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Obesity disproportionately affects African American (AA) women and has been shown to increase ovarian cancer risk, with some suggestions that the association may differ by race.We evaluated body mass index (BMI) and invasive epithelial ovarian cancer (EOC) risk in a pooled study of case-control and nested case-control studies including AA and White women. We evaluated both young adult and recent BMI (within the last 5 years). Associations were estimated using multi-level and multinomial logistic regression models.The sample included 1078 AA cases, 2582 AA controls, 3240 White cases and 9851 White controls. We observed a higher risk for the non-high-grade serous (NHGS) histotypes for AA women with obesity (ORObesity contributes to NHGS EOC risk in AA and White women, but risk across racial groups studied differs by HT use and histotype.

Chlamydia is the most frequently reported sexually transmitted infection. COVID-19 exacerbated the challenges in treating and preventing new Chlamydia trachomatis (CT) infections. This study examined the impact of COVID-19 on treating CT-positive patients discharged from a safety-net women's emergency unit.This was a preretrospective and postretrospective cohort study. Chlamydia trachomatis -positive female patients seen in the women's emergency unit were evaluated. Patients discharged in 2019, the "pre-COVID-19" group, and those discharged in 2020, the "COVID-19" group, were compared. The primary outcome was CT treatment within 30 days, and secondary outcomes included prescription dispensation, repeat tests taken, and expedited partner treatment. A subgroup of patients discharged before treatment who entered a nurse-led follow-up program was also evaluated.Of the 1357 cases included, there were no differences in successful 30-day treatment (709 of 789 [89.9%] vs. 568 of 511 [89.9%], P = 0.969) or repeat positive CT test (74 of 333 [22.2%] vs. 46 of 211 [21.8%]), P = 0.36) between pre-COVID-19 and COVID-19. However, the patients who picked up their prescription (196 of 249 [78.7%] vs. 180 of 206 [87.4%], P = 0.021) and those who were prescribed expedited partner therapy (156 of 674 [23.1%] vs. 292 of 460 [63.5%], Plt; 0.001) increased. Findings in the subgroup of patients who entered the follow-up program were consistent with those in the full cohort.The COVID-19 pandemic did not change treatment patterns of CT-positive patients in this safety-net women's emergency unit. However, patients were more likely to pick up their medications during COVID-19. Despite the perseverance of these programs through the pandemic, most patients are discharged before positive results, and a fair amount remain untreated.

Lay abstract This study describes treatment patterns and outcomes in newly diagnosed multiple myeloma (NDMM) patients in Spain who were not candidates for transplant. The study looked at two patient groups: patients diagnosed between 1 January 2012 and 31 December 2013 and those diagnosed between 1 April 2016 and 31 March 2017. Among the 113 patients considered, the most common first-line therapies were proteasome inhibitor (PI) + alkylator combinations (49%) and PI-based regimens without an alkylator (30%). We saw increased use of PI with immunomodulators (which arm the immune system to battle disease) and decreased use of PI-based regimens without an alkylator or immunomodulator. First-line use of oral regimens was low but increased over time. The median length of first-line treatment for both groups combined was 6.9 months. Finding low use of first-line oral regimens and maintenance therapy and a short duration of first-line treatment, our study highlights the unmet needs that exist in NDMM patients who are not transplant candidates in Spain. Aim: To describe treatment patterns and outcomes in nontransplant newly diagnosed multiple myeloma (NDMM) patients in Spain. Methods: This retrospective study included two cohorts of NDMM patients diagnosed between 1 January 2012 to 31 December 2013 and 1 April 2016 to 31 March 2017. Results: Among 113 patients, proteasome inhibitor (PI) + alkylator combinations (49%) and PI-based regimens without an alkylator (30%) were the most common first-line (1L) therapies. Use of PI + immunomodulatory drug-based regimens increased between the cohorts; PI-based regimens without an alkylator/immunomodulatory drug decreased. Use of 1L oral regimens was low but increased over time; use of maintenance therapy was low across both periods. Median 1L duration of treatment was 6.9 months. Conclusion: Short 1L duration of treatment and low use of 1L oral regimens and maintenance therapy highlight unmet needs in NDMM.

ObjectiveIn our public health system, a survey of reproductive-aged women identified lack of childcare as the most common reason for missing or delaying healthcare. Community-based organisations (CBOs) in our county identified a similar need, so we partnered to develop a hospital-based childcare centre for patients to use during appointments.MethodsIn a large academic public health system, a partnership with a non-profit childcare CBO was formed to address lack of childcare as a barrier to accessing healthcare. Pilot clinics where no-cost childcare would be offered included obstetrics, gynaecology and medical oncology. Transparent communication from the CBO within the electronic medical record was built to minimally impact clinic workflows. Visual and electronic outreach, including patient portal questionnaires, were created to introduce patients to the services. Personalised clinic staff in-services were performed to introduce the service to clinics and leadership. Continual assessments of workflow were conducted and adjusted based on patient and staff feedback and quality checks. At 12 months, overall utilisation of the service was collected.ResultsIn the first 12 months that no-cost childcare was offered, 175 patients enrolled 271 children into the programme. Ninety-seven percent were women, primarily Hispanic (87/175 (50%)) or black (64/175 (37%)), with an average age of 31.8 years. Of the enrollees, 142/175 (81%) patients made 637 childcare appointments and 119/175 (68%) patients used at least one reservation for 191 children. Most patients were verbally referred by clinic staff for childcare or self-referred for childcare from clinic signage or paperwork. Childcare was requested most frequently for obstetrics and gynaecology appointments.

Aim: To understand physician visit patterns among patients with stage IV (including nonmetastatic [M0] and metastatic [M1] disease) urothelial carcinoma (UC) and understand factors associated with a timely referral to a medical oncologist and systemic treatment. Patients & methods: Retrospective analysis of Surveillance, Epidemiology and End Results-Medicare data. Results: First physician encounter was with a urologist (M0: 69%; M1: 53%) or primary care physician ([PCP]; M0: 19%, M1: 25%) for the majority of patients around UC diagnosis. After the index urologist encounter, most patients had a subsequent medical oncologist visit at a median of 52 days (M0: 69.5 days, M1: 33 days). In an adjusted model, older age, index PCP visit, higher comorbidities and M0 disease were negatively associated with a medical oncologist referral. Among those referred to a medical oncologist, older age, Hispanic or non-Hispanic Black race and not being married were negatively associated with subsequent chemotherapy receipt (p < 0.05). Conclusion: Many patients with advanced UC encounter multiple specialists during their disease course. Older patients or those with a first UC-related encounter with a PCP are less likely to be referred to medical oncology. Once referred to medical oncology, social determinants, including race and marital status, are relevant predictors of receiving chemotherapy.

Background In a randomized study, glasdegib (a hedgehog inhibitor) plus low‐dose cytarabine (LDAC) significantly prolonged survival in comparison with LDAC in patients with acute myeloid leukemia (AML). A quality‐adjusted time without symptoms of disease progression or toxicity (Q‐TWiST) approach was used to evaluate comparative quality‐adjusted survival. Methods Overall survival was partitioned into the following: time with any treatment‐emergent grade 3 or higher adverse events (TOX); time without symptoms of disease progression or toxicity (TWiST); and time after treatment discontinuation due to insufficient clinical response, relapse, or death time after progression (REL). Q‐TWiST was calculated by multiplying the restricted mean time in each state by respective utilities and then summing up the utility‐adjusted time. Results At 20 months of follow‐up, the survival probabilities for the glasdegib‐LDAC arm and the LDAC arm were 28.2% and 7.9%, respectively. Glasdegib‐LDAC patients (n = 78), in comparison with LDAC patients (n = 38), had significantly longer mean TWiST (+3.4 months; 95% confidence interval [CI], 1.8‐5.2 months) and TOX (+0.8 months; 95% CI, 0.1‐1.6 months) and longer but nonsignificant REL (+0.3 months; 95% CI, −1.9 to 2.3 months). Q‐TWiST was 4.0 months (95% CI, 2.1‐5.8 months) longer with glasdegib plus LDAC, and this translated into a 75% relative improvement in quality‐adjusted survival with respect to LDAC. Results were robust to the length of follow‐up (6‐24 months) and remained significant when all adverse events, regardless of grade, were included. Conclusions These results suggest that most of the survival benefit from glasdegib plus LDAC versus LDAC alone is TWiST, and this represents added time in relatively “good” health. These results support the clinical value of glasdegib plus LDAC as initial therapy for AML in patients for whom intensive chemotherapy is not an option., This analysis suggests that most of the survival benefit from glasdegib plus low‐dose cytarabine (LDAC) in comparison with LDAC alone is time without symptoms of disease progression or toxicity, which represents added time in relatively “good” health. These results support the clinical value of glasdegib plus LDAC as an initial therapy for acute myeloid leukemia in patients for whom intensive chemotherapy is not an option.

In the United States, racial/ethnic and sexual youth and young adults (YYA) of color are disproportionately affected by HIV. Subsequently, YYA experience HIV stigma and engage in increased risk behaviors and reduced HIV testing. HIV communication has been identified as a potential buffer to HIV stigma, resulting in health-seeking behaviors, such as HIV testing. In this study, we respond to a meaningful gap in the literature by examining different types of HIV communication and their impact on HIV stigma and HIV testing in a diverse sample of YYA. We analyzed secondary data from the Kaiser Family Foundation National Survey of Teens and Young Adults on HIV/AIDS. A 40-question, web-based survey was conducted with 1437 youth (ages 15–24). Recruitment included a dual sampling method from households with: (1) listed phone numbers, (2) unlisted phone numbers, (3) telephones, (4) no telephone, and (5) only cell phone access. The purpose of the survey was to establish participants’ HIV knowledge, communication, experiences, and testing behaviors. Findings suggested an association between intimate-partner HIV communication, increased HIV testing, and reduced HIV stigma. We also identified differentials in HIV testing and stigma based on gender, income, age, and sexual minority status, explained by HIV communication. Further research is needed that examines ways to use intimate-partner HIV communication to reduce stigma and increase HIV testing among YYA of different sociodemographic characteristics and sexual orientations.

The seventh multi-stakeholder Paediatric Strategy Forum focused on chimeric antigen receptor (CAR) T-cells for children and adolescents with cancer. The development of CAR T-cells for patients with haematological malignancies, especially B-cell precursor acute lymphoblastic leukaemia (BCP-ALL), has been spectacular. However, currently, there are scientific, clinical and logistical challenges for use of CAR T-cells in BCP-ALL and other paediatric malignancies, particularly in acute myeloid leukaemia (AML), lymphomas and solid tumours. The aims of the Forum were to summarise the current landscape of CAR T-cell therapy development in paediatrics, too identify current challenges and future directions, with consideration of other immune effector modalities and ascertain the best strategies to accelerate their development and availability to children. Although the effect is of limited duration in about half of the patients, anti-CD19 CAR T cells produce high response rates in relapsed/refractory BCP-ALL and this has highlighted previously unknown mechanisms of relapse. CAR T-cell treatment as first-or second-line therapy could also potentially benefit patients whose disease has high-risk features associated with relapse and failure of conventional therapies. Identifying patients with very early and early relapse in whom CAR T-cell therapy may replace haematopoietic stem cell transplanta-tion and be definitive therapy versus those in whom it provides a more effective bridge to hae-matopoietic stem cell transplantation is a very high priority. Development of approaches to improve persistence, either by improving T cell fitness or using more humanised/fully huma-nised products and co-targeting of multiple antigens to prevent antigen escape, could potentially further optimise therapy. Many differences exist between paediatric B-cell non-Hodgkin lymphomas (B-NHL) and BCP-ALL. In view of the very small patient numbers with relapsed lymphoma, careful prior-itisation is needed to evaluate CAR T-cells in children with Burkitt lymphoma, primary medi-astinal B cell lymphoma and other NHL subtypes. Combination trials of alternative targets to CD19 (CD20 or CD22) should also be explored as a priority to improve efficacy in this pop-ulation. Development of CD30 CAR T-cell immunotherapy strategies in patients with relapsed/refractory Hodgkin lymphoma will likely be most efficiently accomplished by joint paediatric and adult trials.CAR T-cell approaches are early in development for AML and T-ALL, given the unique challenges of successful immunotherapy actualisation in these diseases. At this time, CD33 and CD123 appear to be the most universal targets in AML and CD7 in T-ALL. The results of ongoing or planned first-in-human studies are required to facilitate further understanding. There are promising early results in solid tumours, particularly with GD2 targeting cell ther-apies in neuroblastoma and central nervous system gliomas that represent significant unmet clinical needs. Further understanding of biology is critical to success.The comparative benefits of autologous versus allogeneic CAR T-cells, T-cells engineered with T cell receptors T-cells engineered with T cell receptor fusion constructs, CAR Natural Killer (NK)-cell products, bispecific T-cell engager antibodies and antibody-drug conjugates require evaluation in paediatric malignancies.Early and proactive academia and multi-company engagement are mandatory to advance cellular immunotherapies in paediatric oncology. Regulatory advice should be sought very early in the design and preparation of clinical trials of innovative medicines, for which regu-latory approval may ultimately be sought. Aligning strategic, scientific, regulatory, health technology and funding requirements from the inception of a clinical trial is especially impor-tant as these are very expensive therapies.The model for drug development for cell therapy in paediatric oncology could also involve a 'later stage handoff' to industry after early development in academic hands. Finally, and very importantly, strategies must evolve to ensure appropriate ease of access for children who need and could potentially benefit from these therapies. 2021 The Author(s). Published by Elsevier Ltd. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

To determine predictors of obstructive sleep apnea (OSA) in underweight children and to describe the demographic, clinical, and polysomnographic characteristics of an ethnically diverse population of underweight children with OSA.Case-control study.University of Texas Southwestern Medical Center and Children's Medical Center of Dallas.Underweight children aged 2 to 18 years who underwent a polysomnogram for suspected OSA between January 2014 and December 2020 were included. Underweight was defined as body mass index5th percentile per Centers for Disease Control and Prevention guidelines. Children with apnea-hypopnea index1.0 served as a control group. Univariate and multiple logistic regression analysis was used to determine the predictors of OSA. Significance was set atAn overall 124 children met inclusion criteria: mean age, 6.4 years; 50% female; 44% Hispanic, 31% African American, and 18% Caucasian. A total of 83 children had OSA (apnea-hypopnea index ≥1.0). Height was negatively correlated with OSA (odds ratio, 0.94; 95% CI, 0.88-0.99;Underweight children with OSA, as compared with those without OSA, are more likely to have decreased height, tonsillar hypertrophy, and allergic rhinitis. There are no predictors of severe OSA in underweight children. We recommend polysomnography for the diagnosis of OSA in symptomatic underweight children with large tonsils, especially when they have a history of allergies.

Aim: To describe treatment patterns and outcomes of patients with unresectable stage III and metastatic/stage IV melanoma. Materials & methods: An observational retrospective chart review of patients diagnosed with advanced melanoma before 1 November 2015 who initiated a new line of therapy (LOT) from 1 January 2015 to 31 May 2016. Results: Among 487 patients, ipilimumab monotherapy (27.5%) was the most common first line of therapy (1LOT) in 2015, surpassed by nivolumab monotherapy (21.5%) in 2016. 12-month survival was ≥80.1%; proportions were highest forpatients treated with nivolumab + ipilimumab (86.6%). All treatments relatively well tolerated in real-world setting and adverse events were consistent with the previously reported safety profiles. Conclusion: This study provides important insights into real-world advanced melanoma treatment patterns and demonstrates encouraging treatment safety and patient survival data.

Background: Early antibiotic switch and early discharge protocols have not been widely studied in Latin America. Our objective was to describe real-world treatment patterns, resource use, and estimate opportunities for early switch from intravenous to oral antibiotics and early discharge for patients hospitalized with methicillin-resistant Staphylococcus aureus complicated skin and soft-tissue infections. Materials/methods: This retrospective medical chart review recruited 72 physicians from Brazil to collect data from patients hospitalized with documented methicillin-resistant Staphylococcus aureus complicated skin and soft tissue infections between May 2013 and May 2015, and discharged alive by June 2015. Data collected included clinical characteristics and outcomes, hospital length of stay, methicillin-resistant Staphylococcus aureus-targeted intravenous and oral antibiotic use, and early switch and early discharge eligibility using literature-based and expert-validated criteria. Results: A total of 199 patient charts were reviewed, of which 196 (98.5%) were prescribed methicillin-resistant Staphylococcus aureus -active therapy. Only four patients were switched from intravenous to oral antibiotics while hospitalized. The mean length of methicillin-resistant Staphylococcus aureus-active treatment was 14.7 (standard deviation, 10.1) days, with 14.6 (standard deviation, 10.1) total days of intravenous therapy. The mean length of hospital stay was 22.2 (standard deviation, 23.0) days. The most frequent initial methicillin-resistant Staphylococcus aureus-active therapies were intravenous vancomycin (58.2%), intravenous clindamycin (19.9%), and intravenous daptomycin (6.6%). Thirty-one patients (15.6%) were discharged with methicillin-resistant Staphylococcus aureus -active antibiotics of which 80.6% received oral antibiotics. Sixty-two patients (31.2%) met early switch criteria and potentially could have discontinued intravenous therapy 6.8 (standard deviation, 7.8) days sooner, and 65 patients (32.7%) met early discharge criteria and potentially could have been discharged 5.3 (standard deviation, 7.0) days sooner. Conclusions: Only 2% of patients were switched from intravenous to oral antibiotics in our study while almost one-third were early switch eligible. Additionally, one-third of hospitalized patients with methicillin-resistant Staphylococcus aureus complicated skin and soft tissue infections were early discharge eligible indicating opportunity for reducing intravenous therapy and days of hospital stay. These results provide insight into possible benefits of implementation of early switch/early discharge protocols in Brazil. Keywords: IV-to-PO switch, Length of stay, Clinical criteria, Antibiotic therapy, Economics

Hematopoiesis in the bone marrow (BM) is the primary source of immune cells. Hematopoiesis is regulated by a diverse cellular microenvironment that supports stepwise differentiation of multipotent stem cells and progenitors into mature blood cells. Blood cell production is not static and the bone marrow has evolved to sense and respond to infection by rapidly generating immune cells that are quickly released into the circulation to replenish those that are consumed in the periphery. Unfortunately, infection also has deleterious effects injuring hematopoietic stem cells (HSC), inefficient hematopoiesis, and remodeling and destruction of the microenvironment. Despite its central role in immunity, the role of the microenvironment in the response to infection has not been systematically investigated. Here we summarize the key experimental evidence demonstrating a critical role of the bone marrow microenvironment in orchestrating the bone marrow response to infection and discuss areas of future research.

Objectives While evidence has mounted regarding the short-term effectiveness of pharmacotherapy for opioid use disorder (OUD), little is known about longer-term psychosocial, economic, and health outcomes. We report herein 12-month outcomes for an observational study enrolling participants who had previously taken part in a long-acting buprenorphine subcutaneous injection (BUP-XR) trial for moderate to severe OUD. Methods The RECOVER (Remission from Chronic Opioid Use: Studying Environmental and SocioEconomic Factors on Recovery; NCT03604861) study enrolled participants from 35 US community-based sites. Self-reported sustained opioid abstinence over 12 months and self-reported past-week abstinence at 3-, 6-, 9-, and 12-month visits were assessed. Multiple regression models assessed the association of BUP-XR duration with abstinence, controlling for potential confounders. Withdrawal, pain, health-related quality of life, depression, and employment at RECOVER baseline and 12-month visits were also compared to values collected before treatment in the BUP-XR trial. Results Of 533 RECOVER participants, 425 completed the 12-month visit (average age 42 years; 66% male); 50.8% self-reported sustained 12-month and 68.0% past-week opioid abstinence. In multiple regressions, participants receiving 12-month versus ≤2-month BUP-XR treatment duration had significantly higher likelihood of sustained opioid abstinence (75.3% vs 24.1%; P = 0.001), with similar results for past-week self-reported abstinence over time. During RECOVER, participants had fewer withdrawal symptoms, lower pain, positive health-related quality of life, minimal depression, and higher employment versus pre-trial visit. Conclusions RECOVER participants reported positive outcomes over the 12-month observational period, including high opioid abstinence and stable or improved humanistic outcomes. These findings provide insights into the long-term impact of pharmacotherapy in OUD recovery.

Single molecule fluorescence spectroscopy has been largely implemented using methods which require tethering of molecules to a substrate in order to make high temporal resolution measurements. However, the act of tethering a molecule requires that the molecule be removed from its environment. This is especially perturbative when measuring biomolecules such as enzymes, which may rely on the non-equilibrium and crowded cellular environment for normal function. A method which may be able to un-tether single molecule fluorescence spectroscopy is real-time 3D single particle tracking (RT-3D-SPT). RT-3D-SPT uses active feedback to effectively lock-on to freely diffusing particles so they can be measured continuously with up to photon-limited temporal resolution over large axial ranges. This review gives an overview of the various active feedback 3D single particle tracking methods, highlighting specialized detection and excitation schemes which enable high-speed real-time tracking. Furthermore, the combination of these active feedback methods with simultaneous live-cell imaging is discussed. Finally, the successes in real-time 3D single molecule tracking (RT-3D-SMT) thus far and the roadmap going forward for this promising family of techniques are discussed.

AIMS: Medicare patients with metastatic or surgically unresectable urothelial carcinoma (mUC) often receive platinum-based chemotherapy as first line of therapy (LOT) but invariably progress, requiring additional LOTs and healthcare resource use (HCRU). To better understand the evolving mUC treatment landscape, we estimated the economic burden of chemotherapy-based mUC treatments among US Medicare patients. METHODS: Newly diagnosed Medicare patients with mUC were identified from the Surveillance, Epidemiology, and End Results (SEER)-Medicare database. Patients were followed from diagnosis to death, disenrollment, or end of study to characterize LOTs (first [LOT1], second [LOT2], and third+ [LOT3+]). Kaplan-Meier methods were used to estimate overall survival (OS) by LOT. HCRU and mean costs were reported over the follow-up period, LOT duration, or maximum LOT received. RESULTS: Among 1,873 eligible patients with mUC (median age, 77 years; median follow-up, 7.5 months), 1,035 (55%) received no chemotherapy. Among chemotherapy-treated patients, 61% had LOT1 only, 25% had LOT1 and LOT2 only, and 14% had ≥3 LOTs. Median OS was 8.1 months, range 4.3 (untreated) to 29.8 (LOT3+) months. HCRU frequency increased with additional LOTs. Mean cumulative per-patient cost was $82,912 for all patients, increasing with additional LOTs (untreated, $57,207; LOT1, $99,213; LOT2, $125,190; LOT3+, $163,884). Mean per-patient per-month cost was $18,827 for all patients, decreasing with increasing number of LOTs received (untreated, $27,211; LOT1, $9,601; LOT2, $7,325; LOT3+, $6,017). LIMITATIONS: Potential for treatment misclassification when using the algorithm defining LOTs and non-generalizability of results to younger patients. CONCLUSIONS: Over 50% of Medicare patients with mUC received no chemotherapy. Among chemotherapy-treated patients, most received only one LOT. Additional LOTs led to higher mean costs and HCRU, but as patients were followed longer, monthly costs decreased. As treatments evolve to include immuno-oncology agents, these findings provide a clinically relevant economic benchmark for mUC treatment across different traditional LOTs.

Objectives To describe opportunities for early switch (ES) from intravenous (IV) to oral (PO) antibiotics and early discharge (ED) of patients hospitalized in the Kingdom of Saudi Arabia (KSA) and the United Arab Emirates (UAE) with methicillin-resistant Staphylococcus aureus (MRSA) complicated skin and soft tissue infections (cSSTIs). Methods This retrospective medical chart review study enrolled physicians from 16 KSA and UAE sites to collect data for 107 MRSA cSSTI patients. Results Actual length of MRSA-active treatment was 13.3 ± 9.3 mean days in KSA and 11.2 ± 3.9 mean days in UAE, with a mean of 11.8 ± 9.3 days of MRSA-targeted IV therapy in KSA and 10.7 ± 4.3 days in UAE. 12.5% in KSA met ES criteria and potentially could have discontinued IV therapy 4.0 ± 2.9 days sooner; 44.0% in UAE could have discontinued 6.6 ± 3.6 days sooner. Patients were hospitalized for a mean 28.6 ± 45.0 days in KSA and 13.1 ± 5.9 days in UAE. 25.0% in KSA and 48.0% in UAE met ED criteria and potentially could have been discharged 6.1 ± 8.0 days earlier in KSA and 7.9 ± 5.0 days earlier in UAE. Conclusions A significant proportion of patients hospitalized for MRSA cSSTI could be eligible for ES or ED opportunities, resulting in potential for reductions in IV and bed days.

This retrospective study compared effectiveness of (brentuximab vedotin) BV to other chemotherapies in patients with rrHL following an autologous stem cell transplant (ASCT). Data originated from a medical chart review of patients treated in real-world clinical settings at 50 sites in the United Kingdom and Germany. Inverse probability of treatment weights based on propensity scores were used to adjust for differences in baseline characteristics between treatment groups. Among 312 rrHL patients included, 196 received BV and 116 received physicians' choice chemotherapy. Median PFS was significantly longer (27.0 months vs. 13.4 months; p = .0144) and 12-month OS survival greater (78.1% vs. 65.9%; p = .0129) with BV compared to chemotherapy. Documented adverse events included leukopenia (12.8%) and peripheral neuropathy (8.7%) for BV and leukopenia (12.1%), anemia (5.2%) and diarrhea (5.2%) for chemotherapy. In this real-world study, rrHL patients treated for relapse after ASCT with BV had longer median PFS and 12-month OS than patients receiving chemotherapy.

Objective Brentuximab vedotin (BV) is an anti-CD30 antibody-drug conjugate licensed for the treatment of relapsed/refractory Hodgkin lymphoma (rrHL) following autologous stem cell transplant (ASCT) or at least two prior therapies when ASCT or multi-agent chemotherapy is not an option. The objective of this study was to describe real-world outcomes with BV in rrHL patients considered ASCT-ineligible or who refuse ASCT. Methods This was a retrospective medical chart review study that enrolled patients ≥18 years old who were initially diagnosed with HL between 1 January 2008 and 30 June 2014, considered ASCT-ineligible, and treated in routine care with BV for progressive disease after multi-drug chemotherapy regimens. Clinical outcomes included best response to treatment, progression-free survival (PFS), overall survival (OS), and adverse events. Results A total of 136 patients were included, with a median age of 70 years at initial HL diagnosis. The most common reasons for ASCT-ineligibility were comorbidities (74%) and age (57%). Overall response rate was 74% and PFS and OS were 15.1 and 17.8 months, respectively. Peripheral neuropathy was observed in 9.6% of patients. Conclusion The results of this study provide real-world evidence on the feasibility and effectiveness of BV in elderly or frail ASCT-ineligible patients with rrHL in a real-world setting. This article is protected by copyright. All rights reserved.

OBJECTIVES:The primary aim was to determine the prevalence of International Classification of Diseases, Ninth Revision (ICD-9), sleep disorders diagnosed by pediatric providers in a large, primary care network. Secondary aims were to examine demographic variables related to these diagnoses and to examine the frequency of prescriptions for medications potentially used to treat sleep disorders.METHODS:Electronic medical records were reviewed for 154957 patients (0–18 years) seen for a well-child visit in 2007. Information collected included ICD-9 sleep diagnoses, demographic variables, comorbid attention-deficit/hyperactivity disorder and autism spectrum disorders, provider type, and medications.RESULTS:Across all ages, 3.7% of youths had an ICD-9 diagnosis for a sleep disorder. The most-common diagnoses were sleep disorder not otherwise specified, enuresis, and sleep-disordered breathing. Predictors of sleep disorders varied according to developmental age group and included growth parameters, comorbid attention-deficit/hyperactivity disorder or autism spectrum disorder, and provider type. Potential sleep-related medications were prescribed for 6.1% of the sample subjects.CONCLUSIONS:This study is one of the first to examine comprehensively ICD-9 sleep diagnoses given by primary care providers in a large representative sample of children 0 to 18 years of age. The 3.7% of patients with ICD-9 sleep diagnoses is significantly lower than prevalence rates reported in epidemiological studies, which suggests that primary care providers may be underdiagnosing sleep disorders in children and adolescents. Because sleep disorders are treatable when recognized, the results from this study suggest a significant need for additional education and support for primary care providers in the diagnosis and treatment of pediatric sleep disorders.

Background: A number of studies have concluded that the perceived quality of support is more strongly associated with mental health than with the actual structure of personal networks. This study examined clinical, historical, and phenomenological variables associated cross-sectionally and longitudinally with perceived social support. Methods: Participants included elderly, middle-aged, and young-adult depressed samples derived from the Duke Clinical Research Center for the Study of Depression in Late Life. Results: Cross-sectional multivariate analyses revealed that perceived social support was: (1) for the elderly associated with pessimistic thinking, being divorced, having strange ideas, the degree of social interaction, and instrumental support; (2) for middle-age associated with dysthymia, divorce, pessimistic thoughts, social interaction, and instrumental support; and (3) among young adults with instrumental support only. Longitudinal multivariate analyses indicated that only perceived social support at Time 1 predicted perceived social support 1 year later among elderly and middle-aged subjects, whereas only instrumental support predicted perceived social support 1 year later among the young-adult sample. Limitations: The small number of subjects among the young-adult sample limit conclusions regarding this group. In addition, only patients provided data. Future studies should consider using multiple informants to enhance the accuracy of reported social support. Conclusions: Our findings indicate that in addition to whatever else they do for depressed patients, clinicians must endeavor to address relationship or social support difficulties, especially in the elderly .

Saccharomyces cerevisiae csg2Delta mutants accumulate the sphingolipid inositolphosphorylceramide, which renders the cells Ca2+-sensitive. Temperature-sensitive mutations that suppress the Ca2+ sensitivity of csg2Delta mutants were isolated and characterized to identify genes that encode sphingolipid synthesis enzymes. These temperature-sensitive csg2Delta suppressors (tsc) fall into 15 complementation groups. The TSC10/YBR265w gene was found to encode 3-ketosphinganine reductase, the enzyme that catalyzes the second step in the synthesis of phytosphingosine, the long chain base found in yeast sphingolipids. 3-Ketosphinganine reductase (Tsc10p) is essential for growth in the absence of exogenous dihydrosphingosine or phytosphingosine. Tsc10p is a member of the short chain dehydrogenase/reductase protein family. The tsc10 mutants accumulate 3-ketosphinganine and microsomal membranes isolated from tsc10 mutants have low 3-ketosphinganine reductase activity. His6-tagged Tsc10p was expressed in Escherichia coli and isolated by nickel-nitrilotriacetic acid column chromatography. The recombinant protein catalyzes the NADPH-dependent reduction of 3-ketosphinganine. These data indicate that Tsc10p is necessary and sufficient for catalyzing the NADPH-dependent reduction of 3-ketosphinganine to dihydrosphingosine.

BACKGROUND & PURPOSE: : Lower limb amputation in older adults has a significant impact on balance, gait, and cardiovascular fitness, resulting in diminished community participation. The purpose of this case study was to describe the effects of a balance training program utilizing the Nintendo Wii™ Fit (Nintendo of America, Inc, Redmond, Washington) balance board and body- weight supported gait training on aerobic capacity, balance, gait, and fear of falling in two persons with transfemoral amputation. CASE DESCRIPTIONS: : Participant A, a 62 year-old male 32 months post traumatic transfemoral amputation, reported fear of falling and restrictions in community activity. Participant B, a 58 year-old male 9 years post transfemoral amputation, reported limited energy and balance deficits during advanced gait activities. INTERVENTION: : 6-weeks, 2 supervised sessions per week included 20 minutes of Nintendo™ Wii Fit Balance gaming and 20 minutes of gait training using Body Weight Support. OUTCOMES: : Measures included oxygen uptake efficiency slope (OUES), economy of movement, dynamic balance (Biodex platform system), Activities-Specific Balance Confidence (ABC) Scale, and spatial-temporal parameters of gait (GAITRite). Both participants demonstrated improvement in dynamic balance, balance confidence, economy of movement, and spatial-temporal parameters of gait. Participant A reduced the need for an assistive device during community ambulation. Participant B improved his aerobic capacity, indicated by an increase in OUES. DISCUSSION: : This case study illustrated that the use of Nintendo Wii™ Fit training and Body Weight Support were effective interventions to achieve functional goals for improving balance confidence, reducing use of assistive devices, and increasing energy efficiency when ambulating with a transfemoral prosthesis. Language: en