SLCO1B3 and SLCO2B1 genotypes, androgen deprivation therapy, and prostate cancer outcomes: a prospective cohort study and meta-analysis.

Solute carrier organic anion (SLCO) transporters (OATP transporters) are involved in cellular uptake of drugs and hormones. Germline variants in SLCO1B3 and SLCO2B1 have been implicated in prostate cancer progression and therapy response, including to androgen deprivation and statin medications, but results have appeared heterogeneous. We conducted a cohort study of five single-nucleotide polymorphisms (SNPs) in SLCO1B3 and SLCO2B1 with prior evidence among 3208 men with prostate cancer who participated in the Health Professionals Follow-up Study or the Physicians' Health Study, following participants prospectively after diagnosis over 32 years (median, 14 years) for development of metastases and cancer-specific death (lethal disease, 382 events). Results were suggestive of, but not conclusive for, associations between some SNPs and lethal disease and differences by androgen deprivation and statin use. All candidate SNPs were associated with SLCO mRNA expression in tumor-adjacent prostate tissue. We also conducted a systematic review and harmonized estimates for a dose-response meta-analysis of all available data, including 9 further studies, for a total of 5598 patients and 1473 clinical events. The A allele of the exonic SNP rs12422149 (14% prevalence), which leads to lower cellular testosterone precursor uptake via SLCO2B1, was associated with lower rates of prostate cancer progression (hazard ratio per A allele, 0.80; 95% confidence interval, 0.69-0.93), with little heterogeneity between studies (I2, 0.27). Collectively, the totality of evidence suggests a strong association between inherited genetic variation in SLCO2B1 and prostate cancer prognosis, with potential clinical use in risk stratification related to androgen deprivation therapy.

Call to action: empowering patients and families to initiate clinical ethics consultations.

Clinical ethics consultations exist to support patients, families and clinicians who are facing ethical or moral challenges related to patient care. They provide a forum for open communication, where all stakeholders are encouraged to express their concerns and articulate their viewpoints. Ethics consultations can be requested by patients, caregivers or members of a patient's clinical or supportive team. Although patients and by extension their families (especially in cases of decisional incapacity) are the common denominators in most ethics consultations, these constituents are the least likely to request them. At many healthcare organisations in the USA, ethics consultations are overwhelmingly requested by physicians and other clinicians. We believe it is vital that healthcare institutions bridge the knowledge gaps and power imbalances over access to ethics consultation services through augmented policies, procedures and infrastructure. With enhanced education and support, patients and families may use ethics consultation to elevate their voices and prioritise their unique characteristics and preferences in the delivery of their healthcare. Empowering patients and families to request ethics consultation can only strengthen the patient/family-clinician relationship, enhance the shared decision-making model of care and ultimately lead to improved patient-centred care.

Perioperative gabapentin usage in pediatric patients: A scoping review.

BACKGROUND: There has been a recent focus among anesthesiologists on reducing the use of perioperative opioids in favor of multimodal analgesic regimens. Gabapentin has played an integral role in this evolution of practice. This comprehensive review assesses the current clinical evidence on the efficacy of perioperative gabapentin regarding postoperative pain and opioid requirements among the pediatric surgery population. DATA SOURCES: Pubmed, CINAHL, Embase, Scopus, and Web of Science Review. METHODS: This scoping review of the above databases includes all studies examining the use of gabapentin perioperatively in pediatric patients and its association with postoperative pain intensity and postoperative opioid consumption through July 2021. The inclusion criteria encompassed all studies evaluating gabapentin in the perioperative pediatric population through randomized controlled trials (RCTs) and retrospective studies. Relevant metadata from each study were abstracted and descriptive statistics were used to summarize the results. RESULTS: Fifteen papers met the inclusion criteria for this review, including 11 RCTs and 4 retrospective studies. Sample sizes ranged from 20 to 144 patients. Administered doses varied widely, mainly between 5 and 20 mg/kg. The studies included primarily orthopedic (10) and neck surgery cases (3). Seven papers had gabapentin provided preoperatively only, two postoperative only, and six both pre- and postoperatively. Of the studies assessing postoperative pain, 6/11 studies saw a decrease in postoperative pain in at least one period for the gabapentin group. Of the studies considering opioid requirements, 6/10 reported a reduction, 1/10 an increase, and 3/10 no difference in opioid requirements for the gabapentin groups. Yet, most of these pain and opioid requirement findings were only significant at one to two time points in the study follow-up periods, and the actual decreases had minimal clinical significance. CONCLUSIONS: The current data on perioperative gabapentin in pediatric patients are insufficient to support the routine use of gabapentin in pediatric patients. Additional high-quality RCTs with more standardized protocols for gabapentin administration and outcome measures are necessary to provide more definitive conclusions.

Psychosocial interventions and needs among individuals and families with Li-Fraumeni syndrome: A scoping review.

Li-Fraumeni syndrome (LFS), a rare cancer predisposition syndrome caused by germline mutations in the TP53 gene, is associated with significant lifetime risk of developing cancer and warrants extensive and long-term surveillance. There are psychosocial impacts on individuals and families living with this condition, from the initial diagnosis throughout multiple stages across the lifespan, but these impacts have not been systematically reviewed and organized. The objective of this scoping review was to synthesize and characterize the literature on psychosocial screening and outcomes, educational needs, support services, and available interventions for patients and families with LFS. A systematic search of six databases was most recently conducted in August 2020: (PubMed/MEDLINE (NLM), EMBASE (Elsevier), Cochrane Library (Wiley), CINAHL (EBSCO), PsycINFO (OVID), and Web of Science (Clarivate Analytics). A total of 15 757 titles were screened, and 24 articles included. Several important themes were identified across studies: factors associated with TP53 genetic testing, LFS surveillance, psychological outcomes, and communication. Findings related to these themes were organized into age-specific categories (age agnostic/across the lifespan, childhood, adolescence and young adulthood, and adulthood).

COVID-19 double jeopardy: the overwhelming impact of the social determinants of health.

BACKGROUND: The COVID-19 pandemic has strained healthcare systems by creating a tragic imbalance between needs and resources. Governments and healthcare organizations have adapted to this pronounced scarcity by applying allocation guidelines to facilitate life-or-death decision-making, reduce bias, and save as many lives as possible. However, we argue that in societies beset by longstanding inequities, these approaches fall short as mortality patterns for historically discriminated against communities have been disturbingly higher than in the general population. METHODS: We review attack and fatality rates; survey allocation protocols designed to deal with the extreme scarcity characteristic of the earliest phases of the pandemic; and highlight the larger ethical perspectives (Utilitarianism, non-Utilitarian Rawlsian justice) that might justify such allocation practices. RESULTS: The COVID-19 pandemic has dramatically amplified the dire effects of disparities with respect to the social determinants of health. Patients in historically marginalized groups not only have significantly poorer health prospects but also lower prospects of accessing high quality medical care and benefitting from it even when available. Thus, mortality among minority groups has ranged from 1.9 to 2.4 times greater than the rest of the population. Standard allocation schemas, that prioritize those most likely to benefit, perpetuate and may even exacerbate preexisting systemic injustices. CONCLUSIONS: To be better prepared for the inevitable next pandemic, we must urgently begin the monumental project of addressing and reforming the structural inequities in US society that account for the strikingly disparate mortality rates we have witnessed over the course of the current pandemic.

Autoimmune disease and oral squamous cell carcinoma: A systematic review.

BACKGROUND: Oral cancer is typically related to environmental carcinogen exposure including tobacco and alcohol. Other less investigated risk factors may be related to a suppressed or dysregulated immune state, and in oral cancer, various levels of immune dysregulation have been found to affect survival and recurrence rates. The rationale for this systematic review was to investigate the possible role that a growing chronic host condition like an autoimmune disease may play in this disease. METHODS: A systematic search of the literature was carried out using four electronic databases in order to identify original research of any analytic study design type that investigated the relationship between autoimmune disease and oral cancer. Out of 1,947 identified records, 24 observational studies were included for qualitative synthesis. RESULTS: The studies varied in end points ranging from overall survival (OS), standardized incidence ratio (SIR), and hazard ratio (HR). Due to the heterogenous sampling of studies even within the same study design group, a meta-analysis was not employed. The current state of the literature is varied and heterogenous in both study design and endpoints. CONCLUSION: Major limitations existed introducing significant bias especially in determining cancer risk such as lack of information surrounding known etiologic risk factors such as alcohol and tobacco consumption. Despite these limitations, a signal was seen between autoimmune disease and oral cancer outcomes and risk. Future studies investigating the relationship between autoimmune disease and oral cancer in a more focused and quantitative manner are therefore needed.

Must antidepressants be avoided in patients with neuroendocrine tumors? Results of a systematic review.

OBJECTIVE: Symptoms of depression and anxiety are common in neuroendocrine tumor (NET), yet controversy exists over whether serotonin-mediated antidepressants (SAs) are safe in this population. We sought to address this knowledge gap. METHOD: Following PRISMA guidelines, we conducted a systematic review to identify NET patients who were prescribed SA. RESULTS: We identified 15 articles, reporting on 161 unique patients, 72 with carcinoid syndrome (CS) and 89 without. There was substantial agreement between reviewers at the full-text stage (κ = 0.69). Three of the articles, all with low risk of bias, accounted for most of the cases (149/161; 93%). Among the 72 NET patients with CS prior to antidepressant usage, CS was exacerbated in 6 cases (8%), only 3 (4%) of whom chose to discontinue the antidepressant. The remaining 89 patients had no prior CS symptoms, and none developed CS following antidepressant usage. Overall, no instances of carcinoid crisis or death were reported. CONCLUSIONS: We found no evidence for serious adverse outcomes related to SA usage in NET patients. Previous authors have recommended avoiding antidepressants in NET, but our findings do not support those recommendations. Oncologists should nonetheless monitor for symptom exacerbation when prescribing SA to patients with NET.

A Systematic Review of the Impact of Patient-Physician Non-English Language Concordance on Quality of Care and Outcomes.

BACKGROUND: Approximately 25 million people in the USA are limited English proficient (LEP). When LEP patients receive care from physicians who are truly language concordant, some evidence show that language disparities are reduced, but others demonstrate worse outcomes. We conducted a systematic review of the literature to compare the impact of language-concordant care for LEP patients with that of other interventions, including professional and ad hoc interpreters. METHODS: Data was collected through a systematic review of the literature using PubMed, PsycINFO, Web of Science, Cochrane Library, and EMBASE in October 2017. The literature search strategy had three main components, which were immigrant/minority status, language barrier/proficiency, and healthcare provider/patient relationship. The quality of the articles was appraised using the Downs and Black checklist. RESULTS: The 33 studies were grouped by the outcome measure studied, including quality of care (subdivided into primary care, diabetes, pain management, cancer, and inpatient), satisfaction with care/communication, medical understanding, and mental health. Of the 33, 4 (6.9%) were randomized controlled trials and the remaining 29 (87.9%) were cross-sectional studies. Seventy-six percent (25/33) of the studies demonstrated that at least one of the outcomes assessed was better for patients receiving language-concordant care, while 15% (5/33) of studies demonstrated no difference in outcomes, and 9% (3/33) studies demonstrated worse outcomes in patients receiving language-concordant care. DISCUSSION: The findings of this review indicate that, in the majority of situations, language-concordant care improves outcomes. Although most studies included were of good quality, none provided a standardized assessment of provider language skills. To systematically evaluate the impact of truly language-concordant care on outcomes and draw meaningful conclusions, future studies must include an assessment of clinician language proficiency. Language-concordant care offers an important way for physicians to meet the unique needs of their LEP patients.

Medication overuse in oncology: current trends and future implications for patients and society.

The high cost of cancer care worldwide is largely attributable to rising drugs prices. Despite their high costs and potential toxic effects, anticancer treatments could be subject to overuse, which is defined as the provision of medical services that are more likely to harm than to benefit a patient. We found 30 studies documenting medication overuse in cancer, which included 16 examples of supportive medication overuse and 17 examples of antineoplastic medication overuse in oncology. Few specific agents have been assessed, and no studies investigated overuse of the most toxic or expensive medications currently used in cancer treatment. Although financial, psychological, or physical harms of medication overuse in cancer could be substantial, there is little published evidence addressing these harms, so their magnitude is unclear. Further research is needed to better quantify medication overuse, understand its implications, and help protect patients and the health-care system from overuse.

Alternative payment and care-delivery models in oncology: A systematic review.

Rising US health care costs have led to the creation of alternative payment and care-delivery models designed to maximize outcomes and/or minimize costs through changes in reimbursement and care delivery. The impact of these interventions in cancer care is unclear. This review was undertaken to describe the landscape of new alternative payment and care-delivery models in cancer care. In this systematic review, 22 alternative payment and/or care-delivery models in cancer care were identified. These included 6 bundled payments, 4 accountable care organizations, 9 patient-centered medical homes, and 3 other interventions. Only 12 interventions reported outcomes; the majority (n = 7; 58%) improved value, 4 had no impact, and 1 reduced value, but only initially. Heterogeneity of outcomes precluded a meta-analysis. Despite the growth in alternative payment and delivery models in cancer, there is limited evidence to evaluate their efficacy. Cancer 2018. © 2018 American Cancer Society.

Racial disparities in chemotherapy administration for early-stage breast cancer: a systematic review and meta-analysis.

PURPOSE: We conducted a systematic review and meta-analysis to measure the extent to which race is associated with delayed initiation or receipt of inadequate chemotherapy among women with early-stage breast cancer. METHODS: We performed a systematic search of all articles published from January 1987 until June 2017 within four databases: PubMed/Medline, EMBASE, CINAHL, and Cochrane CENTRAL. Eligible studies were US-based and examined the influence of race on chemotherapy delays, cessation, or dose reductions among women with stage I, II, or III breast cancer. Data were pooled using a random effects model. RESULTS: A total of twelve studies were included in the quantitative analysis. Blacks were significantly more likely than whites to have delays to initiation of adjuvant therapy of 90 days or more (OR 1.41, 95% CI 1.06-1.87; X² = 31.05, p < 0.00001; I² = 90%). There was no significant association between race and chemotherapy dosing. Due to overlap between studies assessing the relationship between race and completion of chemotherapy, we conducted two separate analyses. Black patients were significantly more likely to discontinue chemotherapy, however, this was no longer statistically significant when larger numbers of patients with more advanced (stage III) breast cancer were included. CONCLUSIONS: These results suggest that black breast cancer patients experience clinically relevant delays in the initiation of adjuvant chemotherapy more often than white patients, which may in part explain the increased mortality observed among black patients.

Patient-Reported Physical Function Measures in Cancer Clinical Trials.

Patient-reported outcomes (PROs) are increasingly used to monitor treatment-related symptoms and physical function decrements in cancer clinical trials. As more patients enter survivorship, it is important to capture PRO physical function throughout trials to help restore pretreatment levels of function. We completed a systematic review of PRO physical function measures used in cancer clinical trials and evaluated their psychometric properties on the basis of guidelines from the US Food and Drug Administration. Five databases were searched through October 2015: PubMed/MEDLINE, EMBASE, CINAHL (Cumulative Index of Nursing and Allied Health Literature), Health and Psychosocial Instruments, and Cochrane. From an initial total of 10,233 articles, we identified 108 trials that captured PRO physical function. Within these trials, approximately 67% used the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire and 25% used the Medical Outcomes Study Short Form 36. Both the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire and Medical Outcomes Study Short Form 36 instruments generically satisfy most Food and Drug Administration requirements, although neither sought direct patient input as part of item development. The newer Patient-Reported Outcomes Measurement Information System physical function short form may be a brief, viable alternative. Clinicians should carefully consider the psychometric properties of these measures when incorporating PRO instrumentation into clinical trial design to provide a more comprehensive understanding of patient function.

Evaluating the Impact of Mediated Literature Searches at a Comprehensive Cancer Center.

Research informationists at a comprehensive cancer center sought to evaluate the impact and value of mediated literature searches in support of their users' work activities. An assessment tool was identified in the literature and modified by the investigators to solicit feedback from library users and identify the major reason(s) why scientists and health care professionals request literature searches, how they use the resulting information, and the impact that the results may or may not have on their research or patient care/decision-making activities. Survey results were qualitatively analyzed, and future avenues of outreach and promotion of mediated literature search services were identified.

Facilitating biomedical researchers' interrogation of electronic health record data: Ideas from outside of biomedical informatics.

Electronic health records (EHR) are a vital data resource for research uses, including cohort identification, phenotyping, pharmacovigilance, and public health surveillance. To realize the promise of EHR data for accelerating clinical research, it is imperative to enable efficient and autonomous EHR data interrogation by end users such as biomedical researchers. This paper surveys state-of-art approaches and key methodological considerations to this purpose. We adapted a previously published conceptual framework for interactive information retrieval, which defines three entities: user, channel, and source, by elaborating on channels for query formulation in the context of facilitating end users to interrogate EHR data. We show the current progress in biomedical informatics mainly lies in support for query execution and information modeling, primarily due to emphases on infrastructure development for data integration and data access via self-service query tools, but has neglected user support needed during iteratively query formulation processes, which can be costly and error-prone. In contrast, the information science literature has offered elaborate theories and methods for user modeling and query formulation support. The two bodies of literature are complementary, implying opportunities for cross-disciplinary idea exchange. On this basis, we outline the directions for future informatics research to improve our understanding of user needs and requirements for facilitating autonomous interrogation of EHR data by biomedical researchers. We suggest that cross-disciplinary translational research between biomedical informatics and information science can benefit our research in facilitating efficient data access in life sciences.

The association between clinician-based common terminology criteria for adverse events (CTCAE) and patient-reported outcomes (PRO): a systematic review.

PURPOSE: Symptomatic adverse events (AEs) are monitored by clinicians as part of all US-based clinical trials in cancer via the U.S. National Cancer Institute's Common Terminology Criteria for Adverse Events (CTCAE) for the purposes of ensuring patient safety. Recently, there has been a charge toward capturing the patient perspective for those AEs amenable to patient self-reporting via patient-reported outcomes (PRO). The aim of this review was to summarize the empirically reported association between analogous CTCAE and PRO ratings. METHODS: A systematic literature search was conducted using PubMed, EMBASE, Web of Science, and Cochrane databases through July 2015. From a total of 5658 articles retrieved, 28 studies met the inclusion criteria. RESULTS: Across studies, patients were of mixed cancer types, including anal, breast, cervical, chronic myeloid leukemia, endometrial, hematological, lung, ovarian, pelvic, pharyngeal, prostate, and rectal. Given this mixture, the AEs captured were variable, with many common across studies (e.g., dyspnea, fatigue, nausea, neuropathy, pain, vomiting), as well as several that were disease-specific (e.g., erectile dysfunction, hemoptysis). Overall, the quantified association between CTCAE and PRO ratings fell in the fair to moderate range and had a large variation across the majority of studies (n = 21). CONCLUSIONS: The range of measures used and symptoms captured varied greatly across the reviewed studies. Regardless of concordance metric employed, reported agreement between CTCAE and PRO ratings was moderate at best. To assist with reconciliation and interpretation of these differences toward ultimately improving patient care, an important next step is to explore approaches to integrate PROs with clinician reporting of AEs.

Antipsychotic-induced akathisia in delirium: A systematic review.

OBJECTIVE: Akathisia is a neuropsychiatric syndrome characterized by subjective and objective restlessness. It is a common side effect in patients taking antipsychotics and other psychotropics. Patients with delirium are frequently treated with antipsychotic medications that are well known to induce akathisia as a side effect. However, the prevalence, phenomenology, and management of akathisia in patients with delirium remain largely unknown. The purpose of this review was to examine the medical literature in order to establish the current state of knowledge regarding the prevalence of antipsychotic-induced akathisia in patients with delirium. METHOD: A systematic review of the literature was conducted using the EMBASE, MEDLINE, PsycINFO, and CINAHL databases. Ten studies addressing the incidence of akathisia in patients taking antipsychotic medication for delirium were identified and included in our review. RESULTS: The included studies reported a variable prevalence of antipsychotic-induced akathisia. A higher prevalence was found in patients taking haloperidol. Among atypical antipsychotics, paliperidone and ziprasidone were associated with a higher risk of akathisia. The risk for akathisia appeared to be a dose-related phenomenon. SIGNIFICANCE OF RESULTS: Studies using specific scales for evaluation of akathisia in delirium are lacking. Some populations, such as patients with cancer or terminally ill patients in palliative care settings taking antipsychotics for the treatment of delirium, could be at higher risk for development of akathisia as a side effect.

Assessing the health information needs of unaffiliated health professionals and using training on openly available search tools and resources to provide solutions to their information access challenges and barriers.

This article will describe a year-long (2010-11) joint project between Columbia University Medical Center's Health Sciences Library and the Institute for Family Health (IFH), a network of Federally Qualified Health Centers (FQHCs) serving disadvantaged populations in New York State. This National Institutes of Health-funded pilot project aimed to (a) determine the medical literature and training needs of IFH personnel, (b) develop generic licensing agreements with publishers that would enable a health sciences library to provide access to electronic resources for FQHC personnel, and (c) develop reference/education services for IFH personnel. How the reference and education aims were met will be described and discussed here as the lessons learned from this project may be useful to librarians considering doing instructional outreach to unaffiliated health professionals working at FQHCs nationwide.

'If you build it, they will come to the wrong door: evaluating patient and caregiver-initiated ethics consultations via a patient portal'.

OBJECTIVES: Memorial Sloan Kettering Cancer Center (MSK) sought to empower patients and caregivers to be more proactive in requesting ethics consultations. METHODS: Functionality was developed on MSK's electronic patient portal that allowed patients and/or caregivers to request ethics consultations. The Ethics Consultation Service (ECS) responded to all requests, which were documented and analysed. RESULTS: Of the 74 requests made through the portal, only one fell under the purview of the ECS. The others were primarily requests for assistance with coordinating clinical care, hospital resources or frustrations with the hospital or clinical team. DISCUSSION: To better empower patients and caregivers to engage Ethics, healthcare organisations and ECSs must first provide them with accessible, understandable and iterative educational resources. CONCLUSION: After 19.5 months, the 'Request Ethics Consultation' functionality on the patient portal was suspended. Developing resources on the role of Ethics for our patients and caregivers remains a priority.

Electronic consent in clinical care: an international scoping review.

OBJECTIVE: Digital technologies create opportunities for improvement of consenting processes in clinical care. Yet little is known about the prevalence, characteristics or outcomes of shifting from paper to electronic consenting, or e-consent, in clinical settings. Thus questions remain around e-consent's impact on efficiency, data integrity, user experience, care access, equity and quality. Our objective was to scope all known findings on this critical topic. MATERIALS AND METHODS: Through an international, systematic scoping review, we identified and assessed all published findings on clinical e-consent in the scholarly and grey literatures, including consents for telehealth encounters, procedures and health information exchanges. From each relevant publication, we abstracted data on study design, measures, findings and other study features. MAIN OUTCOME MEASURES: Metrics describing or evaluating clinical e-consent, including preferences for paper versus e-consenting; efficiency (eg, time, workload) and effectiveness (eg, data integrity, care quality). User characteristics were captured where available. RESULTS: A total of 25 articles published since 2005, most from North America or Europe, report on the deployment of e-consent in surgery, oncology and other clinical settings. Experimental designs and other study characteristics vary, but nearly all focus on procedural e-consents. Synthesis reveals relatively consistent findings around improved efficiency and data integrity with, and user preferences for, e-consent. Care access and quality issues are less frequently explored, with disparate findings. DISCUSSION AND CONCLUSION: The literature is nascent and largely focused on issues that are immediate and straightforward to measure. As virtual care pathways expand, more research is urgently needed to ensure that care quality and access are advanced, not compromised, by e-consent.