Effectively integrating depression treatment into HIV care in low-resource settings will require substantially investing in program supervision, building and maintaining the capacity of providers, integrating into existing electronic medical records systems, and ensuring the availability of psychotherapy counselors. Early evaluations of integrating a depression management program using antidepressants and psychotherapy into HIV clinics in Malawi found that depression screening, diagnosis, and treatment initiation were successfully integrated.A follow-up evaluation found that treatment over time was not delivered as intended, clinic staff had mixed attitudes regarding program acceptability, and the program was not sustained.Antidepressants and problem-solving therapy were acceptable evidence-based depression treatments for patients, but clinic staff found delivering these treatments challenging given constrained human resources and infrastructure.Delivery challenges included difficulties identifying and reassessing patients, negative attitudes, lack of integration into the electronic medical records system, medication stock-outs, staff and space availability, cost of transport, generally low retention, and reliance on study staff.Program managers need to invest in program supervision, build and maintain the capacity of providers, integrate into existing electronic medical records systems, and ensure the availability of psychotherapy counselors to more effectively integrate depression treatment into HIV care in these types of settings. Depression is highly prevalent among people living with HIV in Malawi. Depression can undermine engagement in HIV care and worsen HIV morbidity and mortality. The Ministry of Health integrated a pilot depression management program into HIV care at 2 clinics. This program included a measurement-based care protocol for prescribing antidepressants and an adapted Friendship Bench psychotherapy protocol for providing problem solving. Early evaluations indicated successful integration of the initial stages of training and depression screening, diagnosis, and treatment initiation. This follow-up mixed-method investigation contextualizes our previous findings and shares insights from the implementation experience.We conducted a mixed-methods process evaluation drawing on both patient clinical data and qualitative interviews with patients and clinic staff. We focus on the following implementation outcomes: fidelity, acceptability, and sustainability.Although fidelity to depression screening and treatment initiation was high, fidelity to the follow-up treatment protocol was poor. Antidepressants and problem-solving therapy were acceptable to patients, but clinic staff found delivering treatment challenging given constrained human resources and infrastructure. The program was not sustained after the project. Key identified needs included substantial support to supervise the implementation of the program, continue to build and maintain the capacity of providers, integrate the program into the electronic medical records system, and ensure the availability of Friendship Bench counselors.Although initial steps were successful, sustained integration of this depression treatment program into HIV care in this setting met greater challenges. Implementation science studies that support both implementation and evaluation should recognize the potential for clinical implementers to rely on evaluation staff for clinical support and consider distancing evaluation staff from the actual program implementation. Further research is needed to test enhanced implementation strategies for integrating evidence-based mental health interventions into existing health care systems in a sustainable fashion, particularly in low-resource settings. The intervention launched at Clinic A in November 2017 and at Clinic B in April 2018. These public facilities provide services free of charge and encompass an ART clinic or department. Approximately 25 nurses and clinicians provide ART services at each site, although staff turnover is high. Only 1 facility employs a psychiatric nurse who does not regularly offer psychiatric services. Private mental health care specialists irregularly offer mental health clinic days at the facilities. Otherwise, patients can be referred to the psychiatric department at the district hospital. Further details on the health facilities are available in previous publications.–HIV testing and counseling (HTC) counselors and ART providers were trained to conduct depression screening of patients when they were newly initiating ART by using the Patient Health Questionnaire-9 (PHQ-9), a 9-item screening questionnaire that has been widely used in the region.HTC counselors and ART providers were trained to conduct depression screening of patients newly receiving ART and to refer them for antidepressants or counseling as needed.,,,Supplementary Material 1). A standard course of antidepressants should consist of at least 3 consecutive months of antidepressant prescription with dosage adjustments as necessary.For patients with moderate to severe depression (PHQ-9 score ≥10), ART providers were trained to treat them with antidepressants (amitriptyline or fluoxetine) using MBC . MBC is ,For patients with mild depression (PHQ-9 score 5–9), ART providers were trained to refer them to clinic-based community health workers  who were trained to provide Friendship Bench problem-solving therapy . FriendsThroughout the program implementation, the study coordinator held bimonthly meetings at each site to support clinic staff and leadership deliver the program. However, the study staff were otherwise not meant to assist in the provision of daily clinical care and were only meant to consent patients and abstract their clinical data. Before the conclusion of the program evaluation, the study coordinator worked with the health facility staff and leadership to transition ownership of the program entirely to the health facilities. As such, the HIV providers were to continue screening and treating patients according to the Friendship Bench and MBC protocols after the conclusion of the study evaluation. Previous publications provide further details on the program design,Before the program evaluation concluded, ownership of the program transitioned to the health facilities.,After the launch of the intervention, all nonpregnant adults newly initiating ART were exposed to the program and eligible to participate in the program evaluation. Between April 2017 and November 2018 at Clinic A and between April 2018 and November 2018 at Clinic B, study staff approached potential participants during the ART initiation process to invite them to allow their clinical data to be used in the program evaluation. Study staff abstracted sociodemographic information as well as data on depression and HIV care from consenting participants’ clinical records over a 13-month period, starting at ART initiation. Again, further details on enrollment in the program evaluation, clinical data abstraction, and the measures captured have been previously published.–In-depth interviews were conducted between June and December 2018 with the following objectives: (1) explore providers’ and patients’ attitudes toward and experiences with the depression treatment intervention; (2) understand barriers and facilitators to integrating depression treatment into HIV care; and (3) prepare for the long-term sustainability of the program after the conclusion of the program evaluation. The qualitative interviews were conducted with a convenience sample of patients returning for ART care. Patients were eligible to participate if they had previously been identified with depression at ART initiation and either referred to the Friendship Bench or prescribed antidepressants. Additionally, a convenience sample of ART providers, Friendship Bench counselors, and clinic leadership were also interviewed. Before data collection, study staff met with the administrators at both health centers and drew up a list of staff. The study coordinator or interviewer approached staff and leadership at the clinic to schedule interviews. The study staff identified eligible patients returning for ART services and invited these patients to participate. An effort was made to interview a range of men and women because prior research showed that attitudes toward depression and the provision of mental health care may vary by the gender of both providers and patients.Interviews were conducted to explore attitudes towards the depression treatment intervention and the barriers and facilitators to integrating the treatment into HIV care.,After reviewing the transcripts, the author (MS) drafted a thematic codebook that would address the study objectives and capture emerging themes evident from her initial review of the transcripts.We defined the implementation outcomes in line with Proctor and colleagues’ conceptualization of implementation science research outcomesImplementation outcomes were defined by fidelity to the program protocol, acceptability to stakeholders and consumers, and sustainability of the program itself.We examined adherence to the program treatment protocol in terms of content, coverage, frequency, and durationWe used data from the qualitative interviews to explore participants’ views toward treatment delivery and its impact on patient outcomes. We specifically considered providers’ comfort with the depression treatment options, their opinions about the complexity of the program, and structural impediments to program delivery. Additionally, patients’ and providers’ experiences with the program’s effect on patient health outcomes were also reviewed.We examined screening rates soon after the study stopped enrolling participants in the program evaluation (from February to May 2019) and then again in December 2019. We also used discussions with clinic staff and leadership about maintaining the program to help understand these findings.We obtained approval from both the Malawi MOH’s National Health Science Research Committee (NHSRC) institutional review board (IRB) and the Biomedical IRB of the University of North Carolina at Chapel Hill. All participants who agreed to participate in the study provided informed consent. Qualitative study participants were given a travel reimbursement equivalent of 10 USD .We first describe the characteristics of the study participants and then assess fidelity, acceptability, and sustainability. Fidelity was examined at treatment initiation and over time for both the MBC protocols and Friendship Bench protocols. Of note, themes presented in the fidelity section may reflect participants’ comfort with the program and its overall complexity, and these factors may overlap with the program’s acceptability.Of the 936 patients who enrolled in the program after the launch of the intervention, 211 were depressed at the time of ART initiation . A conveThe clinical data demonstrate that ART providers successfully prescribed antidepressants at a therapeutic dose in nearly all (96%) cases of moderate to severe depression, achieving high fidelity to the MBC protocol . Based oWe just prescribe the antidepressants that are in stock at that time, but the first choice is amitriptyline. If amitriptyline is not available, then we give that patient the other antidepressant. —ART providerThe clinical data demonstrate that ART providers successfully prescribed antidepressants at a therapeutic dose to nearly all patients with moderate to severe depression.Leadership and ART providers felt that providers were more familiar with amitriptyline and that it was easier for patients to take. Patients take amitriptyline daily, while they initially take fluoxetine every other day.The provision of MBC over time was challenging. This challenge was partially due to waning retention over the first 6 months of care. The qualitative interviews helped explain why it was difficult to identify depressed patients returning for care and to reassess those patients for depression. ART providers felt that the process of identifying patients with depression and confirming the diagnosis with the PHQ-9 took a lot of time and significantly added to their workload, especially in light of the general shortage of staff and high patient caseload. For context, study staff timed the PHQ-9 administration, and ART providers took about a minute per question. That said, clinic leadership admitted:[ART providers] said they get tired and they don’t even ask the PHQ because they know that “this will take much of my time.” But if we had more personnel more people seeing patients that would have been better. —Clinic leadership staff personThe qualitative interviews helped explain why it was difficult to identify depressed patients returning for care and to reassess those patients for depression.Identifying patients was also difficult because the program was not integrated into the electronic medical records (EMR) system. Providers had to look for stickers on the patients’ health passports that signaled they had previously been diagnosed with depression. If providers noticed the sticker, they would then manually search for the patient’s file, reassess the patient with the PHQ-9, and then provide appropriate treatment. It was difficult for providers to determine when a patient no longer needed to be assessed or had completed their depression treatment. One ART provider ventured:There wouldn’t be a problem if depression questions were in the electronic system. —ART providerAs an extension of these issues, ART providers often had a poor attitude toward the program. This phenomenon was summarized by clinic leadership,The workload [is problematic] when you are alone in the ART room and you need to screen those people, so sometimes people may be annoyed, [thinking] “I should screen this one, but this will delay me.” —Clinic leadership staff personOther interviewed ART providers echoed this sentiment. As a result, ART providers often relied on the study staff to identify patients with depression returning for care, and the accuracy of the follow-up PHQ-9 assessments may have been compromised.Few of those with moderate to severe depression received antidepressants continuously for the recommended minimum 3 months based on analysis of the clinical data . Only 6 The qualitative interviews provided insight into the barriers to achieving the recommended duration of the antidepressant prescription. The main challenge was rooted in identifying patients returning for care, as previously described. While prescribing antidepressants added to ART providers’ workload, providers were much more concerned about the time it took to identify and rescreen patients. When asked specifically about the added workload of prescribing antidepressants, one ART provider responded:The issue is just the time to ask the PHQ only, the time to ask the PHQ is what troubles us. —ART providerThe qualitative interviews provided insight into the barriers to achieving the recommended duration of antidepressant prescription.Additionally, antidepressant stock-outs were common, as noted by an ART provider:It’s very rare whereby you have both [antidepressants] available …, sometimes you find that the one [the patient started taking] is not available so we switch them. —ART providerThese reports from the clinics show that switches in antidepressant prescription were not due to side effects or lack of effect, but necessitated by stock-outs. Ensuring that staff were properly trained on the MBC protocol was also challenging, due to high staff turnover and/or rotation through clinic departments and staff availability to attend the original trainings or the supervision sessions. Clinic leadership spoke to these needs:The training was just one day, so most people were not familiar with the dosages so they need to be reminded here and there. Of course, there are debriefing meetings that are done on Thursdays, but still not everybody attends. So prescribing is difficult just because people forget the dosage of the medication. —Clinic leadership staff personThis feedback highlights the complexity of MBC and a need for ongoing support and training. From a patient perspective, actually taking antidepressants appeared largely acceptable. While some providers were concerned about the added pill burden, patients mostly found the antidepressants both tolerable and acceptable.The clinical data demonstrate that nearly all (86%) of cases of mild depression correctly started the Friendship Bench therapy that same day, achieving high fidelity to the Friendship Bench protocol. However, the study-employed Friendship Bench counselor provided over half of the initial Friendship Bench therapy sessions . As noteMost of the time they [Friendship Bench counselors] are in the field, so we refer them to the [study-employed counselor]. —ART providerThis statement suggested that the clinic-based Friendship Bench counselors were often unavailable, resulting in heavy reliance on the program-employed counselor.The clinical data revealed that although almost all patients with mild depression at ART initiation started the Friendship Bench, few participants received consistent Friendship Bench therapy over their first 6 months in care . The oriThe qualitative interviews help explain the challenges to achieving the recommended number of Friendship Bench sessions. Both patients and providers reported that scheduling weekly Friendship Bench sessions was almost impossible for patients because the cost of transport was prohibitive, clinic wait times were long, and patients would have to take off work. For this reason, patients often chose to schedule their Friendship Bench appointments monthly in conjunction with their ART appointments. As described by one Friendship Bench counselor:Some [challenges] are transport … we [Friendship Bench counselors] give dates and ART give their dates. … So the person weighs the cost … Many are prioritizing coming for [ART] medications rather than just coming for the Friendship Bench.—Friendship Bench counselorBoth patients and providers reported that scheduling weekly Friendship Bench sessions was almost impossible for patients.Beyond highlighting the complexities of attending follow-up Friendship Bench sessions in light of constrained resources, this quote also hints at a disconnect between the ART and weekly depression care for patients on Friendship Bench therapy.The same staffing challenges that impeded initiating Friendship Bench therapy were also raised for providing therapy over time. The Friendship Bench counselors were not always available owing to their competing responsibilities as community health workers, and they felt their workload had substantially increased. While the Friendship Bench counselors strove to share the added workload, the clinics often relied heavily on the program-employed Friendship Bench counselor, as previously described. Friendship Bench counselors felt the provision of the Friendship Bench therapy was hampered by the sheer number of patients who defaulted or failed to attend follow-up sessions. They were frustrated by their inability to adequately trace patients in light of phone numbers not working, difficulties locating patients’ residences, and limited funds for airtime or transport.The qualitative interviews also suggest patient discomfort may have played a role in poor continued engagement in Friendship Bench therapy. Interviewed Friendship Bench counselors believed it was important to develop rapport with patients, create an environment where patients felt comfortable speaking openly, and maintain patient privacy. Patients echoed this sentiment, both as a concern and as something they appreciated about the Friendship Bench therapy. As an extension of this, clinic staff and leadership raised concerns about the availability of confidential spaces. One Friendship Bench counselor noted that other patients were often nearby the Friendship Bench shelters and “when the client sees that, they feel that when we tell them that what we are going to discuss is confidential, we cheat on them because people are passing by.” This suggests that the open, outdoor nature of these shelters may not be conducive to the provision of depression counseling in this setting.The qualitative interviews show that nearly all patients, staff, and leadership believed both MBC and the Friendship Bench helped improve patients’ mental health, relieve their depressive symptoms, and prevent risk of suicide. In contrast, the previously published quantitative evaluation found that the treatment program did not demonstrably improve retention in HIV care, viral suppression, or depression remission 6 months after ART initiation.I am able to talk normally and I do not have any anxiety/depression. I am now able to chat with my friends, just like the way life should be. —PatientNearly all patients, staff, and leadership believed screening and treatment helped improve patients’ mental health, relieve their depressive symptoms, and prevent risk of suicide.While this patient believed taking antidepressants helped manage their anxiety and depression, other patients demonstrated a lack of understanding of depression, their respective depression treatment, and its intended purpose and effect. Patients expressed a reverence for the medical field, often stating that they believed their treatment worked simply because the doctors told them it would. Finally, both Friendship Bench counselors and ART providers recognized that depressed patients may struggle to accept their HIV diagnosis and to take their ARTs consistently. For example, a Friendship Bench counselor and an ART provider commentedBecause of the counseling session, it helped the people … and now they are taking the medications consistently … this person is coming to collect drugs and their outlook [toward their] status has changed.—Friendship Bench counselorTaking antidepressants has helped our friends with depression … to take their ARVs [antiretrovirals] adherently because when they are depressed they don’t even take the ARVs. —ART providerThese descriptions demonstrate that clinic staff perceive that depression treatment supports ART adherence and engagement in HIV care.The clinical data suggest the program was not sustained. After enrollment into the program evaluation ended, the rate of screening dropped sharply . By DeceThe clinical data suggest the program was not sustained and were partially in contrast with staff attitudes toward sustainability.These quantitative findings are partially in contrast with staff attitudes toward sustainability identified in the qualitative interviews. The staff generally expressed a belief that they would continue to screen and manage depression after the study staff left the facilities. As heard from one ART provider,It will continue, because it’s our job as health workers to assist those people, because if we don’t assist, then who will? It’s like most people will not be taking the ARVs. —ART providerIn fact, only 2 ART providers directly expressed any skepticism toward the sustainability of the program:Because there are people who are supporting [us] but if they can move out, it is when the true picture of their [providers’] attitude can be seen. —ART providerThese ART providers acknowledged that the clinics receive a lot of support from the study staff and that challenges to sustainability may become evident after they leave. However, clinic staff and leadership did suggest certain resources would be key to supporting the sustainability of the program. These included increasing the number of trained staff, particularly Friendship Bench providers; offering refresher trainings and opportunities for continued learning; providing ongoing supervision; maintaining the stock of antidepressants; and having space for providing screening and counseling.This mixed-methods evaluation of an integrated depression treatment program found that, while early stages of training, depression screening, diagnosis, and treatment initiation were successfully integrated,Early stages of training, depression screening, diagnosis, and treatment initiation were successfully integrated; however, problems were apparent in the program delivery over time.During the study, clinics failed to deliver Friendship Bench therapy with fidelity to the program protocol, particularly in regards to the low frequency of attended sessions over the 6-month duration of follow-up.,,Providers managed to accurately identify patients with moderate to severe depression and started them on the correct dose of antidepressants, but fidelity to the MBC protocol over time was hampered by stock-outs, ART providers’ level of comfort with fluoxetine and increasing dosages, difficulties identifying depressed patients, lack of integration into the EMR system, and negative attitudes. These findings support previous conclusions around the feasibility of integrating screening and treatment initiation into ART.,Designing implementation science studies to evaluate programs that can readily (and rapidly) be adopted and integrated into routine care in the public sector is challenging.HTC counselors could administer the entire PHQ-9 at ART initiation. This would partially address the added burden of administering the PHQ-9 at ART initiation placed on ART providers, who are still well-positioned to determine a final diagnosis and provide appropriate treatment.The facility pharmacists could ensure an adequate supply of antidepressants through improved communication and coordination with central medical stores. This would allow providers to defer the choice of medication to the informed patient and prevent unnecessary and inappropriate switching of antidepressants.Friendship Bench appointments could be routinely scheduled on the same day as ART follow-up visits to alleviate the patient-side travel and resource burden and also allow the ART providers to consistently reconnect patients in Friendship Bench therapy to the counselors.Several key recommendations have emerged from this experience. As implemented, depression screening, diagnosis, and treatment initiation were successfully integrated into HIV careSome of the implementation challenges appeared to be more immediately remediable and could be addressed through simple solutions.The presence of a salaried, on-site coordinator or champion employed by the Ministry of Health would increase the likelihood of more faithful implementation. Such an individual would be well-positioned to foster clinic ownership of the program and provide the ongoing supervision and training that are needed to effectively build and sustain mental health care capacity.Integration into the EMR system is critical. This integration would help ensure that screening is completed and that returning patients are re-assessed and reinforce mental health capacity building and intervention delivery with fidelity.Finally, successful implementation requires a dedicated, clinic-based Friendship Bench counselor. Task-shifting to an already overburdened cadre of community health workers is an ineffective means of providing depression services.Resolving other challenges would require a fundamental change in the program design or substantially more resources than are currently available in the Malawian public health system. Nevertheless, the clinics would have benefitted from substantially more support, such as the following potential facilitators:,,Findings from this evaluation should be considered in light of limitations due to the program and evaluation design. First, neither the program nor the evaluation design was guided by a formal implementation science framework. However, both were designed in congruence with the key principles of implementation science, using methods that would promote the systematic uptake of evidence-based practices  into routine care.In addition, all the patient participants were from Clinic A owing to the small number of individuals with depression identified at Clinic B after the launch of the intervention. While the shorter study period at Clinic B is largely responsible for the small number of depressed individuals, Clinic B also had a slightly lower prevalence of depression than Clinic A. Given the generally low retention rates, the study team decided to sample patients from Clinic A to achieve the target qualitative sample within the study period. However, this sampling decision does raise the potential for sampling bias, and it limited our ability to explore potential facility-level characteristics that could have been associated with the implementation success or failure.Further, as the main objective of the study was to evaluate a program at the sites where participants worked or received care, it is possible that participants’ responses were subject to social desirability bias. The use of mixed-methods approaches is particularly useful for evaluating implementation outcomes,This mixed-methods evaluation of a depression treatment program using antidepressants and psychotherapy in HIV clinics in Malawi found that although the early stages of integration and treatment initiation were successful,


This study examined the week of a 6-session integrated dementia p program on dementia knowledge, attitude toward dementia, fear of dementia, and dementia prevention behaviors among community dwelling elders. Using a nonequivalent control group, pre-posttest design, study participants were recruited from a senior center in Seoul, Korea. A total of 40 participants completed the study while half of them were in the experimental group and another half were in the control group. They completed survey questionnaires before and after the program. The findings showed that the program was effective only to decrease the fear of dementia of the older adults. Knowledge, attitude toward dementia, and healthy behaviors may be difficult to change in a short period of time. However, the integrated dementia prevention program may be effective to decrease negative emotions, particularly, fear toward dementia among older adults. The fear of dementia needs to be further assessed individually in order to identify particular causes and triggers and provide tailored interventions.


Stress and negative emotions contribute to atrial fibrillation (AF). Mind-body practices decrease stress and negative emotions and may reduce AF episodes and improve quality of life for patients with AF.We examined the effects of a multimodal mind-body program, the SMART Program, on AF-related quality of life in patients with paroxysmal AF (PAF).In this randomized, waitlist-controlled pilot trial, 18 subjects with PAF participated in an 8-week SMART Program delivered online immediately or 3 months later. Validated measures were completed at baseline and at 3 and 6 months (waitlist group only).P = .005) and depression  but not anxiety . Subjects also reported improvements in AF symptom severity (P = .026), distress (P = .014), positive affect (P = .003), and ability to cope with stress (P = .001). Compared to waitlist control subjects, those in the immediate group reported improvement in positive affect  and coping with stress  after participating in the program.Comparing pre- vs post-program scores among all 18 participants, subjects reported improvement in AF-related quality of life (Cohen’s d = 0.75, The SMART Program, delivered virtually, may enhance positive emotions and coping with stress as well as decrease negative emotions and AF symptoms. These results warrant a larger trial to better understand the potential benefits of such programs for patients with PAF. One such program with which we have extensive experience, and which has been shown to improve quality of life and symptoms in multiple patient populations, including patients with coronary artery disease, is the Stress Management and Resiliency Training: Relaxation Response Resiliency Program (SMART-3RP or SMART Program for short).ClinicalTrials.gov (NCT03450993).This study was a randomized, parallel-assignment pilot study to investigate the effects of the Stress Management and Resiliency Training (SMART) ProgramPatients were eligible if they were 18–90 years of age, were able to understand written and spoken English, had documented recurrent symptomatic PAF, were on stable medical therapy for their PAF, and were willing to continue on the same treatment regimen while participating in the study. Individuals were excluded if they had a current daily practice of yoga, meditation, guided imagery, or other similar mind-body techniques; were unwilling or unable to participate in an intervention delivered via video conferencing; unable to come to the research center to complete outcome measures; had end stage renal disease or heart failure or a severe unstable medical or psychiatric disease; or were unable to complete the protocol due to cognitive reasons. Patients on psychoactive medications had their eligibility assessed on a case-by-case basis depending on the stability of their medication regimen.The SMART Program is a manualized psychoeducational program that teaches participants a variety of different skills to more effectively cope with stress and reduce its negative health effects.https://www.vidyo.com/) that allows for encrypted audio and video transmission and were led by a single physician (MLD) experienced in running these groups. Sessions were held in the evening hours during the work week. A study research coordinator worked with each participant prior to the first session of the SMART Program to assist them in downloading the required software and to help them become comfortable connecting with and using the virtual environment.All SMART group sessions were conducted online using a hospital-approved, secure video telehealth platform . Independent samples t tests were used to compare changes in scores for the immediate vs waitlist control group (using the first and second assessments for the control group). As this small study was intended primarily as a hypothesis-generating pilot study, P values were not corrected for multiple comparisons.All analyses were conducted in SPSS v24 . Descriptive statistics were used to assess participant demographics and assess the normality of questionnaire data. Although most of the data were approximately normally distributed, a few measures were not; however, nonparametric tests yielded equivalent inference to the parametric tests for these measures, and thus all reported values are from parametric tests. For the several instances in which a question was skipped by a study participant, data were assumed to be missing at random and missing data were imputed by calculating the average score for a measure for the answered items. To compare pre- vs post-intervention scores for all 18 subjects, paired samples A total of 18 individuals with PAF enrolled in the study . ParticiP = .005), AF symptom severity (P = .026), distress (P = .014), positive affect (P = .003), and stress reactivity/coping (P = .001) with moderate-to-large effect sizes  and positive affect (P = .02) with large effect sizes (Comparison of the immediate intervention group that received the SMART Program to the waitlist control group before they received the SMART Program (9 vs 9 subjects) demonstrated significant improvements in stress reactivity/coping .Although subjects in the waitlist control group were taking more antiarrhythmics and other medications and had a lower quality of life scores on the AFEQT compared to the immediate group, potentially confounding the comparison between the immediate and waitlist control groups, subjects in the waitlist group also noted a significant improvement in their AFEQT score after completing the SMART Program . Participants appreciated not having to travel to the hospital every week to participate in the program, and fewer than 1 session of 8 was missed on average. A prior pilot that we attempted with in-person groups was difficult to enroll, as weekly travel to the hospital was a significant barrier to participation. Nonetheless, several participants had low computer literacy, and their participation was enabled only through one-on-one training with the study coordinator. Thus, even individuals with limited computer literacy can be taught how to engage with, and benefit from, online programs.,,Limitations of our work include the small sample size, that all groups were run by a single clinician, chance confounding between random treatment assignment and use of antiarrhythmics and baseline quality of life scores, a demographically homogeneous sample, and that there was no long-term follow-up. Nonetheless, the diversity of mind-body programs that have demonstrated improved quality of life for patients with PAF suggests that this effect may be real and that further research to understand the mechanisms, as well as larger trials, are warranted. Moreover, even 8-week mind-body skills–based interventions have been reported to have significant benefits out to at least 1 year.We found that an 8-week mind-body program, known as the SMART Program, delivered in a group-based, online format, improves AF-related quality of life, stress reactivity/coping, and happiness in patients with PAF. This program may also decrease negative emotions and AF severity. Given these results, larger trials of the SMART program in this patient population are warranted. If benefit is confirmed, the ability to deliver this intervention virtually will facilitate dissemination of these tools to patients as part of clinical care.We thank the following individuals for their assistance with this study and/or a previous pilot: Jennifer Galvin, Seyed Hosseini, Ihsan Kaadan, Alexander Nguyen, Ayman Shaqdan, Jeena Vaid, and Mohamed Youniss.Osher Center for Integrative Medicine at Harvard Medical School. Funding for preliminary work came from the Harold Grinspoon Charitable Foundation. MLD was funded by K23AT009218 from the National Center for Complementary and Integrative Health (NCCIH) at NIH. The project described was also supported by Grant Numbers 1UL1TR002541-01 and 1UL1TR001102 from NIH. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.Funding for this study was provided by a grant from the GlaxoSmithKline, Mitsubishi Tanabe Pharma America, Prilenia Therapeutics, and UCB Ra Pharma; served as a Steering Committee Member for Biogen and Stoparkinson Healthcare Systems; served as a DSMB member for Novartis Pharmaceuticals and Shire Human Genetic Therapies; and served on advisory boards for Bial Biotech, Cortexyme, Enterin, and Partners Therapeutics. Dr Ruskin has served as a consultant for Advanced Medical Education, InCardia, and Janseen; and has an equity interest in Ablacor, Celero Systems, Element Science, Infobionic, LuxMed, and NewPace. Dr Denninger reports research support for investigator-initiated studies from Basis/Intel and Onyx/Amgen.Dr Dossett is an author for UpToDate. Dr Macklin received grant support through his institution from Alector, Amylyx Pharmaceuticals, Biohaven Pharmaceuticals, Clene Nanomedicine, All authors attest they meet the current ICMJE criteria for authorship.All participants provided written informed consent.The study was approved by the Partners Human Research Committee/IRB and conducted according to the principles of the Declaration of Helsinki.


Although evidence bolstering the efficacy of internet-based cognitive behavioral therapy (iCBT) for treating childhood anxiety has been growing continuously, there is scant empirical research investigating the timing of benefits made in iCBT programs .This study aims to examine the patterns of symptom trajectories (changes in anxiety) across an iCBT program for anxiety (BRAVE Self-Help).This study’s participants included 10,366 Australian youth aged 7 to 17 years  with elevated anxiety who registered for the BRAVE Self-Help program. Participants self-reported their anxiety symptoms at baseline or session 1 and then at the commencement of each subsequent session.The results show that young people completing the BRAVE Self-Help program tend to fall into two trajectory classes that can be reliably identified in terms of high versus moderate baseline levels of anxiety and subsequent reduction in symptoms. Both high and moderate anxiety severity trajectory classes showed significant reductions in anxiety, with the greatest level of change being achieved within the first six sessions for both classes. However, those in the moderate anxiety severity class tended to show reductions in anxiety symptoms to levels below the elevated range, whereas those in the high symptom group tended to remain in the elevated range despite improvements.These findings suggest that those in the high severity group who do not respond well to iCBT on a self-help basis may benefit from the additional support provided alongside the program or a stepped-care approach where progress is monitored and support can be provided as necessary. Anxiety is an increasingly common childhood mental health condition, with potentially significant life-long repercussions for those who do not access early treatment . Interned=0.81 and Cohen d=0.87 for adolescents and children, respectively [The BRAVE Self-Help program is the only widely disseminated iCBT program for childhood anxiety, which is made publicly available, free of charge, to all children and adolescents in Australia. Although the preliminary effects of this self-help iCBT program appear somewhat weaker than those found for the therapist-supported iCBT version , clinicaectively ). Furtheectively . Howeverd=0.59), suggesting that change may occur early and rapidly. Furthermore, in their examination of brief and full versions of a cognitive behavioral therapy (CBT) website (MoodGym) for adults with elevated depression, Christensen et al [Very little research has been conducted on the timing of benefits made in iCBT programs . March et al  demonstren et al  found then et al . There ien et al . In anoten et al  found then et al . HoweverWe examined patterns of symptom trajectories (changes in anxiety) across BRAVE Self-Help program sessions to determine whether BRAVE Self-Help produces a gradual and linear impact on anxiety symptoms or whether the greatest impacts are made early in treatment and to determine distinct trajectories of anxiety symptoms within BRAVE Self-Help participants. Such information will help in determining ideal doses of self-help iCBT and whether small doses of treatment are sufficient. Given that variability is likely to be present in how young people respond to self-help interventions, identifying factors associated with different trajectories may assist in understanding the mechanisms through which the program works and may inform targeting and tailoring of the program. Thus, we aim to identify subgroups of participants  based on latent change trajectories in anxiety scores in response to BRAVE Self-Help. Previous studies have used this analytic approach to determine the trajectories of depressive symptoms and suicidal ideation in internet-based interventions ,21, and BRAVE Self-Help is an interactive internet-based iCBT program for preventing and treating anxiety among youth. The program, described extensively elsewhere ,24, is oDepending on age, participants completed either the child program (7-12 years) or the adolescent program (12-17 years), with 12-year-olds given a choice of either program. Although there were accompanying parent programs, these were not included in this study. BRAVE Self-Help is delivered without any therapist support, and there are no timing restrictions between sessions; however, the sessions must be completed in a predetermined sequence. Automatic reminders to complete sessions are sent to a young person via email.Participants included 10,366 Australian youth aged 7 to 17 years with elevated anxiety  who registered for the BRAVE Self-Help program between July 1, 2014, and October 26, 2018. beyondblue ; self-referred through internet searching ; or referred through other means . A full breakdown of referral sources is provided in The BRAVE Self-Help program is an open-access intervention offered to young people and families throughout Australia; thus, registration does not require referral from a health care professional. Children and adolescents who registered for the program were referred by school-based professionals ; referred by external health professionals ; referred by parents, friends, or family members ; referred through Eligible participants were required to have registered for the BRAVE Self-Help program between July 2014 and October 2018 and to have completed the Children’s Anxiety Scale 8-item (CAS-8)  during tAll measures were embedded within the BRAVE Self-Help program. Further data were collected via BRAVE program analytics regarding adherence to the program.Basic demographic information, including age, gender, and location (postcode), was collected during the registration process. Age was measured in years, and the residential location was assessed using postcode. Postcode data were coded according to the Australian Standard Geographic Classification system , and parnever) to 3 . Items are summed to produce a total score ranging from 0 to 24, with higher scores indicating greater levels of anxiety.Anxiety levels were measured using the CAS-8 . The CASnormal; scores ≥84th percentile  are considered indicative of elevated anxiety and scores ≥94th percentile  indicate clinical levels of anxiety. For this study, and as per procedures of March et al [elevated and scores ≥15 were considered indicative of clinical anxiety. The CAS-8 was completed by participants at baseline or session 1 and then at the commencement of each subsequent session . For example, if a participant had completed five sessions, they would have CAS-8 data at baseline and sessions 2, 3, 4, and 5. The CAS-8 has demonstrated good psychometric properties, with a reliability coefficient α of .89 in previous studies [The CAS-8 has been used in large-scale school-based prevention program trials with subsequent population-level, gender-standardized norms for comparison . Scores  studies  and an aProgram adherence was measured as the number of sessions completed by each participant over a period of 20 weeks from the date of registration. The number of sessions completed was automatically recorded by the program.Data for this study were collected as a part of a large community effectiveness trial of the BRAVE Self-Help program . During the registration process, participants were required to read a developmentally appropriate web-based participant information sheet and provide informed consent. Children aged below 16 years were also required to obtain parental consent to continue with registration. After providing consent, participants created a profile and completed an initial questionnaire, including basic demographic data  and baseline anxiety assessment (CAS-8). Participation in the program was voluntary, and participants could choose to provide anonymous information  if they chose. They could also discontinue using the program or withdraw from the study at any time without adverse consequences.Participant data were recorded for a 20-week period from the date of registration, thus allowing sufficient time for the completion of the 10 sessions. Trajectories of anxiety symptoms based on CAS-8 scores were identified using growth mixture models (GMMs), with intercept, linear change, and quadratic change estimated using all available data from the baseline assessment and up to nine subsequent measurement occasions. GMM was used to identify latent classes of participants with distinct longitudinal trajectories, with all available data included in the models . The GMMThe number of participants completing each session decreased throughout the program. As indicated in P<.001); however, the BLRT for a three-class model was not significant as compared with the two-class model (P=.99). Furthermore, in the three-class model, one of the classes accounted for 0.7%  of the sample. Consequently, a two-class model was selected. Scores on the CAS-8 for the two total classes are shown in high anxiety severity , and moderate anxiety severity . On the basis of the GMM model, the intercept for the CAS-8 scores in the HAS group was 19.72 (SE 0.09), with a negative slope . The intercept for the MAS group was 13.75 (SE 0.04), with a negative slope . A quadratic relationship was also evident in both the HAS  and MAS  groups, showing that the rate of change in CAS-8 scores decreased over time for both classes.The GMM with two classes had a significantly better fit than a single-class solution based on the BLRT statistic (P<.001). For every year increase in age, participants were 4% more likely to fall in the HAS class (P=.007). Females had twice greater odds of being in the HAS class than males (P<.001). Participants of other gender had 47% greater odds of being in the HAS class than females (P=.007). The effects of remoteness of residence were not significant (P=.01). There were no effects on the date of registration or the number of activities completed in session 1.A logistic regression model was used to identify the factors associated with class membership. The outcomes are presented in nificant . In termThis study examined the trajectories of responses to a web-based, open-access, self-help intervention for youth anxiety. The results suggested two classes of trajectories that could be distinguished by high versus moderate baseline levels of anxiety and levels of change over time. Irrespective of trajectory, participants, on average, obtained benefits from the program, with participants generally showing significant linear reductions in anxiety. From a baseline average of around 20 , those in the HAS trajectory class showed reduced anxiety scores of 6.58 points (or 5.68 points based on model estimates that accounted for missing data) on the CAS-8; however, this level remained within the elevated range. In contrast, the MAS trajectory class showed reductions of 3.87 points (or 4.31 points based on model estimates) on the CAS-8 from a baseline of 12.6  to a level in the nonelevated range. Indeed, on average, those in the MAS class obtained a clinically meaningful benefit (scores within the nonelevated range) by session 6.The finding that the HAS class tended to remain in the elevated range of anxiety scores despite showing significant reductions from a very high starting point suggests that at least a proportion of this group may require additional assistance over and above the self-help iCBT program. The finding also revealed that the HAS class completed fewer sessions than their MAS counterparts. It is possible that lower levels of perceived symptom improvement among participants in the HAS class contributed to lower motivation to continue engaging with the program, or a greater difficulty completing sessions due to ongoing symptom severity and difficulty implementing strategies. Thus, a therapist-supported model or stepped-care approach may be beneficial for this group, whereby HAS participants either receive additional support from the outset or are monitored (in terms of anxiety reduction and session compliance) and are referred for additional therapist support as necessary. HAS participants could be easily identified at the beginning of the program , and subsequently referred, monitored, and provided with additional support or intervention elements if their response to the program was poor. Preliminary results from case studies of a stepped-care model of BRAVE highlight the potential of this approach .The study results also suggested that the rate of anxiety reduction decreased over time for both trajectory classes, with greater reductions occurring in the first six sessions than in later sessions. Importantly, in line with the findings of Christensen et al , the resIn terms of predictors of class membership, the study found that adolescents and females were more likely to be in the HAS class compared with MAS class than children and males. These findings are perhaps unsurprising given that anxiety levels are known to increase with age and are higher among women . Given tThe implications of this research’s findings are not limited to the BRAVE program and provide useful insights for other web-based interventions. For example, when there is a broad range of users who engage with an internet intervention, with diverse profiles, particularly related to symptom severity, the results of this study indicate that care should be taken to consider the needs of these subgroups. Particular consideration should be given to whether the service model is appropriate for them, whether the service needs to be tailored to profiles , or whether the service needs to be targeted to those who will benefit the most. However, it is important to note that there are drawbacks to targeting more narrowly—there is still a clear demand for the BRAVE program even among those in the high severity class, which suggests that many young people with anxiety may not be receiving the care they need from other sources (whether web-based or in-person).There are a number of clear strengths of this study. It had a large sample size, included both children and adolescents, used naturalistic data from a clinical service without stringent eligibility criteria, and collected symptom-level data throughout the completion of the program. However, alongside these strengths, this study has a number of limitations. High attrition was observed, and although models were robust to missing data, dropout may be associated with treatment response. All outcome measures were self-reported; thus, there was no clinical verification of the symptom level. Furthermore, as the data were collected in the context of clinical service delivery, there was no control group. This makes it unclear whether factors external to the program may have influenced the trajectories and whether the reductions in anxiety were attributed to the treatment or were the result of spontaneous recovery over time. Finally, limited psychosocial factors were measured; thus, other factors, such as ruminative style, personality, social support, and previous exposure to treatment, may have influenced the observed trajectories.Recent worldwide events have resulted in a significant shift in mental health care service needs, as numerous lockdowns during the COVID-19 pandemic severely impacted face-to-face mental health service access and provision. This subsequently led to the conversion of many services to telehealth, videoconferencing, and other digital modalities to provide continuity of care. With an increased access to digital mental health services, and likely increased experiences of distress at the community level, it will be important to examine whether the use of the BRAVE Program changes throughout and after COVID-19. Future research should examine whether users presenting to the web-based program during and after the pandemic present with different profiles and symptom presentations and whether their experience with the web-based program leads to similar outcomes as standard BRAVE program users.Young people completing the BRAVE Self-Help program tend to fall into two trajectory classes that can be reliably identified in terms of high versus moderate baseline levels of anxiety and subsequent reductions in symptoms. Both classes showed significant reductions in anxiety, with the greatest level of change being achieved within the first six sessions for both classes. Those in the MAS class tended to show reductions in anxiety symptoms to levels below the elevated range, whereas those in the high symptom group tended to remain in the elevated range despite improvements. Thus, those in the high severity group who do not respond well to iCBT on a self-help basis may benefit from a stepped-care approach or additional support.


Endobronchial ultrasound (EBUS) elastography has been used in EBUS-guided transbronchial needle aspiration (EBUS-TBNA) to identify malignant lymph nodes based on tissue stiffness. Rapid onsite cytological evaluation (ROSE) has been widely utilized for onsite evaluation of sample adequacy and for guiding sampling during EBUS-TBNA. The aim of this study was to investigate the diagnostic value of combined EBUS elastography and ROSE in evaluating mediastinal and hilar lymph node status.Retrospective chart review was performed from December 2018 to September 2020. Patient demographics, EBUS elastography scores, and ROSE, pathologic, and clinical outcome data were collected. The EBUS elastography scores were classified as follows: Type 1, predominantly nonblue; Type 2, partially blue and partially nonblue; and Type 3, predominantly blue. A receiver operating characteristic curve was used to compare the sensitivity, specificity, positive predictive value, negative predictive value, positive likelihood ratio, and negative likelihood ratio for evaluation of malignant lymph nodes among the EBUS elastography, ROSE, and EBUS combined with ROSE groups.A total of 245 patients (345 lymph nodes) were included. The sensitivity and specificity of the EBUS elastography group for the diagnosis of malignant lymph nodes were 90.51% and 57.26%, respectively. The sensitivity and specificity in the ROSE group were 96.32% and 79.05%, respectively. The sensitivity, specificity, positive likelihood ratio, and negative likelihood ratio of EBUS elastography combined with ROSE were 86.61%, 92.65%, 11.78, and 0.14, respectively, and the area under the curve was 0.942.Combining EBUS elastography and ROSE significantly increased the diagnostic value of EBUS-TBNA in evaluating mediastinal and hilar lymph node status compared to each method alone.The online version contains supplementary material available at 10.1186/s12890-021-01748-4. Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) technique was developed in 2002. Currently, EBUS-TBNA is highly recommended by the National Comprehensive Cancer Network (NCCN) and the American College of Chest Physicians (ACCP) for diagnosis and preoperative staging of patients with lung cancer. Ultrasonography is frequently used to identify malignant lymph node status and guiding lymph node aspiration. However, conventional ultrasonography has not shown particularly high accuracy in identifying malignant lymph nodes . UltrasoDuring EBUS-TBNA, rapid onsite cytological evaluation (ROSE) has been widely used to evaluate samples for example, guiding following passes and determining adequacy of samples for further immunohistochemistry or next generation sequencing . HoweverRecently, ROSE has been used as an assistive diagnostic technique in some EBUS elastography related studies; however, the diagnostic value of combined EBUS elastography and ROSE remains undetermined , 11. TheA retrospective study was performed to identify patients who underwent the EBUS procedure due to enlargement of mediastinal or hilar lymph nodes in a single institution from December 2018 to September 2020. This study was approved by the Ethics Committee of Zhongda Hospital, School of Medicine, Southeast University. Patients with mediastinal lymphadenopathy were included. Patient demographics, pathologic features, and clinical outcome data were collected by chart review. Lymph node samples were divided into three groups: EBUS elastography, ROSE, and combined EBUS elastography and ROSE.Patient results from routine blood tests, chest high-resolution computerized tomography (CT) scans, and electrocardiograms were reviewed before the procedure. The patients were required to fast for 6–8 h before the procedure, and patients’ status was monitored by an anesthesiologist during the procedure. EBUS-TBNA was performed under conscious sedation combined with local anesthesia and the convex probe EBUS  was inserted via the nasal route. After identifying the lesion, the size of lymph nodes and distribution of the vessels were evaluated,and the EBUS elastography images were analyzed by two pulmonologists individually. At least three passes were performed for each lesion with 15–20 aspirations. The 21 G needles  were used for aspiration.Real-time EBUS B-mode was performed to evaluate the lesion and part of the normal tissue followed by elastography image analysis. During the procedure, the operator gently applied pressure to the convex probe to perform elastography, and the images were recorded for further analysis. The elastography images were divided into three categories according to the scoring system of Izumo et al. : Type 1 ROSE interpretation was performed by a single pulmonologist with at least one year of experience in evaluating ROSE results and who was blinded to the results of EBUS elastography image analysis. The specimens were collected, and smeared on a clean glass slides. The remaining specimens were fixed in 10% formalin and sent to the Pathology Department for routine testing. Diff-Quick staining was used for rapid staining in ROSE according to the manufacturer’s instructions . BrieflyROSE interpretation was performed according to the guidelines of the Papanicolaou Society of Cytopathology System for Reporting Respiratory Cytology. In general, the results were classified into five categories : 1. non-p values were based on two-sided testing, where p values less than 0.05 were considered significant.SPSS  statistical software, version 22.0 was used for statistical analysis. All quantitative data obtained are expressed as the mean ± standard deviation. Receiver operating characteristic (ROC) analysis was performed to determine the test performance of the different methods. The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), positive likelihood ratio, and negative likelihood ratio of EBUS elastography, ROSE, and EBUS elastography combined with ROSE for detecting malignant lymph nodes were compared. All From December 2018 to September 2020, a total of 247 patients were included. Two patients were excluded from the final analysis since there was no final pathological diagnosis. Patient characteristics and clinical information are summarized in Table p < 0.001) or only ROSE groups (p = 0.0202). The combination of EBUS elastography and ROSE thus had the best diagnostic value among the three groups , margin status, presence or absence of central hilar structure, short axis diameter, and coagulative necrosis under B-mode ultrasound to evaluate lesions , 19, 20.Endoscopic elastography has been well developed recently and has demonstrated its superiority in lesion evaluation compared with conventional ultrasound, especially in esophageal endoscopic ultrasound. A previous study showed that the sensitivity, specificity, PPV, NPV, and overall accuracy of endoscopic elastography for diagnosing pancreatic solid tumors were 93%, 66%, 92%, 69%, and 85%, respectively , while tROSE can be used to evaluate the sample during EBUS-TBNA. However, some studies have found no significant difference in the diagnostic value of EBUS-TBNA with or without ROSE . ROSE caIn previous studies, ROSE was only applied as an ancillary technique to evaluate sufficiency of the sampling in EBUS-TBNA , 11. To This study had some limitations. First, it was conducted in a single institution with limited sample sizes. Further studies must be performed in larger populations. Second, this study only compared the value of the elastography score and ROSE, without additional information regarding lymph node size, integrity, or vascularity. Combining these factors could increase the diagnostic value of elastography and ROSE.The combination of elastography and ROSE during EBUS-TBNA for patients with enlarged mediastinal lymph nodes, could increase the clinical diagnostic value compared with ROSE or elastography alone. Combining elastography and ROSE during EBUS-TBNA in clinical practice is recommended.Additional file 1. The number of FN, FP, TP, TN results in three groups.


Bees, ants, and other insects harvest antimicrobial resins from plants and use this material for a variety of purposes, from nest construction to defense against predators and pathogens. Resin use is thought to have facilitated the evolution of sociality in stingless bees, and today, resin use remains fundamentally important for stingless bee colony function. Most species use resin to build brood comb, storage pots for honey and pollen, and various protective structures within the nest. Many also use resin to protect their nests from predators, fortifying nest entrances with a barrier of sticky resin droplets or applying resin directly to would-be invaders. For some species, the presence of resin inside the nest space can also influence the physical properties of the bees themselves, enriching the chemical composition of the outermost layer of their exoskeleton, and possibly shaping the communities of bacteria and fungi that are found on the bees, and in their nests. This article brings together studies from a variety of fields to illustrate the importance of resin use for stingless bee colony function and conservation, and to point towards areas of future research.Stingless bees (Meliponini) are highly social bees that are native to tropical and sub-tropical ecosystems. Resin use is vital to many aspects of stingless bee colony function. Stingless bees use resin to build essential nest structures, repel predators, and kill would-be invaders. Furthermore, resin-derived compounds have been found to enrich the cuticular chemical profiles of many stingless bee species, and resin may play an important role in shaping the microbial communities associated with stingless bees and their nests. Despite its importance for colony function, previous reviews of resin use by stingless bees are lacking. This topic grows increasingly urgent as changes in beekeeping and land use practices occur, potentially diminishing stingless bees’ ability to incorporate resin into the nest environment. In this article, we review existing literature on resin use by stingless bees and discuss potential areas of future research. Stingless bees (Meliponini) are highly social bees that are native to tropical and sub-tropical ecosystems. With approximately 550 species known to science, stingless bees comprise the largest and most diverse group of corbiculate bees . They represent approximately 70% of all eusocial bee species , and exhStingless bees collect the sticky resins that plants secrete and use this material for a variety of purposes. Most species use resin to build essential nest structures such as brood comb, storage pots for honey and pollen, and various protective structures ,10. For Despite the importance of resin use for stingless bee colony function, previous reviews of this topic are lacking. In part, our understanding of resin use is limited because less than half of all meliponine nests have been described by Western science . Of thesIn spite of these challenges, this review brings together research from disparate fields  to examine resin use in stingless bees. Taken together, these studies highlight the centrality of resin use to stingless bee colony function. In the following sections, we review existing literature on the role of resin in stingless bee nest construction and defense, discuss resin foraging and resin handling by stingless bees, and review studies on the effects of resin on bees’ cuticular chemical profiles and their microbial associates. Finally, we point to gaps in knowledge that warrant further study.The chemistry, evolution, ecology, and ethnobotany of plant resins has been reviewed by Langenheim . Plants A wide variety of animals—from humans to coatis to wood ants to bees—harvest resin from plants and use this resource as a medicine, defense, and building material ,27,28,29Nest construction strategies vary widely across stingless bee species, with different species building nests in different spaces. Some species build exposed nests adhered to tree branches, others make use of existing cavities including hollow trees, termite nests, or electric light posts, and others build subterranean nests deep underground ,2,34. NeResin is an effective construction material for several reasons. Resins are malleable when secreted but harden over time, so they can be shaped to build durable structures . They arTrigona species likely used resin to build their nests. Today, resin use persists as a crucial component of nest construction for stingless bees.For many insects and other organisms, managing microbial communities is a key part of building and maintaining a successful nest. These efforts are particularly important in tropical environments, where conditions favor the proliferation of microbes, and in social insect societies, where the risk of disease transmission is increased due to large numbers of genetically similar individuals living in close proximity ,37. ManySchwarzula sp. [Trigona australis [Hypotrigona, Trigonisca, Schwarzula, and Plebeia) contains little to no resin, and is closer to pure wax. Schwarzula sp. appear to use no resin at all, instead farming scale insects within the nest cavity and mixing their wax with self-produced wax to form a cerumen equivalent [Most stingless bees mix resin with wax to produce cerumen, which is the material they use to build brood combs, honey and pollen pots, and various other structures inside the nest  , and in structures such as the nest entrance and batumen . These tTrigona (Trigona) p. pallens [Tetragonisca angustula (Latreille) and Plebeia spp. [Plebeia emerina workers modify deposit-resins using secretions, which might help to maintain their viscosity [Deposit-resins, also referred to as resin deposits or viscous propolis deposits ,49,50, a pallens ; Tetragoeia spp. ,50). Unleia spp. . AlternaA. mellifera propolis is known to be highly variable, and reports of wax content often lack precision [Propolis refers to the resins that stingless bees bring back to the nest and mix with small amounts of salivary gland secretions and, purportedly, wax . Numerourecision . In a derecision  observedSome stingless bees use geopropolis in place of pure propolis. Geopropolis is a mixture of plant resins and soil. This mixture can consist of up to 90% soil, silt, and sand particles . It is lMelipona spp. [Hypotrigona and Trigonisca spp. [exposed batumen is a hard outer layer that surrounds and protects exposed or partially exposed nests. Batumen plates are sturdy plates that surround and protect nests within a cavity, allowing the bees to adjust the cavity size to suit the needs of the colony  [Lining batumen is a thin, continuous resinous lining, generally less than 2 mm in thickness, similar to the so-called propolis envelope that A. mellifera colonies use to coat the rough inner surfaces of the hollow tree cavities where they nest [Laminate batumen consists of multiple layered sheets. The channels found in laminate batumen allow bees to move between layers, and may also facilitate air flow and water evaporation [Propolis and geopropolis are often incorporated into other nest structures such as the nest entrance and batumen. Nest entrances commonly consist of hardened resin tubes, which can extend both inside and outside the nest. Internally, these convoluted maze-like structures are often designed to thwart enemy intruders . The batona spp. ); otherssca spp. ). When psca spp.  describeocandei) . Lining hey nest . Laminatporation ,47. In aLestrimelitta [Bees contend with a variety of predators and parasites. Some examples include lizards, spiders, ants, wasps, assassin bugs, beetles, phorid flies, and parasitic stingless bees from the genus imelitta ,29. SincLepidotrigona, Scaura, Tetragona, Tetragonula, and Trigonisca) fortify their nest entrances with a barrier of fresh resin droplets [Trigona cilipes, Tetragonilla collina, and related species), the continuous application of fresh resin results in long, slender entrance tubes [Pariotrigona klossi (Schwarz) builds a nest entrance consisting of dozens of tubelets that branch like coral. Each tubelet is adorned with strings of clear resin beads which together resemble the “quartz pendants of a chandelier” [Many stingless bee species . The tedroplets ,14,22,61droplets , and aredroplets ,64. Overdroplets ,65. For ce tubes . In the ndelier” . For invMeliplebeia tanganyilcae medionigra (Cockerell) and Plebeiella lendliana (Fries) [Melipona panamica, Melipona flavolineata, and other Melipona species) even keep a designated resin ball on hand for this purpose [Some stingless bees also use resin and cerumen pieces to barricade the nest entrance at night, or when disturbed  ,66. Some purpose . When th purpose ,12.Trigona moorei) initiate a nest, they begin by building a provisional batumen structure to establish ant-free spaces. They then expand this resinous shield as they burrow deeper into the ants’ nest [Scaura latitarsus; these bees form their nest by excavating a cavity in an active termite nest and lining that cavity with a continuous batumen shell [Stingless bees that live in active termite or ant nests often surround their cavities with a full defensive resin barrier. This allows them to inhabit otherwise hostile environments. For instance, when some myrmecophilous stingless bees , and itt et al. . When cet et al. . They tht et al. , or trapt et al. ,14,68,69t et al. .Melipona subnitida, Harano et al. [Tetragonula carbonaria is covered with resin, so that the whole body is sticky; a thin layer of resin has been observed on the legs, head, and thorax of Tetragonsica angustula, and Trigona (Tetragonula) melanocephala nectar foragers have been observed leaving the nest with resin in their corbiculae [Stingless bees do not just apply resin to the bodies of intruders; some species apply resin to their own bodies as well , the head secretions and mandibular gland extract of the robber bee Lestrimelitta limao (Smith) elicited increased resin transport and the barricading of the nest entrance tube with hardened resin balls [Tetragonilla collina, resin foraging activity increased after nest entrances were damaged, and doubled after ant attack; worker bees used resin to elongate their entrance tubes and fortify them with a barrier of resin droplets [Resin-based defenses can be triggered by both visual stimulation and chemical cues. In in balls . In Tetrdroplets .A. mellifera, the presence of a propolis envelope has been found to decrease the severity of multiple brood diseases [Ascosphaera apis, the causative agent of the larval disease chalkbrood. This suggests that honey bee colonies use resin to self-medicate in response to certain pathogens [Lysinibacillus sphaericus, which causes broods to degenerate, there are no known examples of pathogenic microbes in stingless bee colonies . HoweveAlthough resin is essential to many aspects of stingless bee nest construction and defense, little is known about how stingless bees obtain this vital resource. Some information on resin foraging can be gleaned from studies on general foraging behavior ,79,80,81Tetragonula minangkabau, Heterotrigona itama, Trigonella moorei, Melipona bicolor bicolor, Trigona sapiens, and Trigona hockingsi) [Melipona bicolor schencki (Gribodo), Trigona iridipennis (Smith), and Melipona fasciculata (Smith)) [Melipona asilvai [Tetragonula carbonaria, resin foragers can account for up to 50% of the foraging force [Tetragonilla collina, up to 90% of foragers have been observed returning with resin, likely during periods of nest construction [A. mellifera, where resin foragers make up only 1–3% of the foraging force [Resin foragers make up <10% of the foraging force for many species  ,82,83, a(Smith)) ,81,84. H asilvai ). For Teng force . For Tettruction . This isng force .Trigona iridipennis, Melipona asilvai, Melipona bicolor schencki, and Melipona colimana) resin foraging activity fluctuates seasonally, but for other species , resin foraging is constant throughout the year [Melipona bicolor bicolor), resin foraging increases with colony strength (as determined by comb diameter) [Plebeia emerina) hoard resin stores, possibly in preparation for periods of resin scarcity, or in preparation for increased predator or parasite pressure [A variety of environmental  and colony  conditions influence resin foraging frequency at the colony level, and these factors have different effects on different species . For exathe year ,81,84,87iameter) . For othiameter) . For speiameter) . Finallypressure .Tetragonula fuscobalteata (Cameron), Tetragonula (Tetragonula) pagdeni (Schwarz), Tetragonula collina (Smith), and Heterotrigona (Tetrigona) apicalis (Smith)). It is unclear whether and how resin-bearing males contribute to colony function, but since they were not seen depositing their loads in storage pots or on other nest structures, the authors concluded that male bees do not contribute significantly to resin foraging.Resin collection is primarily carried out by worker bees . CuriousMelipona beecheii, Biesmeijer and Tóth [Trigona (Tetragonula) minangkabau (Sakagami and Inoue), Trigona (Heterotrigona) itama (Cockerell), and Trigona (Trigonella) moorei (Schwarz)) and found approximately 50% of foragers to be one-material specialists. In A. mellifera, foragers initiate resin collection when they detect a need for it inside the nest , and use the waggle dance to recruit additional resin foragers [At an individual level, it is unclear what factors drive a forager to choose resin foraging over nectar or pollen foraging. In and Tóth  found thand Tóth . This reand Tóth , who exaforagers . It is uCorymbia torelliana and the stingless bee Tetragonula carbonaria, even minor experimental modifications to a resin odor  resulted in reduced visitation. This demonstrates that stingless bees are capable of learning complex scents and responding to multiple compounds within the resin bouquet, and may be more selective for resin sources than floral sources [When foraging, stingless bees use both visual and olfactory cues to discover and distinguish between resin sources. Specifically, they home in on particular combinations of volatile mono- and sesquiterpenes . This se sources ,23.Trigona fuscipennis and Trigona nigerrima) have been considered pests for agricultural crops [After locating a resin source, stingless bees use their mandibles to gather resin from plant buds, leaves, flowers, or bark. They then use the tarsi and basitarsi on their front and middle legs to load this sticky material onto their corbiculae ,88 see . They real crops . Many stal crops ,65. HowaTrigona jatiformis) seek out resin sources that are too small to be seen with the naked eye; the resin they collect is only identifiable once it has been accumulated in the bees’ corbiculae [Stingless bees demonstrate clear preferences for some resin-producing plants, and neglect others ,24,62. Trbiculae . Larger rbiculae . So far,Plebeia lucii and Frieseomelitta varia foragers seven to thirteen minutes to unload resin back at the hive. Most of this time was spent removing resin residue from their tarsi [Once resin foragers return to the hive, they unload resin from their corbiculae on their own, or with the help of another worker ,55,88. TTetragonisca angustula and the trochanter of invader ant Camponotus sericeiventris. They determined that resin actually adheres more to the smooth bee mandible than it does to the scaled ant trochanter. This suggests that stingless bees must utilize a lubricating substance  to reduce adhesion of resin to mandibles.How do stingless bees handle the sticky substance that they use to immobilize and kill their enemies, without harming themselves? Stingless bee body parts do not appear to possess inherently anti-adhesive properties. Gastauer et al.  used eleT. angustula, Plebeia emerina, and Trigona (Hypotrigona) grihodoi, resin handling is a task reserved for advanced-age workers [P. emerina suggested that when workers reach a certain developmental stage, they begin to produce secretions that help maintain propolis viscosity and allow the bees to handle this material without getting stuck [Some studies suggest that the ability to produce lubricating substances and avoid adhesive hazards is associated with bee age and physiological development. In  workers ,88,95. Ang stuck . The devMelipona quadrifasciata [There is some evidence for a genetic basis for “propolis preparation”—presumably resin handling—in fasciata . In one fasciata . This stFor some stingless bee species, the presence of resin inside the nest space can also influence the physical properties of the bees themselves. The outer layer of the insect cuticle is made up of lipid compounds that serve a variety of functions. These compounds help protect insects from predators, desiccation, and abrasion, and they also play a role in nestmate recognition and other forms of communication . The so-A. mellifera. This trait appears to have emerged separately in multiple stingless bee lineages. It occurs in more evolutionarily derived genera and is generally absent from more basal genera , with at least one exception [Among social insects, stingless bees are the only group known to enrich their cuticular chemical profile with resin-derived compounds ,74. To oxception ,103. Desxception ,103,104.xception ,104. LeoTetragonula carbonaria, a bee that collects extensive amounts of resin, whose cuticular compounds are 50% resin-derived, and Austroplebeia australis, a bee that collects minimal resin, whose cuticular compounds are just 1% resin-derived. In behavioral assays, high-resin T. carbonaria bees repelled predator ants, but low-resin A. australis did not. Washing both bee species diminished the ants’ preference, suggesting that repellant properties can be attributed to the resin-derived compounds found on the bees’ cuticle [Recent studies have demonstrated that a resin-enriched cuticular chemical profile can help protect bees from predators and may reduce interspecific aggression, facilitating nest aggregations. Resin confers repellant properties to the cuticle of some stingless bee species, adding to the effects of the genetically determined repellent compounds that the bees produce themselves . The rep cuticle .Tetragonula melanocephala, a stingless bee whose cuticle lacks sesquiterpenes, and found that applying either pure sesquiterpenes or an extract derived from the sesquiterpene-rich cuticle of Tetragonula collina  to non-nestmates resulted in decreased aggression. Based on these results, the authors suggested that sesquiterpenes may facilitate nesting aggregations in tropical environments, but more research is needed to determine the precise role that resin-derived compounds play in mediating complex inter- and intraspecies interactions.Resin-derived terpenes present in the cuticle might also help facilitate nest aggregations. These compounds may mask chemical differences between bee species, contributing to reduced interspecific aggression . One stuTetragonisca angustula workers to extracts made from nestmate and non-nestmate resin or wax, all treatments resulted in decreased acceptance rates, regardless of the material source. In the same study, Jones et al. [T. angustula. However, it is possible that the artificial transfer of resin-derived compounds  impacted these results. Similarly, conducting behavioral assays only a short time after transferring resin stores from donor colonies to recipient colonies could have led to increased defensive behavior, muddling the nestmate recognition findings. Further studies are needed to determine the potential relationship between nest materials and nestmate recognition in stingless bees.While it is clear that resin-derived compounds contribute to the cuticular chemical profile of many stingless bee species, and this profile is thought to influence nestmate recognition ,107, thes et al.  transferThere is growing interest in sequencing and understanding the functional significance of the microbial communities associated with stingless bees and their nests ,112,113.A. mellifera colonies, researchers have found that the presence of a propolis envelope stabilizes the microbial communities found in bees’ guts and on the cuticle of their mouthparts. The propolis envelope is thought to support the proliferation of putatively beneficial bacterial associates, and reduce the expression of pathogenic or opportunistic microbes [Recent studies provide some insight into these complex interactions. In microbes ,20. HoweFrieseomelitta varia, Melipona quadrifasciata, Tetragonisca angustula, and Trigona spinipes) [One recent study compared the bacterial communities associated with the interior nest surfaces of four stingless bee species (pinipes) . DiffereTetragonula carbonaria and Trigona hockingsii), and one that uses almost no resin . DNA was extracted from six worker bees from ten different colonies, and whole-bee microbiomes were compared. Species-specific differences in microbial communities were observed. However, more species must be sampled to determine whether these changes can be attributed to the presence or absence of resin. Moreover, since many additional species-specific factors  can influence microbial communities [A. mellifera studies) may be instructive.Leonhardt and Kaltenpoth  used seqmunities ,120, witT. carbonaria) and low-resin  bees, to determine whether a resin-rich environment confers antimicrobial properties to the stingless bee cuticle [A. australis has evolved compensatory physiological traits  to replace resin resources, as proposed by Roubik [Another study examined the rate of mold growth on the bodies of some of the same high-resin  impact stingless bee health?How does the presence and prevalence of resin in the nest space impact other aspects of the stingless bee nest ecosystem and colony function? Since resin is present throughout the nest in the form of cerumen and is in direct contact with both brood and food stores, it is possible that resin-derived compounds may leech into stingless bee honey and pollen, enriching these food sources with phytochemicals . Honey ppropolis . Does reAs previously mentioned, the microbiota associated with stingless bees and their nests is a vast and fascinating area, the advancement of which could inform questions relating to the chemical ecology of stingless bees, among other aspects of colony function. For example, do the resin-derived compounds that comprise the cuticular chemical profiles of some stingless bee species impact their cuticular microbiome? How does this affect the ability of the cuticular chemical profile to repel predators, reduce aggression, etc.? Does the cuticular microbiome, in turn, influence the cuticular chemical profile? Does resin help shape the microbiota associated with stingless bees and their nests? How does this impact colony function?A. mellifera? If so, how does immune expression compare in high-resin and low-resin species? Future stingless bee research could draw from recent honey bee research [A. mellifera foragers use olfactory cues to locate resin sources, as occurs in stingless bees, and whether the presence of a propolis envelope influences the cuticular chemical profile of A. mellifera.There are interesting points of overlap—and important differences—in resin use by honey bees and stingless bees. These points of comparison could inform future research in both study systems. For instance, does resin use constitute a social immunity mechanism in stingless bees ? Does reresearch ,32 to inUnderlying all of these questions is the need for more research on the natural history of stingless bees. Many of the predominant natural history studies in this field date back over half a century and cover a relatively small number of species. While informative, these studies cannot be considered representative because stingless bees are so diverse, and resin use is such a variable trait. More research is needed to add further breadth to the foundational studies that figure so strongly into current conceptions of resin use in stingless bees. In this pursuit, and in other areas of future research, there is an important opportunity to partner with and follow the leadership of the stingless beekeepers, indigenous communities, and stewards of local ecological knowledge that have been in relationship with stingless bees for generations.Understanding the role of resin use in stingless bee colony function grows increasingly urgent as changes in beekeeping and land use practices occur, potentially diminishing stingless bees’ ability to incorporate resin into their nest environment ,4,15. InA deeper understanding of the importance of resin use for stingless bee colony function could lend support to the conservation of resin-rich non-floral resources that might otherwise be overlooked . Since b