Patient understanding of pharmacogenomic test results in clinical care.

OBJECTIVE: Previous research has not objectively assessed patients' comprehension of their pharmacogenomic test results. In this study we assessed understanding of patients who had undergone cytochrome P450 2C19 (CYP2C19) pharmacogenomic testing. METHODS: 31 semi-structured interviews with patients who underwent CYP2C19 testing after cardiac catheterization and had been sent a brochure, letter, and wallet card explaining their results. Answers to Likert and binary questions were summarized with descriptive statistics. Qualitative data were analyzed using a grounded theory approach, with particular focus on categorization. RESULTS: No participants knew the name of the gene tested or their metabolizer status. Seven participants (23%) knew whether the testing identified any medications that would have lower effectiveness or increased adverse effects for them at standard doses ("Adequate Understanding"). Four participants (13%) read their results from the letter or wallet card they received but had no independent understanding ("Reliant on Written Materials"). Ten participants remembered receiving the written materials (32%). CONCLUSION: A majority of participants who had undergone CYP2C19 PGx testing did not understand their results at even a minimal level and would be unable to communicate them to future providers. PRACTICE IMPLICATIONS: Further research is necessary to improve patient understanding of PGx testing and their results, potentially through improving patient-provider communication.

Health Status, Quality of Life, Psychosocial Well-being, and Wearables Data of Patients With Active Ulcerative Colitis Receiving Filgotinib Therapy (FilgoColitis Study): Protocol for a Real-world Observational Study.

BACKGROUND: Filgotinib was approved in Germany for treating patients with moderate to severe active ulcerative colitis in November 2021. It represents a preferential Janus kinase 1 inhibitor. The FilgoColitis study began recruiting immediately after approval and aims to assess filgotinib effectiveness under real-world conditions with a particular focus on patient-reported outcomes (PROs). The novelty of the study design is the optional inclusion of 2 innovative wearables, which could provide a new layer of patient-derived data. OBJECTIVE: The study investigates quality of life (QoL) and psychosocial well-being of patients with active ulcerative colitis during long-term exposure to filgotinib. PROs related to QoL and psychometric profiles (fatigue and depression) are collected alongside with disease activity symptom scores. We aim to evaluate physical activity patterns collected by wearables as an addition to traditional PROs, patient-reported health status, and QoL in different phases of disease activity. METHODS: This is a prospective, single-arm, multicentric, noninterventional, observational study with a sample size of 250 patients. QoL is assessed with validated questionnaires: the Short Inflammatory Bowel Disease Questionnaire (sIBDQ) for the disease-specific QoL, the EQ-5D for the general QoL, and the fatigue questionnaire (Inflammatory Bowel Disease-Fatigue [IBD-F]). Physical activity data are collected from patients using wearables (SENS motion leg sensor [accelerometry] and smartwatch, GARMIN vívosmart 4). RESULTS: The enrollment started in December 2021 and was still open at the date of submission. After 6 months of study initiation, 69 patients were enrolled. The study is expected to be completed in June 2026. CONCLUSIONS: Real-world data for novel drugs are important to assess effectiveness outside of highly selected populations represented by randomized controlled trials. We examine whether patients' QoL and other PROs can be supplemented with physical activity patterns measured objectively. Use of wearables with newly defined outcomes represents an additional observational tool for monitoring disease activity in patients with inflammatory bowel disease. TRIAL REGISTRATION: German Clinical Trials Register DRKS00027327; https://drks.de/search/en/trial/DRKS00027327. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/42574.

The Combined Treatment with Ketogenic Diet and Metformin Slows Tumor Growth in Two Mouse Models of Triple Negative Breast Cancer.

BACKGROUND: Many tumors contain hypoxic microenvironments caused by inefficient tumor vascularization. Hypoxic tumors have been shown to resist conventional cancer therapies. Hypoxic cancer cells rely on glucose to meet their energetic and anabolic needs to fuel uncontrolled proliferation and metastasis. This glucose dependency is linked to a metabolic shift in response to hypoxic conditions. METHODS: To leverage the glucose dependency of hypoxic tumor cells, we assessed the effects of a controlled reduction in systemic glucose by combining dietary carbohydrate restriction, using a ketogenic diet, with gluconeogenesis inhibition, using metformin, on two mouse models of triple-negative breast cancer (TNBC). RESULTS: We confirmed that MET - 1 breast cancer cells require abnormally high glucose concentrations to survive in a hypoxic environment in vitro. Then, we showed that, compared to a ketogenic diet or metformin alone, animals treated with the combination regimen showed significantly lower tumor burden, higher tumor latency and slower tumor growth. As a result, lowering systemic glucose by this combined dietary and pharmacologic approach improved overall survival in our mouse model by 31 days, which is approximately equivalent to 3 human years. CONCLUSION: This is the first preclinical study to demonstrate that reducing systemic glucose by combining a ketogenic diet and metformin significantly inhibits tumor proliferation and increases overall survival. Our findings suggest a possible treatment for a broad range of hypoxic and glycolytic tumor types, one that can also augment existing treatment options to improve patient outcomes.

Measuring the Impact of Quantitative Information on Patient Understanding: Approaches for Assessing the Adequacy of Patient Knowledge about Colorectal Cancer Screening.

Background. Guidelines recommend that decision aids disclose quantitative information to patients considering colorectal cancer (CRC) screening, but the impact on patient knowledge and decision making is limited. An important challenge for assessing any disclosure involves determining when an individual has "adequate knowledge" to make a decision. Methods. We analyzed data from a trial that randomized 213 patients to view a decision aid about CRC screening that contained verbal information (qualitative arm) versus one containing verbal plus quantitative information (quantitative arm). We analyzed participants' answers to 8 "qualitative knowledge" questions, which did not cover the quantitative information, at baseline (T0) and after viewing the decision aid (T1). We introduce a novel approach that defines adequate knowledge as correctly answering all of a subset of questions that are particularly relevant because of the participant's test choice ("Choice-Based Knowledge Assessment"). Results. Participants in the quantitative arm answered a higher mean number of knowledge questions correctly at T1 than did participants in the qualitative arm (7.3 v. 6.9, P < 0.05), and they more frequently had adequate knowledge at T1 based on a cutoff of 6 or 7 correct out of 8 (94% v. 83%, P < 0.05, and 86% v. 71%, P < 0.05, respectively). Members of the quantitative group also more frequently had adequate knowledge at T1 when assessed by Choice-Based Knowledge Assessment (87% v. 76%, P < 0.05). Conclusions. Patients who viewed quantitative information in addition to verbal information had greater qualitative knowledge and more frequently had adequate knowledge compared with those who viewed verbal information alone, according to most ways of defining adequate knowledge. Quantitative information may have helped participants better understand qualitative or gist concepts. Trial Registration: ClinicalTrials.gov ID# NCT01415479. Highlights: Patients who viewed quantitative information in a decision aid about colorectal cancer screening were more knowledgeable about nonquantitative information and were more likely to have adequate knowledge according to a variety of approaches for assessing that, compared with individuals who viewed only qualitative information. This result supports the inclusion of quantitative information in decision aids.Researchers assessing patient understanding should consider a variety of ways to define adequate knowledge when assessing decision quality.

A Comprehensive Approach to Improving Emergency Obstetric and Newborn Care in Kigoma, Tanzania.

INTRODUCTION: To address high levels of maternal mortality in Kigoma, Tanzania, stakeholders increased women's access to high-quality comprehensive emergency obstetric and newborn care (EmONC) by decentralizing services from hospitals to health centers where EmONC was delivered mostly by associate clinicians and nurses. To ensure that women used services, implementers worked to continuously improve and sustain quality of care while creating demand. METHODS: Program evaluation included periodic health facility assessments, pregnancy outcome monitoring, and enhanced maternal mortality detection region-wide in program- and nonprogram-supported health facilities. RESULTS: Between 2013 and 2018, the average number of lifesaving interventions performed per facility increased from 2.8 to 4.7. The increase was higher in program-supported than nonprogram-supported health centers and dispensaries. The institutional delivery rate increased from 49% to 85%; the greatest increase occurred through using health centers (15% to 25%) and dispensaries (21% to 46%). The number of cesarean deliveries almost doubled, and the population cesarean delivery rate increased from 2.6% to 4.5%. Met need for emergency obstetric care increased from 44% to 61% while the direct obstetric case fatality rate declined from 1.8% to 1.4%. The institutional maternal mortality ratio across all health facilities declined from 303 to 174 deaths per 100,000 live births. The total stillbirth rate declined from 26.7 to 12.8 per 1,000 births. The predischarge neonatal mortality rate declined from 10.7 to 7.6 per 1,000 live births. Changes in case fatality rate and maternal mortality were driven by project-supported facilities. Changes in neonatal mortality varied depending on facility type and program support status. CONCLUSION: Decentralizing high-quality comprehensive EmONC delivered mostly by associate clinicians and nurses led to significant improvements in the availability and utilization of lifesaving care at birth in Kigoma. Dedicated efforts to sustain high-quality EmONC along with supplemental programmatic components contributed to the reduction of maternal and perinatal mortality.

Improving Maternal and Reproductive Health in Kigoma, Tanzania: A 13-Year Initiative.

The Program to Reduce Maternal Deaths in Tanzania was a 13-year (2006-2019) effort in the Kigoma region that evolved over 3 phases to improve and sustain the availability of, access to, and demand for high-quality maternal and reproductive health care services. The Program intended to bring high-quality care closer to more communities. Cutting across the Program was the routine collection of monitoring and evaluation data. The Program achieved significant reductions in maternal and perinatal mortality, a significant increase in the modern contraceptive prevalence rate, and a significant decline in the unmet need for contraception. By 2017, it was apparent that the Program was on track to meet or surpass many of the targets established by the Government of Tanzania. Over the following 2-plus years, efforts to sustain Program interventions intensified. In April 2019, the Program fully transitioned to Government of Tanzania oversight. Four key lessons were learned during implementation that are relevant to governments, donors, and implementing organizations working to reduce maternal mortality: (1) multistakeholder partnerships are critical; (2) demand creation for services, while critical, must rest on a foundation of well-functioning and high-quality clinical services; (3) it is imperative to not only collect robust monitoring and evaluation data, but to be responsive in real time to what the data reveal; and, (4) it is necessary to develop a deliberate sustainability strategy from the start. The Program in Kigoma demonstrates that decentralizing high-quality maternal and reproductive health services in remote, low-resource settings is both feasible and effective and should be considered in places with similar contexts. By embedding the Program in the existing health system, and through efforts to build local capacity, the improvements seen in Kigoma are likely to be sustained. Follow-up evaluations are planned, providing an opportunity to more directly assess sustainability.

Camp Nursing: A Unique Specialty.

ABSTRACT: Camp nursing offers a unique opportunity for nurses to invest their skills in a novel setting. Nurses fill an essential role in the camp environment and have opportunities to practice a wide variety of tasks with diverse populations of children and teens. The purpose of this article is to inform potential camp nurses of the skill set and aptitudes most inclined to ensure a successful and satisfying camp nursing experience. Serving at a Christian camp also allows nurses to reflect Christ and invest in the faith journey of campers and staff.

Collecting Biospecimens and Obtaining Biobank Consent From Patients in an Academic Health Care Setting: Practical and Ethical Considerations.

Academic health centers and health systems increasingly ask patients to enroll in research biobanks as part of standard care, raising important practical and ethical questions for integrating biobank consent processes into health care settings. This article aims to assist academic health centers and health systems considering implementing these integrated consent processes by outlining the 5 main issues-and the key practical and ethical considerations for each issue-that Indiana University Health and the Indiana Biobank faced when integrating biobank consent into their health system, as well as the key obstacles encountered. The 5 main issues to consider include the specimen to collect (leftover, new collection, or add-ons to clinical tests), whether to use opt-in or opt-out consent, where to approach patients, how to effectively use digital tools for consent, and how to appropriately simplify consent information.

Biobank Participants' Attitudes toward Requiring Understanding for Biobank Consent.

Biobank participants often do not understand the information they are provided during the informed consent process. Ethicists and other stakeholders have disagreed, however, on the appropriate response to these failures in understanding. This paper describes an attempt to address this issue by conducting knowledge tests with 22 recent biobank enrollees, followed by in-depth, semistructured interviews about the goal of understanding in biobank consent. The interviews revealed that while biobank enrollees thought the information on the knowledge test was important, they did not think that performance on the test should affect whether individuals are permitted to enroll in a biobank. Three main themes emerged from the interviews: helping others by contributing to research is more important than understanding consent forms, less understanding is required because biobank-based research is low risk, and only a small amount of information in the consent form is really essential. These perspectives should be considered in discussing the ethics and governance of biobank consent processes.

[Effects of SARS-CoV-2 Infection on Symptoms and Therapy of Inflammatory Bowel Disease]. / Auswirkungen einer SARS-CoV-2-Infektion auf Symptomatik und Therapie chronisch-entzündlicher Darmerkrankungen.

INTRODUCTION: The influence of a SARS-CoV-2 infection on inflammatory bowel disease (IBD) has not yet been well characterized and it is unclear whether this requires an adaptation of the immunosuppressive therapy. METHODS: A national register was established for the retrospective documentation of clinical parameters and changes in immunosuppressive therapy in SARS-CoV-2 infected IBD patients. RESULTS: In total, only 3 of 185 IBD patients (1.6 %) were tested for SARS-CoV-2 infection because of abdominal symptoms. In the course of COVID-19 disease, 43.5 % developed diarrhea, abdominal pain or hematochezia (risk of hospitalization with vs. without abdominal symptoms: 20.0 % vs. 10.6 %, p < 0.01). With active IBD at the time of SARS-CoV-2 detection, there was an increased risk of hospitalization (remission 11.2 %, active IBD 23.3 % p < 0.05). IBD-specific therapy remained unchanged in 115 patients (71.4 %); the most common change was an interruption of systemic therapy (16.2 %). DISCUSSION: New abdominal symptoms often appeared in SARS-CoV-2 infected IBD patients. However, these only rarely led to SARS-CoV-2 testing. A high IBD activity at the time of SARS-CoV-2 detection was associated with an increased risk of hospitalization.

Birth companionship in a government health system: a pilot study in Kigoma, Tanzania.

BACKGROUND: Having a companion of choice throughout childbirth is an important component of good quality and respectful maternity care for women and has become standard in many countries. However, there are only a few examples of birth companionship being implemented in government health systems in low-income countries. To learn if birth companionship was feasible, acceptable and led to improved quality of care in these settings, we implemented a pilot project using 9 intervention and 6 comparison sites (all government health facilities) in a rural region of Tanzania. METHODS: The pilot was developed and implemented in Kigoma, Tanzania between July 2016 and December 2018. Women delivering at intervention sites were given the choice of having a birth companion with them during childbirth. We evaluated the pilot with: (a) project data; (b) focus group discussions; (c) structured and semi-structured interviews; and (d) service statistics. RESULTS: More than 80% of women delivering at intervention sites had a birth companion who provided support during childbirth, including comforting women and staying by their side. Most women interviewed at intervention sites were very satisfied with having a companion during childbirth (96-99%). Most women at the intervention sites also reported that the presence of a companion improved their labor, delivery and postpartum experience (82-97%). Health providers also found companions very helpful because they assisted with their workload, alerted the provider about changes in the woman's status, and provided emotional support to the woman. When comparing intervention and comparison sites, providers at intervention sites were significantly more likely to: respond to women who called for help (p = 0.003), interact in a friendly way (p < 0.001), greet women respectfully (p < 0.001), and try to make them more comfortable (p = 0.003). Higher proportions of women who gave birth at intervention sites reported being "very satisfied" with the care they received (p < 0.001), and that the staff were "very kind" (p < 0.001) and "very encouraging" (p < 0.001). CONCLUSION: Birth companionship was feasible and well accepted by health providers, government officials and most importantly, women who delivered at intervention facilities. The introduction of birth companionship improved women's experience of birth and the maternity ward environment overall.

Layperson Views about the Design and Evaluation of Decision Aids: A Public Deliberation.

PURPOSE: We carried out the first public deliberation to elicit lay input regarding guidelines for the design and evaluation of decision aids, focusing on the example of colorectal ("colon") cancer screening. METHODS: A random, demographically stratified sample of 28 laypeople convened for 4 days, during which they were informed about key issues regarding colon cancer, screening tests, risk communication, and decision aids. Participants then deliberated in small and large group sessions about the following: 1) What information should be included in all decision aids for colon screening? 2) What risk information should be in a decision aid and how should risk information be presented? 3) What makes a screening decision a good one (reasonable or legitimate)? 4) What makes a decision aid and the advice it provides trustworthy? With the help of a trained facilitator, the deliberants formulated recommendations, and a vote was held on each to identify support and alternative views. RESULTS: Twenty-one recommendations ("deliberative conclusions") were strongly supported. Some conclusions matched current recommendations, such as that decision aids should be available for use with and without providers present (conclusions 1-4) and should support informed choice (conclusion 9). Some conclusions differed from current recommendations, at least in emphasis-for example, that decision aids should disclose cost of screening (conclusion 11) and should be kept simple and understandable (conclusion 14). Deliberants recommended that decision aids should disclose the baseline risk of getting colon cancer (conclusions 15, 17). LIMITATIONS: Single location and medical decision. CONCLUSIONS: Guidelines for design of decision aids should consider putting a greater focus on disclosing cost and keeping decision aids simple, and they possibly should recommend disclosing less extensive amounts of quantitative information than currently recommended.

Incorporating Biobank Consent into a Healthcare Setting: Challenges for Patient Understanding.

BACKGROUND: Biobank participants often do not understand much of the information they are provided as part of the informed consent process, despite numerous attempts at simplifying consent forms and improving their readability. We report the first assessment of biobank enrollees' comprehension under an "integrated consent" process, where patients were asked to enroll in a research biobank as part of their normal healthcare experience. A number of healthcare systems have implemented similar integrated consent processes for biobanking, but it is unknown how much patients understand after enrolling under these conditions. Methods: We recruited patients who enrolled in a biobank while in a healthcare setting when receiving ordinary care. We assessed knowledge of consent materials using 11 true/false questions drawn from a well-known biobank knowledge test. After reviewing the results from 114 participants, we revised the consent form and repeated the knowledge assessment with 144 different participants. Results: Participants scored poorly on the knowledge test in both rounds, with no significant differences in overall scores or individual items between the rounds. In Phase 1, participants answered 53% of the questions correctly, 25% incorrectly, and 22% "I don't know." In Phase 2, participants answered 53% of questions correctly, 24% incorrectly, and 23% "I don't know." Participants scored particularly poorly on questions about data sharing and accessing medical records. Conclusions: Enrollees under an integrated consent model had significant misunderstandings that persisted despite an attempt to improve information specifically about those topics in a consent form. These results raise challenges for current approaches that attribute misunderstanding to overly complex consent forms. They also suggest that the pressures of the clinic may compound other problems with patient understanding of biobank consent. As health systems increasingly blend research and care, they may need to rethink their approach to educating patients about participation in a biobank.

Thumb sucking or nail biting in childhood and adolescence is associated with an increased risk of Crohn's disease: results from a large case-control study.

BACKGROUND: The hygiene hypothesis suggests that a reduction in microbial exposure contributes to an impaired immune response later in life and increases the incidence of immune-mediated diseases such as inflammatory bowel diseases (IBD). Thumb sucking and nail biting are two early habits that modulate the oral microbiota composition and antigen load. OBJECTIVE: We hypothesized a lower risk of Crohn's disease (CD) and ulcerative colitis (UC) in adults with prior thumb sucking and nail biting. METHODS: 918 IBD cases and their 918 siblings without IBD were asked to fill out a survey containing 32 questions on environmental factors in childhood and early adulthood. Prevalence of thumb sucking and/or nail biting at the usually well-remembered time of (1) school enrollment and (2) coming-of-age ceremonies was the predefined combined risk factor of this study. RESULTS: 65% of the patients were female and 57% suffered from CD. About 49% of IBD patients but only 44% of their siblings reported thumb sucking/nail biting at the time of school enrollment or coming-of-age (p = .007). Sensitivity analysis revealed that this difference was observed in patients with CD (50% versus 41%; RR= 1.22; 95% CI 1.09-1.37, p = .001) but not in patients with UC (49% versus 48%; RR= 1.02; 95% CI 0.90-1.17; p = .83). CONCLUSION: Contrary to our expectation and challenging the hygiene hypothesis, we found that common oral habits are not protective against IBD. Instead, nail biting at the time of school enrollment and coming-of-age was a statistically significant risk factor for CD in our cohort. Key summary Evidence available before this study: The hygiene hypothesis suggests that a reduction in microbial exposure due to improved health activities has contributed to an immunological imbalance in the intestine and an increased incidence of allergic and autoimmune diseases. A population-based birth cohort study has demonstrated that thumb-sucking and nail biting in children lead to a reduction of the risk of atopic sensitization, asthma, and hay fever. Added value of this study: Contrary to the hypothesis, thumb sucking and nail biting were not associated with a reduced risk of IBD. Instead, thumb sucking and/or nail biting at the usually well-remembered points in time of school enrollment and of religious or secular coming-of-age ceremonies was associated with a higher risk of Crohn's disease but not of ulcerative colitis. Our data did not support the hygiene hypothesis, one pathogenic concept in the context of IBD.