3. Adolescents' Perceptions of Mental Health around the World: Key Findings from a 13-Country Qualitative Study

Purpose: Adolescence (ages 10-19) is a sensitive developmental period for the emergence of mental and behavioral health problems, but there is a lack of multi-country qualitative studies that explore how adolescents themselves understand these critical challenges. As part of UNICEF's 2021 State of the World's Children Report, the Global Early Adolescent Study collaborated with organizations in 13 countries to hold a series of focus group discussions (FGDs) with adolescents focused on mental health. These FGDs aimed to (1) understand adolescents' perspectives on significant mental health challenges in their age group, (2) understand adolescents' perspectives on the key risk and protective factors driving these challenges, and (3) understand the ways in which adolescents cope with these challenges, including barriers and facilitators to help-seeking. Methods: A total of 71 FGDs were conducted across 13 countries between February and June of 2021. Countries were selected to ensure geographic, economic, and cultural diversity, and included: Belgium, Chile, China, the Democratic Republic of Congo, Egypt, Indonesia, Jamaica, Jordan, Kenya, Malawi, Sweden, Switzerland, and the United States. Within each country, FGDs were stratified by sex and age such that there were at least two younger (ages 10-14) and two older (ages 15-19) focus groups. Depending on the COVID-19 restrictions at the time, FGDs were either held in-person or online. All FGDs were held in local languages and lasted between 60 and 90 minutes. FGDs were recorded, transcribed verbatim, and translated into English when necessary. These English translations were then coded and analyzed using an inductive thematic analysis approach. Results: Across diverse cross-cultural settings, a number of consistent findings emerged from the voices of adolescents. In particular, adolescents around the world emphasized the many contexts that drive mental health challenges, including family adversity, community violence, unsupportive school environments, poverty, social media culture, and restrictive gender norms. They also discussed significant barriers to seeking help for mental health challenges, such as community stigma, lack of social support, and fears of invalidation. These barriers frequently resulted in adolescents coping with these challenges without support, often using maladaptive strategies. Importantly, adolescents generally described and understood mental health in terms of distress (e.g., sadness, loneliness, shame, anger) rather than disorder (e.g., depression, anxiety). Conclusions: Above all, it was clear that adolescents around the world need much better formal and informal supports to adequately address mental and behavioral health problems, and that these responses must take into account the many contexts that contribute to these problems. Further, the non-clinical terminology frequently used by adolescents suggests that taking a purely diagnostic approach in addressing mental health challenges may exclude many adolescents in need of assistance. Sources of Support: Wellcome Trust.

HALF OF OLDER ADULTS HOSPITALIZED WITH COVID-19 EXPERIENCE SYMPTOMS ONE YEAR LATER

Older adults hospitalized with severe COVID-19 are at higher risk of experiencing serious in-hospital outcomes and long-term health consequences following discharge. Declines in health and functional ability post-hospitalization are important infection-related outcomes. This study's aim was to examine functional recovery one year following COVID-19 hospitalization. Twenty-one adults ≥60 years of age hospitalized with confirmed COVID-19 infection between 3/2020–5/2020 in Southeast Michigan completed a survey 9–15 months post-discharge including items from the Fried Frailty score, Short Form 36 Physical Assessment, PROMIS Dyspnea Scale, and the World Health Organization Disability Assessment Schedule. Mean age at hospital admission was 69 (standard deviation 7). Half of participants (52%) indicated they had too little energy to do the things they wanted to do, 52% (n=11) indicated moderate to severe shortness of breath when walking up two flights of stairs, and 43% (n=9) indicated they were limited a lot in walking several blocks. Additionally, 57% (n=12) indicated they were severely or extremely emotionally affected by their health due to their COVID-19 infection. Results were similar in only those ≥70 years (n=7). Our survey indicates that half of patients hospitalized with severe COVID-19 from the first infection wave in Southeast Michigan are significantly affected up to a year or more after their initial infection, and may benefit from long-term outpatient care. More research is needed to inform development of effective treatments for the long-term emotional and physical impacts of severe COVID-19.

Practice of cardiac rehabilitation at the beginning of the COVID-19 pandemic: Challenges and responses

Despite the upheavals in health care systems related to the onset of the COVID-19 pandemic, cardiac rehabilitation (CR) needs to continue for inpatients experiencing recent cardiac surgery or severe heart failure because CR improves patient outcomes, reduces readmissions and lowers long-term costs. Our aim is to share the strategies implemented in our facility to minimize the risk of COVID-19 transmission and thus ensure safe and efficient CR for the inpatients. We describe the guidelines that were applied in our cardiac rehabilitation unit (CRU) during the containment phase in France, from March 17 to May 11, 2020. We report the incidence of COVID-19 confirmed cases by RT-PCR testing among symptomatic inpatients and health care workers (HCWs) within the same timeframe. Our strategy was focused on isolation of all inpatients and protection of the professionals. The main measures were systematically placing admitted patients in a single room, generalizing the use of surgical masks for HCWs and inpatients, suspending day hospital activity. The CR program was based on individual exercise and education, plus collective activities involving 2 or 3 patients with respect of enhanced barrier measures. From March 17, to May 11, 2020, 97 patients have been hospitalized in the CRU. The average length of stay was 24 days. Five members of the health care staff (5/205, 2.4%) were suspected cases and all tested negative for COVID-19. Eighteen inpatients (18/97, 18%) tested for COVID-19 and 2 (2/18, 11%) tested positive. Patient No. 1 had a positive test 10 days after her admission to the CRU. Patient No. 2 tested positive on the day of his admission. Both had recent cardiac surgery. They were transferred back to the hospital. No secondary case was detected in the CRU. CR can be performed in a safe way for both inpatients and HCWs during the COVID-19 pandemic era. In our experience, strict isolating and protecting measures are efficient to avoid nosocomial SARS-CoV-2 spread in CRUs.

Discrete Latent Variables Discovery and Structure Learning in Mixed Bayesian Networks

Latent variables pose a challenge for accurate modelling, experimental design, and inference, since they may cause non-adjustable bias in the estimation of effects. While most of the research regarding latent variables revolves around accounting for their presence and learning how they interact with other variables in the experiment, their bare existence is assumed to be deduced based on domain expertise. In this work we focus on the discovery of such latent variables, utilizing statistical hypothesis testing methods and Bayesian Networks learning. Specifically, we present a novel method for detecting discrete latent factors which affect continuous observed outcomes, in mixed discrete/continuous observed data, and device a structure learning algorithm that adds the detected latent factors to a fully observed Bayesian Network. Finally, we demonstrate the utility of our method with a set of experiments, in both controlled and real-life settings, one of which is a prediction for the outcome of COVID-19 test results. © 2021 IEEE.

Results of the PCM-204 phase 2b trial of partial-gland ablation for men with intermediate-risk prostate cancer with padeliporfin (WST11 or TOOKAD) vascular-targeted photodynamic therapy

INTRODUCTION AND OBJECTIVE: Padeliporfin (WST11) vascular-targeted photodynamic therapy (VTP) has shown significant clinical benefit as a localized partial gland ablation (PGA) therapy when compared to active surveillance for low-risk prostate cancer, by curbing progression and the need for radical treatment, leading to its regulatory approval in Europe. This Phase 2b trial prospectively investigated WST11-VTP for intermediate-risk cancers. METHODS: 50 men with unilateral Grade Group 2 (GG2) cancers (Gleason 3+4) evaluated with MRI and ultrasound-guided (TRUS) biopsy were treated with up to 2 sessions of unilateral PGA using padeliporfin VTP. Eligibility criteria included <cT2b, PSA <10, and fusion biopsy for PIRADS 3+ lesions on pretreatment MRI. Contralateral very lowerisk disease was observed. MRI and systematic, 14-core TRUS biopsy (+/- fusion) were performed 3 and 12 months after treatment, evaluating for Gleason Grade 4 or 5 (≥GG2) cancer as the primary endpoint. Additional data included adverse events and patient-reported quality of life. The study was powered using β=0.2 to reject the null hypothesis (r≥70%), using a one-sided exact binomial test with 5% alpha risk. To be valid, 44 evaluable patients were required by the 12-month primary endpoint. Treatment safety and patient-reported quality of life for sexual and urinary function were assessed with validated questionnaires (IIEF-15 and IPSS, respectively). RESULTS: 46 men were evaluable for the 12-month primary endpoint. Before 12 months, 1 man proceeded to prostatectomy (treatment failure), 2 men refused 12-month biopsy, and 1 man died of COVID-19. 12/49 (24%) underwent per-protocol second hemiablation treatment for GG2 tumor at 3 months: 9 for residual cancer and 4 with newly identified contralateral GG2 tumors (1 bilateral). 45 of the 46 evaluable men underwent 12-month biopsy: 38 (83%) had no Gleason grade 4 or 5 cancer, including 11/12 (92%) patients receiving 2 treatments. By 3 months, median decline in IIEF-5 score from baseline was -1.0 (IQR -7,0). Median improvement in IPSS score was -1.0 (IQR -1,5), with pad-free continence observed in 100% of patients. Median change in IIEF score by 12-months was -1.0 (IQR -5,0). Grade 3 treatment-related adverse events occurred in 6 (12%) patients;all procedure-related prostate/pelvic pain resolved by 3 weeks. CONCLUSIONS: These positive trial results show that WST11- VTP is effective for PGA of intermediate-risk prostate cancer with minimal toxicity including impact on urinary and sexual function, consistent with the Phase 3 trial results in low-risk disease. Based on these data this therapy bears consideration for approval as a conservative therapeutic option for selected cases of intermediate risk disease.

Phase 2b trial results of padeliporfin (WST11 or Tookad) vascular-targeted photodynamic therapy for partial gland ablation in men with intermediate-risk prostate cancer

Background: Padeliporfin (WST11) vasculartargeted photodynamic therapy (VTP) has shown significant clinical benefit as a localized partial gland ablation (PGA) therapy when compared to active surveillance for low-risk prostate cancer, by curbing progression and the need for radical treatment, leading to its regulatory approval in Europe. This phase 2b trial prospectively investigated WST11-VTP for intermediate-risk cancers. Methods: Men with unilateral Grade Group 2 (GG2) cancers (Gleason 3+4), evaluated with MRI and ultrasound-guided (TRUS) biopsy, underwent up to two WST11-VTP PGA sessions. Eligibility criteria included <cT2b, PSA < 10, and fusion biopsy for PIRADS 3+ lesions on pretreatment MRI. Contralateral very low-risk disease was observed. The primary endpoint was prevalence of any Gleason Grade 4 or 5 (≥GG2) cancer, determined by MRI and systematic, 14-core TRUS biopsy of the entire gland (+/- fusion) at 3 and 12 months after treatment. Treatment safety and patient-reported quality of life for sexual and urinary function were assessed with validated questionnaires (IIEF-15 and IPSS, respectively). The study was powered using β = 0.2 to reject the null hypothesis (r≤70%), using a one-sided exact binomial test with 5% alpha risk. To be valid, 44 evaluable patients were required for the 12-month primary endpoint assessment. Results: Of the 50 men treated, 46 were evaluable for the 12-month primary endpoint. Before 12 months, 1 man proceeded to prostatectomy (treatment failure), 2 men refused 12-month biopsy, and 1 man died of COVID-19. At 3 months, 12/49 (24%) men underwent per protocol second WST11-VTP PGA session for GG2 tumor: 9 for residual cancer and 4 for newly identified contralateral GG2 tumors (1 bilateral). The 12-month biopsy was performed in 45 men;38 (83%) had no Gleason grade 4 or 5 cancer, including 11/12 (92%) patients who underwent 2 PGA sessions. By 3 months, median decline in erectile function score (IIEF-5) from baseline was -1.0 (IQR -7,0). Median improvement in urinary function score (IPSS) was -1.0 (IQR -1,5), with pad-free continence observed in all patients. Median change in IIEF score by 12-months was -1.0 (IQR -5,0). Grade 3 treatment-related adverse events occurred in 6 (12%) patients. All procedurerelated prostate/pelvic pain resolved by 3 weeks. Conclusions: The positive results from this trial show that WST11-VTP is effective for PGA of intermediate-risk prostate cancer, with minimal toxicity or impact on urinary and sexual function, consistent with the phase 3 trial results in low-risk disease. Based on these data, this therapy bears consideration for approval as a conservative therapeutic option for selected cases of intermediate-risk disease.

A Guide for Urogynecologic Patient Care Utilizing Telemedicine during the COVID-19 Pandemic: Review of Existing Evidence

The novel coronavirus (COVID-19) pandemic has had a major impact on how patients are evaluated and treated for diseases and conditions in normal patient care. Due to lack of effective treatments for this virus or vaccines to prevent infection, focus is placed on infection prevention through use of social distancing, quarantine, and face masks. To prevent COVID-19 infections in healthcare settings, the Centers for Disease Control and Prevention has recommended decreasing or eliminating nonurgent office visits. Telehealth has emerged as an alternative way to deliver effective patient care, while reducing patient and physician exposure to the virus. Telehealth is any remote healthcare process, including provider training or team meetings, whereas telemedicine refers to use of specific technology to connect a patient to a provider. High quality of care can and must be provided by Female Pelvic Medicine and Reconstructive Surgeons (FPMRS) as well as other specialists and health professionals using telemedicine. Because of the health care emergency during the pandemic, the Centers for Medicare and Medicaid Services have broadened access to and reimbursement for telemedicine services. Rapid advances in communications technology and widespread wireless access in many modern households have allowed the adoption and integration of telemedicine into urogynecology and other health practices. There are no clear guidelines for the use of telemedicine in FPMRS. The aim of this study was to conduct an expedited review of the evidence and to provide guidance for managing common outpatient FPRMS conditions during the COVID pandemic using telemedicine. FPMRS conditions were grouped into those that likely to require different treatment with virtual management compared with in-person visits, and those that could use accepted behavioral counseling and not deviate from current management paradigms. Rapid systematic review methodology was used to screen for articles related to 4 topics: (1) telemedicine in FPMRS, (2) pessary management, (3) urinary tract infections, and (4) urinary retention. In addition, 4 other topics were addressed (based on past systematic reviews and national or international society guidelines): (1) urinary incontinence, (2) vaginal prolapse, (3) fecal incontinence, and (4) defecatory dysfunction. Finally, clinical experience and expertise were pooled to reach consensus on 4 remaining areas: (1) FPMRS conditions amenable to virtual management, (2) urgent care scenarios requiring in-person visits, (3) symptoms that should alert providers to a possible COVID infection, and (4) special consideration for managing patients with known or suspected COVID-19. Overall, behavioral, medical, and conservative management provided in a virtual setting (via phone or Internet communication) will be valuable as first-line treatments. Certain situations were identified that require different treatments in the virtual setting than in person, whereas others were shown to require an in-person visit despite risks of COVID-19 exposure and spread of infection. This study presents guidance for treating FPMRS conditions via telemedicine in a format that can be actively referenced. The strengths of the study include use of an expedited review method, extensive experience of the authors in conducting systematic reviews, as well as being seasoned FPMRS practitioners. Main limitations include the rapid methodology, lack of data regarding many of the pertinent questions, and missed salient studies, because of the expedited evidence methods.