Good Publication Practice (GPP) Guidelines for Company-Sponsored Biomedical Research: 2022 Update.

These updated Good Publication Practice (GPP) guidelines include recommendations for publishing company-sponsored biomedical research. The GPP guidelines apply to peer-reviewed or peer-oriented biomedical publications, such as manuscripts, meeting presentations, posters, and abstracts, as well as enhanced content, such as plain-language summaries. The current GPP guidelines incorporate guidance on ethics and transparency as well as the planning, development, review, and approval of biomedical publications and policies and procedures that describe these practices. Supplemental materials lay out processes for steering committees, publication plans, publication working groups, determining authorship, and documentation. Information about new topics, such as alliances and working with patients, has been included where appropriate within these supplemental materials. Incorporating the principles and best practices presented in these GPP guidelines will result in increased transparency and a firm ethical footing. This guidance is also intended to enable the compliant incorporation of new and emerging publication tools for the ethical publication of company-sponsored research.

Loss of endothelial sulfatase-1 after experimental sepsis attenuates subsequent pulmonary inflammatory responses.

Sepsis patients are at increased risk for hospital-acquired pulmonary infections, potentially due to postseptic immunosuppression known as the compensatory anti-inflammatory response syndrome (CARS). CARS has been attributed to leukocyte dysfunction, with an unclear role for endothelial cells. The pulmonary circulation is lined by an endothelial glycocalyx, a heparan sulfate-rich layer essential to pulmonary homeostasis. Heparan sulfate degradation occurs early in sepsis, leading to lung injury. Endothelial synthesis of new heparan sulfates subsequently allows for glycocalyx reconstitution and endothelial recovery. We hypothesized that remodeling of the reconstituted endothelial glycocalyx, mediated by alterations in the endothelial machinery responsible for heparan sulfate synthesis, contributes to CARS. Seventy-two hours after experimental sepsis, coincident with glycocalyx reconstitution, mice demonstrated impaired neutrophil and protein influx in response to intratracheal lipopolysaccharide (LPS). The postseptic reconstituted glycocalyx was structurally remodeled, with enrichment of heparan sulfate disaccharides sulfated at the 6-O position of glucosamine. Increased 6-O-sulfation coincided with loss of endothelial sulfatase-1 (Sulf-1), an enzyme that specifically removes 6-O-sulfates from heparan sulfate. Intravenous administration of Sulf-1 to postseptic mice restored the pulmonary response to LPS, suggesting that loss of Sulf-1 was necessary for postseptic suppression of pulmonary inflammation. Endothelial-specific knockout mice demonstrated that loss of Sulf-1 was not sufficient to induce immunosuppression in non-septic mice. Knockdown of Sulf-1 in human pulmonary microvascular endothelial cells resulted in downregulation of the adhesion molecule ICAM-1. Taken together, our study indicates that loss of endothelial Sulf-1 is necessary for postseptic suppression of pulmonary inflammation, representing a novel endothelial contributor to CARS.

Disparities in Adult Patient Selection for Extracorporeal Membrane Oxygenation in the United States: A Population-Level Study.

Rationale: Disparities in patient selection for advanced therapeutics in health care have been identified in multiple studies, but it is unclear if disparities exist in patient selection for extracorporeal membrane oxygenation (ECMO), a rapidly expanding critical care resource. Objectives: To determine if disparities exist in patient selection for ECMO based on sex, primary insurance, and median income of the patient's neighborhood. Methods: In a retrospective cohort study using the Nationwide Readmissions Database 2016-2019, we identified patients treated with mechanical ventilation (MV) and/or ECMO with billing codes. Patient sex, insurance, and income level for patients receiving ECMO were compared with the patients treated with MV only, and hierarchical logistic regression with the hospital as a random intercept was used to determine odds of receiving ECMO based on patient demographics. Results: We identified 2,170,752 MV hospitalizations with 18,725 cases of ECMO. Among patients treated with ECMO, 36.1% were female compared with 44.5% of patients treated with> MV only (adjusted odds ratio [aOR] for ECMO, 0.73; 95% confidence interval [CI], 0.70-0.75). Of patients treated with ECMO, 38.1% had private insurance compared with 17.4% of patients treated with MV only. Patients with Medicaid were less likely to receive ECMO than patients with private insurance (aOR, 0.55; 95% CI, 0.52-0.57). Patients treated with ECMO were more likely to live in the highest-income neighborhoods compared with patients treated with MV only (25.1% vs. 17.3%). Patients living in the lowest-income neighborhoods were less likely to receive ECMO than those living in the highest-income neighborhoods (aOR, 0.63; 95% CI, 0.60-0.67). Conclusions: Significant disparities exist in patient selection for ECMO. Female patients, patients with Medicaid, and patients living in the lowest-income neighborhoods are less likely to be treated with ECMO. Despite possible unmeasured confounding, these findings were robust to multiple sensitivity analyses. On the basis of previous work describing disparities in other areas of health care, we speculate that limited access in some neighborhoods, restrictive/biased interhospital transfer practices, differences in patient preferences, and implicit provider bias may contribute to the observed differences. Future studies with more granular data are needed to identify and modify drivers of observed disparities.

A 65-Year-Old Man With Weight Loss, Peripheral Neuropathy, and Lower Extremity Swelling.

CASE PRESENTATION: A 65-year-old man with no past medical history sought treatment at the hospital with lower extremity swelling, pain, tingling in a stocking-glove distribution, and syncope. He reported a 23-pound unintentional weight loss. He felt unsteady walking with a couple of falls, and his exercise tolerance was limited to several hundred feet. He did not report vision changes, dysphagia, bowel or bladder problems, tremor, orthopnea, lightheadedness, or chest pain. He did not report any history of substance misuse, high-risk sexual behavior, or concerning exposures. The patient was admitted for further workup.

Food Insecurity among American Indian and Alaska Native People: A Scoping Review to Inform Future Research and Policy Needs.

Food insecurity, defined as insufficient access to nutritious foods, is a social determinant of health that may underpin health disparities in the US. American Indian and Alaska Native (AI/AN) individuals experience many health inequities that may be related to food insecurity, but no systematic analyses of the existing evidence have been published. Thus, the objective of this scoping review was to assess the literature on food insecurity among AI/AN individuals and communities, with a focus on the prevalence of food insecurity and its relations to sociodemographic, nutrition, and health characteristics. Systematic search and data extraction processes were used. Searches were conducted on PubMed as well as peer-reviewed journal and government websites. Of 3174 identified references, 34 publications describing 30 studies with predominantly AI/AN sample populations were included in the final narrative synthesis. Twenty-two studies (73%) were cross-sectional and the remaining 8 (27%) described interventions. The weighted average prevalence of food insecurity across the studies was 45.7%, although estimates varied from 16% to 80%. Most studies used some version of the USDA Food Security Survey Modules, although evidence supporting its validity in AI/AN respondents is limited. Based on the review, recommendations for future research were derived, which include fundamental validity testing, better representation of AI/AN individuals in federal or local food security reports, and consideration of cultural contexts when selecting methodological approaches. Advances in AI/AN food insecurity research could yield tangible benefits to ongoing initiatives aimed at increasing access to traditional foods, improving food environments on reservations and homelands, and supporting food sovereignty.

Stress-Related Disorders of Family Members of Patients Admitted to the Intensive Care Unit With COVID-19.

Importance: The psychological symptoms associated with having a family member admitted to the intensive care unit (ICU) during the COVID-19 pandemic are not well defined. Objective: To examine the prevalence of symptoms of stress-related disorders, primarily posttraumatic stress disorder (PTSD), in family members of patients admitted to the ICU with COVID-19 approximately 90 days after admission. Design, Setting, and Participants: This prospective, multisite, mixed-methods observational cohort study assessed 330 family members of patients admitted to the ICU (except in New York City, which had a random sample of 25% of all admitted patients per month) between February 1 and July 31, 2020, at 8 academic-affiliated and 4 community-based hospitals in 5 US states. Exposure: Having a family member in the ICU with COVID-19. Main Outcomes and Measures: Symptoms of PTSD at 3 months, as defined by a score of 10 or higher on the Impact of Events Scale 6 (IES-6). Results: A total of 330 participants (mean [SD] age, 51.2 [15.1] years; 228 [69.1%] women; 150 [52.8%] White; 92 [29.8%] Hispanic) were surveyed at the 3-month time point. Most individuals were the patients' child (129 [40.6%]) or spouse or partner (81 [25.5%]). The mean (SD) IES-6 score at 3 months was 11.9 (6.1), with 201 of 316 respondents (63.6%) having scores of 10 or higher, indicating significant symptoms of PTSD. Female participants had an adjusted mean IES-6 score of 2.6 points higher (95% CI, 1.4-3.8; P < .001) than male participants, whereas Hispanic participants scored a mean of 2.7 points higher compared with non-Hispanic participants (95% CI, 1.0-4.3; P = .002). Those with graduate school experience had an adjusted mean score of 3.3 points lower (95% CI, 1.5-5.1; P < .001) compared with those with up to a high school degree or equivalent. Qualitative analyses found no substantive differences in the emotional or communication-related experiences between those with high vs low PTSD scores, but those with higher scores exhibited more distrust of practitioners. Conclusions and Relevance: In this cohort study, symptoms of PTSD among family members of ICU patients with COVID-19 were high. Hispanic ethnicity and female gender were associated with higher symptoms. Those with higher scores reported more distrust of practitioners.

Surrogate Informed Consent: A Qualitative Analysis of Surrogate Decision Makers' Perspectives.

Rationale: Clinical critical care research often hinges on surrogate informed consent, as patients commonly lack decision-making capacity because of their acute illness. The surrogate informed consent process has been identified as having flaws and needing improvement. A better understanding of surrogates' perspectives is required to understand and address these shortcomings and thereby improve this process. Objectives: To explore the perspectives of surrogate decision makers of critically ill, mechanically ventilated patients about being approached about having their loved one participate in hypothetical research studies. Methods: We performed semistructured qualitative interviews of surrogate decision makers of critically ill, mechanically ventilated patients, exploring their decisional needs surrounding participation in research. These interviews were recorded and transcribed verbatim. A thematic analysis of transcripts was performed with an iterative group framework using a mixed inductive and deductive approach. Results: A sample of 21 surrogate decision makers were interviewed. Thematic saturation was achieved by the consensus of the investigators. We identified trust as a unifying domain for the themes that emerged through the analytic process. Embedded within the domain of trust, two central themes became apparent: knowledge-based trust and context-based trust. Knowledge-based trust includes subthemes of logistics, accountability, and mutual respect, whereas context-based trust includes trust in the individual clinicians and trust in the hospital system. Conclusions: Our findings highlight the nuanced layers of trust central to the surrogate informed consent process. To enhance the surrogate informed consent process for participation in critical care research studies, it is crucial that researchers recognize the inherent importance of trust to ensure an effective informed consent process.

Journal publication ethics and implications for life science researchers: a COPE perspective.

The quality of the research record in the form of peer-reviewed journal archives is a reflection of not only the quality of the research publication and correction process, but also the quality of the underlying knowledge creation process. Key to the integrity of the research record are honesty and accountability from all parties involved in governing, performing, and publishing scholarly work. A concerted effort is needed to nurture an ethical research publishing culture by promoting ethical practice, relevant training, and effective systems for responding to allegations of research or publication misconduct. The Committee on Publication Ethics (COPE) is a membership organisation that aims to promote integrity in research publishing, for example, by developing and encouraging best practices to ensure that research is reported ethically, completely, and transparently. COPE uses the Principles of Transparency and Best Practice in Scholarly Publishing as part of its criteria when evaluating publishers and journals as members. Researchers can also make use of these guidelines to assess a journal's quality and to gain insights into what peer-reviewed journals expect from authors. The present article outlines and discusses these guidelines to help life science researchers publish ethically, as well as to identify ethical journals as readers, authors, and reviewers.

MR imaging of carotid plaque composition during lipid-lowering therapy a prospective assessment of effect and time course.

OBJECTIVES: The purpose of this study was to test the lipid depletion hypothesis and to establish the time course of change in carotid plaque morphology and composition during lipid therapy using high-resolution magnetic resonance imaging (MRI). BACKGROUND: Lipid therapy is thought to improve plaque stability and reduce cardiovascular events by targeting the plaque rupture risk features such as large lipid core, thin fibrous cap, and high level of inflammatory infiltrates. However, the plaque stabilizing process during lipid therapy has not been clearly demonstrated in humans and in vivo. METHODS: Subjects with coronary or carotid artery disease, apolipoprotein B ≥120 mg/dl, and lipid treatment history <1 year, were randomly assigned to atorvastatin monotherapy or to atorvastatin-based combination therapies with appropriate placebos for 3 years. All subjects underwent high-resolution, multicontrast bilateral carotid MRI scans at baseline and annually for 3 years. All images were analyzed for quantification of wall area and plaque composition blinded to therapy, laboratory results, and clinical course. RESULTS: After 3 years of lipid therapy, the 33 subjects with measurable lipid-rich necrotic core (LRNC) at baseline had a significant reduction in plaque lipid content: LRNC volume decreased from 60.4 ± 59.5 mm(3) to 37.4 ± 69.5 mm(3) (p < 0.001) and %LRNC (LRNC area/wall area in the lipid-rich regions) from 14.2 ± 7.0% to 7.4 ± 8.2% (p < 0.001). The time course showed that %LRNC decreased by 3.2 (p < 0.001) in the first year, by 3.0 (p = 0.005) in the second year, and by 0.91 (p = 0.2) in the third year. Changes in LRNC volume followed the same pattern. Percent wall volume (100 × wall/outer wall, a ratio of volumes) in the lipid-rich regions significantly decreased from 52.3 ± 8.5% to 48.6 ± 9.7% (p = 0.002). Slices containing LRNC had significantly more percent wall volume reduction than those without (-4.7% vs. -1.4%, p = 0.02). CONCLUSIONS: Intensive lipid therapy significantly depletes carotid plaque lipid. Statistically significant plaque lipid depletion is observed after 1 year of treatment and continues in the second year, and precedes plaque regression. (Using Magnetic Resonance Imaging to Evaluate Carotid Artery Plaque Composition in People Receiving Cholesterol-Lowering Medications [The CPC Study]; NCT00715273).

Characteristics of medical research news reported on front pages of newspapers.

BACKGROUND: The placement of medical research news on a newspaper's front page is intended to gain the public's attention, so it is important to understand the source of the news in terms of research maturity and evidence level. METHODOLOGY/PRINCIPAL FINDINGS: We searched LexisNexis to identify medical research reported on front pages of major newspapers published from January 1, 2000 to December 31, 2002. We used MEDLINE and Google Scholar to find journal articles corresponding to the research, and determined their evidence level. Of 734 front-page medical research stories identified, 417 (57%) referred to mature research published in peer-reviewed journals. The remaining 317 stories referred to preliminary findings presented at scientific or press meetings; 144 (45%) of those stories mentioned studies that later matured (i.e. were published in journals within 3 years after news coverage). The evidence-level distribution of the 515 journal articles quoted in news stories reporting on mature research (3% level I, 21% level II, 42% level III, 4% level IV, and 31% level V) differed from that of the 170 reports of preliminary research that later matured (1%, 19%, 35%, 12%, and 33%, respectively; chi-square test, P = .0009). No news stories indicated evidence level. Fewer than 1 in 5 news stories reporting preliminary findings acknowledged the preliminary nature of their content. CONCLUSIONS/SIGNIFICANCE: Only 57% of front-page stories reporting on medical research are based on mature research, which tends to have a higher evidence level than research with preliminary findings. Medical research news should be clearly referenced and state the evidence level and limitations to inform the public of the maturity and quality of the source.

Sources and coverage of medical news on front pages of US newspapers.

BACKGROUND: Medical news that appears on newspaper front pages is intended to reach a wide audience, but how this type of medical news is prepared and distributed has not been systematically researched. We thus quantified the level of visibility achieved by front-page medical stories in the United States and analyzed their news sources. METHODOLOGY: Using the online resource Newseum, we investigated front-page newspaper coverage of four prominent medical stories, and a high-profile non-medical news story as a control, reported in the US in 2007. Two characteristics were quantified by two raters: which newspaper titles carried each target front-page story (interrater agreement, >96%; kappa, >0.92) and the news sources of each target story (interrater agreement, >94%; kappa, >0.91). National rankings of the top 200 US newspapers by audited circulation were used to quantify the extent of coverage as the proportion of the total circulation of ranked newspapers in Newseum. FINDINGS: In total, 1630 front pages were searched. Each medical story appeared on the front pages of 85 to 117 (67.5%-78.7%) ranked newspaper titles that had a cumulative daily circulation of 23.1 to 33.4 million, or 61.8% to 88.4% of all newspapers. In contrast, the non-medical story achieved front-page coverage in 152 (99.3%) newspaper titles with a total circulation of 41.0 million, or 99.8% of all newspapers. Front-page medical stories varied in their sources, but the Washington Post, Los Angeles Times, New York Times and the Associated Press together supplied 61.7% of the total coverage of target front-page medical stories. CONCLUSION: Front-page coverage of medical news from different sources is more accurately revealed by analysis of circulation counts rather than of newspaper titles. Journals wishing to widen knowledge of research news and organizations with important health announcements should target at least the four dominant media organizations identified in this study.