tbuckley/cabot-search huggingface dataset:
Deep Prostate-specific Antigen Response following Addition of Apalutamide to Ongoing Androgen Deprivation Therapy and Long-term Clinical Benefit in SPARTAN
Authors: Fred Saad, Eric J. Small, Felix Y. Feng, Julie N. Graff, David Olmos, Boris A. Hadaschik, Stéphane Oudard, Anil Londhe, Amitabha Bhaumik, Angela Lopez-Gitlitz, Shibu Thomas, Suneel D. Mundle, Simon Chowdhury, Matthew R. Smith
Journal: European Urology (2021)

Apalutamide plus androgen deprivation therapy (ADT) significantly improved metastasis-free survival (MFS), overall survival (OS), and time to prostate-specific antigen (PSA) progression in the placebo-controlled SPARTAN study of high-risk nonmetastatic castration-resistant prostate cancer (nmCRPC).To assess the relationships between PSA kinetics, outcomes, and molecular subtypes in SPARTAN.The authors conducted a post hoc analysis of nmCRPC patients randomized to receive apalutamide (n = 806) or placebo (n = 401) plus ADT and a subset stratified by molecular classifiers.Apalutamide 240 mg/d.The association between PSA kinetics and MFS, OS, time to PSA progression, and molecular subtypes was evaluated using the landmark analysis and Kaplan-Meier methods.By 3 mo, PSA decreased in most apalutamide-treated patients and increased in most placebo-treated patients. After apalutamide, the median time to PSA nadir, confirmed ≥50% PSA reduction, ≥90% PSA reduction, and PSA ≤0.2 ng/ml were 7.4, 1.0, 1.9, and 2.8 mo, respectively. By 6 mo, 90%, 57%, and 32% of apalutamide patients had ≥50% PSA reduction, ≥90% PSA reduction, and PSA ≤0.2 ng/ml, respectively, while only 1.5% of placebo patients experienced ≥50% PSA reduction. PSA reductions were observed within 3 mo and up to 12 mo of apalutamide treatment, and were similar across molecular subtypes. Deep PSA responses (≥90% PSA reduction or PSA ≤0.2 ng/ml) at landmark 6-mo apalutamide treatment were significantly associated with improved time to PSA progression (hazard ratio {HR} [95% confidence interval {CI}] 0.25 [0.18-0.33] or 0.13 [0.08-0.21]), MFS (0.41 [0.29-0.57] or 0.3 [0.19-0.47]), and OS (0.45 [0.35-0.59] or 0.26 [0.18-0.38]; p < 0.001 for all).Apalutamide plus ADT produced rapid, deep, and durable PSA responses by 6-mo treatment regardless of assessed molecular prognostic markers. An early PSA response with apalutamide was associated with clinical benefits, supporting prognostic value of PSA monitoring.In this report, we describe how prostate-specific antigen (PSA) levels relate to outcomes in patients with nonmetastatic castration-resistant prostate cancer treated with apalutamide plus androgen deprivation therapy (ADT). We found that treatment with apalutamide plus ADT resulted in rapid, deep, and durable PSA responses in the majority of patients, including those with high-risk molecular subtypes, which were associated with improved survival.
Effect of universal HIV testing and treatment on socioeconomic wellbeing in rural Kenya and Uganda: a cluster-randomised controlled trial
Authors: Aleksandra Jakubowski, Jane Kabami, Laura B Balzer, James Ayieko, Edwin D Charlebois, Asiphas Owaraganise, Carina Marquez, Tamara D Clark, Douglas Black, Starley B Shade, Gabriel Chamie, Craig R Cohen, Elizabeth A Bukusi, Moses R Kamya, Maya Petersen, Diane V Havlir, Harsha Thirumurthy
Journal: The Lancet Global Health (2021)

BackgroundUniversal testing and treatment for HIV has shown promise as an approach to reduce mortality and lower HIV incidence. Evidence on the economic effects of this approach on individuals and households in low-resource settings is scarce. We aimed to examine the effect of universal HIV testing and treatment on a range of economic outcomes.MethodsWe collected data in household surveys done over a 3-year period in a sample of HIV-positive and HIV-negative adults participating in a cluster-randomised trial of universal HIV testing and treatment in 32 rural communities in Kenya and Uganda. Communities of approximately 10 000 people were pair-matched on the basis of geographical and population characteristics, with the best-matching 16 pairs randomly assigned (1:1) to intervention or control groups. Participants in intervention communities received annual HIV and multidisease testing, universal antiretroviral therapy (ART) eligibility, and patient-centred care. Participants in control communities received baseline testing and medical care according to national guidelines. We analysed employment and health-care utilisation outcomes for working-age adults (age 18–65 years) and education outcomes for school-age children (6–17 years) using data from 3 years after the intervention. This trial is now complete, and is registered with ClinicalTrials.gov, NCT01864603.FindingsBetween July 9, 2013, and June 15, 2017, we collected survey data on 8198 working-age adults and 6755 school-age children. Compared with adults living with HIV in control communities, adults living with HIV in intervention communities were more likely to be employed (difference 9·7% [95% CI 2·1 to 18·3]), less likely to seek health care (–10·3% [–22·0 to 0·1]), and less likely to spend money on health care (–12·7% [–22·4 to 0·6]) 3 years after the intervention. We found no significant differences in outcomes between HIV-negative adults in intervention and control communities. Among children in households with HIV-positive adults, the intervention led to a 7·3% (95% CI 1·0 to 15·1) increase in primary school completion after 3 years in intervention communities compared with control communities.InterpretationUniversal HIV testing and treatment improved employment outcomes and other indicators of socioeconomic wellbeing for HIV-positive adults and children in their households, but had no effect on HIV-negative adults. Our findings suggest that the considerable investments needed to expand ART access might have substantial short-term and long-term economic returns.FundingNational Institutes of Health.
Improved mechanical, degradation, and biological performances of Zn–Fe alloys as bioresorbable implants
Authors: Yingchao Su, Jiayin Fu, Wonsae Lee, Shaokang Du, Yi-Xian Qin, Yufeng Zheng, Yadong Wang, Donghui Zhu
Journal: Bioactive Materials (2021)

Zinc (Zn) is a promising bioresorbable implant material with more moderate degradation rate compared to magnesium (Mg) and iron (Fe). However, the low mechanical strength and localized degradation behavior of pure Zn limit its clinical applications. Alloying is one of the most effective ways to overcome these limitations. After screening the alloying element candidates regarding their potentials for improvement on the degradation and biocompatibility, we proposed Fe as the alloying element for Zn, and investigated the in vitro and in vivo performances of these alloys in both subcutaneous and femoral tissues. Results showed that the uniformly distributed secondary phase in Zn-Fe alloys significantly improved the mechanical property and facilitated uniform degradation, which thus enhanced their biocompatibility, especially the Zn-0.4Fe alloy. Moreover, these Zn-Fe alloys showed outstanding antibacterial property. Taken together, Zn-Fe alloys could be promising candidates as bioresorbable medical implants for various cardiovascular, wound closure, and orthopedic applications.
Letter to the editor: The role of aquaporin 9 in modeling of ornithine transcarbamylase deficiency
Authors: Jun‐Wei Zhang, Quan‐Cheng Cheng, Hui‐Ru Ding, Lei Zhang, Yi‐Yao Xu, Xin‐ting Sang, Hai‐Tao Zhao, Wei‐Guang Zhang, Xin Lu
Journal: Hepatology (2021)
Abstract 17034: Acute Ventricular Septal Rupture Management By The Cardiac Intensivist
Authors: Khoa Nguyen, Clint Kolseth, Srini V Mukundan
Journal: Circulation (2021)

Case Presentation: A 59-year-old male presented with chest pain and electrocardiogram showed convex ST elevations in the inferior leads. He underwent emergent coronary angiography revealing a 99% mid-distal right coronary artery thrombotic occlusion followed by placement of a drug-eluting stent. Transthoracic echocardiogram (TTE) revealed a 2.5 cm muscular ventricular septal rupture (VSR) with a calculated pulmonary-systemic flow ratio (Qp/Qs) of 2.4 in the setting of normal right and left ventricular systolic function. In the intensive care unit, he still had nausea and chest discomfort, along with acute kidney injury and elevated lactate levels. A trial of aggressive medical management was pursued to avoid emergent cardiac surgery. We placed an arterial line and initiated afterload reduction with sodium nitroprusside, utilizing serial bedside TTEs to monitor his Qp/Qs, which trended down to 1.8 over the subsequent 12 hours followed by normalization of lactate and kidney function. His symptoms resolved and he remained stable while transitioning to oral vasodilators. After four weeks of medical therapy, he underwent timely surgical repair of his VSR and discharged home. Discussion: Ventricular septal rupture is a serious complication of inferior myocardial infarctions (MI). From a cardiac intensivist perspective, we maintained the patient at a euvolemic state while using systemic vasodilators to divert the left-to-right shunt flow and augment his systemic flow. We want to highlight the utility of serial bedside TTEs to guide therapy for VSR (Figure 1). Fortunately, our patient did not require mechanical circulatory support to maintain his hemodynamics. We also discussed with our cardiothoracic surgeons about the optimal timing for surgical repair. The guidelines suggest urgent VSR repair following an MI; however, the exact timing is debatable given the fragility of the inflamed post-MI myocardium and better surgical outcomes with maturation of the VSR.
Geriatric Assessment Predicts Non-Fatal Toxicities and Survival for Intensively Treated Elderly Acute Myeloid Leukemia: A Prospective Study
Authors: Gi June Min, Byung Sik Cho, Sung-Soo Park, Silvia Park, Young-Woo Jeon, Seung-Hwan Shin, Seung-Ah Yahng, Jae-Ho Yoon, Sung-Eun Lee, Ki-Seong Eom, Yoo-Jin Kim, Seok Lee, Chang-Ki Min, Seok-Goo Cho, Dong-Wook Kim, Jong Wook Lee, Hee-Je Kim
Journal: Blood (2021)
Remote Speech Analysis in the Evaluation of Hospitalized Patients With Acute Decompensated Heart Failure
Authors: Offer Amir, William T. Abraham, Zaher S. Azzam, Gidon Berger, Stefan D. Anker, Sean P. Pinney, Daniel Burkhoff, Ilan D. Shallom, Chaim Lotan, Elazer R. Edelman
Journal: JACC Heart Failure (2021)

This study assessed the performance of an automated speech analysis technology in detecting pulmonary fluid overload in patients with acute decompensated heart failure (ADHF).Pulmonary edema is the main cause of heart failure (HF)-related hospitalizations and a key predictor of poor postdischarge prognosis. Frequent monitoring is often recommended, but signs of decompensation are often missed. Voice and sound analysis technologies have been shown to successfully identify clinical conditions that affect vocal cord vibration mechanics.Adult patients with ADHF (n = 40) recorded 5 sentences, in 1 of 3 languages, using HearO, a proprietary speech processing and analysis application, upon admission (wet) to and discharge (dry) from the hospital. Recordings were analyzed for 5 distinct speech measures (SMs), each a distinct time, frequency resolution, and linear versus perceptual (ear) model; mean change from baseline SMs was calculated.In total, 1,484 recordings were analyzed. Discharge recordings were successfully tagged as distinctly different from baseline (wet) in 94% of cases, with distinct differences shown for all 5 SMs in 87.5% of cases. The largest change from baseline was documented for SM2 (218%). Unsupervised, blinded clustering of untagged admission and discharge recordings of 9 patients was further demonstrated for all 5 SMs.Automated speech analysis technology can identify voice alterations reflective of HF status. This platform is expected to provide a valuable contribution to in-person and remote follow-up of patients with HF, by alerting to imminent deterioration, thereby reducing hospitalization rates. (Clinical Evaluation of Cordio App in Adult Patients With CHF; NCT03266029).
Karaoke as a feasible alternative therapy to pulmonary rehabilitation for COPD
Authors: Mizuki Yuge, Shinsuke Hori, Kenta Ushida, Ryo Momosaki
Journal: European Respiratory Journal (2021)

<b>Exercise adherence is frequently a concern in pulmonary rehabilitation for COPD. Some people like singing more than physical exercise, so the use of karaoke might be a feasible alternative to pulmonary rehabilitation for COPD.</b>https://bit.ly/3q7l1ea
Ibrutinib Plus Rituximab and Venetoclax (IRV) Followed By Risk-Stratified Observation or Short Course R-Hypercvad/MTX in Young Patients with Previously Untreated Mantle Cell Lymphoma - Phase-II Window-2 Clinical Trial
Authors: Michael Wang, Preetesh Jain, Hun Ju Lee, Chi Young Ok, Holly Hill, Lucy Navsaria, Rashmi Kanagal-Shamanna, Luis Malpica-Castillo, Ranjit Nair, Swaminathan Padmanabhan Iyer, Felipe Samaniego, Wendy Chen, Onyeka Oriabure, Lei Feng, Selvi Thirumurthi, David Santos, Guilin Tang, Francisco Vega, Shaoying Li, Michelle Avellaneda, Maria Badillo, Christopher R. Flowers
Journal: Blood (2021)
EULAR points to consider for the use of imaging to guide interventional procedures in patients with rheumatic and musculoskeletal diseases (RMDs)
Authors: Christian Dejaco, Pedro M Machado, Francesco Carubbi, Philipp Bosch, Lene Terslev, Giorgio Tamborrini, Luca Maria Sconfienza, Carlo Alberto Scirè, Sebastian Ruetten, Jef van Rompay, Fabian Proft, Costantino Pitzalis, Marina Obradov, Rikke Helene Moe, Vasco V Mascarenhas, Clara Malattia, Andrea Sabine Klauser, Alison Kent, Lennart Jans, Wolfgang Hartung, Hilde Berner Hammer, Christina Duftner, Peter V Balint, Alessia Alunno, Xenofon Baraliakos
Journal: Annals of the Rheumatic Diseases (2021)

To develop evidence-based Points to Consider (PtC) for the use of imaging modalities to guide interventional procedures in patients with rheumatic and musculoskeletal diseases (RMDs).European Alliance of Associations for Rheumatology (EULAR) standardised operating procedures were followed. A systematic literature review was conducted to retrieve data on the role of imaging modalities including ultrasound (US), fluoroscopy, MRI, CT and fusion imaging to guide interventional procedures. Based on evidence and expert opinion, the task force (25 participants consisting of physicians, healthcare professionals and patients from 11 countries) developed PtC, with consensus obtained through voting. The final level of agreement was provided anonymously.A total of three overarching principles and six specific PtC were formulated. The task force recommends preference of imaging over palpation to guide targeted interventional procedures at peripheral joints, periarticular musculoskeletal structures, nerves and the spine. While US is the favoured imaging technique for peripheral joints and nerves, the choice of the imaging method for the spine and sacroiliac joints has to be individualised according to the target, procedure, expertise, availability and radiation exposure. All imaging guided interventions should be performed by a trained specialist using appropriate operational procedures, settings and assistance by technical personnel.These are the first EULAR PtC to provide guidance on the role of imaging to guide interventional procedures in patients with RMDs.
Recovery of exercise capacity after COVID-19 pneumonia: Key role of right ventricular-pulmonary circulation unit
Authors: R.F. Rinaldo, M. Guazzi, F. Rusconi, E.M. Parazzini, F. Pitari, M. Mondoni, M. Balbi, F. Di Marco, S. Centanni
Journal: Pulmonology (2021)

Recovery of exercise capacity after COVID-19 pneumonia: Key role of right ventricular-pulmonary circulation unitThe role of pulmonary vasculature in exercise after COVID-19 pneumonia
<i>Erratum:</i> Vol. 70, No. 43
Journal: MMWR Morbidity and Mortality Weekly Report (2021)

In the report "Routine Vaccination Coverage -Worldwide, 2020," on page 1497, in the first column, the first full sentence should have read, "During 2019-2020, the number of zero-dose children was stable in the European Region at 0.3 million but increased in the African (from 7.1 million to 7.7 million), Americas (from 1.6 million to 1.7 million), Eastern Mediterranean (from 1.8 million to 2.3 million), South-East Asia (from 2.0 to 4.1 million), and Western Pacific (from 0.9 million to 1.0 million) regions (Figure)."
Graded exercise therapy for ME/CFS: finding consensus between the royal colleges, patients, and researchers
Authors: Stuart I Brown
Journal: BMJ (2021)

After oral treatment (once daily) for 4 weeks with the potent bradykinin B<sub>1</sub> receptor antagonist methyl 3-chloro-3′-fluoro-4′-{(1<i>R</i>)-1-[({1-[(trifluoroacetyl)amino]cyclopropyl}carbonyl)-amino]ethyl}-1,1′-biphenyl-2-carboxylate (MK-0686), rhesus monkeys (<i>Macaca mulatta</i>) exhibited significantly reduced systemic exposure of the compound in a dose-dependent manner, suggesting an occurrence of autoinduction of MK-0686 metabolism. This possibility is supported by two observations. 1) MK-0686 was primarily eliminated via biotransformation in rhesus monkeys, with oxidation on the chlorophenyl ring as one of the major metabolic pathways. This reaction led to appreciable formation of a dihydrodiol (M11) and a hydroxyl (M13) product in rhesus liver microsomes supplemented with NADPH. 2) The formation rate of these two metabolites determined in liver microsomes from MK-0686-treated groups was ≥2-fold greater than the value for a control group. Studies with recombinant rhesus P450s and monoclonal antibodies against human P450 enzymes suggested that CYP2C75 played an important role in the formation of M11 and M13. The induction of this enzyme by MK-0686 was further confirmed by a concentration-dependent increase of its mRNA in rhesus hepatocytes, and, more convincingly, the enhanced CYP2C proteins and catalytic activities toward CYP2C75 probe substrates in liver microsomes from MK-0686-treated animals. Furthermore, a good correlation was observed between the rates of M11 and M13 formation and hydroxylase activities toward probe substrates determined in a panel of liver microsomal preparations from control and MK-0686-treated animals. Therefore, MK-0686, both a substrate and inducer for CYP2C75, caused autoinduction of its own metabolism in rhesus monkeys by increasing the expression of this enzyme.
Protection from covid-19 at work: health and safety law is fit for purpose
Authors: Raymond M. Agius, Diana Kloss, Denise Kendrick, Marcia Stewart, John FR Robertson
Journal: BMJ (2021)

The 2020 Coronavirus Act and ensuing secondary legislation, as well as official government coronavirus guidance, have provided some limited protection from covid-19 for workers such as by temporarily implementing work from home orders. 1 By contrast, the health of employees and others in workplaces remains potentially well protected by laws dating back at least as far as the 1974 Health and Safety etc at Work Act. 2 -4 This mandates that employers have duties to ensure both the health of their employees and of others affected by the conduct of their undertakings, such as patients, students, and site visitors.Regrettably, government departments, notably the Department of Health and Social Care and the Department for Education, fell short in emphasising the obligations of employers to protect their employees health during the covid-19 pandemic.The Omicron variant has increased transmissibility and likely partial vaccine resistance, and therefore especially warrants appropriate safeguards for employees, particularly front line healthcare and social care workers who will be extremely vulnerable to exposure in the impending outbreak. 5 The most recent guidance on infection prevention and control (IPC), published by the UK Health Security Agency, goes further than earlier iterations in advising compliance with health and safety legislation in protecting healthcare workers. 6However, it is still flawed, for instance, in recommending less respiratory protection for healthcare workers routinely exposed to patients infected with covid-19, which it considers both droplet transmissible and airborne, than for tuberculosis which it deems solely airborne.
Association of Medicaid vs Marketplace Eligibility With Maternal Coverage and Access to Prenatal and Postpartum Care
Authors: Erica L. Eliason, Jamie R. Daw, Heidi L. Allen
Journal: JAMA Network Open (2021)

<h3>Importance</h3> Policy makers are considering insurance expansions to improve maternal health. The tradeoffs between expanding Medicaid or subsidized private insurance for maternal coverage and care are unknown. <h3>Objective</h3> To compare maternal coverage and care by Medicaid vs marketplace eligibility. <h3>Design, Setting, and Participants</h3> A retrospective cohort study using a difference-in-difference research design was conducted from March 14, 2020, to April 22, 2021. Maternal coverage and care use were compared among women with family incomes 100% to 138% of the federal poverty level (FPL) residing in 10 Medicaid expansion sites (exposure group) who gained Medicaid eligibility under the Affordable Care Act and in 5 nonexpansion sites (comparison group) who gained marketplace eligibility before (2011-2013) and after (2015-2018) insurance expansion implementation. Participants included women aged 18 years or older from the 2011-2018 Pregnancy Risk Assessment Monitoring System survey. <h3>Exposures</h3> Eligibility for Medicaid or marketplace coverage under the Affordable Care Act. <h3>Main Outcomes and Measures</h3> Outcomes included coverage in the preconception and postpartum periods, early and adequate prenatal care, and postpartum checkups and effective contraceptive use. <h3>Results</h3> The study population included 11 432 women age 18 years and older (32% age 18-24 years, 33% age 25-29 years, 35% age ≥30 years) with incomes 100% to 138% FPL: 7586 in a Medicaid state (exposure group) and 3846 in a nonexpansion marketplace state (comparison group). Women in marketplace states were younger, had higher educational level and marriage rates, and had less racial and ethnic diversity. Medicaid relative to marketplace eligibility was associated with increased Medicaid coverage (20.3 percentage points; 95% CI, 12.8 to 30.0 percentage points), decreased private insurance coverage (−10.8 percentage points; 95% CI, −13.3 to −7.5 percentage points), and decreased uninsurance (−8.7 percentage points; 95% CI, −20.1 to −0.1 percentage points) in the preconception period, increased postpartum Medicaid (17.4 percentage points; 95% CI, 1.7 to 34.3 percentage points) and increased adequate prenatal care (4.4 percentage points; 95% CI, 0.1 to 11.0 percentage points) in difference-in-difference models. No evidence of significant differences in early prenatal care, postpartum check-ups, or postpartum contraception was identified. <h3>Conclusions and Relevance</h3> In this cohort study, eligibility for Medicaid was associated with increased Medicaid, lower preconception uninsurance, and increased adequate prenatal care use. The lower rates of preconception uninsurance among Medicaid-eligible women suggest that women with low incomes were facing barriers to marketplace enrollment, underscoring the potential importance of reducing financial barriers for the population with low incomes.
The placebo and nocebo effects in functional urology
Authors: Hadi Mostafaei, Sandra Jilch, Greta Lisa Carlin, Keiichiro Mori, Fahad Quhal, Benjamin Pradere, Ekaterina Laukhtina, Victor M. Schuettfort, Abdulmajeed Aydh, Reza Sari Motlagh, Claus G. Roehrborn, Shahrokh F. Shariat, Sakineh Hajebrahimi
Journal: Nature Reviews Urology (2021)
Prednisolone plus itraconazole in acute-stage allergic bronchopulmonary aspergillosis complicating asthma: is the benefit worth the risk?
Authors: Alice Havette, Lucile Regard, Nicolas Roche, Pierre-Régis Burgel
Journal: European Respiratory Journal (2021)

<b>The effect of adding itraconazole to prednisolone shown in an open-labelled study has no firmly established mechanism and could be related to greater exposure to steroids. The risk of selecting azole-resistant <i>A. fumigatus</i> strains should be considered.</b>https://bit.ly/30Nl3zr