Evaluation of Author Instructions for Inclusive Language Guidance in Highly Cited English Language Medical Journals.

BACKGROUND: Diversity, equity, and inclusion (DEI) are at the core of publication ethics, and language around DEI has been shown to affect patient outcomes. Inclusive language is an important piece of effective communication and is one way to demonstrate and foster a welcoming, respectful, and accessible environment. Non-inclusive terminology in research may represent implicit bias, which is not typically corrected through introspection; thus, a systematic approach is needed in scientific writing. The prevalence of inclusive language guidance in leading medical journals is currently unknown. OBJECTIVE: Investigators assess the prevalence and quality of inclusive language guidelines in author instructions in highly cited English language medical journals. DESIGN: A cross-sectional review of author instructions from a convenience sample of 100 highly cited medical journals was completed in January 2023. SUBJECTS: Each journal's author instructions were reviewed for presence of inclusive language guidelines for manuscript submissions. MAIN MEASURES: Guidelines that included specific examples of inclusive language were defined as "strong." Author instructions were also reviewed for the Sex and Gender Equity in Research (SAGER) checklist, and each journal's publisher and impact factor (IF) were recorded. KEY RESULTS: The 100 journals reviewed had an IF range of 3.0-202.7 with a median IF = 19.5 (IQR 11.95, 38.68), and 28 unique publishers were represented. Inclusive language guidance was provided in 23% of medical journals reviewed. Of those, 20 (86.9%) provided strong guidance. Seven journals also recommended use of the SAGER checklist. CONCLUSION: Significant gaps still exist in ensuring use of inclusive language in medical journals.

Administering a Soda Beverage With the Hepatitis C Treatment Sofosbuvir/Velpatasvir and the Proton-Pump Inhibitor Pantoprazole: A Case Report.

PURPOSE: The manufacturer of sofosbuvir/velpatasvir recommends avoiding coadministration with proton pump inhibitors (PPI) due to decreased velpatasvir serum concentrations which could translate to an increased risk of HCV treatment failure. A recent open-label study in healthy adults reported overcoming this interaction through co-administration of velpatasvir and a PPI with soda, but there is no clinical outcome data in HCV-infected patients. SUMMARY: A 64 year-old male with a past medical history significant for decompensated cirrhosis, chronic HCV infection, upper gastrointestinal bleed, anemia, esophagitis, and previous HCV treatment failures required HCV treatment. The patient's medications included a PPI but no other significant DDI were present. The patient was instructed to take one sofosbuvir/velpatasvir tablet, soda, and pantoprazole 40 mg tablet at the same time once daily. Treatment was well tolerated, and clinical cure of HCV was achieved. CONCLUSION: Scenarios may arise during HCV treatment that necessitate coadministration of a PPI. Interfering with optimal absorption of HCV treatment could lead to development of resistance or treatment failure. Future studies should include this strategy for overcoming this common DDI. This case demonstrates sofosbuvir/velpatasvir administered orally with soda and a PPI is potentially safe and effective for treatment of chronic HCV infection.

Gaining Wings to FLY: Using Drosophila Oogenesis as an Entry Point for Citizen Scientists in Laboratory Research.

Citizen science is a productive approach to include non-scientists in research efforts that impact particular issues or communities. In most cases, scientists at advanced career stages design high-quality, exciting projects that enable citizen contribution, a crowdsourcing process that drives discovery forward and engages communities. The challenges of having citizens design their own research with no or limited training and providing access to laboratory tools, reagents, and supplies have limited citizen science efforts. This leaves the incredible life experiences and immersion of citizens in communities that experience health disparities out of the research equation, thus hampering efforts to address community health needs with a full picture of the challenges that must be addressed. Here, we present a robust and reproducible approach that engages participants from Grade 5 through adult in research focused on defining how diet impacts disease signaling. We leverage the powerful genetics, cell biology, and biochemistry of Drosophila oogenesis to define how nutrients impact phenotypes associated with genetic mutants that are implicated in cancer and diabetes. Participants lead the project design and execution, flipping the top-down hierarchy of the prevailing scientific culture to co-create research projects and infuse the research with cultural and community relevance.

Implementation of a novel learning experience in scientific writing, publishing, and peer review into a first year pharmacy practice residency.

BACKGROUND: Pharmacists with competency in writing, publishing, and peer review are essential to continue advancing the pharmacy profession, but structured training of these skills may vary. OBJECTIVE: The authors set out to implement and assess the impact of a structured learning experience into a postgraduate year 1 pharmacy residency training program that provides tangible experience in the processes of scientific writing, publishing, and peer reviewing. METHODS: A quarterly pharmacy newsletter process was augmented to include an editorial board that consisted of residency trained pharmacists with varying levels of experience in scientific writing, publishing, and peer reviewing. The process was designed to provide a structured writing learning experience, to reinforce important concepts and terminology, and to simulate the process of submitting a manuscript to a peer-reviewed publication. Impact of the learning experience on quality of article submissions was assessed by comparing first quarter and last quarter writing submission scores for residents between 2017 and 2020. RESULTS: A statistically significant difference was observed in both raw scores (27 vs. 42.5 points out of 50 points possible, P < 0.05) and the proportion of pass or fail when comparing writing submission scores from the first quarter of the learning experience to submission scores from the last quarter (25% passing rate vs. 83% passing rate, P = 0.007). CONCLUSION: This novel learning experience was successfully integrated into a quarterly pharmacy newsletter and resulted in improved writing scores. This structured writing learning experience can be readily integrated into pharmacy residency training programs, and it provides hands-on training in scientific writing, publishing, and peer review for both residents and preceptors.

Impact of Glucagon-Like Peptide-1 Receptor Agonists (GLP-1RA) on Food Content During Esophagogastroduodenoscopy (EGD).

BACKGROUND: Glucagon-like peptide-1 receptor agonists (GLP-1RA) have delayed gastric emptying properties; however, the impact on esophagogastroduodenoscopy (EGD) visualization is unknown. OBJECTIVE: This study examines the impact of GLP-1RA use on EGD visualization and gastric content retention. METHODS: This was a retrospective cohort study with matched controls. The primary endpoint was the odds of retained food documented during EGD. Secondary endpoints included incidence of lavage and need for repeat EGD due to poor visualization and were compared using Fisher exact test. Analyses were performed in R Studio. RESULTS: There were 59 patients in the cohort prescribed a GLP-1RA with 118 matched controls. Food retention was documented with 4 patients (6.8%) in the GLP-1RA cohort versus 2 patients (1.7%) in the control group (odds ratio [OR] 4.22 [95% CI 0.87-20.34]). No difference was observed in the need for lavage during EGD or in the need for repeat EGD attributed to poor visualization. CONCLUSION AND RELEVANCE: This study addresses a previously uninvestigated question in clinical practice. GLP-1RA did not significantly increase odds of retained food on EGD. Although a numerical difference was observed, it did not reach statistical difference. No cases required repeat EGD due to poor visualization, and no change to EGD pre-procedure instructions were warranted at the study facility.

Deinduction of P-glycoprotein resulting in delayed viral response during hepatitis C treatment.

WHAT IS KNOWN AND OBJECTIVE: Drug-drug interactions can involve inhibition or induction of cell membrane transporters. Deinduction occurs after an inducing agent is stopped. CASE SUMMARY: This case describes suspected P-glycoprotein (P-gp) deinduction by carbamazepine resulting in a slow viral response during treatment of chronic hepatitis C virus (HCV) infection. Evidence of deinduction occurred beyond clearance of carbamazepine and resulted in extension of HCV treatment. WHAT IS NEW: The understanding of the role P-gp transport plays in drug elimination is relatively new and evidence of P-gp deinduction is variable. CONCLUSION: Clinicians should consider deinduction when starting and stopping medications involving strong inducers of P-gp transport proteins.

Identifying Missed Opportunities for the Pneumococcal Conjugate Vaccine (PCV13).

Background: The recommendation for the pneumococcal conjugate vaccine (PCV13) in adults 65 years and older is recent, and the dosing schedule of PCV13 and the pneumococcal polysaccharide vaccine (PPSV23) can be complex in this population. Objective: The authors assessed the rate of PCV13 immunization in patients 65 years of age and older and identified barriers that contributed to missed opportunities for PCV13. Methods: This retrospective review evaluated outpatient Veterans age 65 years or older who did not receive PCV13 at a scheduled primary care appointment despite an electronic reminder. Investigators recorded any documented reason for the patient not receiving PCV13. Results: The rate of PCV13 immunizations administered during the primary care visit study period was 37% (89 of 239 PCV13 eligible patients). Of the 150 patients identified who did not receive PCV13, 92% were not offered the vaccine, 6.7% declined vaccination, and 0.7% reported an allergy to vaccination. Electronic immunization records revealed that 48 of the 150 patients who did not receive PCV13 at their clinic appointment did receive PCV13 later the same year. Most patients received PCV13 in influenza vaccine season on the same day as receiving the influenza vaccine. Conclusion: The main barrier identified was not offering the vaccination during primary care visits. Pneumococcal vaccine administration was delayed until the influenza vaccine season in a significant portion of patients. This unexpected finding represents a target for education: ensuring health care professionals are reminded that PCV13 is not a seasonal vaccine like the influenza vaccine, but should be offered throughout the year.

Treatment of Chronic Hepatitis C Virus Infection With Crushed Ledipasvir/Sofosbuvir Administered via a Percutaneous Endoscopic Gastrostomy Tube.

INTRODUCTION: Ledipasvir/sofosbuvir (Harvoni®) is a fixed-dose tablet indicated for the treatment of chronic hepatitis C virus (HCV) infection. There are currently no data available on the safety and efficacy of crushed ledipasvir/sofosbuvir tablets. CASE SUMMARY: This report describes the first documented case of successful treatment of chronic HCV infection in a patient crushing ledipasvir/sofosbuvir for administration via a percutaneous endoscopic gastrostomy (PEG) tube. The patient was treatment experienced and had evidence of compensated cirrhosis. Treatment duration was 24 weeks, and HCV RNA was undetectable 12 weeks after completion of treatment (SVR12) which is the accepted measure of a clinical cure. DISCUSSION: Issues may arise during or prior to starting HCV treatment that necessitate crushing tablets. Stopping or interrupting HCV treatment could lead to development of resistance or treatment failure. CONCLUSION: This is the first published case in which crushed ledipasvir/sofosbuvir administered via a PEG tube is documented as a safe and effective option for treatment of chronic HCV infection.

Successful treatment of chronic hepatitis C virus infection in a patient receiving daily peritoneal dialysis.

PURPOSE: Successful use of a 4-drug oral fixed-dose combination therapy to treat chronic hepatitis C in a patient receiving peritoneal dialysis (PD) is reported. SUMMARY: New highly effective treatments for chronic hepatitis C virus (HCV) infection are now available, but safety and efficacy data on the use of anti-HCV therapies in patients with renal failure, particularly those requiring PD, remain limited. A 73-year-old black man with chronic HCV genotype 1a infection and stage 5 chronic renal disease requiring daily automated PD was referred for HCV treatment prior to renal transplantation. HCV treatment was initiated with paritaprevir-ritonavir-ombitasvir- dasabuvir, or "PrOD" (a combination tablet containing paritaprevir 75 mg, ritonavir 50 mg, and ombitasvir 12.5 mg to be taken once daily and a dasabuvir sodium 250-mg tablet to be taken twice daily), in conjunction with ribavirin 200 mg once daily. After a 12-week course of PrOD therapy, during which ribavirin therapy was tapered and then discontinued at week 10 and subcutaneous epoetin alfa was administered for anemia control from weeks 4 to 12, the patient's HCV viral load was undetectable; a sustained virologic response at 12 weeks (SVR12) was noted. CONCLUSION: A patient with end-stage renal disease requiring PD was treated successfully for HCV genotype 1a infection with PrOD fixed-dose combination therapy plus ribavirin therapy. The patient achieved an SVR12 despite withdrawal of ribavirin at treatment week 10, with minimal adverse effects reported.

Improving Pressure Ulcer Reconstruction: Our Protocol and the COP (Cone of Pressure) Flap.

BACKGROUND: Surgical treatment of pressure ulcers is challenging for high recurrence rates. Deepithelialized flaps have been used previously with the aim to eliminate shearing forces and the cone of pressure (COP) effect. The goal of this study is to adopt a standardized protocol and evaluate if 2 different flap techniques affect outcomes. METHODS: The novel COP flap is illustrated. Twenty patients were prospectively treated with flap coverage over a 36-month period. According to the flap type, patients were assigned to 2 groups: group 1 with 11 patients treated with the COP flap and group 2 with 9 patients treated with conventional flap without anchoring technique. We adopted a standardized protocol of debridement, tissue cultures, and negative-pressure wound therapy. Rotation fasciocutaneous flaps were used for both groups and mean follow-up was 19 months. The COP flap is a large deepithelialized rotation flap inset with transcutaneous nonabsorbable bolster sutures. The 2 groups were comparable for demographics and ulcer location and size (P < 0.05). Five patients showed positive cultures and were treated with antibiotics and negative-pressure therapy before surgery. RESULTS: Recurrence rates were 12% in the COP flap group and 60% in the conventional flap coverage group (P < 0.001). Results were compared at 16-month follow-up. CONCLUSIONS: The COP flap significantly reduces recurrences and eliminates shearing forces, suture ripping, and tension on superficial soft-tissue layers. The technique can be applied to both ischial and sacral pressure sores. The flap provides padding over bony prominence without jeopardizing flap vascularity.

A Primary Hospital Antimicrobial Stewardship Intervention on Pneumonia Treatment Duration.

A primary hospital pharmacy intervention resulted in a significant decrease in antibiotic therapy duration for the treatment of uncomplicated pneumonia.

Invasive Squamous Cell Carcinoma of the Scalp and Calvarium: A Multidisciplinary Approach.

Objective: The correlation between immunosuppression-associated skin cancer and lymphoma has been well established. This includes squamous cell carcinoma and chronic lymphocytic leukemia. When a lesion requires excision, reconstruction can be challenging based on the depth and size of the tumor. We present a patient with chronic lymphocytic leukemia and invasive squamous cell carcinoma of the scalp that extended through the calvarium to the dura mater. His tumors were badly neglected for a long period of time and presented at an advanced stage. Methods: This type of reconstruction was performed utilizing a multidisciplinary approach. Our patient required calvarial reconstruction with titanium mesh, dural reconstruction, latissimus dorsi free flap, and an overlying skin graft. Results: The patient had appropriate resection of his tumor while maintaining flap viability. Postoperatively, he presented with excellent soft-tissue thickness and aesthetic result. Conclusion: We believe that this type of reconstruction was best, considering our patient had a significant scalp and calvarial defect at presentation. Using a latissimus dorsi free flap bestows a robust blood supply to help decrease infections and improve healing and circulation, especially in light of the need of further radiation therapy.

Constituents and functional implications of the rat default mode network.

The default mode network (DMN) has been suggested to support a variety of self-referential functions in humans and has been fractionated into subsystems based on distinct responses to cognitive tasks and functional connectivity architecture. Such subsystems are thought to reflect functional hierarchy and segregation within the network. Because preclinical models can inform translational studies of neuropsychiatric disorders, partitioning of the DMN in nonhuman species, which has previously not been reported, may inform both physiology and pathophysiology of the human DMN. In this study, we sought to identify constituents of the rat DMN using resting-state functional MRI (rs-fMRI) and diffusion tensor imaging. After identifying DMN using a group-level independent-component analysis on the rs-fMRI data, modularity analyses fractionated the DMN into an anterior and a posterior subsystem, which were further segregated into five modules. Diffusion tensor imaging tractography demonstrates a close relationship between fiber density and the functional connectivity between DMN regions, and provides anatomical evidence to support the detected DMN subsystems. Finally, distinct modulation was seen within and between these DMN subcomponents using a neurocognitive aging model. Taken together, these results suggest that, like the human DMN, the rat DMN can be partitioned into several subcomponents that may support distinct functions. These data encourage further investigation into the neurobiological mechanisms of DMN processing in preclinical models of both normal and disease states.

Enhancing Tax Compliance through Coercive and Legitimate Power of Tax Authorities by Concurrently Diminishing or Facilitating Trust in Tax Authorities.

Both coercion, such as strict auditing and the use of fines, and legitimate procedures, such as assistance by tax authorities, are often discussed as means of enhancing tax compliance. However, the psychological mechanisms that determine the effectiveness of each strategy are not clear. Although highly relevant, there is rare empirical literature examining the effects of both strategies applied in combination. It is assumed that coercion decreases implicit trust in tax authorities, leading to the perception of a hostile antagonistic tax climate and enforced tax compliance. Conversely, it is suggested that legitimate power increases reason-based trust in the tax authorities, leading to the perception of a service climate and eventually to voluntary cooperation. The combination of both strategies is assumed to cause greater levels of intended compliance than each strategy alone. We conducted two experimental studies with convenience samples of 261 taxpayers overall. The studies describe tax authorities as having low or high coercive power (e.g., imposing lenient or severe sanctions) and/or low or high legitimate power (e.g., having nontransparent or transparent procedures). Data analyses provide supportive evidence for the assumptions regarding the impact on intended tax compliance. Coercive power did not reduce implicit trust in tax authorities; however, it had an effect on reason-based trust, interaction climate, and intended tax compliance if applied solely. When wielded in combination with legitimate power, it had no effect.

Genetic variation in the toll-like receptor 4 and prostate cancer incidence and mortality.

BACKGROUND: Common genetic variants in the Toll-like receptor 4 (TLR4), which is involved in inflammation and immune response pathways, may be important for prostate cancer. METHODS: In a large nested case-control study of prostate cancer in the Physicians' Health Study (1982-2004), 10 single nucleotide polymorphisms (SNPs) were selected and genotyped to capture common variation within the TLR4 gene as well as 5 kb up and downstream. Unconditional logistic regression was used to assess associations of these SNPs with total prostate cancer incidence, and with prostate cancers defined as advanced stage/lethal (T3/T4, M1/N1(T1-T4), lethal) or high Gleason grade (7 (4 + 3) or greater). Cox-proportional hazards regression was used to assess progression to metastases and death among prostate cancer cases. RESULTS: The study included 1,267 controls and 1,286 incident prostate cancer cases, including 248 advanced stage/lethal and 306 high grade cases. During a median follow-up of 10.6 years, 183 men died of prostate cancer or developed distant metastases. No statistically significant associations between the TLR4 SNPs were found for total prostate cancer incidence, including SNPs for which an association was reported in other published studies. Additionally, there were no significant associations with TLR4 SNPS and the incidence of advanced stage/lethal, or high grade cancers; nor was there evidence among prostate cancer cases for associations of TLR4 SNPs with progression to prostate cancer specific mortality or bony metastases. CONCLUSIONS: Results from this prospective nested case-control study suggest that genetic variation across TLR4 alone is not strongly associated with prostate cancer risk or mortality.

Radical prostatectomy versus watchful waiting in early prostate cancer.

BACKGROUND: In 2008, we reported that radical prostatectomy, as compared with watchful waiting, reduces the rate of death from prostate cancer. After an additional 3 years of follow-up, we now report estimated 15-year results. METHODS: From October 1989 through February 1999, we randomly assigned 695 men with early prostate cancer to watchful waiting or radical prostatectomy. Follow-up was complete through December 2009, with histopathological review of biopsy and radical-prostatectomy specimens and blinded evaluation of causes of death. Relative risks, with 95% confidence intervals, were estimated with the use of a Cox proportional-hazards model. RESULTS: During a median of 12.8 years, 166 of the 347 men in the radical-prostatectomy group and 201 of the 348 in the watchful-waiting group died (P=0.007). In the case of 55 men assigned to surgery and 81 men assigned to watchful waiting, death was due to prostate cancer. This yielded a cumulative incidence of death from prostate cancer at 15 years of 14.6% and 20.7%, respectively (a difference of 6.1 percentage points; 95% confidence interval [CI], 0.2 to 12.0), and a relative risk with surgery of 0.62 (95% CI, 0.44 to 0.87; P=0.01). The survival benefit was similar before and after 9 years of follow-up, was observed also among men with low-risk prostate cancer, and was confined to men younger than 65 years of age. The number needed to treat to avert one death was 15 overall and 7 for men younger than 65 years of age. Among men who underwent radical prostatectomy, those with extracapsular tumor growth had a risk of death from prostate cancer that was 7 times that of men without extracapsular tumor growth (relative risk, 6.9; 95% CI, 2.6 to 18.4). CONCLUSIONS: Radical prostatectomy was associated with a reduction in the rate of death from prostate cancer. Men with extracapsular tumor growth may benefit from adjuvant local or systemic treatment. (Funded by the Swedish Cancer Society and the National Institutes of Health.).

mRNA expression signature of Gleason grade predicts lethal prostate cancer.

PURPOSE: Prostate-specific antigen screening has led to enormous overtreatment of prostate cancer because of the inability to distinguish potentially lethal disease at diagnosis. We reasoned that by identifying an mRNA signature of Gleason grade, the best predictor of prognosis, we could improve prediction of lethal disease among men with moderate Gleason 7 tumors, the most common grade, and the most indeterminate in terms of prognosis. PATIENTS AND METHODS: Using the complementary DNA-mediated annealing, selection, extension, and ligation assay, we measured the mRNA expression of 6,100 genes in prostate tumor tissue in the Swedish Watchful Waiting cohort (n = 358) and Physicians' Health Study (PHS; n = 109). We developed an mRNA signature of Gleason grade comparing individuals with Gleason ≤ 6 to those with Gleason ≥ 8 tumors and applied the model among patients with Gleason 7 to discriminate lethal cases. RESULTS: We built a 157-gene signature using the Swedish data that predicted Gleason with low misclassification (area under the curve [AUC] = 0.91); when this signature was tested in the PHS, the discriminatory ability remained high (AUC = 0.94). In men with Gleason 7 tumors, who were excluded from the model building, the signature significantly improved the prediction of lethal disease beyond knowing whether the Gleason score was 4 + 3 or 3 + 4 (P = .006). CONCLUSION: Our expression signature and the genes identified may improve our understanding of the de-differentiation process of prostate tumors. Additionally, the signature may have clinical applications among men with Gleason 7, by further estimating their risk of lethal prostate cancer and thereby guiding therapy decisions to improve outcomes and reduce overtreatment.

Managing localized prostate cancer by radical prostatectomy or watchful waiting: Cost analysis of a randomized trial (SPCG-4).

OBJECTIVE: The cost of radical prostatectomy (RP) compared to watchful waiting (WW) has never been estimated in a randomized trial. The goal of this study was to estimate long-term total costs per patient associated with RP and WW arising from inpatient and outpatient hospital care. MATERIAL AND METHODS: This investigation used the Scandinavian Prostate Cancer Group Study Number 4 (SPCG-4) trial, comparing RP to WW, and included data from 212 participants living in two counties in Sweden from 1989 to 1999 (105 randomized to WW and 107 to RP). All costs were included from randomization date until death or end of follow-up in July 2007. Resource use arising from inpatient and outpatient hospital costs was measured in physical units and multiplied by a unit cost to come up with a total cost per patient. RESULTS: During a median follow-up of 12 years, the overall cost in the RP group was 34% higher (p < 0.01) than in the WW group, corresponding to €6123 in Sweden. The difference was driven almost exclusively by the cost of the surgical procedure. The cost difference between RP and WW was two times higher among men with low (2-6) than among those with high (7-10) Gleason score. CONCLUSION: In this economic evaluation of RP versus WW of localized prostate cancer in a randomized study, RP was associated with 34% higher costs. This difference, attributed exclusively to the cost of the RP procedure, was not overcome during extended follow-up.