Can biased search results change people's opinions about anything at all? a close replication of the Search Engine Manipulation Effect (SEME).

In previous experiments we have conducted on the Search Engine Manipulation Effect (SEME), we have focused on the ability of biased search results to shift voting preferences. In three new experiments with a total of 1,137 US residents (mean age = 33.2), we sought to determine whether biased search rankings could shift people's opinions on topics that do not involve candidates or elections. Each of the new experiments looked at a different topic, and participants were pre-screened to make sure they didn't have strong opinions about these topics. The topics were: Is artificial intelligence useful or dangerous? Is fracking helpful or dangerous? And: Are people born gay or do they choose to be gay? All participants were first asked various demographic questions, then shown brief summaries of the "pro" and "anti" views on each topic, and then asked their opinions about each topic. Next, participants were allowed to conduct an online search using our mock search engine (Kadoodle) lasting up to 15 minutes. In each experiment, one-third of the participants saw biased search results favoring one perspective; one-third saw biased search results favoring the opposing perspective; and one-third (the control group) saw mixed search results. After completing their search, participants were again asked for their opinions about the topic. Our primary dependent variable was Manipulation Power (MP), the percentage increase in the number of participants favoring one viewpoint after having viewed search rankings favoring that viewpoint. The MPs in the three experiments were 25.0%, 30.9%, and 17.8%, respectively. Corresponding shifts were also found for how persuasive participants found each viewpoint to be and for how much they trusted each viewpoint. We conclude that search rankings favoring one viewpoint on a wide range of topics might be able to cause people who have not yet formulated a strong opinion on such topics to adopt the favored perspective. If our findings prove to be robust, we are exposing what might be considered an unforeseen consequence of the creation of search engines, namely that even without human interference, search algorithms will inevitably alter the thinking and behavior of billions of people worldwide on perhaps any topic for which they have not yet formed strong opinions.

Is everyone a mix of straight and gay? A social pressure theory of sexual orientation, with supporting data from a large global sample.

Sigmund Freud, Alfred Kinsey, E.O. Wilson, and others have suggested that social pressure suppresses natural tendencies for humans to express bisexuality, the apparent norm for one of our two closest genetic relatives, the bonobo. An analysis of data obtained from a new online sample of 1,150,938 people in 215 countries and territories (63.9% from the United States, United Kingdom, and Canada) who completed the English version of a validated questionnaire of sexual orientation lends support to this idea. A histogram of scores from 0 (exclusive opposite-sex inclinations) to 18 (exclusive same-sex inclinations) forms a near-normal distribution. Although this distribution was likely caused to some extent by sampling bias, it may also reflect the unusual honesty people show when taking online tests anonymously, as an increasing body of evidence demonstrates. We present a formal mathematical expression of a social pressure theory of sexual orientation, along with empirical evidence and computational explorations that support the theory. We also present an analysis of the new data set. Among other findings: sexual orientation labels corresponded to broad, skewed, overlapping distributions of scores. Self-labeled gays/lesbians and, to a greater extent, self-labeled straights, reported that the larger the mismatch between their sexual orientation label and their actual sexual inclinations, the more distress they felt regarding their sexual orientation, a finding that is predictable from cognitive dissonance theory. Educating the public about the true nature of sexual orientation might quell the often rancorous public debates on this topic, as well as give comfort to a large number of mislabeled people.

What would happen if twitter sent consequential messages to only a strategically important subset of users? A quantification of the Targeted Messaging Effect (TME).

The internet has made possible a number of powerful new forms of influence, some of which are invisible to users and leave no paper trails, which makes them especially problematic. Some of these effects are also controlled almost exclusively by a small number of multinational tech monopolies, which means that, for all practical purposes, these effects cannot be counteracted. In this paper, we introduce and quantify an effect we call the Targeted Messaging Effect (TME)-the differential impact of sending a consequential message, such as a link to a damning news story about a political candidate, to members of just one demographic group, such as a group of undecided voters. A targeted message of this sort might be difficult to detect, and, if it had a significant impact on recipients, it could undermine the integrity of the free-and-fair election. We quantify TME in a series of four randomized, controlled, counterbalanced, double-blind experiments with a total of 2,133 eligible US voters. Participants were first given basic information about two candidates who ran for prime minister of Australia in 2019 (this, to assure that our participants were "undecided"). Then they were instructed to search a set of informational tweets on a Twitter simulator to determine which candidate was stronger on a given issue; on balance, these tweets favored neither candidate. In some conditions, however, tweets were occasionally interrupted by targeted messages (TMs)-news alerts from Twitter itself-with some alerts saying that one of the candidates had just been charged with a crime or had been nominated for a prestigious award. In TM groups, opinions shifted significantly toward the candidate favored by the TMs, and voting preferences shifted by as much as 87%, with only 2.1% of participants in the TM groups aware that they had been viewing biased content.

Futibatinib for FGFR2-Rearranged Intrahepatic Cholangiocarcinoma.

BACKGROUND: Alterations in fibroblast growth factor receptor 2 (FGFR2) have emerged as promising drug targets for intrahepatic cholangiocarcinoma, a rare cancer with a poor prognosis. Futibatinib, a next-generation, covalently binding FGFR1-4 inhibitor, has been shown to have both antitumor activity in patients with FGFR-altered tumors and strong preclinical activity against acquired resistance mutations associated with ATP-competitive FGFR inhibitors. METHODS: In this multinational, open-label, single-group, phase 2 study, we enrolled patients with unresectable or metastatic FGFR2 fusion-positive or FGFR2 rearrangement-positive intrahepatic cholangiocarcinoma and disease progression after one or more previous lines of systemic therapy (excluding FGFR inhibitors). The patients received oral futibatinib at a dose of 20 mg once daily in a continuous regimen. The primary end point was objective response (partial or complete response), as assessed by independent central review. Secondary end points included the response duration, progression-free and overall survival, safety, and patient-reported outcomes. RESULTS: Between April 16, 2018, and November 29, 2019, a total of 103 patients were enrolled and received futibatinib. A total of 43 of 103 patients (42%; 95% confidence interval, 32 to 52) had a response, and the median duration of response was 9.7 months. Responses were consistent across patient subgroups, including patients with heavily pretreated disease, older adults, and patients who had co-occurring TP53 mutations. At a median follow-up of 17.1 months, the median progression-free survival was 9.0 months and overall survival was 21.7 months. Common treatment-related grade 3 adverse events were hyperphosphatemia (in 30% of the patients), an increased aspartate aminotransferase level (in 7%), stomatitis (in 6%), and fatigue (in 6%). Treatment-related adverse events led to permanent discontinuation of futibatinib in 2% of the patients. No treatment-related deaths occurred. Quality of life was maintained throughout treatment. CONCLUSIONS: In previously treated patients with FGFR2 fusion or rearrangement-positive intrahepatic cholangiocarcinoma, the use of futibatinib, a covalent FGFR inhibitor, led to measurable clinical benefit. (Funded by Taiho Oncology and Taiho Pharmaceutical; FOENIX-CCA2 ClinicalTrials.gov number, NCT02052778.).

Retrospective Review of Radiographic Imaging of Tibial Bony Stress Injuries in Adolescent Athletes With Positive MRI Findings: A Comparative Study.

BACKGROUND: It is difficult to diagnose and grade bony stress injury (BSI) in the athletic adolescent population without advanced imaging. Radiographs are recommended as a first imaging modality, but have limited sensitivity and, even when findings are present, advanced imaging is often recommended. HYPOTHESIS: It was hypothesized that the significance of radiographs is underestimated for BSI in the adolescent with positive clinical examination and history findings. STUDY DESIGN: Case series. LEVEL OF EVIDENCE: Level 4. METHODS: A total of 80 adolescent athletes with a history of shin pain underwent clinical examination by an orthopaedic surgeon. On the day of clinical examination, full-length bilateral tibial radiographs and magnetic resonance imaging (MRI) scans were obtained. MRI scans were reviewed using Fredericson grading for BSI. At the completion of the study, radiographic images were re-evaluated by 2 musculoskeletal (MSK) radiologists, blinded to MRI and clinical examination results, who reviewed the radiographs for evidence of BSI. Radiographic results were compared with clinical examination and MRI findings. Sensitivity, specificity, negative predictive value, and positive predictive value were calculated based on comparison with MRI. RESULTS: All radiographs were originally read as normal. Of the tibia studied, 80% (127 of 160) showed evidence of BSI on MRI. None of the original radiographs demonstrated a fracture line on initial review by the orthopaedic surgeons. Retrospective review by 2 MSK radiologists identified 27% of radiographs (34 of 127) with evidence of abnormality, which correlated with clinical examination and significant findings on MRI. Review of radiographs found evidence of new bone on 0 of 28 Fredericson grade 0, 0 of 19 Fredericson grade I, 11 of 80 (13.7%) Fredericson grade II, 18 of 28 (64%) Fredericson grade III, and 5 of 5 (100%) Fredericson grade IV. Sensitivity of radiographs showed evidence of new bone on 27% (34 of 127) of initial radiographs, with presence more common with greater degree of BSI, as 23 of 33 (70%) were higher-grade injuries (III of IV) of BSI. Specificity and positive predictive value were 100%, while negative predictive value was 17%. CONCLUSION: These findings highlight the importance of initial radiographs in identifying high-grade BSI. As radiographs are readily available in most office settings of sports medicine physicians, this information can influence the management of adolescent athletic BSI without the need to delay treatment to obtain an MRI. CLINICAL RELEVANCE: Adolescent athletes with radiographic evidence of BSI should be treated in a timely and more conservative manner, given the likelihood of higher-grade BSI. In addition, clinicians knowledgeable of the radiographic findings of high-grade BSI should feel more confident that a negative initial radiograph is not likely to be a high-grade BSI and can modify their treatment plans accordingly.

Successful Non-operative Management of Metacarpophalangeal Collateral Ligament and Sagittal Band Rupture of the Long Finger: A Case Report.

The metacarpophalangeal (MCP) joint is surrounded by various structures critical to its stability and function. Though the ligamentous injury to the digits is common, rupture of the metacarpophalangeal collateral ligament and a sagittal band of the same finger is not well represented in the literature. We report a chronic case of a concurrent metacarpophalangeal collateral ligament and sagittal band injury. Though surgery would have been the most appropriate treatment soon after the injury, restrictions on elective procedures due to the COVID-19 pandemic precluded surgical treatment. The patient was alternatively treated with buddy tape, and a close follow-up was done. This is the first reported case of a concurrent metacarpophalangeal collateral ligament, and sagittal band injury successfully treated using nonoperative management.

The Answer Bot Effect (ABE): A powerful new form of influence made possible by intelligent personal assistants and search engines.

We introduce and quantify a relatively new form of influence: the Answer Bot Effect (ABE). In a 2015 report in PNAS, researchers demonstrated the power that biased search results have to shift opinions and voting preferences without people's knowledge-by up to 80% in some demographic groups. They labeled this phenomenon the Search Engine Manipulation Effect (SEME), speculating that its power derives from the high level of trust people have in algorithmically-generated content. We now describe three experiments with a total of 1,736 US participants conducted to determine to what extent giving users "the answer"-either via an answer box at the top of a page of search results or via a vocal reply to a question posed to an intelligent personal assistant (IPA)-might also impact opinions and votes. Participants were first given basic information about two candidates running for prime minister of Australia (this, in order to assure that participants were "undecided"), then asked questions about their voting preferences, then given answers to questions they posed about the candidates-either with answer boxes or with vocal answers on an Alexa simulator-and then asked again about their voting preferences. The experiments were controlled, randomized, double-blind, and counterbalanced. Experiments 1 and 2 demonstrated that answer boxes can shift voting preferences by as much as 38.6% and that the appearance of an answer box can reduce search times and clicks on search results. Experiment 3 demonstrated that even a single question-and-answer interaction on an IPA can shift voting preferences by more than 40%. Multiple questions posed to an IPA leading to answers that all have the same bias can shift voting preferences by more than 65%. Simple masking procedures still produced large opinion shifts while reducing awareness of bias to close to zero. ABE poses a serious threat to both democracy and human autonomy because (a) it produces large shifts in opinions and voting preferences with little or no user awareness, (b) it is an ephemeral form of influence that leaves no paper trail, and (c) worldwide, it is controlled almost exclusively by just four American tech companies. ABE will become a greater threat as people increasingly rely on IPAs for answers.

Impact of Hypomethylating Agent Use on Hospital and Emergency Room Visits, and Predictors of Early Discontinuation in Patients With Higher-Risk Myelodysplastic Syndromes.

BACKGROUND: Previous analyses using the SEER-Medicare database have reported substantial underutilization of hypomethylating agents (HMAs) among patients with higher-risk myelodysplastic syndromes (MDS), and an association between poor HMA persistence and high economic burden. We aimed to compare rates of hospitalizations and emergency room (ER) visits among patients with higher-risk MDS according to use or non-use of HMA therapy, and to explore factors associated with early discontinuation of HMA therapy. PATIENTS AND METHODS: We used the 2010-2016 SEER-Medicare database to identify patients aged ≥66 years with a new diagnosis of refractory anemia with excess blasts (RAEB; a surrogate for higher-risk MDS) between 2011 and 2015. New hospitalizations and ER visits during the 12 months following MDS diagnosis were determined. Treatment discontinuation was defined as stopping HMA therapy before 4 cycles. RESULTS: Overall, 664 (55.8%) patients were HMA users and 526 (44.2%) non-users. Non-users had more hospitalizations (mean 0.47 vs. 0.30, P < .001) and ER visits (mean 0.69 vs. 0.41, P = .005) per month than HMA users. Among HMA users, 193 (29.1%) discontinued HMA therapy before 4 cycles, and 91 (47.2%) of these after 1 cycle. Older age and poor performance status were associated with higher risk of HMA discontinuation. CONCLUSION: An increased rate of hospitalizations and ER visits occurred in HMA non-users vs. HMA users. Approximately one-third of patients discontinued HMA therapy early. Predictors of discontinuation included older age and poor performance status. Novel approaches are needed to improve utilization and persistence with HMA therapy and associated outcomes, particularly among these higher-risk groups.

Treatment patterns and burden of myelosuppression for patients with small cell lung cancer: A SEER-medicare study.

PURPOSE: To depict the treatment journey for patients with small cell lung cancer (SCLC) and evaluate health care resource utilization (HCRU) associated with myelosuppression, a complication induced by chemotherapy or chemotherapy plus radiation therapy. PATIENTS AND METHODS: This was a descriptive, retrospective study of patients with SCLC aged ≥65 years, identified from linked Surveillance, Epidemiology, and End Results (SEER)-Medicare data curated between January 2012 and December 2015. Treatment types (chemotherapy, radiation therapy, surgery) were classified as first, second, or third line, depending on the temporal sequence in which regimens were prescribed. For each year, the proportions of patients completing 4- or 6-cycle chemotherapy regimens, with hospital admissions associated with myelosuppression, or who used granulocyte colony-stimulating factors (G-CSFs), blood/platelet transfusions, or erythropoiesis-stimulating agents (ESAs), were calculated. RESULTS: Chemotherapy was administered as initial treatment in 7,807/11,907 (65.6%) patients whose treatment journey was recorded. Approximately one-third (n = 3,985) subsequently received radiation therapy. In total, 5,791 (57.8%) patients completed the guideline-recommended 4-6 cycles of chemotherapy. Among all chemotherapy-treated patients, 10,370 (74.3%) experienced ≥1 inpatient admission associated with myelosuppression (anemia, 7,366 [52.8%]; neutropenia, 4,642 [33.3%]; thrombocytopenia, 2,375 [17.0%]; pancytopenia, 1,983 [14.2%]). Supportive care interventions included G-CSF (6,756 [48.4%] patients), ESAs (1,534 [11.0%]), and transfusions (3,674 [26.3%]). CONCLUSION: Chemotherapy remains a cornerstone of care for patients with SCLC. Slightly over half of patients completed the recommended number of cycles, underscoring the frailty of patients and aggressiveness of SCLC. HCRU associated with myelosuppression was prominent, suggesting a substantial burden on older patients with SCLC.

The surprising power of a click requirement: How click requirements and warnings affect users' willingness to disclose personal information.

What kinds of information and alerts might cause internet users to be more cautious about what they reveal online? We used a 25-item survey to determine whether the strength of Terms of Service (TOS) warnings and the inclusion of a click requirement affect people's willingness to admit to engaging in inappropriate behaviors. A racially and ethnically diverse group of 1,500 people participated in the study; 98.3% were from the US and India and the remainder from 18 other countries. Participants were randomly assigned to five different groups in which warnings and click requirements varied. In the control condition, no warning was provided. In the four experimental groups, two factors were varied in a 2 × 2 factorial design: strength of warning and click requirement. We found that strong warnings were more effective than weak warnings in decreasing personal disclosures and that click requirements added to the deterrent power of both strong and weak warnings. We also found that a commonly used TOS warning has no impact on disclosures. Participants in the control group provided 32.8% more information than participants in the two click requirement groups combined and 24.3% more information than participants in the four experimental groups combined. The pattern according to which people dropped out of the five different groups sheds further light on the surprising power of the click requirement, as well as on the importance of tracking attrition in online studies.

Assessing the transition from intravenous to subcutaneous delivery of rituximab: Benefits for payers, health care professionals, and patients with lymphoma.

Subcutaneous (SC) administration of rituximab provides an opportunity for reduced patient treatment burden and increased healthcare efficiencies as an alternative to intravenous (IV) rituximab. There is minimal evidence comparing costs associated with SC and IV rituximab in a US setting. This research assessed the impact of transitioning patients from IV to SC rituximab for treatment of non-Hodgkin's lymphoma (NHL) from the US payer, provider, and patient perspective. We developed a model to estimate cost differences for transitioning 20% of a patient cohort from IV to SC rituximab. We included patients with incident diffuse large B-cell lymphoma, incident and recurrent follicular lymphoma, and incident and recurrent chronic lymphocytic leukemia. In the model, each patient received the same number of doses and that there was no difference in discontinuation between cohorts due to non-inferior efficacy and a similar safety profile. Model inputs were collected from published literature and publicly available data. Scenario analyses tested the impact of availability of low-cost biosimilars. In the base case (1,000,000 covered lives), we estimated a total of 157 patients, with 769 total drug administrations. A transition of 20% of patients from IV to SC was projected to generate $153,000 in payer savings, increase provider capacity by 270 hours, and free 470 hours of patient time. Scenario analyses suggest SC administration will be cost saving for payers even with a market where biosimilars approach 50% market share. A 20% transition to SC rituximab in a single cohort of patients has the potential to generate significant US health system value in the form of payer savings, increased practice capacity, and patient time.

Real-world burden of chemotherapy-induced myelosuppression in patients with small cell lung cancer: a retrospective analysis of electronic medical data from community cancer care providers.

AIMS: Chemotherapy-induced myelosuppression, which commonly exhibits as neutropenia, anemia, or thrombocytopenia, represents a substantial burden for patients with cancer that affects health-related quality of life and increases healthcare resource utilization (HCRU). We evaluated the burden of myelosuppression among chemotherapy-treated patients with small cell lung cancer (SCLC) using real-world data from community cancer care providers in the Western United States. MATERIALS AND METHODS: This was a retrospective, observational analysis of electronic medical records (EMRs) from Providence St. Joseph Health hospital-associated oncology clinics between January 2016 and December 2019. Patient demographics were assessed from the date of first SCLC diagnosis in adult patients with chemotherapy-induced grade ≥3 myelosuppression in first-line (1L) or second-line-and-beyond (2L+) treatment settings. Myelosuppressive adverse events (AEs), treatment patterns, and HCRU were assessed from the date of chemotherapy initiation (index date) until 12 months, date of the last visit, date of death, or study end, whichever occurred earliest. RESULTS: Of 347 eligible patients with SCLC who had received chemotherapy (mean age 66; 49% female), all had received at least 1L treatment, and 103 (29.7%) had a 2L + treatment recorded within the EMR during the study period. Of 338 evaluable patients with longitudinal laboratory data, 206 (60.9%) experienced grade ≥3 myelosuppressive AEs, most commonly neutropenia, anemia, and thrombocytopenia (44.9, 41.1, and 25.4 per 100 patients, respectively). Rates of granulocyte colony-stimulating factor use and red blood cell transfusions were 47.0 and 41.7 per 100 patients, respectively. There was a trend toward increasing the use of supportive care interventions and visits to inpatient and outpatient facilities in patients with myelosuppressive AEs in more than one cell lineage. CONCLUSIONS: Chemotherapy-induced myelosuppression places a substantial real-world burden on patients with SCLC in the community cancer care setting. Innovations to protect bone marrow from chemotherapy-induced damage have the potential to reduce this burden.

PLAIN LANGUAGE SUMMARYThis study looked at the medical records of people with a particular type of lung cancer known as small cell lung cancer. When treated with chemotherapy, people with this cancer may develop a condition called myelosuppression. This causes people to have fewer blood cells, which can lead to tiredness, or increase the risk of infection or bleeding. The study looked at what types of chemotherapy people with small cell lung cancer were given, what the side effects of myelosuppression were, how often the side effects were reported, and what treatments were given to manage these side effects. The study also looked at whether people with side effects from myelosuppression needed more visits to the doctor or hospital. Around 3 out of 5 people in the study experienced serious side effects resulting in reduced numbers of white blood cells (which fight infection), red blood cells (which carry oxygen), or platelets (which help the blood to clot), and many needed drugs or blood transfusions to treat these side effects. On average, people with side effects from myelosuppression had more visits to healthcare facilities than those people without these side effects. The findings suggest that myelosuppression places a large burden on people with small cell lung cancer who are treated with chemotherapy.

Motivational and Cognitive Factors in Pathways to Offending Amongst Women who Have Sexually Offended.

Data-driven models, addressing the internal motivations, pathways to offending, and supportive cognitions amongst women who have sexually offended have emerged in recent years, with significant consequences for understanding risk factors and developing treatment programmes. In the current research, recent empirically based models were explored in a national sample consisting of all women who had committed sexual offences and were assessed over a 12-year period (n = 28). The utility of the motivational and cognitive models tested was supported, although not all cases could be easily coded, and new categories are suggested in order to better characterize the unique aspects of sex offending amongst women who have sexually offended. Key findings included fewer women than expected who reported being coerced by a male partner, frequent conjunction between sex and intimacy needs, and a lack of a clear relationship between offence-related cognitions and motivational pathways. The results support the importance of integrating and further developing gender-specific clinical factors within a gender-neutral treatment paradigm.

Real-world use and outcomes of hypomethylating agent therapy in higher-risk myelodysplastic syndromes: why are we not achieving the promise of clinical trials?

Myelodysplastic syndromes are hematological malignancies characterized by ineffective hematopoiesis and a high risk of progression to acute myeloid leukemia. Hypomethylating agents (HMAs), azacitidine and decitabine, are standard of care therapy for higher-risk myelodysplastic syndromes. However, outcomes reported for real-world studies fall short of those achieved in clinical trials. We conducted a targeted literature review exploring real-world utilization, persistence and outcomes with intravenous and subcutaneous HMA therapies to better understand barriers to achieving optimal outcomes in clinical practice. The potential benefits of oral HMA therapy were also explored. Underutilization and poor persistence with HMA therapy are associated with suboptimal outcomes, highlighting the need for approaches to improve utilization and persistence, so that patients achieve the optimum benefit from HMA therapy.

Lay abstract Myelodysplastic syndromes (MDS) are bone marrow disorders affecting the production of blood cells. In some patients, MDS can progress to acute myeloid leukemia (AML), an aggressive blood cancer with poor prognosis. Patients with higher-risk MDS are often treated with a type of chemotherapy called hypomethylating agents (HMAs). Studies conducted in real-world clinical practice have shown HMAs to be less effective than has been found in clinical trials. We reviewed available studies exploring real-world utilization, persistence and outcomes with current HMA therapies to better understand any barriers to patients achieving the best outcomes. Two important factors were found to be the underuse of HMAs and poor persistence with HMA therapy, highlighting the need for approaches to improve HMA utilization and persistence.

Payer Perspectives on Intravenous versus Subcutaneous Administration of Drugs.

The coronavirus disease 2019 (COVID-19) pandemic has brought increased attention to vulnerable populations such as older or immunocompromised patients and heightened the focus on alternatives to intravenous (IV) formulations, particularly those that may be administered in a non-clinical setting. Among these alternative formulations are subcutaneous (SC) injections, which comprise an increasing share of commercialized and pipeline therapies. While much has been published about the benefits and limitations of IV versus SC administration to patients and health systems, less attention has been given to payer considerations regarding these routes of administration. Accordingly, this article provides payer perspectives on some of the key differences between IV and SC administration as they relate to management and billing, cost, treatment adherence and safety, and patient preference and quality of life. The benefits and limitations of these drug administration routes to key healthcare stakeholders-namely patients, physicians, and payers-are also discussed. Considerations of relevance are highlighted, including the potential for misalignment of stakeholder interests and countervailing factors that may impact decision-making about IV and SC formulations.

Topo-Pachimetric Accelerated Epi-On Cross-Linking Compared to the Dresden Protocol Using Riboflavin with Vitamin E TPGS: Results of a 2-Year Randomized Study.

In the present study (clinical trial registration number: NCT05019768), we compared the clinical outcome of corneal cross-linking with either the standard Dresden (sCXL) or the accelerated custom-fast (aCFXL) ultraviolet A irradiation protocol using riboflavin-D-α-tocopheryl poly(ethylene glycol)-1000 succinate for progressive keratoconus. Fifty-four eyes of forty-one patients were randomized to either of the two CXL protocols and checked before treatment and at the 2-year follow-up. The sCXL group was subjected to CXL with 30 min of pre-soaking and 3 mW/cm2 UVA irradiation for 30 min. The aCFXL group was subjected to CXL with 10 min of pre-soaking and UVA irradiation of 1.8 ± 0.9 mW/cm2 for 10 min ± 1.5 min. In both groups, a solution of riboflavin-vitamin E TPGS was used. Uncorrected distance visual acuity, corrected distance visual acuity, pachymetry, Scheimpflug tomography, and corneal hysteresis were performed at baseline and after 24 months. Both groups showed a statistically significant improvement in corrected distance visual acuity, and keratometric and corneal hysteresis compared to baseline conditions; no statistically significant differences in outcomes between the two groups were observed. Improvement in refractive, topographic, and biomechanical parameters were observed after sCXL and aCFXL, making the riboflavin-VE-TPGS solution an effective option as a permeation enhancer in CXL procedures. Deeper stromal penetration of riboflavin could be complemented by photo-protection against UVA and free radicals formed during photoinduced processes.

Abaloparatide Real-World Patient Experience Study.

Despite the availability of various osteoporosis treatments, adherence remains suboptimal. One contributing factor may be patient experience with therapy. This US, multicenter, combined retrospective chart review and patient questionnaire study included postmenopausal women at high risk for fracture and is the first study to describe real-world patient experience with abaloparatide (ABL) injection. Eight geographically diverse secondary care sites in the United States participated (n = 193). Mean ± SD age was 67.4 ±8.62 years. Most patients (86%) were satisfied with the ABL regimen, especially with ease of preparation (82%), ease of storage (87%), and storage convenience (89%), an attribute 83% of the patients thought was important. The majority of patients reported complete satisfaction with the ABL regimen allowing for their ability to conduct daily activities (85%) and convenience to fit into their daily schedule (84%). All reported taking ABL as directed, by injection in the lower abdomen, and 83% of patients reported medium or high adherence. Patients were satisfied with the needle size (76% completely satisfied), and 93% reported never deliberately missing a dose. Although injecting medication (18%) and higher out-of-pocket costs (17%) were deemed the most bothersome attributes, the majority (69%) noted their healthcare team understands how osteoporosis impacts their lives. In multivariable analyses, ease of preparation (OR = 2.62; 95% CI, 1.01-6.81; p = 0.048) and fracture history (OR = 1.72; 95% CI, 1.03-2.86; p = 0.037) were significantly associated with overall satisfaction. Ease of preparation was a predictor of higher satisfaction with treatment convenience (coefficient = 13.60; 95% CI, 8.08-19.12; p = 0.00). Remembering to take the medication was a significant predictor of self-reported adherence (OR = 16.66; 95% CI, 3.30-84.24; p = 0.001). In conclusion, the majority of patients were satisfied with ABL and found it convenient/easy to prepare and store. High self-reported adherence may be associated with positive patient experience including ease of use and adequate support from healthcare providers. © 2020 The Authors. JBMR Plus published by Wiley Periodicals LLC. on behalf of American Society for Bone and Mineral Research.

How SARS-CoV-2 and Comparable Pathogens Can Be Defeated in a Single Day: Description and Mathematical Model of the Carrier Separation Plan (CSP).

A simple, common-sense, three-component procedure-the Carrier Separation Plan (CSP)-can immediately halt the transmission of SARS-CoV-2 or a comparable pathogen, allow the safe reopening of an entire economy without the need for social distancing, and quickly eradicate the pathogen from the population (assuming the pathogen can be killed by the immune systems of the carriers). The three components are (a) nearly simultaneous self-testing for the pathogen by an entire population, followed rapidly by (b) nearly simultaneous self-isolation of carriers, and (c) secondary screening at entrances to facilities where people congregate. After a period of preparation lasting roughly 5-10 weeks, these steps could and probably should be taken in a single day. The power of this methodology has already been demonstrated in varying degrees with groups ranging in size from 1,000 to 11 million. Although this plan might seem daunting, its costs are minimal compared to the losses we have incurred by relying on half measures, and the US and other countries have the technological, logistical, and industrial capacities to implement this plan in a matter of weeks. With proper messaging during the weeks leading up to the testing, compliance in such a program is likely to be high given the potential benefits, and because participation is voluntary and testing is noninvasive, the legal and ethical issues associated with such a program are minimal - trivial, in fact, compared to those associated with imposing a months-long lockdown on an entire population. A SIRD/CSP model suggests that the single-day testing and separation procedure will substantially lower the number of infections, even if compliance with the procedure is modest. Modeling also suggests that when long-term secondary screening is added to the 1-day procedure, over time, the pathogen is eradicated from the population. This can occur even when compliance with secondary screening is itself relatively low.

Cancer Patients' Perspectives and Experiences of Chemotherapy-Induced Myelosuppression and Its Impact on Daily Life.

PURPOSE: To evaluate which side effects of chemotherapy are considered most burdensome by patients with cancer, identify which health care professionals pay most attention to symptoms associated with chemotherapy-induced myelosuppression (CIM) from the patient perspective, and capture the "patient voice" describing how CIM impacts their daily lives. PARTICIPANTS AND METHODS: Online survey of participants with breast, lung, or colorectal cancer who had received chemotherapy within the past 12 months and experienced ≥1 episode of CIM in the past year. Participants were asked to answer close-ended questions and provide qualitative responses to: "In your own words, please describe how side effects from myelosuppression have impacted your life." RESULTS: Among 301 survey participants, fatigue was the most frequently reported side effect of chemotherapy; 55% of participants rated fatigue as highly bothersome (9 or 10 on a 1-10 scale of "bothersomeness"). Participants rated symptoms associated with CIM, including fatigue, weakened immune system (infections), bleeding and/or bruising, and shortness of breath, as being as bothersome as other side effects of chemotherapy, including alopecia, neuropathy, and nausea/vomiting. Overall, 24-43% of participants thought that CIM and its symptoms had a negative impact on their daily lives, including their ability to complete tasks at home and work, and to socialize. Qualitative responses supported these findings; participants highlighted that CIM-related symptoms, particularly fatigue and fear of infections, affected their ability to be physically active, complete work, or continue meaningful relationships with friends and family. CONCLUSION: Participants described a real-world impact of CIM that often isolates them from family and friends, and means that they are unable to work or perform tasks of daily living. Using measures that help patients to recognize and communicate the signs and symptoms of CIM might increase the likelihood of maintaining daily lives as close to normal as possible, during and after chemotherapy treatment.

Compaction of very thin corneas from ultraviolet A riboflavin-vitamin E transepithelial cross-linking.

The purpose of the study was to determine the decrease in pachymetry of very thin corneas with advanced keratoconus due to corneal compaction from the ultraviolet-A (UV-A) irradiation phase of transepithelial (epi-on) cross-linking. Twenty removed corneal buttons were obtained from patients who underwent penetrating keratoplasty for advanced keratoconus. Removed corneal buttons selected from among the post-surgical specimens for this study had intact epithelium, no scarring or surgical cautery, endothelial cell density >2500 cells/mm2, and average pachymetry over the measured points of below 400 µm. Corneas were mounted in a Franz chamber. Each epithelial surface was soaked in isotonic riboflavin and D-alpha-tocopheryl polyethylene glycol 1000 succinate (Ribocross® IROMED Group, Italy) for 15 min. Pachymetry was measured at three points over both the shielded and unshielded corneal halves for each corneal button. Surfaces were then washed in saline to remove the Ribocross®. Shields from UV-A irradiation over half of each cornea were then fixed to stand 5 mm above the test corneas. UV-A irradiation using the custom fast cross-linking (CF-CXL) protocol was then performed for the typical 10 ± 1.5 min, for a total energy of 1.08 ± 0.6 J/cm2 after which pachymetry was re-measured. The average percent change in pachymetry was -0.43% ± 0.38% (maximum -1.06%) in the shielded half. Pachymetry change was -6.2% ± 2.2% (maximum 12%) in the cross-linked halves. In conclusion, we estimate that the change in corneal thickness from corneal compaction due to the cross-linking reaction itself was -5.8% ± 2.2%. Scanning electron microscopy of cross-linked corneal segments showed stromal fiber contraction.