Effectiveness of training primary care internal medicine residents in etonogestrel implants and impact on their future practice: A cross-sectional study.

OBJECTIVE: To evaluate the impact of an etonogestrel implant training program within a primary care Internal Medicine residency training program. STUDY DESIGN: We surveyed graduates of our primary care Internal Medicine residency program in the Bronx, New York who performed implant procedures though the first 32 months after implementation of a monthly faculty-supervised resident implant clinic. We assessed the number of implants placed and removed per graduate, and surveyed graduates' satisfaction with the implant training program, perceived competence with implant procedures, and intent and ability to perform implant procedures and barriers to performing implant procedures postgraduation. RESULTS: Between July 2017 and February 2020, 14 residents placed a total of 34 devices and removed four. All 14 program graduates completed the survey in August 2020. All but one respondent felt this training was valuable and 11 felt competent placing implants without supervision. Although 10 planned to provide implants following graduation, none have been able to, largely because of credentialing and clinic-practice level barriers. CONCLUSIONS: The primary care Internal Medicine program graduates we surveyed (n = 14) valued our etonogestrel implant training program and perceived competence, particularly with implant placement. However, even those who intended to provide etonogestrel implants postgraduation were unable to do so. IMPLICATIONS: Internal Medicine residents trained to place and remove etonogestrel implants are most comfortable with implant placement. However, these physicians may face barriers related to credentialing and ambulatory practice scope when attempting to provide this care in clinical practice.

Tumor-targeted CD28 bispecific antibodies enhance the antitumor efficacy of PD-1 immunotherapy.

Monoclonal antibodies that block the programmed cell death 1 (PD-1) checkpoint have revolutionized cancer immunotherapy. However, many major tumor types remain unresponsive to anti-PD-1 therapy, and even among responsive tumor types, most of the patients do not develop durable antitumor immunity. It has been shown that bispecific antibodies activate T cells by cross-linking the TCR/CD3 complex with a tumor-specific antigen (TSA). The class of TSAxCD3 bispecific antibodies have generated exciting results in early clinical trials. We have recently described another class of "costimulatory bispecifics" that cross-link a TSA to CD28 (TSAxCD28) and cooperate with TSAxCD3 bispecifics. Here, we demonstrate that these TSAxCD28 bispecifics (one specific for prostate cancer and the other for epithelial tumors) can also synergize with the broader anti-PD-1 approach and endow responsiveness-as well as long-term immune memory-against tumors that otherwise do not respond to anti-PD-1 alone. Unlike CD28 superagonists, which broadly activate T cells and induce cytokine storm, TSAxCD28 bispecifics display little or no toxicity when used alone or in combination with a PD-1 blocker in genetically humanized immunocompetent mouse models or in primates and thus may provide a well-tolerated and "off the shelf" combination approach with PD-1 immunotherapy that can markedly enhance antitumor efficacy.

Undocumented African Immigrants' Experiences of HIV Testing and Linkage to Care.

In the United States, undocumented African immigrants living with HIV enter care late, potentially leading to adverse individual and population health outcomes, yet little is known about the specific experiences of HIV diagnosis and linkage to care among this population. We conducted individual, semi-structured interviews with adults who were undocumented African immigrants living with HIV in New York City. Interviews explored perspectives regarding individual, social, institutional, and societal barriers and facilitators of HIV testing and linkage to care. Of 14 participants from 9 different African countries, 9 were women and the median age was 44 years (interquartile range: 42-50). Participants described fear of discovery by immigration authorities as a substantial barrier to HIV testing and linking to initial medical appointments. Actual and perceived structural barriers to both testing and care linkage included difficulty obtaining health insurance and a belief that undocumented immigrants are ineligible for any health services. Participants also expressed reluctance to be tested because of HIV-related stigma within the immigrant communities that they heavily relied on. After diagnosis, however, participants overwhelmingly described a positive role of health and social service providers in facilitating linkage to HIV care. Concerns about immigration status and HIV-related stigma are significant barriers to HIV testing and linkage to care among undocumented African immigrants. Multilevel efforts to reduce stigma and increase awareness of available services could enhance rates of HIV testing and care linkage in this population.

Quantification of facial skeletal shape variation in fibroblast growth factor receptor-related craniosynostosis syndromes.

BACKGROUND: fibroblast growth factor receptor (FGFR) -related craniosynostosis syndromes are caused by many different mutations within FGFR-1, 2, 3, and certain FGFR mutations are associated with more than one clinical syndrome. These syndromes share coronal craniosynostosis and characteristic facial skeletal features, although Apert syndrome (AS) is characterized by a more dysmorphic facial skeleton relative to Crouzon (CS), Muenke (MS), or Pfeiffer syndromes. METHODS: Here we perform a detailed three-dimensional evaluation of facial skeletal shape in a retrospective sample of cases clinically and/or genetically diagnosed as AS, CS, MS, and Pfeiffer syndrome to quantify variation in facial dysmorphology, precisely identify specific facial features pertaining to these four syndromes, and further elucidate what knowledge of the causative FGFR mutation brings to our understanding of these syndromes. RESULTS: Our results confirm a strong correspondence between genotype and facial phenotype for AS and MS with severity of facial dysmorphology diminishing from Apert FGFR2(S252W) to Apert FGFR2(P253R) to MS. We show that AS facial shape variation is increased relative to CS, although CS has been shown to be caused by numerous distinct mutations within FGFRs and reduced dosage in ERF. CONCLUSION: Our quantitative analysis of facial phenotypes demonstrate subtle variation within and among craniosynostosis syndromes that might, with further research, provide information about the impact of the mutation on facial skeletal and nonskeletal development. We suggest that precise studies of the phenotypic consequences of genetic mutations at many levels of analysis should accompany next-generation genetic research and that these approaches should proceed cooperatively.

Risk factors for Kaposi's sarcoma among HIV-positive individuals in a case control study in Cameroon.

BACKGROUND: Individuals co-infected with Kaposi's sarcoma herpesvirus (KSHV) and Human Immunodeficiency Virus (HIV) are at greatly increased risk of developing Kaposi's sarcoma (KS). The objective of the current analysis is to identify risk cofactors for KS among HIV-positive individuals. METHODS: We conducted a case-control study of KS in Cameroon on 161 HIV-positive and 14 HIV-negative cases and 680 HIV-positive and 322 HIV-negative controls. Participants answered a physician-administered questionnaire and provided blood and saliva specimens. Antibodies against KSHV lytic, K8.1, and latent, ORF73, antigens were measured by ELISA to determine KSHV serostatus. Conditional logistic regression was performed to determine multivariate odds ratios (OR) and 95% confidence intervals (CI) for risk factors associated with KS among HIV-positive cases and controls. RESULTS: Overall, 98% (158) of HIV-positive cases, 100% (14) of HIV-negative cases, 81% (550) of HIV-positive controls, and 80% (257) of HIV-negative controls were KSHV seropositive. Risk factors for KS among HIV-positive individuals included KSHV seropositivity (OR=9.6; 95% CI 2.9, 31.5), non-use of a mosquito bed net (OR 1.9; 95% CI 1.2, 2.9), minority ethnicity (OR=3.1; 95% CI 1.1, 9.3), treatment from a traditional healer (OR=2.3; 95% CI 1.5, 3.7), history of transfusion (OR=2.4; 95% CI 1.5, 3.9), and family history of cancer (OR=1.9; 95% CI 1.1, 3.1). CONCLUSION: KSHV seroprevalence of ≥80% indicates a high prevalence in the general population in Cameroon. Among HIV-positive individuals, the strong association of KS with non-use of mosquito nets and treatment from traditional healers are compelling findings, consistent with recently reported data from East Africa.

Unilateral and bilateral expression of a quantitative trait: asymmetry and symmetry in coronal craniosynostosis.

Bilateral symmetry in vertebrates is imperfect and mild asymmetries are found in normal growth and development. However, abnormal development is often characterized by strong asymmetries. Coronal craniosynostosis, defined here as consisting of premature suture closure and a characteristic skull shape, is a complex trait. The premature fusion of the coronal suture can occur unilaterally associated with skull asymmetry (anterior plagiocephaly) or bilaterally associated with a symmetric but brachycephalic skull. We investigated the relationship between coronal craniosynostosis and skull bilateral symmetry. Three-dimensional landmark coordinates were recorded on preoperative computed tomography images of children diagnosed with coronal nonsyndromic craniosynostosis (N = 40) and that of unaffected individuals (N = 20) and analyzed by geometric morphometrics. Our results showed that the fusion pattern of the coronal suture is similar across individuals and types of coronal craniosynostosis. Shape analysis showed that skulls of bilateral coronal craniosynostosis (BCS) and unaffected individuals display low degrees of asymmetry, whereas right and left unilateral coronal craniosynostosis (UCS) skulls are asymmetric and mirror images of one another. When premature fusion of the coronal suture (without taking into account cranial dysmorphology) is scored as a qualitative trait, the expected relationship between trait frequency and trait unilateral expression (i.e. negative correlation) is confirmed. Overall, we interpret our results as evidence that the same biological processes operate on the two sides in BCS skulls and on the affected side in UCS skulls, and that coronal craniosynostosis is a quantitative trait exhibiting a phenotypic continuum with BCS displaying more intense shape changes than UCS.