Cytomegalovirus Esophagitis in an Immunocompromised Patient.

Cytomegalovirus (CMV) can present with end-organ disease (EOD), particularly in patients with a CD4 cell count <50/mm3. While EOD in immunocompromised patients commonly presents as CMV retinitis (30%) and CMV colitis (5-10%), CMV esophagitis is rare. CMV is the third most common infectious esophagitis following Candida and Herpes Simplex. CMV esophagitis presents with odynophagia, dysphagia, and abdominal pain. Endoscopic exam may reveal large, linear distal esophageal ulcers. Histopathology or serology studies are diagnostic, though serology may be unreliable in the extremely immunosuppressed. Current treatment consists of antivirals such as ganciclovir and valganciclovir. Esophageal disease due to CMV carries a poor prognosis in the immunocompromised. We present the case of a 56-year-old male with a medical history of HIV/AIDS and stage III rectal squamous cell cancer who presented with shortness of breath, weakness, and chronic diarrhea. His HIV was previously well-controlled on antiretroviral therapy. However, due to his malignancy, he was undergoing treatment with chemotherapy and radiation. Initial labs revealed a CD4 count of 42. His clinical course consisted of Escherichia coli septicemia, new-onset atrial fibrillation with a rapid ventricular response, worsening pneumonia, possible metastasis, progressive diarrhea, and potential oropharyngeal candidiasis. Despite several broad-spectrum antimicrobial regimens, he remained symptomatic with new complaints of dysphagia and odynophagia. Eventually, the appearance of vesicular lesions on the lips and a repeat CD4 count of 13 garnered a suspicion of HSV or CMV. This complicated case highlights the necessity for a high index of suspicion of rare manifestations of CMV EOD in an immunocompromised patient presenting with confounding clinical symptoms and extensive diagnoses.

Adenocarcinoma of an Unknown Primary Site: Presentation, Diagnosis, and Management.

Carcinoma of unknown primary (CUP) is a rare metastatic disease in which a primary tumor site cannot be identified. CUP is a diagnosis of exclusion requiring prior workup to identify a primary site. We present a case of a 64-year-old male with vague abdominal pain, a history of gastroesophageal reflux disease (GERD), gastritis, esophagitis, hepatitis C, alcoholic pancreatitis, liver hemangioma, and Warthin tumor, and family history of cancer that was found to have CUP. The diagnosis was made after an extensive workup was done including serum tumor markers, computed tomography (CT) and ultrasound (US) imaging, flow cytometry, and an array of immunohistochemistry stains positive for only cytokeratin 7.

The Past, Present, and Future of Psychotherapy Manuals: Protocol for a Scoping Review.

BACKGROUND: Psychotherapy manuals are critical to the dissemination of psychotherapy treatments. Psychotherapy manuals typically serve several purposes, including, but not limited to, establishing new psychotherapy treatments, training providers, disseminating treatments to those who deliver them, and providing guidelines to deliver treatments with fidelity. Yet, the proliferation of psychotherapy manuals has not been well-understood, and no work has aimed to assess or review the existing landscape of psychotherapy manuals. Little is known about the breadth, scope, and foci of extant psychotherapy manuals. OBJECTIVE: This scoping review aims to identify and explore the landscape of existing book-based psychotherapy manuals. This review aims to specify the defining characteristics (ie, foci, clinical populations, clinical targets, treatment type, treatment modality, and adaptations) of existing book-based psychotherapy manuals. Further, this review will demonstrate how this information, and psychotherapy manuals more broadly, has changed over time. This project aims to make a novel contribution that will have critical implications for current methods of developing, aggregating, synthesizing, and translating knowledge about psychotherapeutic treatments. METHODS: This scoping review will review book-based psychotherapy manuals published from 1950 to 2022.This scoping review will be informed by guidance from the Joanna Briggs Institute Scoping Review Methodology Group and prior scoping reviews. Traditional search and application programming interface-based search methods will be used with search terms defined a priori to identify relevant results using 3 large book databases: Google Books, WorldCat, and PsycINFO. This review will leverage machine learning methods to enhance and expedite the screening process. Primary screening of results will be conducted by at least 2 authors. Data will be extracted and double-coded by research assistants using an iteratively defined codebook. RESULTS: The search process produced 78,600 results, which were then iteratively deduplicated. Following deduplication, 50,583 results remained. The scoping review is expected to identify common elements of psychotherapy manuals, establish how the foci and content of manuals have changed over time, and illustrate coverage and gaps in the landscape of psychotherapy manuals. Results from this scoping review will be critical for future work focused on developing, aggregating, synthesizing, and disseminating knowledge about psychotherapeutic treatments. CONCLUSIONS: This review will provide knowledge about the vast landscape of psychotherapy manuals that exist. Findings from this study will inform future efforts to develop, aggregate, synthesize, and translate knowledge about psychotherapeutic treatments. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/47708.

Psychosocial effects of whole-body MRI screening in adult high-risk pathogenic TP53 mutation carriers: a case-controlled study (SIGNIFY).

BACKGROUND: Germline TP53 gene pathogenic variants (pv) cause a very high lifetime risk of developing cancer, almost 100% for women and 75% for men. In the UK, annual MRI breast screening is recommended for female TP53 pv carriers. The SIGNIFY study (Magnetic Resonance Imaging screening in Li Fraumeni syndrome: An exploratory whole body MRI) study reported outcomes of whole-body MRI (WB-MRI) in a cohort of 44 TP53 pv carriers and 44 matched population controls. The results supported the use of a baseline WB-MRI screen in all adult TP53 pv carriers. Here we report the acceptability of WB-MRI screening and effects on psychosocial functioning and health-related quality of life in the short and medium terms. METHODS: Psychosocial and other assessments were carried out at study enrolment, immediately before MRI, before and after MRI results, and at 12, 26 and 52 weeks' follow-up. RESULTS: WB-MRI was found to be acceptable with high levels of satisfaction and low levels of psychological morbidity throughout. Although their mean levels of cancer worry were not high, carriers had significantly more cancer worry at most time-points than controls. They also reported significantly more clinically significant intrusive and avoidant thoughts about cancer than controls at all time-points. There were no clinically significant adverse psychosocial outcomes in either carriers with a history of cancer or in those requiring further investigations. CONCLUSION: WB-MRI screening can be implemented in TP53 pv carriers without adverse psychosocial outcomes in the short and medium terms. A previous cancer diagnosis may predict a better psychosocial outcome. Some carriers seriously underestimate their risk of cancer. Carriers of pv should have access to a clinician to help them develop adaptive strategies to cope with cancer-related concerns and respond to clinically significant depression and/or anxiety.

Psychosocial morbidity in TP53 mutation carriers: is whole-body cancer screening beneficial?

Germline TP53 mutation carriers are at high risk of developing a range of cancers. Effective cancer risk management is an important issue for these individuals. We assessed the psychosocial impact in TP53 mutation carriers of WB-MRI screening as part of the Surveillance in Multi-Organ Cancer (SMOC+) protocol, measuring their unmet needs, anxiety and depression levels as well as cancer worry using psychological questionnaires and in-depth interviews about their experiences of screening. We present preliminary psychosocial findings from 17 participants during their first 12 months on the trial. We found a significant reduction in participants' mean anxiety from baseline to two weeks post WB-MRI (1.2, 95% CI 0.17 to 2.23 p = 0.025), indicative of some benefit. Emerging qualitative themes show most participants are emotionally supported and contained by the screening program and are motivated by their immediate concern about staying alive, despite being informed about the current lack of evidence around efficacy of screening for people with TP53 mutations in terms of cancer morbidity or mortality. For those that do gain emotional reassurance from participating in the screening study, feelings of abandonment by the research team are a risk when the study ends. For others, screening was seen as a burden, consistent with the relentless nature of cancer risk associated with Li-Fraumeni syndrome, though these patients still declared they wished to participate due to their concern with staying alive. Families with TP53 mutations need ongoing support due to the impact on the whole family system. These findings suggest a comprehensive multi-organ screening program for people with TP53 mutations provides psychological benefit independent of an impact on cancer morbidity and mortality associated with the syndrome. The benefits of a multi-organ screening program will be greater still if the screening tests additionally reduce the cancer morbidity and mortality associated with the syndrome. These findings may also inform the care of individuals and families with other multi-organ cancer predisposition syndromes.

Suicidal ideation in American Indian/Alaska Native and White adolescents: The role of social isolation, exposure to suicide, and overweight.

Social isolation, exposure to suicide, and overweight increase suicidal ideation in adolescents, but no study to date has examined their relative significance in American Indian and Alaska Native (AI/AN) youth. Generalized estimating equations and path analyses were used to measure the significance and mediation of these variables in the suicidal ideation of 721 AI/ANs and 12,107 White adolescents. Social isolation, exposure to suicide, and overweight were risk factors for suicidal ideation in both races, and the associations among the variables of interest and suicidal ideation varied by race. Interventionists need to consider race in the prevention of suicidal ideation in AI/AN and White youth.

Pre-eclampsia in American Indians/Alaska Natives and Whites: The Significance of Body Mass Index.

Introduction The prevalence of pre-eclampsia, a major cause of maternal morbidity, varies by race, being greater in African Americans, and lower in Asians and Hispanics than in White women. Little is known about its prevalence in American Indians/Alaska Natives (AI/ANs). We estimated pre-eclampsia risk in AI/ANs compared to Whites, with consideration of the potential effect of obesity, a major risk factor for pre-eclampsia, and a condition disproportionately affecting AI/AN women. Methods This retrospective cohort study of linked birth-hospital discharge data from Washington State (2003-2013) included all AI/AN women and a sample of White first-time mothers with singleton deliveries. Logistic regression was used to estimate odds ratio (OR) and 95 % confidence intervals (CI) for pre-eclampsia risk in AI/ANs compared to Whites, first controlling for several important risk factors, and subsequently with additional adjustment for pre-pregnancy body mass index (BMI). Results AI/ANs had an increased risk of pre-eclampsia compared to Whites after controlling for all covariates except BMI (OR 1.17, 95 % CI 1.06-1.29). After further adjustment for BMI, the racial disparity in pre-eclampsia risk was greatly attenuated (OR 1.05, 95 % CI 0.95-1.16). Discussion This population-based study suggests that any increased risk in AI/ANs relative to Whites may be at least partly due to differences in BMI.

Medical Comorbidity and Complications.

Like their peers in the general youth population, youth with chronic medical conditions (YCMC) are at risk for substance use, including nonmedical use of prescription medications. However, given dangerous disease-substance interactions, the stakes for detecting and intervening on substance use are perhaps even higher for YCMC. Given the risk for nonadherence with chronic disease management, it is incumbent on primary care providers, specialty providers, and behavioral health specialists to be vigilant in asking about substance use and providing brief counseling and referral to substance use treatment when appropriate.

Blueprint for Action: Visioning Summit on the Future of the Workforce in Pediatrics.

The Federation of Pediatric Organizations engaged members of the pediatric community in an 18-month process to envision the future of the workforce in pediatrics, culminating in a Visioning Summit on the Future of the Workforce in Pediatrics. This article documents the planning process and methods used. Four working groups were based on the 4 domains that are likely to affect the future workforce: Child Health Research and Training, Diversity and Inclusion, Gender and Generations, and Pediatric Training Along the Continuum. These groups identified the issues and trends and prioritized their recommendations. Before the summit, 5 key megatrends cutting across all domains were identified:1. Aligning Education to the Emerging Health Needs of Children and Families 2. Promoting Future Support for Research Training and for Child Health Research 3. Striving Toward Mastery Within the Profession 4. Aligning and Optimizing Pediatric Practice in a Changing Health Care Delivery System 5. Taking Advantage of the Changing Demographics and Expertise of the Pediatric Workforce At the Visioning Summit, we assembled members of each of the working groups, the Federation of Pediatric Organizations Board of Directors, and several invited guests to discuss the 5 megatrends and develop the vision, solutions, and actions for each megatrend. Based on this discussion, we offer 10 recommendations for the field of pediatrics and its leading organizations to consider taking action.

Long-Term Worries after Colposcopy: Which Women Are at Increased Risk?

BACKGROUND: A colposcopy examination is the main management option for women with an abnormal cervical screening test result. Although some women experience adverse psychological effects after colposcopy, those at greatest risk are unknown. We investigated predictors of worries about cervical cancer, sex, future fertility and general health during 12 to 30 months after colposcopy. METHODS: We invited 1,515 women, aged 20 to 59 years with low-grade cervical cytology who attended colposcopy to complete questionnaires at recruitment (∼8 weeks after cytology result) and after 12, 18, 24, and 30 months of follow up. Outcomes were worries about having cervical cancer, having sex, future fertility, and general health at any time during follow-up. Factors significantly associated with each outcome were identified using multiple logistic regression. RESULTS: At one or more time points during follow-up, 40% of women reported worries about having cervical cancer, 26% about having sex, 24% about future fertility, and 60% about general health. For all outcomes except sex, worries reported at recruitment were associated with significantly increased risk of worries during follow-up. Significant anxiety at recruitment was associated with all worries during follow-up. Women diagnosed with CIN2+ had significantly higher risks of worries about cervical cancer and future fertility. Management received was associated significantly with worries about cervical cancer and having sex. Younger women significantly more often reported worries about future fertility, whereas women who had children had reduced risk of future fertility worries but increased risk of cervical cancer worries. CONCLUSION: Clinical, sociodemographic, lifestyle, and psychological factors predicted risk of reporting worries after colposcopy.

Women with large (≥3 cm) and locally advanced breast cancers (T3, 4, N1, 2, M0) receiving neoadjuvant chemotherapy (NAC: cyclophosphamide, doxorubicin, docetaxel): addition of capecitabine improves 4-year disease-free survival.

PURPOSE: To determine whether capecitabine (X), combined with docetaxel (T) following doxorubicin (A) and cyclophosphamide (C), enhanced the pathological complete response (pCR) in the breast and axillary lymph nodes (ALNs) of women with large or locally advanced breast cancers (LLABCs) improving outcome, and the effect on quality of life (QoL). PATIENTS AND METHODS: 117 women were enrolled, 112 randomised to 2 cycles of AC (60 mg/m(2), 600 mg/m(2)) given 3 weekly. Tumour responses were assessed by magnetic resonance mammography. Responders (n = 77) received 2 further cycles of AC and were randomised to 4 cycles of T (100 mg/m(2)) (Group A) or T (75 mg/m(2)) and X (2000 mg/m(2)/day), day one to 14 of each 3 weekly cycle (Group B). Non-responders (n = 35) were randomised to 6 cycles of T (Group C) or T + X (Group D). QoL questionnaires were completed at each chemotherapy visit. Pathological responses were evaluated using established criteria. RESULTS: The groups were comparable in patient and tumour characteristics (79.5% T2, 85.7% ductal, 73.2% ER +ve, 22.3% HER2 +ve, 42% involved ALNs). Overall breast pCR was 27.1%, Groups A + C versus B + D (p = 0.446). ALN +ve pCR was 41.9%, Groups A + C versus B + D (p = 0.231). 4-year disease-free survival (DFS) was significantly improved with X (p = 0.016) but not overall survival (p = 0.056). Triple -ve and HER2 +ve tumours, and persistent ALN disease were risk factors for metastases. X increased severe nail changes (p = 0.0002) and hand-foot syndrome (p = 0.014) without affecting QoL. CONCLUSION: NAC-X did not increase breast and ALN pCR but improved 4-year DFS, without detriment to QoL.

Diversity and inclusion training in pediatric departments.

BACKGROUND AND OBJECTIVE: The diversifying US population of children necessitates assessing the diversity of the pediatric academic workforce and its level of cultural competency training. Such data are essential for workforce and educational policies. METHODS: An 8-question survey was sent to 131 US pediatric chairs to assess plans for diversity, targeted groups, departmental diversity, diversity measures, perceived success in diversity, and presence and type of cultural competency training. RESULTS: In all, 49.6% of chairs responded, and three-quarters of them reported having a plan for diversity, which targeted racial; ethnic; gender; lesbian, gay, bisexual, and transgender; disabled; and social class groups. Of the residents, 75% were women, as compared with 54% of faculty and 26% of chairs. Racial and ethnic diversity was limited among trainees, faculty, and leaders; <10% of each group was African American, Hispanic, or Native American. Asian Americans were more common among trainees (15%-33%) but were less common in faculty and leadership positions (0%-14%). Lesbian, gay, bisexual, and transgender physicians were represented in some groups. Measures of diversity included the number of trainees and faculty, promotion success, climate assessments, and exit interviews. Overall, 69% of chairs reported being successful in diversity efforts. A total of 90% reported cultural competency training for trainees, and 74% reported training for faculty and staff. Training in cultural competency included linguistic training, primarily in Spanish. CONCLUSIONS: Pipeline issues for minorities are ongoing challenges. Pediatric leadership needs more representation of racial and ethnic minorities, women, and LGBT. Suggestions for workforce and educational policies are made.

Synthesis and Investigation of Novel Spiro-isoxazolines as Anti-Cancer Agents.

A series of structurally diverse 4-bromo spiro-isoxazolines possessing a variety of aromatic and aliphatic substituents at the 3 position, were synthesized through a 1,3-dipolar cycloaddition followed by intramolecular cyclization of a pendant hydroxyl or carboxylic acid group. The biochemical antiproliferative activity was evaluated in vitro by using two breast cancer cell lines (MCF-7 and MDA-MB-231) and two prostate cancer cell lines (PC-3 and DU-145) using the MTT viability assay, and the IC50 values were obtained. Spiro-isoxazoline derivatives bearing a p-chloro or an o-dichloro aromatic substituent at the 3-position of the isoxazoline showed considerable antitumor activities in all four cell lines with IC50 value ranging from 43µM to 56µM.

Investing in the health and well-being of young adults.

Contrary to popular perception, young adults-ages approximately 18-26 years-are surprisingly unhealthy. They are less healthy than adolescents, and they also show a worse health profile than those in their late 20s and 30s. The Affordable Care Act provisions to extend coverage for young adults are well known, and some states had already been pursuing similar efforts before the Affordable Care Act was enacted. These initiatives have resulted in important gains in young adults' heath care coverage. However, too little attention has been paid to the care that young adults receive once they are in the system. Given young adults' health problems, this is a critical omission. The Institute of Medicine and National Research Council recently released a report titled Investing in the Health and Well-Being of Young Adults. The report concludes that young adulthood is a critical developmental period and recommends that young adults ages 18-26 years be treated as a distinct subpopulation in policy, planning, programming, and research. The report also recommends action in three priority areas to improve health care for young adults: improving the transition from pediatric to adult medical and behavioral health care, enhancing preventive care for young adults, and developing evidence-based practices.