Risk of interpersonal violence during and after pregnancy among people with schizophrenia: a population-based cohort study.

BACKGROUND: Schizophrenia is associated with increased risk of experiencing interpersonal violence. Little is known about risk specifically around the time of pregnancy. METHODS: This population-based cohort study included all individuals (aged 15-49 yr) listed as female on their health cards who had a singleton birth in Ontario, Canada, between 2004 and 2018. We compared those with and without schizophrenia on their risk of an emergency department (ED) visit for interpersonal violence in pregnancy or within 1 year postpartum. We adjusted relative risks (RRs) for demographics, prepregnancy history of substance use disorder and history of interpersonal violence. In a subcohort analysis, we used linked clinical registry data to evaluate interpersonal violence screening and self-reported interpersonal violence during pregnancy. RESULTS: We included 1 802 645 pregnant people, 4470 of whom had a diagnosis of schizophrenia. Overall, 137 (3.1%) of those with schizophrenia had a perinatal ED visit for interpersonal violence, compared with 7598 (0.4%) of those without schizophrenia, for an RR of 6.88 (95% confidence interval [CI] 5.66-8.37) and an adjusted RR of 3.44 (95% CI 2.86-4.15). Results were similar when calculated separately for the pregnancy (adjusted RR 3.47, 95% CI 2.68-4.51) period and the first year postpartum (adjusted RR 3.45, 95% CI 2.75-4.33). Pregnant people with schizophrenia were equally likely to be screened for interpersonal violence (74.3% v. 73.8%; adjusted RR 0.99, 95% CI 0.95-1.04), but more likely to self-report it (10.2% v. 2.4%; adjusted RR 3.38, 95% CI 2.61-4.38), compared with those without schizophrenia. Among patients who did not self-report interpersonal violence, schizophrenia was associated with an increased risk for a perinatal ED visit for interpersonal violence (4.0% v. 0.4%; adjusted RR 6.28, 95% CI 3.94-10.00). INTERPRETATION: Pregnancy and postpartum are periods of higher risk for interpersonal violence among people with schizophrenia compared with those without schizophrenia. Pregnancy is a key period for implementing violence prevention strategies in this population.

Disability and Interpersonal Violence in the Perinatal Period.

OBJECTIVE: To compare the risk of interpersonal violence experienced by pregnant and postpartum individuals with physical disabilities, sensory disabilities, or intellectual or developmental disabilities with those without disabilities, and to examine whether a prepregnancy history of interpersonal violence puts individuals with disabilities, at excess risk of interpersonal violence in the perinatal period. METHOD: This population-based study included all individuals aged 15-49 years with births in Ontario, Canada, from 2004 to 2019. Individuals with physical (n=147,414), sensory (n=47,459), intellectual or developmental (n=2,557), or multiple disabilities (n=9,598) were compared with 1,594,441 individuals without disabilities. The outcome was any emergency department visit, hospital admission, or death related to physical, sexual, or psychological violence between fertilization and 365 days postpartum. Relative risks (RRs) were adjusted for baseline social and health characteristics. Relative excess risk due to interaction (RERI) was estimated from the joint effects of disability and prepregnancy violence history; RERI>0 indicated positive interaction. RESULTS: Individuals with physical (0.8%), sensory (0.7%), intellectual or developmental (5.3%), or multiple disabilities (1.8%) were more likely than those without disabilities (0.5%) to experience perinatal interpersonal violence. The adjusted RR was 1.40 (95% CI 1.31-1.50) in those with physical disabilities, 2.39 (95% CI 1.98-2.88) in those with intellectual or developmental disabilities, and 1.96 (95% CI 1.66-2.30) in those with multiple disabilities. Having both a disability and any violence history produced a positive interaction for perinatal interpersonal violence (adjusted RERI 0.87; 95% CI 0.47-1.29). CONCLUSION: The perinatal period is a time of relative high risk for interpersonal violence among individuals with pre-existing disabilities, especially those with a history of interpersonal violence.

Mobile Health Divide Between Clinicians and Patients in Cancer Care: Results From a Cross-Sectional International Survey.

BACKGROUND: Mobile technologies are increasingly being used to manage chronic diseases, including cancer, with the promise of improving the efficiency and effectiveness of care. Among the myriad of mobile technologies in health care, we have seen an explosion of mobile apps. The rapid increase in digital health apps is not paralleled by a similar trend in usage statistics by clinicians and patients. Little is known about how much and in what ways mobile health (mHealth) apps are used by clinicians and patients for cancer care, what variables affect their use of mHealth, and what patients' and clinicians' expectations of mHealth apps are. OBJECTIVE: This study aimed to describe the patient and clinician population that uses mHealth in cancer care and to provide recommendations to app developers and regulators to generally increase the use and efficacy of mHealth apps. METHODS: Through a cross-sectional Web-based survey, we explored the current utilization rates of mHealth in cancer care and factors that explain the differences in utilization by patients and clinicians across the United States and 5 different countries in Europe. In addition, we conducted an international workshop with more than 100 stakeholders and a roundtable with key representatives of international organizations of clinicians and patients to solicit feedback on the survey results and develop insights into mHealth app development practices. RESULTS: A total of 1033 patients and 1116 clinicians participated in the survey. The proportion of cancer patients using mHealth (294/1033, 28.46%) was far lower than that of clinicians (859/1116, 76.97%). Accounting for age and salary level, the marginal probabilities of use at means are still significantly different between the 2 groups and were 69.8% for clinicians and 38.7% for patients using the propensity score-based regression adjustment with weighting technique. Moreover, our analysis identified a gap between basic and advanced users, with a prevalent use for activities related to the automation of processes and the interaction with other individuals and a limited adoption for side-effect management and compliance monitoring in both groups. CONCLUSIONS: mHealth apps can provide access to clinical and economic data that are low cost, easy to access, and personalized. The benefits can go as far as increasing patients' chances of overall survival. However, despite its potential, evidence on the actual use of mobile technologies in cancer care is not promising. If the promise of mHealth is to be fulfilled, clinician and patient usage rates will need to converge. Ideally, cancer apps should be designed in ways that strengthen the patient-physician relationship, ease physicians' workload, be tested for validity and effectiveness, and fit the criteria for reimbursement.

The cancer experience map: an approach to including the patient voice in supportive care solutions.

The perspective of the patient, also called the "patient voice", is an essential element in materials created for cancer supportive care. Identifying that voice, however, can be a challenge for researchers and developers. A multidisciplinary team at a health information company tasked with addressing this issue created a representational model they call the "cancer experience map". This map, designed as a tool for content developers, offers a window into the complex perspectives inside the cancer experience. Informed by actual patient quotes, the map shows common overall themes for cancer patients, concerns at key treatment points, strategies for patient engagement, and targeted behavioral goals. In this article, the team members share the process by which they created the map as well as its first use as a resource for cancer support videos. The article also addresses the broader policy implications of including the patient voice in supportive cancer content, particularly with regard to mHealth apps.

A model to support shared decision making in electronic health records systems.

Shared decision making (SDM) is an approach to medical care based on collaboration between provider and patient, with both sharing in medical decisions. When patients' values and preferences are incorporated in decision making, care is more appropriate, ethically sound, and often lower in cost. However, SDM is difficult to implement in routine practice because of the time required for SDM methods, the lack of integration of SDM approaches into electronic health record (EHR) systems, and absence of explanatory mechanisms for providers on the results of patients' use of decision aids. This article discusses potential solutions, including the concept of a "personalize button" for EHRs. Leveraging a 4-phase clinical model for SDM, this article describes how computer decision support (CDS) technologies integrated into EHRs can help ensure that health care is delivered in a way that is respectful of those preferences. The architecture described herein, called CDS for SDM, is built on recognized standards that are currently integrated into certification requirements for EHRs as part of meaningful use regulations. While additional work is needed on modeling of preferences and on techniques for rapid communication models of preferences to clinicians, unless EHRs are redesigned to support SDM around and during clinical encounters, they are likely to continue to be an unintended barrier to SDM. With appropriate development, EHRs could be a powerful tool to promote SDM by reminding providers of situations for SDM and monitoring ongoing care to ensure treatments are consistent with patients' preferences.

Gene expression of types I, II, and VI collagen, aggrecan, and chondroitin-6-sulfotransferase in the human annulus: in situ hybridization findings.

BACKGROUND CONTEXT: Within each lamellar bundle in the annulus, disc cells produce a complex and sophisticated architectural organization which acts to meet the unique biomechanical needs of the disc. How cells coordinate expression of genes throughout the disc is an important but as yet poorly understood process. For the annulus, such coordination probably involves cell-cell communication as well as growth factor and mechanoreceptor signaling to appropriately maintain the disc extracellular matrix (ECM) for the prevention of annular tears. PURPOSE: To determine the percentage and patterns of gene expression for types I, II, and VI collagen, aggrecan, and chondroitin-6-sulfotransferase in the human annulus. STUDY DESIGN/SETTING: Human annulus specimens were obtained from surgical subjects and a control donor in a study approved by the authors' Human Subjects Institutional Review Board. PATIENT SAMPLE: Four Thompson grade II, three grade III, and four grade IV annulus specimens were evaluated with in situ hybridization to determine gene expression. OUTCOME MEASURES: The percentages of cells in the human annulus expressing type I, II, and VI collagen, aggrecan, and chondroitin-6-sulfotransferase. METHODS: In situ hybridization, a technique with high temporal and spatial resolution, was used to detect gene expression of types I, II, and VI collagen, aggrecan, and chondroitin-6 sulfotransferase in cells in adjacent sections of annulus from discs with Thompson grades of II, III, and IV. RESULTS: Overall, 30.8% of cells expressed aggrecan, 38.4% type I collagen, 45.6% type II collagen, 48.1% type VI collagen, and 57.7% chondroitin-6-sulfotransferase. An important finding was that adjacent cells could be expressing, or not expressing, the gene of interest. These data could not have been gained from other global molecular techniques such as microarray analysis or reverse transcription polymerase chain reaction (RT-PCR). Information on gene expression by individual disc cells is important to better understand disc matrix homeostasis, the pathogenesis of disc degeneration, and to formulate potential biologic therapies for disc degeneration. CONCLUSIONS: This in situ hybridization study revealed the important finding that adjacent cells differ in their gene expression patterns for specific genes. Factors that could contribute to this difference in adjacent cell gene expression include cellular heterogeneity within the annulus, the presence of senescent cells with altered gene expression, and/or loss of coordinated disc cell function as a result of disruption of cell-cell communication.

Demographic factors that influence human disc cell proliferation in vitro.

BACKGROUND CONTEXT: Although previous work has shown that greater age, greater disc degeneration, female gender, and surgical derivation of disc tissue had deleterious effects on cell proliferative potential, relatively little is known about the association between disc cell proliferation in vitro and clinical donor characteristics. PURPOSE: To identify the relationships between donor characteristic and the in vitro proliferative potential of human disc cells from the annulus. STUDY DESIGN/SETTING: Studies were approved by the human subjects Institutional Review Board. Donor data included donor source, ethnicity, age, gender, smoking history, height, weight, number of years of back pain, and Thompson score. Cells cultured from the annulus were tested for proliferation. PATIENT SAMPLE: There were two study populations: 1) Comparison Group (32 control donors and 33 control surgical subjects; 60 Caucasians, 5 African-Americans). Cell proliferation, age, Thompson score, height, weight, and smoking history were statistically analyzed for control donors versus control surgical group. No significant differences were present, and these two groups were pooled to form the Comparison Group. 2) Nineteen subjects from the United Arab Emirates who underwent disc surgery. OUTCOME MEASURES: Linear models were fit to the data to determine the best prediction of cell proliferation as the outcome variable; multiple R-squared was used to determine model goodness of fit. METHODS: Control donor specimens were obtained from the National Cancer Institute Cooperative Human Tissue Network, and control donor surgical specimens from disc surgeries. A standardized cell proliferation assay was used to evaluate monolayer and three-dimensional agarose cell proliferation. Data were expressed as mean cpm[(3)H]-thymidine per microgram deoxyribonucleic acid+/-SEM. Standard statistical methods used the SAS system for data analysis. RESULTS: No differences were present in the Comparison Group versus the Middle Eastern group for mean Thompson score (both averaged grade III), mean age (44.3 vs. 43.0 years, respectively), gender, height, weight, length of time with back pain (1.9 years vs. 2.1 years respectively), or smoking history. Three-dimensional proliferation in agarose was not significantly different for the two groups. Monolayer proliferation, however, was significantly different (17,434+/-2,929 vs. 6,693+/-2,103, respectively), p=.019. Linear regression models were fit to the data to determine the best prediction using proliferation as the outcome variable. In the Middle Eastern group, monolayer cell proliferation bore a significant negative correlation to age (p=.02, r=-.32), whereas the Comparison Group showed no such relationship. The following equation was derived to fit these data: Log(10) of proliferation (cpm/mug deoxyribonucleic acid)=10.915-0.7919 (Middle Eastern ethnicity)-0.0296 (Age). The r(2) for this equation is 0.203 (ie, 20.3% of the change in proliferation is explained by age and Middle Eastern ethnicity). Middle Eastern ethnicity and age were significant in this equation (p=.04 and .0003, respectively). CONCLUSIONS: Studies have shown that familial history, age, and smoking are important risk factors for disc degeneration in Arabic pedigrees. It is interesting that our present findings also point to age and familial history as important significant factors influencing monolayer proliferation. Further research is needed to identify the cellular basis for this influence on cellular proliferative capacity.

Three-dimensional culture of human disc cells within agarose or a collagen sponge: assessment of proteoglycan production.

The objective of the present study was to assess proteoglycan production by human intervertebral disc cells cultured in vitro in selected cell carriers. Based on previous studies which evaluated disc cells seeded into collagen sponge, collagen gel, agarose, alginate or fibrin gel three-dimensional (3D) cell carriers, collagen sponge and agarose were found to provide superior microenvironments for formation of extracellular matrix (ECM). A standardized test design was used to evaluate ECM formed after 14 days of culture using the 1,9-dimethylmethylene blue (DMB) assay to assess sulfated glycosaminoglycan (S-GAG) production. Although agarose culture showed higher S-GAG levels compared to collagen sponge (2.94+/-2.20 (19) microg/ml S-GAG (mean+/-S.D. (n)) vs. 0.94+/-0.77 (22), respectively, p=0.0003), this is off-set by the significantly lower proliferation rate associated with culture of disc cells in agarose.

Cellular, but not matrix, immunolocalization of SPARC in the human intervertebral disc: decreasing localization with aging and disc degeneration.

STUDY DESIGN: Human intervertebral disc anulus tissue was obtained in a prospective study of immunolocalization of SPARC (secreted protein, acidic and rich in cysteine) (osteonectin). Experimental studies were approved by the authors' Human Subjects Institutional Review Board. Discs were obtained from surgical specimens and from control donors. OBJECTIVES: To determine whether SPARC could be detected in the disc with immunohistochemistry and to determine the incidence of SPARC-positive cells. SUMMARY OF THE BACKGROUND DATA: SPARC is a glycoprotein that has an important role in modulating interactions between cells and matrix. It influences remodeling, collagen fibrillogenesis, metalloproteinase expression, and cytokine expression. Little is known about SPARC in the disc, and one previous study reported the absence of its immunolocalization in fetal and adult disc tissue. METHODS: Eight normal human discs from subjects aged newborn to 10 years, and 11 disc specimens from control donors or surgical patients aged 15to 76 years were examined for immunolocalization of SPARC. Anulus cells were also tested for the presence of SPARC in vitro in monolayer or three-dimensional agarose culture. RESULTS: In discs of subjects aged newborn to 0.19 years, SPARC was present in all cells in the outer anulus, in 76.4% of inner anulus cells, and 76.0% of nucleus cells. Localization was significantly lower in anulus cells of study participants aged 4.7 to 76 years (66.7%, P = 0.04). Anulus cells cultured in agarose or monolayer showed positive localization in all cells. CONCLUSIONS: Findings show decreased presence of SPARC in disc cells of older subjects with disc degeneration and point to the importance of future studies designed to elucidate the unrecognized role of SPARC in disc remodeling, aging, and degeneration.

Colony formation and matrix production by human anulus cells: modulation in three-dimensional culture.

STUDY DESIGN: Human intervertebral disc cells from the anulus were tested in a study of colony formation and extracellular matrix (ECM) production during long-term three-dimensional culture with exposure to selected cytokines. Experimental studies were approved by the authors' Human Subjects Institutional Review Board. OBJECTIVES: To quantitatively evaluate colony formation and qualitatively assess ECM production (using immunohistochemistry and in situ hybridization) in cells derived from Thompson Grades I to V discs and tested in culture with cytokines and nutrient supplementation. SUMMARY OF THE BACKGROUND DATA: Human intervertebral disc cells offer special in vitro challenges because of the slow-growing nature of these cells and their need for specialized three-dimensional in vitro conditions, which permit the expression and production of proteoglycans and Type II collagen, two ECM products that are important for disc cell biology. METHODS: Discs from 9 human subjects (2 control donors and 7 surgical patients, Thompson Grades I-V), mean age 35.8 years, were used to obtain anulus cells to be tested in three-dimensional agarose culture. Tests of specialized growth conditions included treatment with ITS (insulin-transferrin-sodium selenite supplement), insulin-like growth factor I (IGF-I), and transforming growth factor-beta1 (TGF-beta1). Cultures were evaluated after 14 to 36 days of culture for % colony formation and cell numbers/colony; immunocytochemistry, in situ hybridization, and quantitative histology were used to evaluate colony formation and ECM production. RESULTS: : Data showed that compared with the average 17.5% colony formation observed in controls, ITS, TGF-beta1 and ITS with IGF-I significantly increased colony formation (28.4%, 30.4%, and 30.4%, respectively, P < or = 0.04). Even cells derived from Thompson Grade V disc showed responsiveness to cytokines and improved production of ECM in vitro. CONCLUSIONS: : Findings indicated that cells derived from discs with advanced degeneration were still responsive to cytokines and could be modulated to produce Type II collagen and proteoglycans in three-dimensional culture by the addition of enriched media and selected cytokines. Such findings are important since they advance our understanding of how to modulate disc cell behavior in vitro, and may have application to potential future biologic therapies for disc degeneration.

Cell-based tissue engineering for the intervertebral disc: in vitro studies of human disc cell gene expression and matrix production within selected cell carriers.

BACKGROUND CONTEXT: Little is known about how disc cells attach, proliferate and form extracellular matrix (ECM) within carrier materials. Such information is needed to help formulate criteria for successful cell-carrier interactions in tissue engineering. PURPOSE: To compare proliferation, ECM production and gene expression in annulus cells cultured in a variety of cell carrier materials with potential application in tissue engineering of the disc. STUDY DESIGN: Human intervertebral disc cells from the annulus were used in a prospective study of proliferation, ECM production and gene expression within selected cell carriers. METHODS: Annulus cells from discs of 29 individuals were tested in collagen sponge, collagen gel, agarose, alginate or fibrin gel formulations. In situ hybridization assessed ECM gene expression of Types I and II collagen, aggrecan and chondroitin-6 sulfotransferase. Cell proliferation, cell shape, attachment and ECM production were evaluated. RESULTS: Collagen sponges provided the best microenvironment for disc cell ECM production and gene expression. Although collagen gels often could support good cell growth, such constructs did not result in either abundant ECM production or ECM gene expression, as shown by in situ hybridization. Growth and ECM production and gene expression in alginate, agarose and fibrin microenvironments were inferior. CONCLUSIONS: Tissue engineering techniques open new therapeutic possibilities for use of autologous disc cells, but fundamental questions on how these cells interact with cell carriers are unexplored. Results provide novel data on disc cell gene expression within diverse microenvironments. The collagen sponge proved to be a superior microenvironment.

Autologous intervertebral disc cell implantation: a model using Psammomys obesus, the sand rat.

STUDY DESIGN: Work presented here used a small animal model to illustrate the feasibility of autologous disc cell implantation. OBJECTIVES: To develop a small animal model for autologous disc cell implantation. SUMMARY OF THE BACKGROUND DATA: The use of autologous disc cells in the potential treatment of disc degeneration offers attractive possibilities for novel therapies. Results are presented on the use of the sand rat (Psammomys obesus), a small rodent that spontaneously develops disc degeneration during aging, in experimental studies in which cells were harvested from a lumbar intervertebral disc, expanded in monolayer tissue culture, labeled with agents that allow subsequent immunolocalization of these cells, and implanted in a second disc site of the donor animal. METHODS: Tissue culture, disc surgery, histology, and immunocytochemistry were used. Cells were either engrafted in a bioresorbable carrier tested for cell compatibility or injected into the recipient disc. Results were assessed with radiographic examination of the implantation site and with histology and immunocytochemistry. CONCLUSION: Data from 15 animals were obtained with engraftment resident in the animal for up to 33 weeks. Immunocytologic identification of engrafted cells showed that they integrated into the disc and were surrounded by normal matrix at time points up to 8 months postengraftment. Engrafted cells exhibited either a spindle-shaped morphology in the annulus or a rounded chondrocyte-like morphology in the nucleus. Although technically challenging, the authors' experience showed that autologous disc cell implantation can be successful and that the sand rat is a valuable model for autologous disc cell studies.

Expression and localization of estrogen receptor-beta in annulus cells of the human intervertebral disc and the mitogenic effect of 17-beta-estradiol in vitro.

BACKGROUND: Recent evidence suggests that estrogens exert effects in different tissues throughout the body, and that the estrogen receptor beta (ERbeta) may be important for the action of estrogen (17-beta-estradiol) on the skeleton. The cellular localization of ERbeta in the human intervertebral disc, however, has not yet been explored. METHODS: Human disc tissue and cultured human disc cells were used for immunocytochemical localization of ERbeta. mRNA was isolated from cultured human disc cells, and RT-PCR amplification of ERbeta was employed to document molecular expression of this receptor. Cultured human disc cells were tested to determine if 17-beta-estradiol stimulated cell proliferation. RESULTS: In this report data are presented which provide evidence for ERbeta gene expression in human intervertebral disc cells in vivo and in vitro. Culture of annulus cells in the presence of 10-7 M 17-beta-estradiol significantly increased cell proliferation. CONCLUSIONS: These data provide new insight into the biology of cells in the annulus of the intervertebral disc.