Drivers of Scope of Practice in Family Medicine: A Conceptual Model.

PURPOSE: The purpose of this study was to explore family medicine graduates' attitudes and perspectives on modifiable and unmodifiable factors that influenced their scope of practice and career choices. By understanding how these factors intersect to influence desired and actual scope of practice decisions, we hope to inform strategies to address training and health care workforce needs. METHODS: During 5 focus group discussions, comprised of a total of 32 family physicians who either resided in or attended a residency program in western North Carolina, we explored family physicians' attitudes and perspectives on their desired and actual scope of practice. We used thematic analysis to identify patterns in the qualitative data. RESULTS: We created a conceptual framework to understand the complex factors which influence family physicians' scope of practice. Personal factors were found to impact desired scope, while workplace, environmental, and population factors influenced actual scope of practice. Stressors in each of these 4 categories often caused family physicians to narrow their scope of practice. Our study highlights specific supports that, if in place, enable physicians to maintain their desired broad scope of practice. CONCLUSIONS: Our study indicates that the national trend toward family physicians narrowing their scope of practice can be addressed by providing specific supports during training, residency, and mid-career. Understanding personal, workplace, environmental, and population factors that influence scope of practice can inform specific interventions that create desirable jobs for family physicians and improve their ability to meet changing population needs.

Methods and strategies for effectively surveying the LGBTQ+ population.

The Lesbian, Gay, Bisexual, Transgender, and Queer (LGBTQ) population is at a substantially elevated risk for myriad health complications, due in large part to structural and social inequities. As such, the LGBTQ population is an important demographic to survey regarding their health. As with many populations facing inequality, the LGBTQ population is often hard to sample. In light of this challenge, several approaches may be required in order to effectively surveying this population. Specifically, advances in sampling methodologies, leveraging community partnerships, and culturally aware question design appear to increase the likelihood of a successful LGBTQ-focused health survey. The Southern LGBTQ Health Study is examined as a case study in effectively conducting a large, multi-state LBTQ health survey. They used a simple snowball sampling strategy where their online health survey was distributed through a wide network of community organizations across several states. They also employed members of the LGBTQ community as "Survey Ambassadors" to help recruit their peers to participate in the study. This case study demonstrated several successful methods. Their combined sampling methodology resulted in almost 6000 respondents. Their question for sexual orientation ("Check all that apply") resulted in rich, easy to interpret data and was well received by the participants. However, this case study also provided valuable learning opportunities. Had they used a more formalized approach to their sampling, they would have had greater generalizability to their target population. Also, the use of an open-ended question regarding gender identity generated data that was not conducive to formal analysis without significant resources dedicated to cleaning the data.

Family inclusion in diabetes education: a nationwide survey of diabetes educators.

PURPOSE: The purpose of this study was to investigate perceptions about family inclusion and support in diabetes self-management education. METHODS: Surveys were mailed to certified diabetes educators (CDEs) in all 50 states and the District of Columbia, with a return of 225 surveys. Descriptive and inferential statistics (eg, t test, analysis of variance, correlation, and chi-square) were used as appropriate. RESULTS: Levels of importance placed on family involvement in diabetes education were significantly related to the emphasis placed on family during CDEs' formal or preprofessional education. CDEs' formal exposure to family theory influenced perceptions of their knowledge about family and the frequency that family support was emphasized in self-management activities but was unrelated to perceptions of their skillfulness in educating family members. Diabetes educators' personal values of family support were significantly related to how frequently family members were asked to participate in formal diabetes education classes. CDEs perceived that they were meeting individuals' self-management needs significantly better than those of families. Regional differences did not appear to be a factor in how CDEs incorporated family in diabetes education. CONCLUSIONS: Diabetes educators without formal exposure to family theory may be overestimating how much they emphasize family support in diabetes education. Increasing formal education about the importance of family involvement in self-management behaviors could positively affect individual diabetes self-management outcomes.

Controlling glycation of recombinant antibody in fed-batch cell cultures.

Protein glycation is a non-enzymatic glycosylation that can occur to proteins in the human body, and it is implicated in the pathogenesis of multiple chronic diseases. Glycation can also occur to recombinant antibodies during cell culture, which generates structural heterogeneity in the product. In a previous study, we discovered unusually high levels of glycation (>50%) in a recombinant monoclonal antibody (rhuMAb) produced by CHO cells. Prior to that discovery, we had not encountered such high levels of glycation in other in-house therapeutic antibodies. Our goal here is to develop cell culture strategies to decrease rhuMAb glycation in a reliable, reproducible, and scalable manner. Because glycation is a post-translational chemical reaction between a reducing sugar and a protein amine group, we hypothesized that lowering the concentration of glucose--the only source of reducing sugar in our fed-batch cultures--would lower the extent of rhuMAb glycation. When we decreased the supply of glucose to bioreactors from bolus nutrient and glucose feeds, rhuMAb glycation decreased to below 20% at both 2-L and 400-L scales. When we maintained glucose concentrations at lower levels in bioreactors with continuous feeds, we could further decrease rhuMAb glycation levels to below 10%. These results show that we can control glycation of secreted proteins by controlling the glucose concentration in the cell culture. In addition, our data suggest that rhuMAb glycation occurring during the cell culture process may be approximated as a second-order chemical reaction that is first order with respect to both glucose and non-glycated rhuMAb. The basic principles of this glycation model should apply to other recombinant proteins secreted during cell culture.

Decreasing lactate level and increasing antibody production in Chinese Hamster Ovary cells (CHO) by reducing the expression of lactate dehydrogenase and pyruvate dehydrogenase kinases.

Large-scale fed-batch cell culture processes of CHO cells are the standard platform for the clinical and commercial production of monoclonal antibodies. Lactate is one of the major by-products of CHO fed-batch culture. In pH-controlled bioreactors, accumulation of high levels of lactate is accompanied by high osmolality due to the addition of base to control pH of the cell culture medium, potentially leading to lower cell growth and lower therapeutic protein production during manufacturing. Lactate dehydrogenase (LDH) is an enzyme that catalyzes the conversion of the substrate, pyruvate, into lactate and many factors including pyruvate concentration modulate LDH activity. Alternately, pyruvate can be converted to acetyl-CoA by pyruvate dehydrogenases (PDHs), to be metabolized in the TCA cycle. PDH activity is inhibited when phosphorylated by pyruvate dehydrogenase kinases (PDHKs). In this study, we knocked down the gene expression of lactate dehydrogenase A (LDHa) and PDHKs to investigate the effect on lactate metabolism and protein production. We found that LDHa and PDHKs can be successfully downregulated simultaneously using a single targeting vector carrying small inhibitory RNAs (siRNA) for LDHa and PDHKs. Moreover, our fed-batch shake flask evaluation data using siRNA-mediated LDHa/PDHKs knockdown clones showed that downregulating LDHa and PDHKs in CHO cells expressing a therapeutic monoclonal antibody reduced lactate production, increased specific productivity and volumetric antibody production by approximately 90%, 75% and 68%, respectively, without appreciable impact on cell growth. Similar trends of lower lactate level and higher antibody productivity on average in siRNA clones were also observed from evaluations performed in bioreactors.