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Two phase 3 randomized controlled trials (OTT-0101, RTOG-9413) and a meta-analysis have shown an impact of sequencing of androgen deprivation therapy (ADT) and radiation therapy on oncologic outcomes in prostate cancer (PCa). However, the impact of sequencing strategy on health-related quality of life (HR-QoL) is unclear. Here, we present the patient-reported HR-QoL outcomes from the OTT-0101 study.In this trial, patients with PCa with Gleason score ≤7, clinical stage T1b to T3a, and prostate-specific antigen level30 ng/mL were randomly assigned to neoadjuvant and concurrent ADT for 6 months, starting 4 months before or concurrent with prostate radiation therapy, or concurrent and adjuvant ADT for 6 months, starting simultaneously with prostate radiation therapy. HR-QoL was assessed using European Organisation for Research and Treatment of Cancer QoL questionnaires. Time until definitive deterioration was defined as time from random allocation to the first deterioration of at least 10 points with no further improvement of ≥10 points or if the patient experienced progression, died, or dropped out after deterioration, resulting in missing data. Stratified log-rank tests were applied for between-group comparisons of time-to-event estimates.Overall, 393 patients (194 and 199 in the 2 arms, respectively) were evaluable, except 214 (101 and 113 in the 2 arms, respectively) for sexual function. Five-year rates of freedom from definitive deterioration of urinary symptoms, bowel symptoms, and sexual activity were 33.5%, 33.1%, and 38.5% in the neoadjuvant group and 34.1%, 35.4%, and 36.7% in the adjuvant group, respectively, with no significant between-group differences. The adjuvant approach was associated with a reduced risk of definitive deterioration of sexual function (hazard ratio, 0.68; 95% confidence interval, 0.49-0.94; P = .02). With respect to clinical relevance, the mean change in score for sexual function showed only a small to moderate difference favoring the adjuvant group at and beyond 3 years.In this study, no differences were found in the bowel or urinary symptoms between the adjuvant and neoadjuvant approach. Considering a significant likelihood of type I and type II errors and because of a lack of a persistent and clinically meaningful between-group difference in mean score changes over time, our findings do not confer a clear and conclusive picture of the impact of sequencing strategy on sexual function.

This article describes a rare case of lactation ketoacidosis in a patient who started a ketogenic diet while nursing an infant and toddler. The patient presented to the ED with a history of nausea, vomiting, and postural dizziness, and was found to have a significant metabolic acidosis and elevated lipase level. The metabolic changes induced in this patient could occur in anyone with high metabolic demands who also is on a strict ketogenic diet. The case highlights the importance of a dietary history in patients with unexplained metabolic derangements.

OBJECTIVES Design, implement, and evaluate a rounding checklist with deeply embedded, dynamic electronic health record integration. DESIGN Before-after quality-improvement study. SETTING Quaternary PICU in an academic, free-standing children's hospital. PATIENTS All patients in the PICU during daily morning rounds. INTERVENTIONS Implementation of an updated dynamic checklist (eSIMPLER) providing clinical decision support prompts with display of relevant data automatically pulled from the electronic health record. MEASUREMENTS AND MAIN RESULTS The prior daily rounding checklist, eSIMPLE, was implemented for 49,709 patient-days (7,779 patients) between October 30, 2011, and October 7, 2018. eSIMPLER was implemented for 5,306 patient-days (971 patients) over 6 months. Checklist completion rates were similar (eSIMPLE: 95% [95% CI, 88-98%] vs eSIMPLER: 98% [95% CI, 92-100%] of patient-days; p = 0.40). eSIMPLER required less time per patient (28 ± 1 vs 47 ± 24 s; p < 0.001). Users reported improved satisfaction with eSIMPLER (p = 0.009). Several checklist-driven process measures-discordance between electronic health record orders for stress ulcer prophylaxis and user-recorded indication for stress ulcer prophylaxis, rate of venous thromboembolism prophylaxis prescribing, and recognition of reduced renal function-improved during the eSIMPLER phase. CONCLUSIONS eSIMPLER, a dynamic, electronic health record-informed checklist, required less time to complete and improved certain care processes compared with a prior, static checklist with limited electronic health record data. By focusing on the "Five Rights" of clinical decision support, we created a well-accepted clinical decision support tool that was integrated efficiently into daily rounds. Generalizability of eSIMPLER's effectiveness and its impact on patient outcomes need to be examined.

Parkinson's disease (PD) is one of the most common neurodegenerative diseases after Alzheimer's disease (AD), afflicting adults above the age of sixty irrespective of gender, race, ethnicity, and social status. PD is characterized by motor dysfunctions, displaying resting tremor, rigidity, bradykinesia, and postural imbalance. Non-motor symptoms, including rapid eye movement (REM) behavior disorder, constipation, and loss of sense of smell, typically occur many years before the appearance of the PD motor symptoms that lead to a diagnosis. The loss of dopaminergic neurons in the substantia nigra, which leads to the motor symptoms seen in PD, is associated with the deposition of aggregated, misfolded α-Synuclein (α-Syn, SNCA) proteins forming Lewy Bodies. Additionally, dysregulation of miRNA (a short form of mRNA) may contribute to the developing pathophysiology in PD and other diseases such as cancer. Overexpression of α-Syn and miRNA in human samples has been found in PD, AD, and dementia. Therefore, evaluating these molecules in urine, present either in the free form or in association with extracellular vesicles of biological fluids, may lead to early biomarkers for clinical diagnosis. Collection of urine is non-invasive and thus beneficial, particularly in geriatric populations, for biomarker analysis. Considering the expression and function of α-Syn and miRNA, we predict that they can be used as early biomarkers in the diagnosis and prognosis of neurodegenerative diseases.

In patients presenting with metastatic prostate cancer, the role of local therapy is evolving. Two recently reported large-scale randomized trials suggest that radiotherapy (RT) directed at the prostate improves overall survival (OS) in patients with low metastatic burden. We reviewed the experience of prostate RT in this setting at our center. The study population consisted of men with newly-diagnosed metastatic hormone-sensitive prostate cancer (mHSPC) referred to a comprehensive cancer center between 2005 and 2015 and treated initially with androgen deprivation therapy. Patients were eligible for inclusion if they received (1) prostate RT with biological effective dose (BED) at least that of a course of 40 Gy in 15 fractions or (2) no prostate RT. The association between receipt of prostate RT and OS was studied. OS was estimated using the Kaplan–Meier method and Cox regression was used to identify factors associated with OS. The cohort consisted of 410 patients, of whom 128 received prostate RT. Median follow-up 61.0 months. On univariate analysis, receipt of prostate RT was associated with improved OS (HR 0.59, 95% CI 0.45–0.77, p = 0.0001). Median OS in those patients receiving prostate RT was 47.4 months versus 26.3 months in those not receiving prostate RT. In a multivariate Cox model, receipt of prostate RT remained associated with improved OS (HR 0.69, 95% CI 0.50–0.94, p = 0.02). In those treated with prostate RT, increasing BED was also associated with improved OS (HR 0.87 per 10 Gy increase, 95% CI 0.76–0.99, p = 0.03). This cohort represents the largest single-center experience of primary tumor-directed RT in mHSPC reported to date. In this population, receipt of prostate RT was associated with improved OS and the magnitude of the OS benefit was clinically significant. The possibility of an RT dose-response gradient in this setting merits further study.

The South American Ctenomys is the most speciose genus among both hystricomorphs and subterranean rodents of the world. Here, we present the most exhaustive phylogenies and timetree of living and e...

Several classes of concomitant medications have been shown to affect oncological outcomes in patients with prostate cancer (PCa). We assessed the association between the use of commonly prescribed concomitant medications and biochemical relapse-free survival (bRFS) in patients with localised PCa treated with radiotherapy and androgen deprivation therapy (ADT).A secondary pooled analysis of two phase III randomised trials was carried out. In the first trial, patients with localised PCa with clinical stage T1b-T3, prostate-specific antigen30 ng/ml and Gleason score ≤7 were treated with radical radiotherapy and 6 months of ADT starting 4 months before or concomitantly with radiotherapy. In the second trial, patients with high-risk PCa were treated with radical radiotherapy and 36 months of ADT with randomisation to three-dimensional conformal or intensity-modulated radiotherapy. Information on concomitant medications was collected from the medical record. Univariable and multivariable Cox regression was used to identify factors associated with bRFS.Overall, 486 patients were evaluable. The median follow-up was 125 months; 10-year bRFS was 83.7%. On univariable analysis, receipt of metformin was significantly associated with worse bRFS. Ten-year bRFS was 73% and 85% for patients with and without concomitant metformin (adjusted hazard ratio 2.11, 95% confidence interval 1.03-4.33). Similar evidence of an association was observed with sulfonamide-based α1-receptor blockers (adjusted hazard ratio 2.72, 95% confidence interval 1.31-5.66). However, no such association was seen with receipt of quinazoline-based α1-receptor blockers (adjusted hazard ratio 1.09, 95% confidence interval 0.42-2.82). There was no significant association between bRFS and receipt of all other medication classes considered.In this population of patients with localised PCa treated with radiotherapy and ADT, receipt of concomitant metformin and sulfonamide-based α1-receptor blockers was associated with inferior biochemical outcome. Randomised trials are required to assess the true effect of these medications on oncological outcomes in localised PCa.

Summary Background Progressive supranuclear palsy is a neurodegenerative disorder associated with tau protein aggregation. Tilavonemab (ABBV-8E12) is a monoclonal antibody that binds to the N-terminus of human tau. We assessed the safety and efficacy of tilavonemab for the treatment of progressive supranuclear palsy. Methods We did a phase 2, multicentre, randomised, placebo-controlled, double-blind study at 66 hospitals and clinics in Australia, Canada, France, Germany, Italy, Japan, Spain, and the USA. Participants (aged ≥40 years) diagnosed with possible or probable progressive supranuclear palsy who were symptomatic for less than 5 years, had a reliable study partner, and were able to walk five steps with minimal assistance, were randomly assigned (1:1:1) by interactive response technology to tilavonemab 2000 mg, tilavonemab 4000 mg, or matching placebo administered intravenously on days 1, 15, and 29, then every 28 days through to the end of the 52-week treatment period. Randomisation was done by the randomisation specialist of the study sponsor, who did not otherwise participate in the study. The sponsor, investigators, and participants were unaware of treatment allocations. The primary endpoint was the change from baseline to week 52 in the Progressive Supranuclear Palsy Rating Scale (PSPRS) total score in the intention-to-treat population. Adverse events were monitored in participants who received at least one dose of study drug. Prespecified interim futility criteria were based on a model-based effect size of 0 or lower when 60 participants had completed the 52-week treatment period and 0·12 or lower when 120 participants had completed the 52-week treatment period. This study is registered at ClinicalTrials.gov, number NCT02985879. Findings Between Dec 12, 2016, and Dec 31, 2018, 466 participants were screened, 378 were randomised. The study was terminated on July 3, 2019, after prespecified futility criteria were met at the second interim analysis. A total of 377 participants received at least one dose of study drug and were included in the efficacy and safety analyses (2000 mg, n=126; 4000 mg, n=125; placebo, n=126). Least squares mean change from baseline to week 52 in PSPRS was similar in all groups (between-group difference vs placebo: 2000 mg, 0·0 [95% CI –2·6 to 2·6], effect size 0·000, p>0·99; 4000 mg, 1·0 [–1·6 to 3·6], –0·105, p=0·46). Most participants reported at least one adverse event (2000 mg, 111 [88%]; 4000 mg, 111 [89%]; placebo, 108 [86%]). Fall was the most common adverse event (2000 mg, 42 [33%]; 4000 mg, 54 [43%]; placebo, 49 [39%]). Proportions of patients with serious adverse events were similar among groups (2000 mg, 29 [23%]; 4000 mg, 34 [27%]; placebo, 33 [26%]). Fall was the most common treatment-emergent serious adverse event (2000 mg, five [4%]; 4000 mg, six [5%]; placebo, six [5%]). 26 deaths occurred during the study (2000 mg, nine [7%]; 4000 mg, nine [7%]; placebo, eight [6%]) but none was drug related. Interpretation A similar safety profile was seen in all treatment groups. No beneficial treatment effects were recorded. Although this study did not provide evidence of efficacy in progressive supranuclear palsy, the findings provide potentially useful information for future investigations of passive immunisation using tau antibodies for progressive supranuclear palsy. Funding AbbVie Inc.

The Peruvian stick insect Oreophoetes peruana is the only known animal source for unsubstituted quinoline in nature. When disturbed, these insects discharge a defensive secretion containing quinoli...

We performed a secondary analysis of a phase 3 randomized trial to determine the influence of sequencing of radiation therapy and androgen deprivation therapy (ADT) on posttreatment testosterone recovery and implications of testosterone recovery on subsequent relapse.Patients with localized prostate cancer with Gleason score ≤7, clinical stage T1b to T3a, and prostate-specific antigen30 ng/mL were randomized to neoadjuvant and concurrent ADT for 6 months starting 4 months before prostate radiation therapy (NHT arm) or concurrent and adjuvant ADT for 6 months starting simultaneously with radiation therapy (CAHT arm). Full testosterone recovery (FTR) was defined as recovery of testosterone to10.5 nmol/L in patients with baseline ≥10.5 nmol/L or to baseline level in patients with baseline10.5 nmol/L. Restricted mean survival time (RMST) since ADT initiation to supracastrate testosterone level (1.7 nmol/L), and to FTR was compared between the arms using a truncation time point of 36 months.The adjusted difference in RMST to supracastrate testosterone between the CAHT and NHT arm was 1.5 months (95% confidence interval [CI], 0.5-2.5; P = .005). No difference was noted in RMST to FTR between the arms (18.7 vs 18.5 months, adjusted difference: 0.5; 95% CI, -1.4 to 2.4; P = .61). There was no evidence of heterogeneity of treatment effect (interaction P = .76) on risk of relapse over subgroups stratified by testosterone recovery to supracastrate level at 15 months after start of ADT. Based on a multistate Markov model, no independent effect of time to FTR on risk of subsequent relapse was observed (adjusted hazard ratio: 1.02; 95% CI, 0.96-1.08).Patients should be counseled that an additional 12 months on average is needed for FTR to occur after treatment with prostate radiation therapy and 6 months of ADT. This is independent of the sequencing of ADT and radiation therapy. Furthermore, recovery of testosterone does not appear to affect the risk of subsequent relapse.

This essay posits in Vaginal Davis's 1987 video That Fertile Feeling a strategy of resistance to HIV/AIDS rooted in the dynamic of transfeminine pregnancy and fertility, arguing that Davis develops a range of aesthetic strategies for undermining, inverting, and appropriating mainstream discourses of reproduction as they intersect with legal strictures and cultural scripts around normative understandings of embodiment, health, and the notion of morality embedded in the period's dominant set of “family values.” AIDS is not, on the surface of things, a central referent in That Fertile Feeling, but the author shows how precisely this submerged status of the crisis as a signifier in the video allows Davis to visualize a broad biopolitical field and situate the epidemic within that field to address the interrelated, mutually supporting injustices perpetuated at its peak in Los Angeles. The figure of the excessively fertile trans woman emerges as useful for theorizing this oblique yet radiant approach to developing a coalitional ethos to confront both the politics around the AIDS crisis in LA at the time and its material and psychic impact.

Background There is an urgent need for insecticides with novel modes of action against mosquito vectors. Broflanilide is a meta-diamide, discovered and named Tenebenal™ by Mitsui Chemicals Agro, Inc., which has been identified as a candidate insecticide for use in public health products. Methods To evaluate its potential for use in public health, Tenebenal™ was screened using an array of methodologies against Anopheles and Aedes strains. Initially it was assessed for intrinsic efficacy by topical application. Tarsal contact bioassays were then conducted to further investigate its efficacy, as well as its potency and speed of action. The potential of the compound for use in indoor residual spray (IRS) applications was investigated by testing the residual efficacy of a prototype IRS formulation on a range of typical house building substrates, and its potential for use in long-lasting insecticidal nets (LLIN) was tested using dipped net samples. Finally, bioassays using well-characterized insecticide-resistant mosquito strains and an in silico screen for mutations in the insecticide’s target site were performed to assess the risk of cross-resistance to Tenebenal™. Results Tenebenal™ was effective as a tarsal contact insecticide against both Aedes and Anopheles mosquitoes, with no apparent cross-resistance caused by mechanisms that have evolved to insecticides currently used in vector control. Topical application showed potent intrinsic activity against a Kisumu reference strain and an insecticide-resistant strain of Anopheles gambiae. Applied to filter paper in a WHO tube bioassay, Tenebenal™ was effective in killing 100% of susceptible and resistant strains of An. gambiae and Aedes aegypti at a concentration of 0.01%. The discriminating concentration of 11.91 µg/bottle shows it to be very potent relative to chemistries previously identified as having potential for vector control. Mortality occurs within 24 h of exposure, 80% of this mortality occurring within the first 10 h, a speed of kill somewhat slower than seen with pyrethroids due to the mode of action. The potential of Tenebenal™ for development in LLIN and IRS products was demonstrated. At least 12 months residual efficacy of a prototype IRS formulation applied at concentrations up to 200 mg of AI/sq m was demonstrated on a range of representative wall substrates, and up to 18 months on more inert substrates. A dipped net with an application rate of around 2 g/sq m Tenebenal™ killed 100% of exposed mosquitoes within a 3-min exposure in a WHO cone test. Conclusions Tenebenal™ is a potent insecticide against adult Aedes and Anopheles mosquitoes, including strains resistant to classes of insecticide currently used in vector control. The compound has shown great potential in laboratory assessment and warrants further investigation into development for the control of pyrethroid-resistant mosquitoes.

Health risk behaviors are leading contributors to morbidity, premature mortality associated with chronic diseases, and escalating health costs. However, traditional interventions to change health behaviors often have modest effects, and limited applicability and scale. To better support health improvement goals across the care continuum, new approaches incorporating various smart technologies are being utilized to create more individualized digital behavior change interventions (DBCIs). The purpose of this study is to identify context-aware DBCIs that provide individualized interventions to improve health. A systematic review of published literature (2013–2020) was conducted from multiple databases and manual searches. All included DBCIs were context-aware, automated digital health technologies, whereby user input, activity, or location influenced the intervention. Included studies addressed explicit health behaviors and reported data of behavior change outcomes. Data extracted from studies included study design, type of intervention, including its functions and technologies used, behavior change techniques, and target health behavior and outcomes data. Thirty-three articles were included, comprising mobile health (mHealth) applications, Internet of Things wearables/sensors, and internet-based web applications. The most frequently adopted behavior change techniques were in the groupings of feedback and monitoring, shaping knowledge, associations, and goals and planning. Technologies used to apply these in a context-aware, automated fashion included analytic and artificial intelligence (e.g., machine learning and symbolic reasoning) methods requiring various degrees of access to data. Studies demonstrated improvements in physical activity, dietary behaviors, medication adherence, and sun protection practices. Context-aware DBCIs effectively supported behavior change to improve users’ health behaviors., Digital health technologies can effectively reach individuals within the context of their daily lives to improve health behaviors.

Anecdotal evidence suggests that patients with isolated traumatic facial fractures have high narcotic usage, yet there is a lack of literature delineating this relationship. This study aimed to characterize total amount and factors predictive of narcotic usage following isolated traumatic facial fracture. Study participants (n = 35) were predominantly male (91.4%), mean age 40.5, Caucasian (34.3%), suffered some form of assault (62.9%), and remained hospitalized for an average of 3.0 days. Average morphine milligram equivalent (MME) use in the inpatient setting was 967.6 for operative (n = 30) and 37.5 for nonoperative (n = 5) patients. Average total narcotic use across inpatient and outpatient settings was 1256.6 MME for operative and 105 MME for nonoperative patients. Operative intervention predicted a significant difference in total inpatient narcotic usage (P = 0.009). For patients who underwent surgical intervention, significant variations in narcotic usage were found based on mechanism of injury (24-hour postoperative, P = 0.030), but not injury severity or number of procedures. Specifically, individuals suffering highly traumatic fractures (eg, gunshot wound) demonstrated increased total postoperative narcotic usage of 1194.1 MME (P = 0.004). Interestingly, non-narcotic analgesic use including acetaminophen and lidocaine-epinephrine resulted in significantly lower narcotic usage in the postoperative setting. These findings suggest a role for narcotic-reducing enhanced recovery after surgery protocols in the setting of isolated facial trauma.

To evaluate the ability of unenhanced magnetic resonance imaging (MRI) to detect metastatic lymphadenopathy in men with stage 1 testicular cancer on surveillance. With IRB approval, we identified 23 consecutive men with stage 1 testicular cancer (diagnosed after orchiectomy) undergoing surveillance with unenhanced MRI of the abdomen and pelvis. Three blinded radiologists (2 inexperienced R1/R2 and 1 experienced R3) independently assessed MRI for: presence, location and size of abnormal lymph nodes and degree of confidence (5-point Likert scale) in diagnosis. Diagnostic accuracy was tabulated and compared between groups using ROC. Inter-observer agreement was assessed using Cohen’s kappa statistic. 17.4% (4/23) men developed 6 metastatic lymph nodes (reference standard: interval development from baseline, size > 1.0 cm short axis). R1 and R2 detected 75% (3/4) patients with abnormal lymph nodes, compared to R3 who detected all four cases. False positive interpretations occurred in: 5.2% (1/19) R1, 10.5% (2/19) R2 and no patients for R3. Sensitivity, specificity and area under the ROC curve (AUC) were: R1: 75% (95% CI 19.4–99.4%), 94.7% (74.0–99.9%) and 0.85 (0.59–1.00), R2: 75% (19.4–99.4%), 89.5% (66.9–98.7%) and 0.82 (0.57–1.00) and, R3: 100% (95% 39.8–100.0%), 100% (82.4–100%) and 1.00 (1.00–1.00) with no difference in AUC between readers (p = 0.383). Comparison in accuracy between readers is limited due to the small sample size. Inter-observer agreement was substantial (K = 0.62). Median (range) degree of confidence scores were rated: R1 5 (5–5), R2 4 (3–5) and, R3 5 (5–5). In this study, unenhanced MRI was adequate for surveillance of stage 1 testicular cancer; however, radiologist inexperience may lead to errors.

PROBLEM IDENTIFICATION. Hot flashes (HF) are common and bothersome in breast and prostate cancer and can adversely impact patients’ quality of life. The best approach to manage them is unclear. We sought to perform network meta-analyses (NMA) of the available evidence to compare interventions previously studied in the literature. LITERATURE SEARCH. A librarian searched Medline, Embase, and additional databases for randomized controlled trials (RCTs) evaluating the effects of one or more interventions for hot flashes in patients with a history of breast or prostate cancer. DATA EVALUATION. Outcomes of interest included changes in HF severity, HF frequency, quality of life, and harms. Two reviewers were involved in the phases of study selection, data collection and risk of bias appraisal. Pairwise meta-analyses and NMAs were performed where feasible, with narrative synthesis used where required. SYNTHESIS. 40 RCTs studying drugs, psychological interventions, natural health products and exercise were included. Most interventions were assessed in only one trial, typically versus inactive control. The outcomes of interest were not consistently available from the included studies, and NMAs were feasible for HF frequency and HF score. Findings from NMA for HF frequency suggested several therapies may offer benefits compared to no treatment, though little data suggested differences between active therapies. Findings from NMA for HF score were similar. For remaining outcomes including HF severity, QoL measures and harms, studies were summarized narratively due to limited availability of data. Limited evidence of clear benefits was found for the therapies assessed. IMPLICATIONS FOR RESEARCH. While many interventions may offer improvements for HFs versus no treatment, few data suggest important differences between therapies. Future research is needed to enrich available evidence for decision-making. REVIEW REGISTRATION #: CRD42015024286

Introduction Craniofacial conditions (CFCs) profoundly influence health-related quality of life (HRQoL). In children with CFCs, patient-reported outcome measures have become an integral adjunct to more objective surgical outcome measures. Patient-reported outcome measures are designed to assess HRQoL domains. Few studies have evaluated parent and child agreement about HRQoL in the context of CFCs. The aims of this study were to explore the impact of CFCs on HRQoL domains in children and their parents and to determine whether patient and parent perspectives converge. Methods The Craniofacial Conditions Quality of Life Scale (CFC-QoL) is a newly developed 5-domain survey available in child self-report and parent report and in English- and Spanish-language versions. The 5 domains are the following: social impact, psychological function, physical function, family impact, and appearance impact. Children with CFCs (ages 7-21 years) and parents of children with CFCs were recruited via the craniofacial care team clinic at a major metropolitan children's hospital. All children and parents completed the CFC-QoL Scale in their preferred language of English or Spanish. Scale internal consistencies were calculated for child patients and parents, for English and Spanish versions. Scores on the 5 domains were compared for children and parents across English versus Spanish versions. Results For children with CFCs (N = 75), the sex was distributed almost equally. Patients were mostly Hispanic (69.3%), and their ages ranged from 7 to 21 years old (M = 13.2, SD = 3.62). The mean values for patient and parent scores were low, suggesting good HRQoL across all 5 domains. Pearson correlation coefficients were computed to explore the interrelationships between patient and parent report for each of the 5 CFC-QoL subscales. For the total sample, patient and parent scores were significantly and moderately positively correlated for all subscales. When analyzed separately based on sex, ethnicity, and diagnostic group, the correlation patterns were not identical to those found for the total sample. When analyzed separately for diagnostic group, there was less consistency in patterns, with patient-parent dyads showing different levels of agreement based on child's diagnostic grouping. Conclusions Although there is substantial agreement between parents and patients when considered on a group level, there is moderate agreement between patients and parents when considered at the dyadic level, underscoring the importance of measuring and considering both perspectives.

Supramolecular and dynamic biomaterials hold promise to recapitulate the time-dependent properties and stimuli-responsiveness of the native extracellular matrix (ECM). Host-guest chemistry is one of the most widely studied supramolecular bonds, yet the binding characteristics of host-guest complexes (beta-CD/adamantane) in relevant biomaterials have mostly focused on singular host-guest interactions or nondiscrete multivalent pendent polymers. The stepwise synergistic effect of multivalent host-guest interactions for the formation of dynamic biomaterials remains relatively unreported. In this work, we study how a series of multivalent adamantane (guest) cross-linkers affect the overall binding affinity and ability to form supramolecular networks with alginate-CD (Alg-CD). These binding constants of the multivalent cross-linkers were determined via NMR titration and showed increases in binding constants occurring with multivalent constructs. The higher multivalent cross-linkers enabled hydrogel formation; furthermore, an increase in binding and gelation was observed with the inclusion of a phenyl spacer to the cross-linker. A preliminary screen shows that only cross-linking Alg-CD with an 8-arm-multivalent guest results in robust gel formation. These cytocompatible hydrogels highlight the importance of multivalent design for dynamically cross-linked hydrogels. These materials hold promise for development toward cell- and small molecule-delivery platforms and allow discrete and fine-tuning of network properties.

© This open access article is distributed under Creative Commons Attribution-NonCommercialNoDerivatives License 4.0 (CC BY-NC-ND). How predictable are life trajectories? We investigated this question with a scientific mass collaboration using the common task method; 160 teams built predictive models for six life outcomes using data from the Fragile Families and Child Wellbeing Study, a high-quality birth cohort study. Despite using a rich dataset and applying machine-learning methods optimized for prediction, the best predictions were not very accurate and were only slightly better than those from a simple benchmark model. Within each outcome, prediction error was strongly associated with the family being predicted and weakly associated with the technique used to generate the prediction. Overall, these results suggest practical limits to the predictability of life outcomes in some settings and illustrate the value of mass collaborations in the social sciences.

Patients with end-stage renal disease (ESRD) are 8–10 times more likely to suffer from a stroke compared with the general public. Despite this risk, there are minimal data elucidating which hemodialysis modality is best for patients with ESRD following a stroke, and guidelines for their management are lacking. We retrospectively queried the US Renal Data System administrative database for all-cause mortality in ESRD stroke patients who received either intermittent hemodialysis (IHD) or continuous renal replacement therapy (CRRT). Acute ischemic stroke and hemorrhagic stroke were identified using the International Classification of Diseases 9th Revision (ICD-9)/ICD-10 codes, and hemodialysis modality was determined using Healthcare Common Procedure Coding System (HCPCS) codes. Time to death from the first stroke diagnosis was the outcome of interest. Cox proportional hazards modeling was used, and associations were expressed as adjusted HRs. From the inclusion cohort of 87,910 patients, 92.9% of patients received IHD while 7.1% of patients received CRRT. After controlling for age, race, sex, ethnicity, and common stroke risk factors such as hypertension, diabetes, tobacco use, atrial fibrillation, and hyperlipidemia, those who were placed on CRRT within 7 days of a stroke had an increased risk of death compared with those placed on IHD (HR=1.28, 95% CI 1.25 to 1.32). It is possible that ESRD stroke patients who received CRRT are more critically ill. However, even when the cohort was limited to only those patients in the intensive care unit and additional risk factors for mortality were controlled for, CRRT was still associated with an increased risk of death (HR=1.32, 95% CI 1.27 to 1.37). Therefore, further prospective clinical trials are warranted to address these findings.

Randomized controlled trials (RCTs) have shown that addition of docetaxel or androgen receptor axis-targeted therapy (ARAT) to androgen deprivation therapy (ADT) or addition of ARAT to ADT and docetaxel improves overall survival (OS) in metastatic hormone-sensitive prostate cancer (mHSPC). However, it is unknown whether docetaxel, when given as part of triplet therapy, has an independent OS benefit.To compare the efficacy of ADT plus ARAT with the triplet of ADT, ARAT, and docetaxel through a network meta-analysis (NMA) of RCTs in mHSPC.Bibliographic databases and conference proceedings were searched in March 2022 for RCTs that evaluated the addition of docetaxel, ARAT, or both to ADT in mHSPC. The primary endpoint was OS. Standard random-effect NMA and Bayesian analyses were performed to compare ADT plus ARAT with triplet therapy.Eleven RCTs (n = 11 546) were eligible. Compared with ADT plus ARAT, the triplet had a nonsignificant OS benefit (hazard ratio [HR] 0.89, 95% confidence interval [CI] 0.68-1.16), while ADT plus docetaxel (HR 1.16 [0.94-1.43]) and ADT alone (HR 1.46 [1.30-1.64]) had an increased risk of death. By P-score ordering, the triplet was the most effective treatment strategy (P score = 0.936) followed by ADT plus ARAT (P score = 0.704). The triplet had a 77% likelihood of being the best treatment strategy compared with a 23% likelihood for ADT plus ARAT.The triplet of ADT, ARAT, and docetaxel was the highest ranked treatment strategy, but it did not confer a statistically significant OS benefit over ADT plus ARAT. This NMA provides the highest-level comparative evidence for these treatment approaches in the initial management of mHSPC.We synthesized the available evidence from clinical trials conducted in newly diagnosed metastatic prostate cancer to compare the survival of patients receiving triplet therapy (androgen receptor axis-targeted therapy [ARAT], androgen deprivation therapy [ADT], and docetaxel) with those receiving only ARAT and ADT. We conclude that the triplet is a somewhat more effective treatment approach.

Metastatic castrate sensitive prostate cancer (mCSPC) is a heterogeneous disease state with variable prognosis. Although several life-prolonging systemic agents are available, there is no robust multivariable model to predict prognosis and improve risk stratification in mCSPC. The objective of this study was to build and validate a multivariable prognostic model to predict overall survival (OS) in mCSPC.We used data from LATITUDE, a phase III randomized controlled trial in which men with de novo mCSPC were randomly allocated to either ADT plus abiraterone or ADT with placebo. Patients with non-missing data (n = 1,058) were randomly split in a 70:30 ratio to training (n = 743) and testing (n = 315) sets. Elastic net regression was used for variable selection. A multivariable Cox regression model for OS was then fitted using the selected variables. The predictive accuracy of the model was assessed on the testing set using the time-dependent area under curve (tAUC) with bootstrapped confidence intervals [CI] primarily for OS and secondarily for radiographic progression-free survival (rPFS).The 11 prognostic variables in the final model were performance status, number of skeletal metastases, Gleason score, presence of liver metastasis, worst pain score, albumin, lactate dehydrogenase, prostate-specific antigen, hemoglobin, and treatment regimen. The tAUC for predicting OS at 2- and 3-years was 0.74 (95% CI, 0.67-0.80) and 0.72 (95% CI, 0.65-0.77), respectively. The tAUC for rPFS at 2- and 3-years was 0.72 (95% CI, 0.65-0.77) and 0.77 (95% CI, 0.70-0.82), respectively.A prognostic model for men with de novo mCSPC was developed and validated in an independent testing set. Our model had high accuracy for predicting OS and rPFS. The model includes commonly used clinical and laboratory parameters and can guide risk stratification of these patients for participation in future trials.

Introduction Malnutrition represents a common complication in femur fracture patients and is primarily caused by poor dietary intake. Malnutrition is associated with poor clinical outcomes, and is the strongest independent risk factor for recurrent femur fracture. High protein oral nutrition supplements (ONS) have been associated with improved clinical outcomes after femur fracture, including reduced complications, length of hospital stay, mortality and bone mineral density loss, and increases in functional status and quality of life (Volkert, Beck, Cederholm et al., Clinical Nutrition, 38, 10–47)). Accordingly, the European Society for Clinical Nutrition and Metabolism (ESPEN) advocates the use of ONS with all femur fracture patients in hospital. Aim To improve nutritional support for post-surgical femur fracture patients at St Mary’s Hospital, London. Methods We plan to carry out three PDSA cycles to evaluate whether two separate interventions are effective in increasing the prescription rate of ONS in post-surgical femur patients. Each PDSA cycle included all patients who underwent surgical treatment for femur fracture during a one month period. Results ‘Cycle 1’ included 18 patients (mean age: 84.6 years; range: 68–98 years) treated in March 2021. ONS were prescribed in 11% (2/18) post-surgical femur fracture patients. ‘Intervention 1’ comprised a dietician-led presentation during the Geriatric department weekly teaching session on 17/05/21. ‘Cycle 2’ data will be collected one month after ‘Intervention 1’. Conclusion ‘Cycle 1’ results revealed low rates of ONS prescriptions for post-surgical femur patients. We anticipate higher ONS prescription rates following ‘Intervention 1’. We believe that doctors’ and dieticians’ awareness of the importance of nutritional support for post-surgical femur fracture patients is key to the success of this quality improvement project.

Introduction Constipation is a common cause of morbidity in the elderly. Its management is particularly challenging in the inpatient population, where many factors exacerbate constipation. We describe a Quality Improvement Project to reduce the rates of constipation on a female Medicine for the Elderly ward. Aims Our aim was to increase bowel chart documentation (nursing and doctor entries) and increase patient frequency of bowel motions to at least once every two days. In particular we focused on conservative measures such as the use of footstools to optimise posture when using commodes and toilets [R Hari Krishnan, Proc Inst Mech Eng H, 2019, 233(4):464–475]. Method • Weekly monitoring of ward inpatients. • Measurements taken were: days since last bowel motion, laxatives prescribed, bowel chart and ward round documentation, and episodes of diarrhoea over the past week. • One episode of diarrhoea was defined as 3 motions of type 6 or type 7 stool in 24 hours. • A new intervention was introduced every two weeks, over a total of 2 months. Interventions: 1. Recording bowel motions at the daily ‘Board Round’ Multi-Disciplinary Meeting. 2. Ward staff education sessions. 3. Footstools for use with commodes and toilets. 4. High-fibre foods to patients with constipation. Results Level of constipation was successfully reduced, with 100% patients moving bowels every 2 days from a baseline of 68%. Ward round and bowel chart documentation improved to 100% and 93.3% respectively (from 41.3% and 33.3%). However, incidence of diarrhoea increased from 0 episodes/week to 8 episodes/week, with laxative prescriptions similarly increased from 50% to 86%. Conclusion Constipation improved with our interventions, but at the unintended cost of laxative-associated diarrhoea. Our next steps will be to reduce laxative prescriptions in favour of conservative measures, in order to reduce episodes of loose stool while maintaining our improved constipation rates.

Background The number of opioid prescriptions in older patients has increased dramatically and it is recognised that opioids are the fourth most likely drug to cause preventable hospital admissions. The adverse effects of opioids occur more frequently in the geriatric population. Little is known about the impact of postoperative pain in older adults. NICE recommends paracetamol with additional opioids if there is insufficient postoperative pain relief. Multidisciplinary management with early and then daily physiotherapy is critical. We have assessed pre-morbid, immediate and prolonged use of opioids in patients following hip fracture. Local problem Pre-intervention analysis identified 79% (57/72) of all patients being discharged on opiates. At 4-months, 37% (17/46) of those were still using them. This represents 28% (17/61) of all patients. Methods Analysis of all patients (excluding poly-trauma) with hip fractures over the age of 60 years admitted to St Mary’s Hospital. Interventions Development of local guideline on analgesia prescribing; particularly focusing senior geriatrician led decision making. Prescribing oxycodone for first 72-hours and initially using nerve block. Avoidance of transdermal preparations and withdrawing stronger opioids prior to discharge. Clear instructions for GP’s on a stop date and need for community review. Patient information leaflet dispensed with all discharge opioid prescriptions. Results Post-intervention cycle; 17% (11/63) of patients were taking prescribed opioids prior to admission (similar to the pre-cohort). 52% (33/63) were discharged on opiates, down from 79%. At 4-months, of those discharged on opioids, 30% (9/30) were still using them; lower than in the first cycle (37%). Overall reduction from 28% to 16% of patients on opioids at 4-months. Conclusion The use of specific hip fracture analgesia guideline, senior geriatrician decision-making and support to community colleagues can reduce in-patient and community opiate prescribing, and stem the growing problem of opioid addiction, misuse and iatrogenic re-admission.

Introduction Constipation is a common and difficult issue in elderly surgical patients, often contributing to prolonged stay on inpatient wards (Sethi et al, Am J Gastroenterol. 2014;109:250–256). Increasing dietary fibre is a commonsense tactic to mitigate against constipation. However it is rarely formally employed on NHS wards. Prunes are beneficial in increasing fibre intake and are a natural source of sorbitol, which acts as an osmotic laxative (Stacewicz-Sapuntzakis et al, Crit Rev Food Sci Nutr. 2001;41:251–86.) Method We performed a closed-loop audit on the use of prunes in reducing constipation. We collected data from surgical inpatients over 60 years, including the number of days since bowels were last opened, and the number of laxatives that each patient was taking. Patients were then given a prune product (either 3 dried prunes, 125 mL prune juice or 70 g prune puree) three times a week. Following the intervention, the data was recollected to complete the audit cycle. Results In our cohort of 36 patients, the mean time since bowels were last opened reduced from 1.49 to 1.17 days (p = 0.1624) after introducing prunes three times a week, and the mean number of laxatives reduced from 1.81 to 1.50 (p = 0.1671). Conclusion Surgical patients are at increased risk of constipation (Davies et al, J Clin Pharm Ther. 2008; 31:561–566) due to multiple factors including immobility, poor oral intake and opiate use. Constipation is more common in the elderly (Talley et al, Am J Gastroenterol. 1996;91:19–25), who are also at increased risk of polypharmacy (Morin et al, Clin Epidemiol. 2018;10:289–298). These results show that using prunes to aid regular bowel motion can have a positive impact on reducing pharmacy and increasing frequency of bowels opening. We hope that, by introducing tactics to promote regular bowel motions in hospital, we can reduce polypharmacy and instill good health habits post-discharge.