Patient-reported outcomes version of the common terminology criteria for adverse events and quality-of-life linear analogue self-assessment in breast cancer patients receiving radiation therapy: single-institution prospective registry

Purpose/objectives We sought to investigate the impact of patient-reported outcomes version of the common terminology criteria for adverse events (PRO-CTCAE) on overall quality-of-life (QOL) employing linear analogue self-assessment (LASA) in breast cancer (BC) patients undergoing radiation therapy (RT). Materials/methods All patients treated with RT for BC with curative intent from 2015 to 2019 at our institution were included. Breast specific PRO-CTCAE and overall QOL LASA questionnaires were administered at baseline, end-of-treatment, 3, 6, 12 months, and then annually. Minimal clinically important difference in overall QOL was a 10-point change in LASA. Hypofractionation was any treatment > 2 Gy per fraction. Mixed models for repeated measures were used to determine the association of PRO-CTCAE and overall QOL LASA. Results Three hundred thirty-one (331) patients with a median follow-up of 3.1 years (range 0.4–4.9) were included. Average overall QOL LASA scores were 78.5 at baseline, 79.8 at end-of-treatment, 79.8 at 3 months, 77.1 at 6 months, 79.4 at 12 months, and 79.7 at 24 months. On univariate analysis, patients reporting a grade ≥ 3 PRO-CTCAE had, on average, a 10.4-point reduction in overall LASA QOL (p < 0.0001). On multivariate analysis, not being treated with hypofractionation and higher BMI were predictive for worse overall LASA QOL with a 10-point reduction in LASA for patients reporting a grade ≥ 3 PRO-CTCAE (p < 0.0001). Conclusions Patients reporting a grade ≥ 3 PRO-CTCAE experienced statistically significant and clinically meaningful deterioration in overall QOL LASA. Hypofractionation improved QOL while higher BMI predicted for worse QOL. PRO-CTCAE should be integrated into future clinical trials.

The Rise and Fall of India’s Relative Investment Price: A Tale of Policy Error and Reform

India’s relative price of investment rose 44 percent from 1981 to 1991 and fell 26 percent from 1991 to 2006. We build a simple DGE model, calibrated to Indian data, in order to explore the impact of capital import substitution policies and their reform post-1991 in accounting for this rise and fall. Our model delivers a 23 percent rise before reform and a 31 percent fall thereafter. GDP per effective labor was 3 percent lower in 1991 compared to 1981 due to import restrictions on capital goods. Their removal, and a 71 percentage point reduction in tariff rates, raised GDP per effective labor permanently by 20 percent. (JEL E22, E23, F13, O11, O16, O19)

A Randomized Clinical Trial of Linagliptin vs. Standard of Care in Patients Hospitalized With Diabetes and COVID-19

ObjectiveTo assess the effect of linagliptin vs. standard therapy in improving clinical outcomes in patients hospitalized with diabetes and coronavirus disease 2019 (COVID-19).Materials and MethodsWe did an open-label, prospective, multicenter, randomized clinical trial in 3 Israeli hospitals between October 1, 2020, and April 4, 2021. Eligible patients were adults with type 2 diabetes mellitus and a diagnosis of COVID-19. A total of 64 patients, 32 in each group, were randomized to receive linagliptin 5 mg PO daily throughout the hospitalization or standard of care therapy. The primary outcome was time to clinical improvement within 28 days after randomization, defined as a 2-point reduction on an ordinal scale ranging from 0 (discharged without disease) to 8 (death).ResultsThe mean age was 67 ± 14 years, and most patients were male (59.4%). Median time to clinical improvement was 7 days (interquartile range (IQR) 3.5-15) in the linagliptin group compared with 8 days (IQR 3.5–28) in the standard of care group (hazard ratio, 1.22; 95% CI, 0.70–2.15; p = 0.49). In-hospital mortality was 5 (15.6%) and 8 (25.0%) in the linagliptin and standard of care groups, respectively (odds ratio, 0.56; 95% CI, 0.16–1.93). The trial was prematurely terminated due to the control of the COVID-19 outbreak in Israel.ConclusionsIn this randomized clinical trial of hospitalized adult patients with diabetes and COVID-19 who received linagliptin, there was no difference in the time to clinical improvement compared with the standard of care.Clinical Trial RegistrationClinicalTrials.gov, identifier NCT04371978.

Poverty in American Higher Education

A substantial share of college students experience housing insecurity and too many students leave higher education before earning a credential. Both of these experiences are more common among students from low-income families who often lack adequate resources. While prior conceptual and qualitative investigations suggest that housing insecurity is associated with poorer student outcomes, this relationship has not been tested due to quantitative data limitations. In this paper, I use data from a state-wide longitudinal study of students from low-income families to conduct the first empirical test of the relationship between housing insecurity early in college and later college achievement and attainment. Findings show that housing insecurity is a statistically significant predictor of academic success, net of background factors. Specifically, housing insecurity is associated with an 8 to 12 percentage-point reduction in the probability of later degree attainment or enrollment. In the short-term, housing insecurity is also associated with lower mean GPA, a lower probability of obtaining at least a 2.0 GPA, and a higher probability of enrolling part-time rather than full-time, indicating that housing insecurity affects students’ college academic experiences in multiple ways. Efforts to promote college attainment should be expanded to consider students’ housing security. There are likely several points in time and multiple ways that higher education institutions, nonprofit agencies, and policymakers can intervene to promote secure housing and college success.

Safety and efficacy of autologous non-hematopoietic enriched stem cell nebulization in COVID-19 patients: a randomized clinical trial, Abu Dhabi 2020

Background The novel SARS-CoV-2 has caused the coronavirus disease 2019 (COVID-19) pandemic. Currently, with insufficient worldwide vaccination rates, identifying treatment solutions to reduce the impact of the virus is urgently needed. Method An adaptive, multicentric, open-label, and randomized controlled phase I/II clinical trial entitled the “SENTAD-COVID Study” was conducted by the Abu Dhabi Stem Cells Center under exceptional conditional approval by the Emirates Institutional Review Board (IRB) for COVID-19 Research Committee from April 4th to July 31st, 2020, using an autologous peripheral blood non-hematopoietic enriched stem cell cocktail (PB-NHESC-C) administered by compressor (jet) nebulization as a complement to standard care therapy. The primary endpoints include safety and efficacy assessments, adverse events, the mortality rate within 28 days, and the time to clinical improvement as measured by a 2-point reduction on a seven-category ordinal scale or discharge from the hospital whichever occurred first. Results The study included a total of 139 randomized COVID-19 patients, with 69 in the experimental group and 70 in the control group (standard care). Overall survival was 94.20% for the cocktail-treated group vs. 90.27% for the control group. Adverse events were reported in 50 (72.46%) patients receiving PB-NHESC-C and 51 (72.85%) in the control group (p = 0.9590), with signs and symptoms commonly found in COVID-19. After the first 9 days of the intervention, 67.3% of cocktail-treated patients recovered and were released from hospitals compared to 53.1% (RR = 0.84; 95% CI, 0.56–1.28) in the control group. Improvement, i.e., at least a 2-point reduction in the severity scale, was more frequently observed in cocktail-treated patients (42.0%) than in controls (17.0%) (RR = 0.69; 95% CI, 0.56–0.88). Conclusions Cocktail treatment improved clinical outcomes without increasing adverse events. Thus, the nebulization of PB-NHESC-C was safe and effective for treatment in most of these patients. Trial registration ClinicalTrials.gov. NCT04473170. It was retrospectively registered on July 16th, 2020.

Analysis of Mechanistic Pathways in the Treatment of Non-Alcoholic Steatohepatitis. Evidence from a Bayesian Network Meta-Analysis

Background and Aims: Non-alcoholic steatohepatitis (NASH) is the most common cause of liver disease contributing to significant disease burden worldwide. However, there is lack of comparison of efficacy between different NASH drug classes. We conducted a network meta-analysis evaluating drug classes through comparing histological outcomes and targets of drugs. Approach & Results: Medline, EMBASE and CENTRAL were searched for articles evaluating NASH drugs in biopsy-proven NASH patients. Primary outcomes included NASH resolution without worsening of fibrosis, 2-point reduction in Non-alcoholic fatty liver disease Activity Score (NAS) without worsening of fibrosis and 1-point reduction in fibrosis. Treatments were classified into inflammation, energy, bile acid, and fibrosis modulators. The analysis was conducted with Bayesian network model and surface under the cumulative ranking curve (SUCRA) analysis. From the 48 trials included, treatments modulating energy (Risk ratio (RR): 1.84, Credible intervals (Crl): 1.29 - 2.65) were the most likely to achieve NASH resolution followed by treatments modulating fibrosis (RR 1.68, Crl: 0.55 - 5.28), bile acids (RR: 1.34, Crl: 0.78 - 2.26) and inflammation (RR: 0.94, Crl: 0.59 - 1.46). Energy and bile acids modulation were effective in 2-point NAS reduction without worsening of fibrosis (RR: 1.60, Crl 1.13 - 2.30 and RR: 1.79, Crl 1.14 - 2.86) and 1-point fibrosis (RR: 1.27, Crl:1.05 - 1.52 and RR: 1.54, Crl: 1.20 - 1.97). Conclusions: This network analysis demonstrates the relative superiority of drugs modulating energy pathways and bile acids in NASH treatment. This guides the development and selection of drugs for combination therapies.

Health Effects of Trade Liberalization: Evidence from US Counties

This paper explores the potential externality of trade liberalization between the US and China on air pollution and infants’ health outcomes. Exploiting the differential impact of tariff reductions due to trade liberalization across industries combined with compositional variations of industry-specific employment across counties as the main source of identification strategy and using the universe of birth records in the US over the years 1990-2017 (over 97 million observations), we document substantial improvements in birth outcomes of mothers residing in counties with higher exposure to trade policy change. The exposed counties experienced sharp drops in employment specifically for manufacturing industries and revealed sharp reductions in a wide array of pollutants. A 1 percent reduction in tariff rates is associated with an 11.5 and 12.7 percentage point reduction in the likelihood of low birth weight and preterm birth, respectively.

Factors affecting improvement of neurologic status evaluated by Quantitative Myasthenia Gravis Score for patients with thymomatous myasthenia gravis after extended thymectomy

Background The length of time for clinical improvement of patients with thymomatous myasthenia gravis (MG) after extended thymectomy is not clear. The purpose of this study was to determine the length of time after thymectomy in patients with thymomatous MG to achieve a 3-point reduction of Quantitative Myasthenia Gravis Score (QMGS), and identify variables associated with a failure to achieve the reduction. Methods The records of patients with thymomatous MG who underwent extended thymectomy from January 2005 to December 2018 were retrospectively reviewed. The primary end point was a reduction of 3 points of QMGs and the secondary end point was another reduction of 3 points of QMGs. Results A total of 481 patients were included in the analysis, the mean age of the patients was 41.63 ± 8.55 years, and approximately 60% were male. The median time to achieve a 3 point decrease in QMGS was 6 months, and the median time to achieve another 3 point decrease was 30 months. Multivariable analysis indicated that age ≥ 42 years and Masaoka-Koga stage > I were associated with a lower probability of achieving a 3 point decrease in QMGS (HR = 0.55 and 0.65, respectively). Likewise, multivariable analysis indicated that age ≥ 42 years and Masaoka-Koga stage > I were associated with a lower probability of achieving a second 3 point decrease in QMGS (HR = 0.53 and 0.53, respectively). Conclusions In patients with thymomatous MG who receive thymectomy, age ≥ 42 years and Masaoka-Koga stage > I are associated with a worse prognosis and failure to achieve a 3 point decrease in QMGS.

Randomised, double-blind comparison of a fixed co-formulation of intra-articular polynucleotides and hyaluronic acid versus hyaluronic acid alone in the treatment of knee osteoarthritis: two-year follow-up

Background A first-year interim analysis of this two-year study suggested that intra-articular injections of highly purified, natural-origin polynucleotides and hyaluronic acid (HA) as a fixed combination (PNHA) might improve knee function and joint pain more effectively than HA alone in patients with knee osteoarthritis (OA). The purpose of the second-year analysis herein described was to verify whether the first-year interim outcomes persist over the whole two-year period. Methods Randomised, double-blind, HA-controlled clinical trial in 100 knee OA patients (98 randomised, 79 completing the study) in a high-specialisation tertiary care setting. The hypothesised difference of efficacy between PNHA and HA for the original sample size estimate is 20%. Treatment cycle: three intra-articular knee injections of either PNHA or HA, at baseline and weekly for two weeks. Evaluations: Western Ontario and McMaster Universities (WOMAC) score and Knee Society Score (KSS) as, respectively, primary and secondary endpoints, evaluated at baseline and after 2, 6, 12, and 24 months; synovial fluid levels of mediators (at baseline and the end of the treatment cycle). Adverse effects investigated at each control visit. Statistical analysis: Kruskal-Wallis test for independent samples (nonparametric one-way analysis of variance) after correction of means for age, Body Mass Index and Kellgren-Lawrence grade. If significant, pairwise post-hoc Sidak multiple comparisons. Results KSS total score and KSS pain item: significant improvement in both groups, with significantly more pain improvement in patients treated with PNHA (2-point reduction) than HA (1-point reduction). Both groups experienced significant long-term reductions in WOMAC total scores: significantly stronger in PNHA-treated patients after 24 months with a steady difference of 16% favouring PNHA in WOMAC pain subscore. No clinically significant adverse events in either group. Conclusions The outcomes of the 2-year study confirmed that a short cycle of intra-articular treatment (3 weekly double-blind injections) with polynucleotides (long-acting viscosupplementation properties, chondrocyte activation, pain-relieving properties) in fixed combination with high molecular weight hyaluronic acid is more effective in improving knee function and pain in knee OA patients than HA alone. PNHA may be elective for viscosupplementation in knee OA patients with fastidious and resistant pain and worsening disease. Trial registration NCT02417610. Registration, 15/04/2015. ClinicalTrials.gov database link: