bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pricing and Paying for Cancer Drugs
Authors: Hyman David A. , Silver Charles 
Published: July 2020

Abstract
The US system for pricing and paying for cancer drugs is badly broken. The evidence is all around us—whether we focus on total spending, the breathtakingly high prices for chimeric antigen receptor T-cell therapy, the exceedingly high prices for many recently introduced drugs that offer only marginal improvements over existing treatments, or the increasing unaffordability of patient copayments. These problems are compounded by the distortions created by our payment policies, which do not take account of the value of competing treatment options and are structured in ways that distort physicians' incentives. We review the key drivers of cancer drug spending and consider the trade-offs of various policy options for addressing this problem.
Relationship Between Work Experience and Safety Climate in Veterans Affairs Nursing Homes Nationwide
Authors: Quach Emma D. , Kazis Lewis E. , Zhao Shibei , McDannold Sarah E. , Clark Valerie A. , Hartmann Christine W. 
Published: July 2020

Objectives
Staff values and beliefs about resident safety (safety climate) represent one potential driver of nursing home safety. Staff with more work experience (length of service) may possess richer knowledge of resident safety for strengthening safety climate. We investigated the association of length of service with safety climate in the U.S. Department of Veterans Affairs nursing homes or Community Living Centers (CLCs).

Methods
Fifty-six of 134 CLCs participated in 2017 and then 2018 in the previously validated CLC Employee Survey of Attitudes about Resident Safety, which comprised 7 safety climate domains and employee characteristics. We conducted 2 cross-sectional analyses of length of service on each safety climate domain, controlling for occupation, shift, work hours, and clustering by VA hospital, service network, and geographic region, in mixed random-effect regression models.

Results
A total of 1397 and 1645 staff participated in the survey (26% and 28% response rates) at round 1 and 2, respectively. At each round participants working greater than 6 months were less positive than those working less than 6 months about supervisor commitment to safety, coworker interactions around safety, and CLC global ratings.

Conclusions
Differences in work experience contributed to incongruence in perceptions about supervisors, coworkers, and the facility. Workers with more experience may have higher perceived job aptitude and thus higher expectations of supervisory recognition and more criticisms of coworkers. Pairing experienced workers with newer ones may narrow the knowledge gap and increase collaboration. Huddles, team meetings, and organizational initiatives represent opportunities to recognize and leverage experienced workers’ accumulated safety knowledge.
Cost-effectiveness of integrated HIV prevention and family planning services for Zambian couples
Authors: Wall Kristin M. , Kilembe William , Inambao Mubiana , Hoagland Alexandra , Sharkey Tyronza , Malama Kalonde , Vwalika Bellington , Parker Rachel , Sarkar Supriya , Hunter Ken , Streeb Gordon , Mazarire Christine , Tichacek Amanda , Allen Susan 
Published: July 2020

Objective:
To present the incremental cost from the payer's perspective and effectiveness of couples’ family planning counseling (CFPC) with long-acting reversible contraception (LARC) access integrated with couples’ voluntary HIV counseling and testing (CVCT) in Zambia. This integrated program is evaluated incremental to existing individual HIV counseling and testing and family planning services.

Design:
Implementation and modelling.

Setting:
Fifty-five government health facilities in Zambia.

Subjects:
Patients in government health facilities.

Intervention:
Community health workers and personnel promoted and delivered integrated CVCT+CFPC from March 2013 to September 2015.

Main outcome measures:
We report financial costs of actual expenditures during integrated program implementation and outcomes of CVCT+CFPC uptake and LARC uptake. We model primary outcomes of cost-per-: adult HIV infections averted by CVCT, unintended pregnancies averted by LARC, couple-years of protection against unintended pregnancy by LARC, and perinatal HIV infections averted by LARC. Costs and outcomes were discounted at 3% per year.

Results:
Integrated program costs were $3 582 186 (2015 USD), 82 231 couples received CVCT+CFPC, and 56 409 women received LARC insertions. The program averted an estimated 7165 adult HIV infections at $384 per adult HIV infection averted over a 5-year time horizon. The program also averted 62 265 unintended pregnancies and was cost-saving for measures of cost-per-unintended pregnancy averted, cost-per-couple-year of protection against unintended pregnancy, and cost-per-perinatal HIV infection averted assuming 3 years of LARC use.

Conclusion:
Our intervention was cost-savings for CFPC outcomes and CVCT was effective and affordable in Zambia. Integrated couples-focused HIV and family planning was feasible, affordable, and leveraged HIV and unintended pregnancy prevention.
Exploring patterns and predictors of suicidal ideation among pregnant and postpartum women living with HIV in Kilimanjaro, Tanzania
Authors: Knettel Brandon A. , Mwamba Rimel N. , Minja Linda , Goldston David B. , Boshe Judith , Watt Melissa H. 
Published: July 2020

Objective:
Pregnant and postpartum women living with HIV face disproportionate risk of depression and suicide, particularly in low-income and middle-income countries. This study examined patterns and predictors of suicidal ideation among women living with HIV in antenatal care in Kilimanjaro, Tanzania.

Design:
We conducted a longitudinal cohort study of 200 pregnant women living with HIV, with surveys conducted during pregnancy and 6 months postpartum.

Methods:
Pregnant women were recruited during HIV and antenatal care visits at nine clinics. A structured questionnaire was verbally administered in Kiswahili by a trained study nurse. We used simple frequencies and t-tests to measure patterns of suicidal ideation and logistic regression to assess factors associated with suicidal ideation.

Results:
Suicidal ideation was endorsed by 12.8% of women during pregnancy and decreased significantly to 3.9% by 6 months postpartum. Ideation was not significantly greater among participants newly diagnosed with HIV. In univariable analyses, suicidal ideation was associated with depression, anxiety, HIV stigma, single relationship status, unknown HIV status of the father of the baby, negative attitudes about antiretroviral medication, and low social support. In the multivariable model, women experiencing anxiety and HIV stigma were significantly more likely to endorse suicidal ideation during pregnancy.

Conclusion:
Suicidal ideation and associated feelings of hopelessness are a critical challenge in antenatal care among women living with HIV, with important implications for quality of life, care engagement, and survival. To better support patients, targeted approaches to address anxiety, depression, stigma, and hopelessness must be prioritized, including crisis support for suicide prevention.
Ultradeep sequencing reveals HIV-1 diversity and resistance compartmentalization during HIV-encephalopathy
Authors: Giatsou Eleni , Abdi Basma , Plu Isabelle , Desire Nathalie , Palich Romain , Calvez Vincent , Seilhean Danielle , Marcelin Anne-Geneviève , Jary Aude 
Published: July 2020

Objectives:
To examine viral diversity and resistance mutations in different brain areas in cases of HIV-encephalopathy.

Design:
Twelve postmortem brain areas from three cases of possible or certain HIV-encephalopathy were analyzed.

Methods:
After amplification of the reverse transcriptase and the V3 loop region of the gp120 protein, ultradeep sequencing was performed with Illumina technology. Phylogenetic analysis was performed with Fastree v2.1 using the generalized time-reversible (GTR) model. Identification of resistant viral variants was performed on Geneious software, according to HIV-1 genotypic drug resistance interpretation's algorithms, 2018 administered by the French Agency for Research on AIDS and Viral Hepatitis.

Results:
Phylogenetic analysis revealed significant inter-regional and intra-regional diversity reflecting persistent HIV-1 viral replication in the different brain areas. Although some cerebral regions shared HIV-variants, most of them harbored a specific HIV-subpopulation reflecting HIV compartmentalization in the central nervous system. Furthermore, proportion and distribution of resistance mutations to nucleoside and non-nucleoside reverse transcriptase inhibitors differed among different brain areas of the same case suggesting that penetration of antiretroviral treatment may differ from one compartment to another.

Conclusion:
This study, performed with a powerful sequencing technique, confirmed HIV compartmentalization in the central nervous system already shown by classical sequencing, suggesting that there are several reservoirs within the brain.
Higher frequencies of functional HIV-envelope-specific memory B cells are associated with nonprogressive HIV infection in Indian population
Authors: Dhande Jayshree R. , Saikia Kasturi , Singh Dharmendra P. , Bagul Rajani D. , Kulkarni Smita S. , Ghate Manisha V. , Thakar Madhuri R. 
Published: July 2020

Objective:
The HIV-1-specific antibodies are being considered for prevention and therapy in HIV infection. For effective antibody response, presence of functionally competent memory B cells (MEBs) is important; however, HIV-infection is known to alter the B-cell functionality. Very limited data are available on the HIV-specific memory B-cell population in HIV-infected Indian population.

Methods:
In this study, the frequencies of HIV-gp140-specific MEBs were measured in individuals with nonprogressive [long-term-nonprogressors (LTNPs), N = 20] and progressive (N = 19) HIV infection using multicolor flow cytometry. The activation and functional status of these MEBs were assessed as frequencies and mean fluorescence intensity (MFI) of the CD38 and CD40 expression, respectively.

Results:
The percentages of gp140 + MEBs were higher in LTNPs than seen in progressors (P = 0.0475) and associated with higher CD4+ cell count (P = 0.0312, r = 0.2833). As compared with the progressors, LTNPs also showed higher functional (CD40+) gp140 + MEBs both frequencies (P < 0.0001) and CD40 MFI (P = 0.0222), whereas the frequencies (<0.0001) and the MFI (P = 0.0047) of CD38 expression was significantly lower. Higher CD4+ cell counts and lower plasma viral load values were associated with higher frequencies of CD40+ gp140 + MEBs (P < 0.0001, r = 0.4962) (P = 0.0036, r = −0.4202) and lower frequencies (P = 0.0008, r = −0.4231) and CD38 expression (MFI) (P = 0.004, r = −0.3719) (P = 0.0066, r = 0.4033).

Conclusion:
Our study suggests that LTNPs have functional HIV-specific memory B-cell compartment with reduced activation that may lead to effective HIV-specific humoral immune responses contributing to their nondisease progression status. These findings would help in better understanding of the characteristics of the HIV-specific memory B-cell population in nonprogressive HIV infection.
Population attributable fractions of mortality in people living with HIV: roles of delayed antiretroviral therapy, hepatitis coinfections and social factors
Authors: Santos Melina E. , Protopopescu Camelia , Ribero Rachel A. , Benzaken Adele S. , Pereira Gerson F.M. , Stevens Antony , Nishimwe Marie L. , Yaya Issifou , Carrieri Patrizia , Araújo Wildo N. 
Published: July 2020

Objectives:
Despite free access to antiretroviral therapy (ART) from 1996 onward, and treatment for all people living with HIV (PLWHIV) from 2013, mortality in Brazil has not homogeneously decreased. We investigated to what extent delayed ART, hepatitis coinfections and sociodemographic factors predict all-cause mortality in Brazilian PLWHIV.

Design:
We included PLWHIV at least 18 years, with complete CD4+ cell count data, followed up between 2007 and 2015 in Brazil.

Methods:
After multiple imputation, an extended Cox model helped estimate the effects of fixed and time-varying covariates on mortality.

Results:
The study population (n = 411 028) were mainly male (61%), white (55%), 40 years or less (61%), heterosexually HIV infected (71%), living in the Southeast region (48%) and had basic education (79%). Hepatitis C virus and hepatitis B virus coinfection prevalences were 2.5 and 1.4%, respectively. During a 4-year median follow-up, 61 630 deaths occurred and the mortality rate was 3.45 (95% confidence interval: 3.42–3.47) per 100 person-years. Older age, male sex, non-white ethnicity, illiteracy/basic education and living outside the Southeast and Central-West regions were independently associated with increased mortality. The main modifiable predictors of mortality were delayed ART (i.e. CD4+ cell count <200 cells/μl at ART initiation) (adjusted population attributable fraction: 14.20% [95% confidence interval: 13.81–14.59]), being ART-untreated (14.06% [13.54–14.59]) and ART-treated with unrecorded CD4+ at ART initiation (5.74% [5.26–6.21]). Hepatitis C virus and hepatitis B virus coinfections accounted for 2.44 [2.26–2.62] and 0.42% [0.31–0.53] of mortality, respectively.

Conclusion:
The current study demonstrates that besides early ART and coinfection control, actions targeting males, non-whites and illiterate people and those with basic education are important to reduce avoidable deaths among Brazilian PLWHIV.
Advanced HIV disease in the Botswana combination prevention project: prevalence, risk factors, and outcomes
Authors: Lebelonyane Refeletswe , Mills Lisa A. , Mogorosi Chipo , Ussery Faith , Marukutira Tafireyi , Theu Joe , Kapanda Max , Matambo Stembile , Block Lisa , Raizes Elliot , Makhema Joseph , Lockman Shahin , Bachanas Pamela , Moore Janet , Jarvis Joseph N. 
Published: July 2020

Objective(s):
To determine the proportion of individuals linking to HIV-care with advanced HIV-disease (CD4+ cell counts ≤200 cells/μl) in the Botswana Combination Prevention Project, describe the characteristics of these individuals, and examine treatment outcomes.

Design:
A subanalysis of a cluster-randomized HIV-prevention trial. HIV status was assessed in 16–64-year-olds through home and mobile testing. All HIV-positive persons not on antiretroviral therapy were referred to local Ministry of Health and Wellness clinics for treatment.

Methods:
Analysis was restricted to the 15 intervention clusters. The proportion of individuals with advanced HIV disease was determined; associations between advanced HIV disease and sex and age explored; and rates of viral suppression determined at 1-year. Mortality and retention in care were compared between CD4+ strata (CD4+ cell counts ≤200 vs. >200 cells/μl).

Results:
Overall, 17.2% [430/2499; 95% confidence interval (CI) 15.7–18.8%] of study participants had advanced HIV disease (CD4+ cell counts ≤200 cells/μl) at time of clinic linkage. Men were significantly more likely to present with CD4+ cell counts 200 cells/μl or less than women [23.7 vs. 13.4%, adjusted odds ratio 1.9, 95% CI 1.5–2.3]. The risk of advanced HIV disease increased with increasing age (adjusted odds ratio 2.2, 95% CI 1.4–3.2 >35 vs. <25 years). Patients with CD4+ cell counts 200 cells/μl or less had significantly higher rates of attrition from care during follow-up (hazards ratio 1.47, 95% CI 1.1–2.1).

Conclusion:
Advanced HIV disease due to late presentation to or disengagement from antiretroviral therapy care remains common in the Treat All era in Botswana, calling for innovative testing, linkage, and treatment strategies to engage and retain harder-to-reach populations in care.
Computed Tomography Coronary Plaque Characteristics Predict Ischemia Detected by Invasive Fractional Flow Reserve
Authors: Velangi Pratik S. , Maharaj Valmiki , Athwal Satyajit S. , Bartos Jason A. , Markowitz Jeremy , Duval Sue , Nijjar Prabhjot S. 
Published: July 2020

Purpose:
Coronary computed tomography angiography (CCTA) plaque quantification has been proposed to be of incremental value in the prediction of ischemia, although prior studies have shown conflicting results. We aimed to determine whether CCTA plaque features assessed on a commercial vendor platform predict invasive fractional flow reserve (FFR)/instantaneous wave-free ratio (IFR).

Methods:
Consecutive patients who underwent CCTA for evaluation of suspected stable coronary artery disease followed by invasive coronary physiology testing within 60 days at a single academic center were identified retrospectively. Semiautomated plaque quantification of the vessel proximal to the location of FFR/IFR measurement was carried out in TeraRecon, along with simple visual assessment for high-risk plaque features of positive remodeling, spotty calcification, low-attenuation plaque (LAP), and lesion length. Ischemia was defined by FFR ≤0.80 or IFR ≤0.89.

Results:
A total of 134 patients (62% male, mean age 62±10 y) were included in this study. On univariate logistic regression, the following visual plaque analysis parameters were predictive of ischemia: positive remodeling (odds ratio [OR] with 95% confidence interval [CI]: 4.96; 2.25-10.95; P<0.001), lesion length (OR for every 1 mm with 95% CI: 1.24; 1.14-1.34; P<0.001), spotty calcification (OR with 95% CI: 6.67; 1.67-26.64; P=0.007), and LAP (OR with 95% CI: 30; 3.78-246; P=0.001). None of the semiautomated plaque quantification parameters, such as noncalcified plaque volume or LAP volume, were predictive of ischemia. On stepwise multivariable logistic regression, lesion length (OR with 95% CI: 1.25; 1.14-1.37; P<0.0001) and LAP (OR with 95% CI: 43; 4.4-438; P=0.001) were significant predictors of ischemia, improving the area under the curve of CCTA from 0.53 to 0.87.

Conclusions:
Simple visual plaque assessment for high-risk plaque features improved the performance of CCTA to predict ischemia. Semiautomated plaque quantification performed on a commercial vendor platform was not predictive of ischemia.
The evolving options in metastatic castration-sensitive prostate cancer
Authors: Hamilou Zineb 
Published: July 2020

Purpose of review
Leading trials CHAARTED, STAMPEDE, GETUG-AFU15 and LATITUDE established docetaxel and abiraterone acetate addition to androgen deprivation therapy (ADT) as a treatment guideline for patients with metastatic castration-sensitive prostate cancer.

Recent findings
Two recent combinations, enzalutamide with ADT and apalutamide with ADT were tested in metastatic castration-sensitive prostate cancer in three randomized controlled trials. Both combinations provided survival gain, expanding our options of treatment. Moreover, additional evidence behind radiotherapy for the primary tumor in metastatic prostate cancer is emerging.

Summary
In this updated article, we review the data of these trials and highlight the distinctions between these therapies, in order to better personalize the care for patients with metastatic prostate cancer.
Use of short-acting opioids in the management of breathlessness: an evidence-based review
Authors: Hui David , Bruera Eduardo 
Published: July 2020

Purpose of review
To provide an evidence-based review on the use of short-acting opioids for management of breathlessness in patients with advanced diseases.

Recent findings
We identified 28 randomized controlled trials that examined the effect of short-acting opioids on breathlessness under three study settings: as a prophylactic dose given prior to exertion; as a rescue dose for treatment of breathlessness at rest or episodic breathlessness; or as a scheduled medication for overall reduction of breathlessness. These trials varied widely in regard to patient population (opioid naive or tolerant), opioid (formulation, dose, timing of administration, and scheduling) and control intervention. Taken together, there is good evidence to support that short-acting opioids can reduce breathlessness and improve activity level when given before exertion. There is some evidence that parenteral opioids are efficacious for the as needed treatment of episodic breathlessness or breathlessness at rest. However, there is only limited evidence to support scheduled short-acting opioids for overall relief of breathlessness.

Summary
There is evidence to support that short-acting opioids have a pharmacologic effect on breathlessness. More research is needed to clarify how opioids can be prescribed to optimize breathlessness relief, function, and quality of life.
Analysis of Auditory Function of Patients With Parkinson Disease Based on Mandarin
Authors: Liu Jie , Huang Zhaoming , Zhao Hang , Fu Yicheng , Ding Zhongbing , Yu Bo 
Published: July 2020

Objective:
This study aimed to assess hearing loss and speech recognition impairment in patients with Parkinson disease (PD) based on Mandarin through pure-tone audiometry and speech audiometry.

Methods:
In total, 32 PD patients and 32 age-matched normal controls were enrolled for pure-tone audiometry and speech audiometry using a GSI arrow audiometer together with the BOSCH Chinese speech audiometry system.

Results:
The results of pure-tone audiometry showed that PD patients exhibited more severe low-, medium-, or high-frequency hearing loss than normal controls, especially at higher frequencies, and there were significant differences in gender. In addition, the results of speech audiometry showed that the speech recognition threshold of PD patients was significantly higher than that of normal controls. Furthermore, at any of the 3 hearing levels of 70, 50, and 30 dB HL, the recognition rates of initials, finals, and tones were successively decreased in PD patients, especially initials.

Conclusion:
PD patients exhibited significant hearing loss and speech recognition impairment. The initial recognition was more dependent on the hearing levels.
STAKEHOLDER ENGAGEMENT IN A COMPARATIVE EFFECTIVENESS/IMPLEMENTATION STUDY TO PREVENT CA-MRSA INFECTION RECURRENCE: CA-MRSA Project (CAMP2)
Authors: D’Orazio Brianna , Ramachandran Jessica , Khalida Chamanara , Gonzalez Johana , Kost Rhonda G. , Vasquez Kimberly S. , Evering Teresa H. , Hassen Getaw Worku , Hammock Regina , Nguyen Rosalee , Davis Ronette , Millan Keenan , Parola Claude , Coller Barry S. , Tobin Jonathan N. 
Published: July 2020

ABSTRACTBackgroundMethicillin-Resistant (MRSA) or Methicillin-Sensitive (MSSA) Staphylococcus aureus skin and soft tissue infections (SSTIs) pose serious clinical and public health challenges. Few protocols exist for outpatient education, decolonization and decontamination.ObjectivesThis trial implemented infection prevention protocols in homes via Community Health Workers/promotoras.MethodsWe engaged clinicians, patients, clinical and laboratory researchers, New-York-based Federally Qualified Health Centers and community hospital Emergency Departments. The Clinician and Patient Stakeholder Advisory Committee (CPSAC) convened in-person and remotely for shared decision-making and trial oversight.ResultsThe trial consented 186 and randomized 119 participants with SSTIs with MRSA (n=59) or MSSA (n=59), completed home visits, obtained surveillance cultures from index patients and household members and sampled household environmental surfaces at baseline and three months.Lessons LearnedThe retention of the CPSAC during the trial demonstrated high levels of engagement.ConclusionsCPSAC was highly effective throughout design and execution by troubleshooting recruitment and home visit challenges.
Surges in COVID-19 are led by lax government interventions in initial outbreaks
Authors: Yuan Hsiang-Yu , Wu Lindsey , Wang Dong-Ping 
Published: July 2020

AbstractSharp increases in COVID-19 cases occurred after reopening in the United States. We show that the post-intervention effective reproduction number is a strong predictor of the surge in late June. Lax interventions in the early stages coupled with elevated virus spread are primarily responsible for surges in most affected states.