The Impact of Social Determinants of Health on Medication Adherence: a Systematic Review and Meta-analysis.

BACKGROUND: Medication adherence (MA) is critical to successful chronic disease management. It is not clear how social determinants of health (SDH) impact MA. We conducted a systematic review and meta-analysis to summarize the evidence on the relationship between SDH and MA. METHODS: We conducted a systematic review of the literature using a Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) format. A literature search was performed using three databases: PubMed, Scopus, and Cochrane Clinical Trials Register in December of 2018. Included studies were completed in the USA, included adults aged 18 years and older, measured at least one social determinant of health, and medication adherence was the primary outcome measure. Data from included full texts were independently extracted using a standardized data extraction form. We then conducted a meta-analysis and pooled the odds ratios from the included studies for each social determinant as well as for all SDH factors collectively. RESULTS: A total of 3137 unduplicated abstracts were identified from our database searches. A total of 173 were selected for full text review after evaluating the abstract. A total of 29 articles were included for this systematic review. Economic-related SDH factors and MA were mostly commonly examined. The meta-analysis revealed a significant relationship between food insecurity (aOR = 0.56; 95% CI 0.42-0.7), housing instability (aOR = 0.64; 95% CI 0.44-0.93), and social determinants overall (aOR = 0.75; 95% CI 0.65-0.88) and medication adherence. DISCUSSION: Food insecurity and housing instability most consistently impacted medication adherence. Although included studies were heterogenous and varied widely in SDH and MA measurements, adverse social determinants overall were significantly associated with lower MA. The relationship between SDH and MA warrants more attention and research by health care providers and policymakers.

Study of comparative surgical exposure to the petroclival region using patient-specific, petroclival meningioma virtual reality models.

OBJECTIVE: Despite advancement of surgical techniques, the attachments of petroclival meningiomas near the central clival depression (CCD) remain difficult to visualize. With existing methods, the amount of tumor near the CCD that is inaccessible through various approaches cannot be compared. Tumors distort the brainstem, changing the size of the operative corridor for some but not all approaches; therefore, using cadavers with normal posterior fossae makes it impossible to compare different approaches to the tumor. The authors used virtual reality (VR) models created from the imaging data of patients to compare various surgical approaches that have otherwise been incomparable in previous studies. METHODS: CT and MRI data obtained in 15 patients with petroclival meningiomas were used to create anatomically accurate 3D VR models. For each model, various surgical approaches were performed, and the surgical freedom to 6 targets of the regions were measured. Furthermore, portions of the tumor that were visually blocked by the brainstem or bony structures were segmented and recorded as blinded volumes for comparison. RESULTS: The extended retrosigmoid approach generated excellent exposure of the petroclival region, but for most specimens, there was inaccessible tumor volume adjacent to the brainstem (mean 641.3 mm3, SE 161.8). In contrast, the brainstem sides of the tumors were well-visualized by all the transpetrosal approaches. The blinded volume of the tumor was largest for the retrolabyrinthine approach, and this was statistically significant compared with all other approaches (mean 2381.3 mm3, SE 185.4). CONCLUSIONS: The authors performed a novel laboratory study by using patient CT and MRI data to generate 3D virtual models to compare surgical approaches. Since it is impossible to perform various approaches in separate surgeries in patients for comparison, VR represents a viable alternative for such comparative investigations.

Transorbital Surgical Corridor: An Anatomic Analysis of Ocular Globe Retraction and the Associated Exposure for the Transpalpebral Orbital Rim Preserving Endoscopic Orbitotomy (TORPEDO) Approach.

BACKGROUND AND OBJECTIVES: The transorbital approach varies by the extent of bony removal and the target. Orbital rim-sparing transorbital approach with removal of only the orbit's posterior wall provides optimal cosmetic results, without the need for reconstruction. The size of this corridor, limited by the medial globe retraction, has not yet been defined and is difficult to determine in cadavers because of postmortem tissue desiccation. By using patient-specific models in virtual reality, precise areas and degrees of surgical freedom (AOF and DOF, respectively) provided by globe retraction were calculated. These measurements define a potential maximum safe AOF and DOF, as well as the globe retraction, needed to achieve a sufficient surgical corridor. METHODS: Using a virtual reality system, transorbital rim-preserving craniectomies were performed. The axial and sagittal DOF as well as AOF were calculated lateral to the globe, limited by the orbital rim and globe, with an anterior clinoid target. The DOFs and AOFs were calculated for each degree of medial globe retraction and analyzed using paired t tests. RESULTS: With only 5 mm of retraction, the AOF was 886 mm 2 , while at 10 mm, the AOF was 1546 mm 2 . This increase between 5 and 10 mm allowed for the largest increase in surgical working corridor ( P = .02). At 15 mm of retraction (previously studied point at which intraocular pressure raises), the AOF averaged 2189 mm 2 and axial DOF averaged 23.1°. Eighteen DOF (a previously studied point needed to achieve sufficient working space for 2 instruments) was achieved at 11 mm on average, generating 1675 mm 2 AOF. CONCLUSION: Globe retraction of 11 mm is needed to achieve sufficient DOF for 2 surgical instruments, and 15 mm of retraction is a conservative limit that provides comparable AOFs with similar cranial approaches.

Progressive Orbitotomy and Graduated Expansion of the Supraorbital Keyhole: A Comparison with Alternative Minimally Invasive Approaches to the Paraclinoid Region.

BACKGROUND: Various minimally invasive approaches, such as supraorbital (SO), minipterional (MPT), and translateral orbital (TLO), can access the paraclinoid region. Studies have described these approaches individually but have not directly compared all of them in the same anatomic specimen. METHODS: Using virtual reality models generated from computed tomography studies of living subjects, we simulated TLO, MPT, and variations of SO approaches, without and with removal of the orbital rim and sphenoid wing. We measured the area of freedom (AOF), distance, and angle of attack to 4 paraclinoid targets: anterior clinoid process, optic foramen, lateral superior orbital fissure, and maxillary strut. RESULTS: For superiorly positioned targets, such as anterior clinoid process and optic foramen, MPT provided a larger AOF compared with the supraorbital approach. However, with progressive drilling of the orbital roof and lesser wing of the sphenoid, the SO corridor AOF was equivalent to MPT at the anterior clinoid process and larger at the optic foramen (P = 0.003). To the lateral superior orbital fissure, TLO had the most limited AOF, and MPT had the greatest (P < 0.01 for all comparisons). For the maxillary strut, MPT, TLO, and SO with orbitotomy and sphenoidectomy all provided a similar AOF. CONCLUSIONS: For surgical targets in the paraclinoid region, MPT provided a greater AOF and shorter distance compared with TLO and limited SO approaches. With progressive enlargement of the SO corridor, SO with orbitotomy and sphenoidectomy matched and occasionally superseded the AOF of MPT. However, the AOF to inferomedial targets such as the maxillary strut was similar among all approaches.

Targeted Screening for HIV Pre-Exposure Prophylaxis Eligibility in Two Emergency Departments in Washington, DC.

Pre-exposure prophylaxis (PrEP) is an effective method to prevent HIV acquisition in high-risk individuals. This cross-sectional survey study estimated the proportion of patients who were PrEP eligible among a targeted sample of emergency department (ED) patients with chief complaints indicative of HIV risk. Research assistants screened a convenience sample of adult patients who presented to two hospital EDs in Washington, DC, during a 6-month period with genitourinary, substance use, or intentional injury-related complaints. Patients with these complaints who reported being sexually active within the past 6 months and HIV negative completed a computer-assisted survey that included questions on sexual practices and partners, substance use, and attitudes and knowledge about PrEP. We used the Centers for Disease Control and Prevention (CDC) clinical guidelines to determine whether PrEP use was indicated. We report differences in PrEP eligibility by demographic characteristics, knowledge, and attitudes. Of the 410 participants, the majority were black (85%), and heterosexual females (72%). PrEP use was indicated in 20% (N = 84), most commonly because of condomless sex with a person of unknown HIV status (82%) and/or a sexually transmitted infection (STI) diagnosis (41%). One-third (34%) of participants had heard of PrEP. Overall, 36% of the sample (N = 148) wanted to learn more about PrEP while in the ED. The percentage who wanted to learn more about PrEP was higher among PrEP-eligible patients (52%) compared with PrEP-ineligible patients (32%). Using CDC criteria, targeted screening identified that a substantial proportion of ED patients are PrEP eligible based on their self-reported behaviors.

Combining DNMT and HDAC6 inhibitors increases anti-tumor immune signaling and decreases tumor burden in ovarian cancer.

Novel therapies are urgently needed for ovarian cancer, the deadliest gynecologic malignancy. Ovarian cancer has thus far been refractory to immunotherapies that stimulate the host immune system to recognize and kill cancer cells. This may be because of a suppressive tumor immune microenvironment and lack of recruitment and activation of immune cells that kill cancer cells. Our previous work showed that epigenetic drugs including DNA methyltransferase inhibitors and histone deacetylase 6 inhibitors (DNMTis and HDAC6is) individually increase immune signaling in cancer cells. We find that combining DNMTi and HDAC6i results in an amplified type I interferon response, leading to increased cytokine and chemokine expression and higher expression of the MHC I antigen presentation complex in human and mouse ovarian cancer cell lines. Treating mice bearing ID8 Trp53-/- ovarian cancer with HDAC6i/DNMTi led to an increase in tumor-killing cells such as IFNg+ CD8, NK, and NKT cells and a reversal of the immunosuppressive tumor microenvironment with a decrease in MDSCs and PD-1hi CD4 T cells, corresponding with an increase in survival. Thus combining the epigenetic modulators DNMTi and HDAC6i increases anti-tumor immune signaling from cancer cells and has beneficial effects on the ovarian tumor immune microenvironment.

Epigenetic therapy for ovarian cancer: promise and progress.

Ovarian cancer is the deadliest gynecologic malignancy, with a 5-year survival rate of approximately 47%, a number that has remained constant over the past two decades. Early diagnosis improves survival, but unfortunately only 15% of ovarian cancers are diagnosed at an early or localized stage. Most ovarian cancers are epithelial in origin and treatment prioritizes surgery and cytoreduction followed by cytotoxic platinum and taxane chemotherapy. While most tumors will initially respond to this treatment, recurrence is likely to occur within a median of 16 months for patients who present with advanced stage disease. New treatment options separate from traditional chemotherapy that take advantage of advances in understanding of the pathophysiology of ovarian cancer are needed to improve outcomes. Recent work has shown that mutations in genes encoding epigenetic regulators are mutated in ovarian cancer, driving tumorigenesis and resistance to treatment. Several of these epigenetic modifiers have emerged as promising drug targets for ovarian cancer therapy. In this article, we delineate epigenetic abnormalities in ovarian cancer, discuss key scientific advances using epigenetic therapies in preclinical ovarian cancer models, and review ongoing clinical trials utilizing epigenetic therapies in ovarian cancer.

Confounding risk factors and preventative measures driving nephrolithiasis global makeup.

Nephrolithiasis is increasing in developed and developing countries at an alarming rate. With the global spike in kidney stone diseases, it is crucial to determine what risk factors are influencing the current global landscape for kidney stones. Our aims for this review are: to identity and analyze the four categories of risk factors in contributing to the global scale of stone formation: lifestyle, genetics, diet, and environment; and discuss preventative measures for kidney stone formation. We also performed data search through the published scientific literature, i.e., PubMed® and found that there is a significant link between lifestyle and obesity with cases of calcium stones. Food and Agriculture Organization of the United Nations and World Health Organization factor indicators for dietary intake and obesity, along with climate data were used to create the projected total risk world map model for nephrolithiasis risk. Complete global analyses of nephrolithiasis deplete of generalizations is nearly insurmountable due to limited sources of medical and demographic information, but we hope this review can provide further elucidation into confounding risk factors and preventative measures for global nephrolithiasis analysis.