Multidecadal mangrove forest change in Macajalar Bay, Northern Mindanao, Philippines (1950-2020) using remote sensing and geographic information systems.

The mangrove forest in Macajalar Bay is regarded as an important coastal ecosystem since it provides numerous ecosystem services. Despite their importance, the clearing of mangroves has been rampant and has reached critical rates. Addressing this problem and further advancing its conservation require accurate mangrove mapping. However, current spatial information related to mangroves is sparse and insufficient to understand the historical change dynamics. In this study, the synergy of 1950 vegetation maps and Landsat images was explored to provide multidecadal monitoring of mangrove forest change dynamics in Macajalar Bay, Philippines. Vegetation maps containing the 1950 mangrove extent and Landsat images were used as input data to monitor the rates of loss over 70 years. In 2020, the mangrove forest cover was estimated to be 201.73 ha, equivalent to only 61.99% of the 325.43 ha that was estimated in 1950. Between 1950 and 2020, net mangrove loss in Macajalar Bay totaled 324.29 ha. The highest clearing rates occurred between 1950 and 1990 when it recorded a total of 258.51 ha, averaging 6.46 ha/year. The original mangrove forest that existed in 1950 only represents 8.56% of the 2020 extent, suggesting that much of the old-growth mangrove had been cleared before 2000 and the existing mangrove forest is mainly composed of secondary mangrove forest stands. Across Macajalar Bay, intensified clearing that happened between 1950 and 1990 has been driven by large-scale aquaculture developments. Mangrove gains on the other hand were evident and have increased the total extent by 79.84 ha since 2000 as a result of several afforestation programs. However, approximately half of these gains that were observed since 2010 exhibited low canopy cover. As of writing, approximately 85% of the 2020 mangrove forest stands fall outside the 1950 original mangrove extent. Examining the viability of the original mangrove forest for mangrove reforestation together with promoting site-species matching, and biophysical assessment are necessary undertakings to advance current mangrove conservation initiatives in Macajalar Bay.

Towards equitable representation in long-term residential care: widening the circle to ensure "essential voices" in research teams.

The COVID-19 pandemic exposed long-standing inequities in Canada's long-term residential care (LTRC) sector with life-threatening consequences. People from marginalized groups are overrepresented among those who live in, and work in LTRC facilities, yet their voices are generally silenced in LTRC research. Concerns about these silenced voices have sparked debate around ways to change LTRC policy to better address long-standing inequities and enhance the conditions that foster dignity for those who live and work in LTRC. Weaving an analysis of historical and cultural attitudes about LTRC, and promising strategies for engaging people with lived experience, we argue that the voices of people with lived experience of life and work (paid and unpaid) in LTRC are essential for ethically and effectively shifting long-standing inequities. Lessons from a 4-year, national, multi-disciplinary research study, known as the Seniors Adding Life to Years (SALTY) project, suggest that resident-determined quality of life can be prioritized by centring the perspectives of residents, their family/friends, direct care workers, volunteers, and people living with dementia in the research process. Accordingly, we highlight strategies to include these voices so that meaningful and impactful system change can be realized.

This article argues that long-term residential care facilities in Canada have a long history of perpetuating social inequalities, beginning with seventeenth century poor houses and almshouses, from which long-term residential care facilities evolved in North America. We highlight that those who currently reside in long-term residential care are more likely to be people with less social power­for example women, people living with dementia, and people with low-income. These residents are rarely included in research projects as co-designers of research, co-producers of knowledge, or experts on the realities of long-term residential care. We explore strategies for addressing these underrepresented voices and inequalities in research by highlighting promising examples of resident, family, and worker-engagement emerging from a pre-pandemic to early pandemic pan-Canadian research project on quality of life in long-term residential care. We argue that long-term residential care residents, their family/friend caregivers, people living with dementia, and direct care workers have voices that are essential in residential care design and research engagement strategies. By prioritizing these voices in research, we can better amplify their critical perspectives in broader policy and decision-making processes that guide meaningful and impactful system change.

Psychometric Evaluation of an Adapted Short-Form Spirituality Scale in a Sample of Predominantly White Adults in an Inpatient Substance Use Disorder Treatment Program.

Spirituality is an important aspect of treatment and recovery for substance use disorders (SUDs), but ambiguities in measurement can make it difficult to incorporate as part of routine care. We evaluated the psychometric properties of an adapted short-form version of the Spirituality Scale (the Spirituality Scale-Short-Form; SS-SF) for use in SUD treatment settings. Participants were adult patients (N = 1,388; Mage = 41.23 years, SDage = 11.55; 68% male; 86% White) who entered a large, clinically mixed inpatient SUD treatment program. Factor analysis supported the two-dimensional structure, with factors representing Self-Discovery and Transcendent Connection. Tests of measurement invariance demonstrated that the scale was invariant across age and gender subgroups. The SS-SF exhibited convergent and concurrent validity via associations with participation in spiritual activities, hopefulness, life satisfaction, 12-step participation, and depressive symptoms. Finally, scores on the SS-SF were significantly higher at discharge compared to admission, demonstrating short-term sensitivity to change. These findings support use of the SS-SF as a concise, psychometrically sound measure of spirituality in the context of substance use treatment.

Understanding Collective Human Behavior in Social Media Networks Via the Dynamical Hypothesis: Applications to Radicalization and Conspiratorial Beliefs.

The dynamical hypothesis has served to explore the ways in which cognitive agents can be understood dynamically and considered dynamical systems. Originally used to explain simple physical systems as a metaphor for cognition (i.e., the Watt governor) and eventually more complex animal systems (e.g., bird flocks), we argue that the dynamical hypothesis is among the most viable approaches to understanding pressing modern-day issues that arise from collective human behavior in online social networks. First, we discuss how the dynamical hypothesis is positioned to describe, predict, and explain the time-evolving nature of complex systems. Next, we adopt an interdisciplinary perspective to describe how online social networks are appropriately understood as dynamical systems. We introduce a dynamical modeling approach to reveal information about emergent properties in social media, where radicalized conspiratorial beliefs arise via coordination between user-level and community-level comments. Lastly, we contrast how the dynamical hypothesis differs from alternatives in explaining collective human behavior in social networks.

Suicide-related care among patients who have experienced an opioid-involved overdose.

OBJECTIVE: Our objective was to describe suicide prevention care for individuals prescribed opioids or with opioid use disorder (OUD) and identify opportunities for improving this care. METHODS: Adult patients (n = 65) from four health systems with an opioid-involved overdose and clinicians (n = 21) who had contact with similar patients completed 30-60-min semi-structured interviews. A community advisory board contributed to development of all procedures, and interpretation and summary of findings. RESULTS: Patients were mostly female (59%), White (63%) and non-Hispanic (77%); 52 were prescribed opioids, 49% had diagnosed OUD, and 42% experienced an intentional opioid-involved overdose. Findings included: 1) when prescribed an opioid or treated for OUD, suicide risks were typically not discussed; 2) 35% of those with an intentional opioid-involved overdose and over 80% with an unintentional overdose reported no discussion of suicidal ideation when treated for the overdose; and 3) suicide-related follow-up care was uncommon among those with unintentional overdoses despite suicidal ideation being reported by >20%. Clinicians reported that when prescribing opioids or treating OUD, post-overdose suicide-related screening or counseling was not done routinely. CONCLUSIONS: There were several opportunities to tailor suicide prevention care for patients who were treated for opioid-involved overdoses within health systems.

Understanding Nursing Workplace Violence Trends for Safer Clinical Oncology Settings.

BACKGROUND: Workplace violence (WPV) against nursing professionals by patients and visitors occurs frequently, and rates of WPV increased during the COVID-19 pandemic. All nursing teams, including oncology nursing professionals, are at risk for WPV and need current WPV-related information applicable to their clinical experiences. OBJECTIVES: This overview aims to increase awareness of trends and personal safety issues related to clinical oncology nursing practice and provide strategies and resources to enhance personal safety in nursing practice. METHODS: This overview used literature reviews, publicly reported sources, other scholarly resources, and real-world examples to identify and synthesize WPV trends related to clinical nursing. FINDINGS: This overview's findings suggest that the COVID-19 pandemic contributed to the increased rate of WPV and subsequent harm to nursing staff victims. Oncology nursing professionals can implement best practices to reduce their risk of being harmed, and healthcare institutions can operationalize best practices by having systems and resources in place that prevent and mitigate WPV.

Centers for Disease Control and Prevention Harvard Program Evaluation Practicum: 10 Years of Partnership in Public Health Program Evaluation.

The Centers for Disease Control and Prevention (CDC)'s Division of Reproductive Health and Harvard T.H. Chan School of Public Health (HSPH) Program Evaluation Practicum (CDC/HSPH Practicum) is a mutually beneficial workforce development partnership formed to provide state, local, and tribal public health organizations with an evaluation plan for a maternal and child health (MCH) program. State, local, and tribal public health organizations submit an MCH program in need of evaluation for inclusion consideration. Student pairs are matched with the selected programs in a 3-week practical field-based experience. This Practicum provides didactic training for both program staff and students followed by field work at the public health organizations. Students provide organizations with comprehensive evaluation plans, complete with logic model, methodology, and indicators. Since the Practicum's inception in 2013, 104 HSPH graduate students have been trained and 30 states and 1 territory have participated and received evaluation plans for their MCH programs. The utility and importance of the CDC/HSPH Practicum is evidenced by program staff and student feedback. Multiple states have implemented the plans designed by the students, with some evaluations leading to program enhancements. The CDC/HSPH Practicum prepares students for the workforce and adds much needed capacity to public health organizations by providing them with evaluation knowledge and skills, and usable evaluation plans to improve MCH-a win-win for all.

Can alcohol policy prevent harms to women and children from men's alcohol consumption? An overview of existing literature and suggested ways forward.

The World Health Organization's list of cost-effective alcohol control policies is a widely-used resource that highlights strategies to address alcohol-related harms. However, there is more evidence on how recommended policies impact harms to people who drink alcohol-such as physical health problems caused by heavy alcohol use-than on secondhand harms inflicted on someone other than the person drinking alcohol, i.e., alcohol's harms to others. In this essay, we describe evidence of impacts of alcohol policy on harms to women and children resulting from men's alcohol consumption, as well as options for making policies more relevant for reducing intimate partner violence and child abuse. We begin with an overview of harms to women and children resulting from men's alcohol consumption and review cost-effective alcohol policies with potential to reduce these harms based on likely mechanisms of action. Next, we present a rapid review of reviews to describe existing evidence of impacts of these policies on the outcomes of physical violence, sexual violence, and child abuse and neglect. We found little evidence of systematic evaluation of impacts of these important alcohol policies on harms to women and children. Thus, we advocate for increased attention in evaluation research to the impacts of alcohol policies on harms experienced by women and children who are exposed to men who drink alcohol. We also argue for more consideration of a broader range of policies and interventions to reduce these specific types of harm. Finally, we present a conceptual model illustrating how alcohol policies may be supplemented with other interventions specifically tailored to reduce alcohol-related harms commonly experienced by women and children as a result of men's alcohol use.

The Clinical Relevance of Impulsivity in Substance Use Disorder Treatment: Examining Within-Treatment Changes and Relationship to Psychiatric Symptoms and Cravings in a Large Inpatient Sample.

OBJECTIVE: Impulsivity is a multidimensional construct consistently associated with problematic substance use, but less is known about its relevance to clinical outcomes. The current study examined whether impulsivity changed over the course of addiction treatment and whether the changes were associated with changes in other clinical outcomes. METHOD: Participants were patients in a large inpatient addiction medicine program (N = 817; 71.40% male). Impulsivity was assessed using a self-report measure of delay discounting (i.e., overvaluation of smaller immediate rewards) and the UPPS-P Impulsive Behavior Scale, a self-report measure of impulsive personality traits. Outcomes were psychiatric symptoms including depression, anxiety, posttraumatic stress disorder, and drug cravings. RESULTS: Within-subjects analyses of variance revealed significant within-treatment changes in all UPPS-P subscales, all psychiatric indicators, and craving (ps < .005), but not delay discounting. Changes in all UPPS-P traits, except for sensation seeking, were significantly positively associated with changes in psychiatric symptoms and cravings over the course of treatment (ps < .01). CONCLUSIONS: These findings reveal that facets of impulsive personality change across addiction treatment and are generally related to positive changes in other clinically relevant outcomes. Evidence of change despite no explicit intervention targeting suggests that impulsive personality traits may be viable treatment targets in substance use disorder treatment.

Reframing Cognitive Science as a Complexity Science.

Complexity science is an investigative framework that stems from a number of tried and tested disciplines-including systems theory, nonlinear dynamical systems theory, and synergetics-and extends a common set of concepts, methods, and principles to understand how natural systems operate. By quantitatively employing concepts, such as emergence, nonlinearity, and self-organization, complexity science offers a way to understand the structures and operations of natural cognitive systems in a manner that is conceptually compelling and mathematically rigorous. Thus, complexity science both transforms understandings of cognition and reframes more traditional approaches. Consequently, if cognitive systems are indeed complex systems, then cognitive science ought to consider complexity science as a centerpiece of the discipline.

Hematopoietic stem cells preferentially traffic misfolded proteins to aggresomes and depend on aggrephagy to maintain protein homeostasis.

Hematopoietic stem cells (HSCs) regenerate blood cells throughout life. To preserve their fitness, HSCs are particularly dependent on maintaining protein homeostasis (proteostasis). However, how HSCs purge misfolded proteins is unknown. Here, we show that in contrast to most cells that primarily utilize the proteasome to degrade misfolded proteins, HSCs preferentially traffic misfolded proteins to aggresomes in a Bag3-dependent manner and depend on aggrephagy, a selective form of autophagy, to maintain proteostasis in vivo. When autophagy is disabled, HSCs compensate by increasing proteasome activity, but proteostasis is ultimately disrupted as protein aggregates accumulate and HSC function is impaired. Bag3-deficiency blunts aggresome formation in HSCs, resulting in protein aggregate accumulation, myeloid-biased differentiation, and diminished self-renewal activity. Furthermore, HSC aging is associated with a severe loss of aggresomes and reduced autophagic flux. Protein degradation pathways are thus specifically configured in young adult HSCs to preserve proteostasis and fitness but become dysregulated during aging.

Should we Target Complete Endoscopic Healing in Patients with Acute Severe Ulcerative Colitis?

BACKGROUND: Achieving endoscopic healing is a recommended target in ulcerative colitis [UC]. However, little is known about desirable goals in patients with acute severe UC [ASUC]. Taking advantage of the long-term follow-up of clinical trial patients with steroid-refractory ASUC, the present analysis aimed to quantify the observed association between the Mayo endoscopic sub-score [MES], 0 or 1, at clinical trial end and patients' long-term disease outcome. METHODS: Patients in the prospective CYSIF clinical trial were included in the present analysis if they had achieved steroid-free clinical remission with an MES of 0 or 1 at the end of the trial, at day 98. Events during long-term follow-up had been retrospectively collected. The primary endpoint for this complementary analysis was the occurrence of an event, death or disease relapse [defined by recurrence of symptoms with need for a new systemic treatment or colectomy]. RESULTS: Forty-four patients were included in the present analysis. When censoring follow-up at 5 years, six and nine events were observed among 26 and 18 patients having an MES of 0 and 1, respectively. Survival without disease relapse at 1, 2 and 5 years was respectively 88 ±â€…6, 81 ±â€…8 and 77 ±â€…8% in patients with MES of 0, and 72 ±â€…11, 53 ±â€…12 and 46 ±â€…12% in those with MES of 1 [hazard ratio: 2.8; 95% confidence interval: 1.0-8.0; p = 0.042]. CONCLUSION: In a cohort of patients admitted for ASUC in whom clinical and endoscopic healing has been achieved with a second-line medical therapy, better survival without disease relapse was observed with complete endoscopic healing.

With COVID Comes Complexity: Assessing the Implementation of Family Visitation Programs in Long-Term Care.

BACKGROUND AND OBJECTIVES: Coronavirus disease 2019 (COVID-19) pandemic visitor restrictions to long-term care facilities have demonstrated that eliminating opportunities for family-resident contact has devastating consequences for residents' quality of life. Our study aimed to understand how public health directives to support family visitations during the pandemic were navigated, managed, and implemented by staff. RESEARCH DESIGN AND METHODS: Guided by the Consolidated Framework for Implementation Research, we conducted video/telephone interviews with 54 direct care and implementation staff in six long-term care homes in two Canadian provinces to assess implementation barriers and facilitators of visitation programs. Equity and inclusion issues were examined in the program's implementation. RESULTS: Despite similar public health directives, implementation varied by facility, largely influenced by the existing culture and processes of the facility and the staff understanding of the program; differences resulted in how designated family members were chosen and restrictions around visitations (e.g., scheduling and location). Facilitators of implementation were good communication networks, leadership, and intentional planning to develop the visitor designation processes. However, the lack of consultation with direct care staff led to logistical challenges around visitation and ignited conflict around visitation rules and procedures. DISCUSSION AND IMPLICATIONS: Insights into the complexities of implementing family visitation programs during a pandemic are discussed, and opportunities for improvement are identified. Our results reveal the importance of proactively including direct care staff and family in planning for future outbreaks.

Childhood Lead Poisoning 1970-2022: Charting Progress and Needed Reforms.

CONTEXT: Childhood lead poisoning prevention in the United States was marked by a largely failed medical approach from 1971 to 1990; an emergent (but small) healthy housing primary prevention strategy from 1991 to 2015; and implementation of large-scale proven interventions since then. PROGRAM: Childhood Lead Poisoning Prevention & Healthy Housing. METHODS: Historic and recent health and housing data from the National Health and Nutrition Examination Survey (NHANES) and the American Healthy Homes Survey (AHHS) were retrieved to analyze trends and associated policy gaps. EVALUATION: Approximately 590 000 US children aged 1 through 5 years had elevated blood lead levels of 3.5 µg/dL and greater in 2016, and 4.3 million children resided in homes with lead paint in 2019. Despite large improvements, racial and other disparities remain stubbornly and statistically significant. The NHANES and the AHHS require larger sample sizes. The Centers for Disease Control and Prevention has not published children's blood lead surveillance and NHANES data in several years; the Department of Housing and Urban Development (HUD) has no analogous housing surveillance system; and the Environmental Protection Agency (EPA) and the Occupational Safety and Health Administration (OSHA) have not updated training, Superfund, and occupational standards in decades. DISCUSSION: The nation has been without a plan and an associated budget for more than 2 decades. Congress has not reformed the nation's main lead poisoning prevention laws in more than 30 years. Such reforms include stopping US companies from producing new residential lead paint in other countries; enabling the disclosure law to identify all residential lead hazards; closing loopholes in federally assisted housing regulations and mortgage insurance standards; harnessing tax policy to help homeowners mitigate lead hazards; streamlining training requirements; increasing the size of health and housing surveys and surveillance systems; and updating housing codes, medical guidance, dust lead standards, training, Superfund, and worker exposure limits. Congress and the president should reauthorize a cabinet-level task force (dormant since 2010) to develop a new strategic plan with an interagency budget to implement it. These reforms will scale and optimize markets, subsidies, enforcement, and other proven interventions to end ineffective, costly, harmful, and irrational cost shifting that threatens children, workers, and affordable housing.

Lipschutz Ulcers in an Adolescent After Sars-CoV-2 Infection.

This case report describes a 15-year-old female who presented with acute onset of painful genital ulcers. She denied being sexually active and tested positive for severe acute respiratory coronavirus 2 five days prior. Associated symptoms on days 1 to 3 included fatigue, nausea, headaches, and fever. Lipschutz ulcers (LUs), also known as aphthous ulcers, acute genital ulcers, and acquired genital ulcerations; are an uncommon, self-limiting, nonsexually transmitted condition characterized by the rapid onset of painful, necrotic ulcerations of the vulva or lower vagina. The pathogenesis of LUs is unclear, and the diagnosis is one of exclusion.

Hepatitis B prevalence and associated factors in adults presenting for infection screening in northern Thailand.

Background and aims: Hepatitis B is a leading cause of morbidity and mortality worldwide. In view of the World Health Organization 2030 targets, effective screening of chronic infection is crucial. We have assessed the prevalence and risk factors of hepatitis B surface antigen in adults presenting for screening. Methods: Free-of-charge and anonymous services for simultaneous hepatitis B, hepatitis C, human immunodeficiency virus and syphilis screening and counseling were provided in four facilities in northern Thailand. Analyses were performed separately in clients born before integration into the 1992 hepatitis B vaccine Thailand's Expanded Program on Immunization and in clients born afterwards. Results: Between October 2015 and August 2020, hepatitis B surface antigen prevalence was 7.2 % (185/2578) in clients born before 1992 (95 % confidence interval [CI] = 6.2%-8.2 %). In the multivariable analysis, characteristics independently associated with a higher risk of infection were being born male (adjusted odds ratio [aOR] = 1.49, 95 % CI = 1.10-2.01) and being part of a hill tribe (aOR = 1.65, 95 % CI = 1.01-2.70). Forty-two percent were unaware of their infection. In clients born in 1992 or afterwards, prevalence was 1.5 % (43/2933) (95 % CI = 1.1%-2.0 %) and characteristics independently associated with a higher risk were being born between 1992 and 1995 (aOR = 1.90, 95 % CI = 1.00-3.61), being born male (aOR = 2.60, 95 % CI = 1.34-5.07), being part of a hill tribe (aOR = 5.09, 95 % CI = 2.52-10.26) and having ever injected drugs (aOR = 4.33, 95 % CI = 1.23-15.24). Conclusions: Risk factor-based screening would miss many chronic hepatitis cases. Screening all adults once in their lifetime may be beneficial until the second generation of immunized infants have reached adult age.

Uptake, acceptability and interpretability of 3-in-1 rapid blood self-testing for HIV, hepatitis B and hepatitis C.

INTRODUCTION: Early diagnosis is key to achieving the goal of eliminating transmission of HIV and hepatitis B and C. We assessed the uptake, acceptability and interpretability of self-testing using a 3-in-1 rapid diagnostic test (RDT) in facility-based services. METHODS: Stand-alone testing services were provided free of charge to consenting individuals aged ≥15 years in five facilities in northern Thailand. Clients were invited to choose between self-testing by fingerprick or venepuncture by a healthcare worker (HCW). In each facility, several clients could simultaneously self-test in separate private areas using TriQuik™ (Genlantis, San Diego, CA, USA), a single immunochromatographic cassette detecting HIV-1/2 antibody, hepatitis B surface antigen (HBsAg) and hepatitis C antibody (HCAb). An interactive program on a tablet computer was developed to collect socio-demographic, behavioural and satisfaction data and provide information to guide the self-test process, including video instructions, results interpretation and a picture of the cassette for immediate remote review by the HCW. When the HCW interpreted an HIV self-test as positive, the HCW collected blood by venepuncture for immediate confirmation. RESULTS: Between October 2020 and April 2022, 4119 clients presented for testing for the first time as part of the project. Of them, 3462 (84.0%) opted for self-testing. Among self-testers, 1801 (52.0%) were born female, the median age was 27 years (interquartile range, 22-36), 661 (19.1%) belonged to at least one key population and 2124 (61.4%) had never been tested for HIV; 3329 (99.8% of those who answered) reported being "very satisfied" or "satisfied" with the testing process. The proportions of test results interpreted as positive by self-testers among those interpreted as positive by HCWs were 95% for HIV-1/2 antibody, 95% for HBsAg and 78% for HCAb. CONCLUSIONS: These proportions were higher than those observed in a previous study evaluating another 3-in-1 RDT for HIV, HBsAg and HCAb, possibly due to the use of video instructions instead of paper-based instructions, lower prevalence and co-infection rates, or lower percentages of clients with low education level. Multiplex self-testing simplified and streamlined the service delivery process and was well accepted. HCW assistance proved to be essential in a limited number of cases.

Ethical and regulatory issues of stem cell-derived 3-dimensional organoid and tissue therapy for personalised regenerative medicine.

BACKGROUND: Regenerative medicine has the potential to treat genetic disorders and replace damaged or missing tissue. The use of donor or animal tissue raises many well-known issues, including limited tissue availability, the possibility of rejection and patient infection. Stem cell therapy raised hope of overcoming these issues, but created new risks including tumour formation and limited benefit if the desired target tissue does not form. The recent development of 3-dimensional tissues, including organoids, allows the creation of more complex tissues for personalised regenerative medicine. METHODS: This article details the potential health risks of 3-dimensional organoid and tissue therapy versus dissociated stem cell therapy. The current ethical and regulatory issues surrounding 3-dimensional organoid and tissue therapy are presented with a focus on the highly influential FDA and International Society of Stem Cell Research (ISSCR) guidelines. CONCLUSIONS: The potential use of 3-dimensional organoid and tissue therapy may deliver greater patient benefits than other regenerative medicine approaches, but raises new health and ethical risks. Preclinical testing of these therapies will not mitigate some of their risks; they may only be understood after first-in-human trials. The potential irreversibility and high risk of these therapies affects how clinical trials should be structured, including post-trial care for participants.