS: Lifelong multidisciplinary follow-up and management are complex but necessary. As these patients grow into their adolescence, they may have the desire to become involved in personal relationships and have sexual interactions. Their healthcare team needs to be increasingly sensitive to these aspects.

Fertility and sexuality issues in congenital lifelong urology patients: male aspects.

PURPOSE: To review existing literature about fertility and sexuality of boys born with complex congenital genitourinary anomalies. METHODS: A Pubmed review was performed in December 2018 to identify the most relevant original manuscripts regarding male complex congenital conditions affecting the urogenital system in male patients including spina bifida (SB), bladder exstrophy-epispadias complex (BEEC) and hypospadias. A comprehensive review was drafted exploring sexual dysfunction from a medical, psychosexual, surgical and reproductive point of view during transition from childhood (or adolescence) to adulthood. RESULTS: About 75% of men with SB have erectile dysfunction (ED) (Gamé et al. in Urology 67(3):566-570, 2006; Diamond et al. in 58(4):434-435, 1986). Most SB patients have impaired sexual development mainly due to diminished self-esteem, dependence on caregivers and lack of privacy (Blum et al. in Pediatrics 88(2):280-285, 1991). Men with BEEC have fewer intimate relationships than women because of the greater difficulties with issues regarding their genitalia and sexual activities (Deans et al. in Am J Obstet Gynecol 206(6):496.e1-496.e6, 2012). However, a good quality of life is achievable with the effective use of coping strategies (Deng et al. in Transl Androl Urol 7:941, 2018; Rikken et al. in BMC Womens Health 18(1):163, 2018; Friedler et al. in Reprod Biomed Online 32(1):54-61, 2016). Chordee occurs in 25% of all hypospadias patients. More severe hypospadias is related to a greater risk for complications. The long-term sexual quality of life (QoL) in men who underwent hypospadias surgery is influenced by a lot of factors. Therefore, an interactive and dynamic biopsychosocial model of sexual QoL was proposed. CONCLUSIONS: The care of patients with congenital urologic conditions becomes a challenge especially in the period of 'transition'. The goal of follow-up is a holistic management viewed from a medical, psychosexual, surgical end reproductive point. All patients should be asked for specific urinary, fecal or sexual concerns.

The association of delay in curative intent treatment with survival among breast cancer patients: findings from the Women's Health Initiative.

PURPOSE: Delays in adjuvant breast cancer (BC) therapy have been shown to worsen outcomes. However, thus far studies have only evaluated delays to initial treatment, or a particular modality, such as chemotherapy, leaving uncertainty about the role of delay to subsequent therapy and the effects of cumulative delay, on outcomes. We investigated the associations of delays across treatment modalities with survival. METHODS: We included 3368 women with incident stage I-III BC in the Women's Health Initiative (WHI) enrolled in fee-for-service Medicare who underwent definitive surgery. This prospective analysis characterized treatment delays by linking WHI study records to Medicare claims. Delays were defined as > 8 weeks to surgery, chemotherapy, and radiation from diagnosis or prior treatment. We used Cox proportional hazards models to estimate BC-specific mortality (BCSM) and all-cause mortality (ACM) in relation to treatment delays. RESULTS: We found 21.8% of women experienced delay to at least one therapy modality. In adjusted analysis, delay to chemotherapy was associated with a higher risk of BCSM (HR = 1.71; 95% CI 1.07-2.75) and ACM (HR = 1.39; 95% CI 1.02-1.90); delay in radiation increased BCSM risk (HR = 1.49; 95% CI 1.00-2.21) but not ACM risk (HR = 1.19; 95% CI 0.99-1.42). Delays across multiple treatment modalities increased BCSM risk threefold (95% CI 1.51-6.12) and ACM risk 2.3-fold (95% CI 1.50-3.50). CONCLUSIONS: A delay to a single treatment modality and delay to a greater extent an accumulation of delays were associated with higher BCSM and ACM after BC. Timely care throughout the continuum of breast cancer treatment is important for optimal outcomes.

Contemporary multicenter outcomes of continent cutaneous ileocecocystoplasty in the adult population over a 10-year period: A Neurogenic Bladder Research Group study.

AIMS: Evidence is sparse on the long-term outcomes of continent cutaneous ileocecocystoplasty (CCIC). We hypothesized that obesity, laparoscopic/robotic approach, and concomitant surgeries would affect morbidity after CCIC and aimed to evaluate the outcomes of CCIC in adults in a multicenter contemporary study. METHODS: We retrospectively reviewed the charts of adult patients from sites in the Neurogenic Bladder Research Group undergoing CCIC (2007-2017) who had at least 6 months of follow-up. We evaluated patient demographics, surgical details, 90-day complications, and follow-up surgeries. the Mann-Whitney U test was used to compare continuous variables and χ² and Fisher's Exact tests were used to compare categorical variables. RESULTS: We included 114 patients with a median age of 41 years. The median postoperative length of stay was 8 days. At 3 months postoperatively, major complications occurred in 18 (15.8%), and 24 patients (21.1%) were readmitted. During a median follow-up of 40 months, 48 patients (42.1%) underwent 80 additional related surgeries. Twenty-three patients (20.2%) underwent at least one channel revision, most often due to obstruction (15, 13.2%) or incontinence (4, 3.5%). Of the channel revisions, 10 (8.8%) were major and 14 (12.3%) were minor. Eleven patients (9.6%) abandoned the catheterizable channel during the follow-up period. Obesity and laparoscopic/robotic surgical approach did not affect outcomes, though concomitant surgery was associated with a higher rate of follow-up surgeries. CONCLUSIONS: In this contemporary multicenter series evaluating CCIC, we found that the short-term major complication rate was low, but many patients require follow-up surgeries, mostly related to the catheterizable channel.

Frequency of patient-reported UTIs is associated with poor quality of life after spinal cord injury: a prospective observational study.

STUDY DESIGN: Cross-sectional survey of the Neurogenic Bladder Research Group (NBRG) registry; a multicenter prospective observation study. OBJECTIVES: To assess how patient-reported urinary tract infections (PRUTIs) in spinal cord injury (SCI) affect quality of life (QOL). SETTING: Multiple United States hospitals. METHODS: 1479 participants with SCI were asked about neurogenic bladder-related QOL. Eligibility: age ≥ 18 years with acquired SCI. PRUTI frequency over the last year was classified as 0, 1-3, 4-6, or >6. Four UTI QOL domains were assessed: (1) UTIs limited daily activities, (2) UTIs caused increased muscle spasms, (3) UTIs would not go away, and (4) UTIs made me avoid going out. Multivariable regression identified variables associated with poor QOL. RESULTS: PRUTI frequency was 0 in 388 patients (26%), 1-3 in 677 (46%), 4-6 in 223 (15%), and more than 6 in 190 (13%). Increasing PRUTI rate was independently associated with worse QOL for all four questions. Compared with those with 0 PRUTIs, participants reporting >6 were more likely to limit daily activities (OR 9.0 [95% CI 8.1-21.2] p < 0.0001), experience increased muscle spasms (OR 12.4 [95% CI 7.5-20.6] p < 0.0001), perceive a UTI would not go away (OR 30.1 [95% CI 15.0-60.4] p < 0.0001), and avoid going out because of UTIs (OR 7.2 [95% CI 4.2-12.4] p < 0.0001). CONCLUSIONS: An increasing rate of PRUTIs is independently associated with worse QOL. Thorough evaluation and treatment may improve QOL in this population.

Epidural Analgesia Decreases Narcotic Requirements in Patients with Low Level Spina Bifida Undergoing Urological Laparotomy for Neurogenic Bladder and Bowel.

PURPOSE: Concerns regarding anatomical anomalies and worsening neurological symptoms have prevented widespread use of epidural catheters in patients with low level spina bifida. We hypothesize that thoracic epidural placement in the T9 to T10 interspace is safe and decreases narcotic requirements following major open lower urinary tract reconstruction in patients with low level spina bifida. MATERIALS AND METHODS: We reviewed consecutive patients with low level spina bifida who underwent lower urinary tract reconstruction and received epidurals for postoperative pain control. Controls were patients with low level spina bifida who received single injection transversus abdominis plane blocks and underwent similar procedures. Complications of epidural placement, including changes in motor and sensory status, were recorded. Opioid consumption was calculated using equivalent intravenous morphine doses. Mean and maximum pain scores on postoperative days 0 to 3 were calculated. RESULTS: Ten patients with low level spina bifida who underwent lower urinary tract reconstruction with epidural were matched to 10 controls with low level spina bifida who underwent lower urinary tract reconstruction with transverse abdominis plane block. Groups were demographically similar. All patients had full abdominal sensation and functional levels at or below L3. No epidural complications or changes in neurological status were noted. The epidural group had decreased opioid consumption on postoperative days 0 to 3 (0.75 mg/kg vs 1.29 mg/kg, p = 0.04). Pain scores were similar or improved in the epidural group. CONCLUSIONS: Thoracic epidural analgesia appears to be a safe and effective opioid sparing option to assist with postoperative pain management following lower urinary tract reconstruction in individuals with low level spina bifida.

Radiographic abnormalities, bladder interventions, and bladder surgery in the first decade of life in children with spina bifida.

BACKGROUND: Spina bifida (SB) patients are at increased risk for hydronephrosis, bladder storage and emptying problems, and renal failure that may require multiple bladder surgeries. METHODS: We retrospectively reviewed patients born with SB 2005-2009, presenting to our institution within 1 year of birth. Outcomes at 8-11 years old included final renal/bladder ultrasound (RBUS) results, clean intermittent catheterization (CIC) use, anticholinergic use, surgical interventions, and final renal function. We excluded those without follow-up past age 8 and/or no RBUS or fluoroscopic urodynamic images (FUI) within the first year of life. Imaging was independently reviewed by four pediatric urologists blinded to radiologists' interpretation and initial findings compared with final outcomes. RESULTS: Of 98 children, 62 met inclusion criteria (48% male, 76% shunted). Median age at last follow-up was 9.6 years. Upon initial imaging, 74% had hydronephrosis (≥ SFU grade 1), decreasing to 5% at 10 years (p < 0.0001). Initially, 9% had ≥ SFU grade 3 hydronephrosis, decreasing to 2% (p = 0.13). CIC and anticholinergic use increased from 61% and 37% to 87% and 86%, respectively (p = 0.001 and p < 0.0001, respectively). With follow-up, 55% had surgical intervention and 23% had an augmentation. Of children with a serum creatinine/cystatin-C at 8-11 years old, one had confirmed chronic kidney disease (stage 2). CONCLUSIONS: Despite initial high incidence of hydronephrosis, this was low grade and resolved in the first decade of life. Additionally, the 8-11-year incidence of kidney disease and upper tract changes was low due to aggressive medical management.

Patient subjective assessment of urinary tract infection frequency and severity is associated with bladder management method in spinal cord injury.

STUDY DESIGN: The Neurogenic Bladder Research Group (NBRG) registry is a multicenter prospective observational study. This manuscript is retrospective based on a cross-sectional survey. OBJECTIVES: To assess patient subjective assessment of urinary tract infection (UTI) frequency and severity are associated with the degree of use of catheters or incontinence products. SETTING: Multiple hospitals across the United States. METHODS: Eligibility included: age > 18 years and acquired SCI. Over 1.5 years, 1479 eligible participants were enrolled. We excluded those with surgical reconstruction or diversion of the bladder. In total, 1282 participants were grouped by bladder management: (1) indwelling catheter (IDC), (2) clean intermittent catheterization (CIC), (3) external devices (pads/condom), and (4) volitional voiding (Void). UTI frequency was classified as 0, 1-3, 4-6, or > 6 over the prior year. UTI severity was determined by hospitalization for UTI in the prior year. Multivariate regression compared these factors across groups. RESULTS: UTIs were least frequent in Void followed by pads/condom, CIC, and IDC (all p ≤ 0.001). UTI severity followed a similar pattern. Controlling for covariates, the adjusted odds of UTI frequency (Void = reference) were 2.28 (1.38-3.76) for pads/condom, 3.42 (2.25-5.18) for CIC, and 4.3 (2.59-6.70) for IDC (all p ≤ 0.001). CONCLUSIONS: Patient subjective assessment of UTI frequency is highest with IDC, followed by CIC, pads/condom, and lowest with spontaneous voiding. The odds of hospitalization for UTI were three times higher for IDC than spontaneous voiding. UTI risk should be considered when counseling patients about bladder management options. These associations do not imply causation but warrant further investigation in a prospective manner. SPONSORSHIP: Patient-Centered Outcomes Research Institute (PCORI) Award (CER14092138).

Kinematically aligned total knee arthroplasty limits high tibial forces, differences in tibial forces between compartments, and abnormal tibial contact kinematics during passive flexion.

PURPOSE: Following total knee arthroplasty (TKA), high tibial forces, large differences in tibial forces between the medial and lateral compartments, and anterior translation of the contact locations of the femoral component on the tibial component during passive flexion indicate abnormal knee function. Because the goal of kinematically aligned TKA is to restore native knee function without soft tissue release, the objectives were to determine how well kinematically aligned TKA limits high tibial forces, differences in tibial forces between compartments, and anterior translation of the contact locations of the femoral component on the tibial component during passive flexion. METHODS: Using cruciate retaining components, kinematically aligned TKA was performed on thirteen human cadaveric knee specimens with use of manual instruments without soft tissue release. The tibial forces and tibial contact locations were measured in both the medial and lateral compartments from 0° to 120° of passive flexion using a custom tibial force sensor. RESULTS: The average total tibial force (i.e. sum of medial + lateral) ranged from 5 to 116 N. The only significant average differences in tibial force between compartments occurred at 0° of flexion (29 N, p = 0.0008). The contact locations in both compartments translated posteriorly in all thirteen kinematically aligned TKAs by an average of 14 mm (p < 0.0001) and 18 mm (p < 0.0001) in the medial and lateral compartments, respectively, from 0° to 120° of flexion. CONCLUSIONS: After kinematically aligned TKA, average total tibial forces due to the soft tissue restraints were limited to 116 N, average differences in tibial forces between compartments were limited to 29 N, and a net posterior translation of the tibial contact locations was observed in all kinematically aligned TKAs during passive flexion from 0° to 120°, which are similar to what has been measured previously in native knees. While confirmation in vivo is warranted, these findings give surgeons who perform kinematically aligned TKA confidence that the alignment method and surgical technique limit high tibial forces, differences in tibial forces between compartments, and anterior translation of the tibial contact locations during passive flexion.

Increases in tibial force imbalance but not changes in tibiofemoral laxities are caused by varus-valgus malalignment of the femoral component in kinematically aligned TKA.

PURPOSE: The purposes of this study were to quantify the increase in tibial force imbalance (i.e. magnitude of difference between medial and lateral tibial forces) and changes in laxities caused by 2° and 4° of varus-valgus (V-V) malalignment of the femoral component in kinematically aligned total knee arthroplasty (TKA) and use the results to detemine sensitivities to errors in making the distal femoral resections. Because V-V malalignment would introduce the greatest changes in the alignment of the articular surfaces at 0° flexion, the hypotheses were that the greatest increases in tibial force imbalance would occur at 0° flexion, that primarily V-V laxity would significantly change at this flexion angle, and that the tibial force imbalance would increase and laxities would change in proportion to the degree of V-V malalignment. METHODS: Kinematically aligned TKA was performed on ten human cadaveric knee specimens using disposable manual instruments without soft tissue release. One 3D-printed reference femoral component, with unmodified geometry, was aligned to restore the native distal and posterior femoral joint lines. Four 3D-printed femoral components, with modified geometry, introduced V-V malalignments of 2° and 4° from the reference component. Medial and lateral tibial forces were measured during passive knee flexion-extension between 0° to 120° using a custom tibial force sensor. Eight laxities were measured from 0° to 120° flexion using a six degree-of-freedom load application system. RESULTS: With the tibial component kinematically aligned, the increase in the tibial force imbalance from that of the reference component at 0° of flexion was sensitive to the degree of V-V malalignment of the femoral component. Sensitivities were 54 N/deg (medial tibial force increasing > lateral tibial force) (p < 0.0024) and 44 N/deg (lateral tibial force increasing > medial tibial force) (p < 0.0077) for varus and valgus malalignments, respectively. Varus-valgus malalignment did not significantly change varus, internal-external rotation, anterior-posterior, and compression-distraction laxities from 0° to 120° flexion. At only 30° of flexion, 4° of varus malalignment increased valgus laxity 1° (p = 0.0014). CONCLUSION: At 0° flexion, V-V malalignment of the femoral component caused the tibial force imbalance to increase significantly, whereas the laxities were relatively unaffected. Because tibial force imbalance has the potential to adversely affect patient-reported outcomes and satisfaction, surgeons should strive to limit errors in resecting the distal femoral condyles to within ± 0.5 mm which in turn limits the average increase in tibial force imbalance to 68 N. Because laxities were generally unaffected, instability resulting from large increases in laxity is not a clinical concern within the ± 4° range tested. LEVEL OF EVIDENCE: Therapeutic, Level II.

Internal-external malalignment of the femoral component in kinematically aligned total knee arthroplasty increases tibial force imbalance but does not change laxities of the tibiofemoral joint.

PURPOSE: The purposes of this study were to quantify the increase in tibial force imbalance (i.e. magnitude of difference between medial and lateral tibial forces) and changes in laxities caused by  2° and 4° of internal-external (I-E) malalignment of the femoral component in kinematically aligned total knee arthroplasty. Because I-E malalignment would introduce the greatest changes to the articular surfaces near 90° of flexion, the hypotheses were that the tibial force imbalance would be significantly increased near 90° flexion and that primarily varus-valgus laxity would be affected near 90° flexion. METHODS: Kinematically aligned TKA was performed on ten human cadaveric knee specimens using disposable manual instruments without soft tissue release. One 3D-printed reference femoral component, with unmodified geometry, was aligned to restore the native distal and posterior femoral joint lines. Four 3D-printed femoral components, with modified geometry, introduced I-E malalignments of 2° and 4° from the reference component. Medial and lateral tibial forces were measured from 0° to 120° flexion using a custom tibial force sensor. Bidirectional laxities in four degrees of freedom were measured from 0° to 120° flexion using a custom load application system. RESULTS: Tibial force imbalance increased the greatest at 60° flexion where a regression analysis against the degree of I-E malalignment yielded sensitivities (i.e. slopes) of 30 N/° (medial tibial force > lateral tibial force) and 10 N/° (lateral tibial force > medial tibial force) for internal and external malalignments, respectively. Valgus laxity increased significantly with the 4° external component with the greatest increase of 1.5° occurring at 90° flexion (p < 0.0001). CONCLUSION: With the tibial component correctly aligned, I-E malalignment of the femoral component caused significant increases in tibial force imbalance. Minimizing I-E malalignment lowers the increase in the tibial force imbalance. By keeping the resection thickness of each posterior femoral condyle to within ± 0.5 mm of the thickness of the respective posterior region of the femoral component, the increase in imbalance can be effectively limited to 38 N. Generally laxities were unaffected within the ± 4º range tested indicating that instability is not a clinical concern and that manual testing of laxities is not useful to detect I-E malalignment.

A novel technique for direct visualization of reservoir placement for penoscrotal inflatable penile prostheses using a single incision.

INTRODUCTION: We aim to present a modified technique and outcomes of a novel method allowing for direct visualization of the reservoir placement during a penoscrotal inflatable penile prosthesis (IPP). METHODS: Out of165 patients who underwent IPP placement from August 2012 to March 2015, 157 underwent a modified technique and comprised the cohort of this study. A Deaver's retractor was placed lateral to the penis and over the pubic bone to allow for direct visualization of the tissues overlying the lower abdomen. After dissecting through the superficial layers, the Deaver's was slowly advanced, allowing for visualization of the fascia, which was incised. Using blunt dissection, a space for the reservoir was created between the bladder and the pubic bone. The reservoir was then placed safely into this space and the Deaver's retractor was removed. RESULTS: The causes of ED in the study cohort included postprostatectomy ED (n = 107), organic impotence (n = 40), Peyronie's disease (n = 3), ED following cystoprostatectomy (n = 2), ED due to spinal cord injury (n = 2), ED resulting from priapism (n = 2), and ED after pelvic injury (n = 1); all of which were refractory to medical management. The median age of study population was 66 years and the mean (standard deviation) operative time was 72.8 (14.7) min. Eighty percent of the procedures were performed on outpatient basis. Complication rates were low (<5%), with four infections, one proximal pump migration, one scrotal hematoma, and one urinary tract infection. CONCLUSION: The modified technique for placement of the IPP's spherical reservoir under direct visualization through a penoscrotal incision is quick, safe, and effective.

Survival Gains from First-Line Systemic Therapy in Metastatic Non-Small Cell Lung Cancer in the U.S., 1990-2015: Progress and Opportunities.

BACKGROUND: Approximately 190,000 Americans are diagnosed with non-small cell lung cancer (NSCLC) annually, and about half have metastatic (Stage IV) disease. These patients have historically had poor survival prognosis, but several new therapies introduced since 2000 provide options for improved outcomes. The objectives of this study were to quantify survival gains from 1990, when best supportive care (BSC) only was standard, to 2015 and to estimate the impact of expanded use of systemic therapies in clinically appropriate patients. MATERIALS AND METHODS: We developed a simulation model to estimate survival gains for patients with metastatic NSCLC from 1990-2015. Survival estimates were derived from major clinical trials and extrapolated to a lifetime horizon. Proportions of patients receiving available therapies were derived from the Surveillance, Epidemiology, and End Results database and a commercial treatment registry. We also estimated gains in overall survival (OS) in scenarios in which systemic therapy use increased by 10% and 30% relative to current use. RESULTS: From 1990-2015, one-year survival proportion increased by 14.1% and mean per-patient survival improved by 4.2 months (32,700 population life years). Increasing treated patients by 10% or 30% increased OS by 5.1 months (39,700 population life years) and 6.9 months (53,800 population life years), respectively. CONCLUSION: Although survival remains poor in metastatic NSCLC relative to other common cancers, meaningful progress in per-patient and population-level outcomes has been realized over the past 25 years. These advances can be improved even further by increasing use of systemic therapies in the substantial proportion of patients who are suitable for treatment yet who currently receive BSC only. The Oncologist 2017;22:304-310 IMPLICATIONS FOR PRACTICE: Approximately 93,500 Americans are diagnosed with metastatic non-small cell lung cancer (NSCLC) annually. Historically, these patients have had poor survival prognosis, but newer therapies provide options for improved outcomes. This simulation modeling study quantified metastatic NSCLC survival gains from 1990-2015. Over this period, the one-year survival proportion and mean per-patient survival increased by 14.1% and 4.2 months, respectively. Though metastatic NSCLC survival remains poor, the past 25 years have brought meaningful gains. Additional gains could be realized by increasing systemic therapy use in the substantial proportion of patients who are suitable for treatment, yet currently receive only supportive care.

A qualitative study exploring why individuals opt out of lung cancer screening.

Background: Lung cancer screening with annual low-dose computed tomography is relatively new for long-term smokers in the USA supported by a US Preventive Services Task Force Grade B recommendation. As screening programs are more widely implemented nationally and providers engage patients about lung cancer screening, it is critical to understand behaviour among high-risk smokers who opt out to improve shared decision-making processes for lung cancer screening. Objective: The purpose of this study was to explore the reasons for screening-eligible patients' decisions to opt out of screening after receiving a provider recommendation. Methods: Semi-structured qualitative telephone interviews were performed with 18 participants who met lung cancer screening criteria for age, smoking and pack-year history in Washington State from November 2015 to January 2016. Two researchers with cancer screening and qualitative methodology expertise conducted data analysis using thematic content analytic procedures from audio-recorded interviews. Results: Five primary themes emerged for reasons of opting out of lung cancer screening: (i) Knowledge Avoidance; (ii) Perceived Low Value; (iii) False-Positive Worry; (iv) Practical Barriers; and (v) Patient Misunderstanding. Conclusion: The participants in our study provided insight into why some patients make the decision to opt out of low-dose computed tomography screening, which provides knowledge that can inform intervention development to enhance shared decision-making processes between long-term smokers and their providers and decrease decisional conflict about screening.

Characterization and Correction of Errors in Computing Contact Location Between Curved Articular Surfaces: Application to Total Knee Arthroplasty.

In total knee arthroplasty (TKA), one common metric used to evaluate innovations in component designs, methods of component alignment, and surgical techniques aimed at decreasing the high rate of patient-reported dissatisfaction is tibiofemoral contact kinematics. Tibiofemoral contact kinematics are determined based on the movement of the contact locations in the medial and lateral compartments of the tibia during knee flexion. A tibial force sensor is a useful instrument to determine the contact locations, because it can simultaneously determine contact forces and contact locations. Previous reports of tibial force sensors have neither characterized nor corrected errors in the computed contact location (i.e., center of pressure) between the femoral and tibial components in TKA that, based on a static analysis, are caused by the curved articular surface of the tibial component. The objectives were to experimentally characterize these errors and to develop and validate an error correction algorithm. The errors were characterized by calculating the difference between the errors in the computed contact locations when forces were applied normal to the tibial articular surface and those when forces were applied normal to the tibial baseplate. The algorithm generated error correction functions to minimize these errors and was validated by determining how much the error correction functions reduced the errors in the computed contact location caused by the curved articular surface. The curved articular surface primarily caused bias (i.e., average or systematic error) which ranged from 1.0 to 2.7 mm in regions of high curvature. The error correction functions reduced the bias in these regions to negligible levels ranging from 0.0 to 0.6 mm (p < 0.001). Bias in the computed contact locations caused by the curved articular surface of the tibial component as small as 1 mm needs to be accounted for, because it might inflate the computed internal-external rotation and anterior-posterior translation of femur on the tibia leading to false identifications of clinically undesirable contact kinematics (e.g., internal rotation and anterior translation during flexion). Our novel error correction algorithm is an effective method to account for this bias to more accurately compute contact kinematics.