Building Successful Models in Primary Care to Improve the Management of Adult Patients with Obesity.

Although several obesity clinical practice guidelines are available and relevant for primary care, a practical and effective medical model for treating obesity is necessary. The aim of this study was to develop and implement a holistic population health-based framework with components to support primary care-based obesity management in US health care organizations. The Obesity Care Model Collaborative (OCMC) was conducted with guidance and expertise of an advisory committee, which selected participating health care organizations based on prespecified criteria. A committee comprising obesity and quality improvement specialists and representatives from each organization developed and refined the obesity care framework for testing and implementing guideline-based practical interventions targeting obesity. These interventions were tracked over time, from an established baseline to 18 months post implementation. Ten geographically diverse organizations, treating patients with diverse demographics, insurance coverage, and health status, participated in the collaborative. The key interventions identified for managing obesity in primary care were applicable across the 4 OCMC framework domains: community, health care organization, care team, and patient/family. Care model components were developed within each domain to guide the primary care of obesity based on each organization's structure, resources, and culture. Key interventions included development of quality monitoring systems, training of leadership and staff, identifying clinical champions, patient education, electronic health record best practice alerts, and establishment of community partnerships, including the identification of external resources. This article describes the interventions developed based on the framework, with a focus on implementation of the model and lessons learned.

An Adult Immunization Best Practices Learning Collaborative: Impact, Scale Up, and Spread.

The research objective was to rapidly scale up and spread a proven learning collaborative approach (intervention) for adult vaccination rates for influenza and pneumococcal disease from 7 to 39 US health care organizations and to examine improvement in adult immunization rates after scale-up. Comparative analyses were conducted between intervention and nonintervention propensity score-matched providers on vaccination rates using a difference-in-differences approach. Qualitative data, collected during site visits and in-person and virtual meetings, were used to enhance understanding of quantitative results. In 2017-2018, an analysis of a subset of sites (n = 9) from 2 intervention cohorts (∼20 sites each) demonstrated greater improvement than their matched providers in pneumococcal vaccinations (PV) for patients ages ≥65 years (treatment effect range: 1.4%-3.7%, P < 0.01) and PV for high-risk patients (eg, with immunocompromising conditions) aged 19-64 years (0.8%-1.6%, P < 0.01). Significant effects were observed in one of the study cohorts for PV for at-risk patients (eg, with diabetes) aged 19-64 years (1.7%, P < 0.01), and influenza vaccination rates (2.4%, P < 0.001). Individual health systems demonstrated even greater improvements across all 4 vaccinations: 9.5% influenza; 8.7% PV ages ≥65 years; 11.8% PV high-risk; 16.3% PV at-risk (all P < 0.01). Results demonstrated that a 7-site pilot could be successfully scaled to 39 additional sites, with similar improvements in vaccination rates. Between 2014 and 2018, vaccination improvements among all 46 groups (7 pilot, 39 in subsequent cohorts) resulted in an estimated 5.5 million adult vaccinations administered or documented in 27 states.

Impact of a Learning Collaborative Approach on Influenza and Pneumococcal Immunization Rates in US Adults: A Mixed Methods Approach.

The objective of this research was to test the impact of a learning collaborative model (intervention) on adult vaccination rates for influenza and pneumococcal disease. A mixed methods approach was used to identify changes in adult vaccination rates over time and organizational factors contributing to successful programs. Provider-level propensity scores were used to match intervention to non-intervention providers to control for inherent selection bias of participating organizations. Comparative analyses were conducted between intervention and non-intervention sites on vaccination rates, using a difference-in-differences approach. Qualitative data (eg, semi-structured interviews) were analyzed using a constant comparison approach to identify themes related to successful strategies. From 2014-2016, intervention providers demonstrated greater improvement than their matched providers in pneumococcal vaccinations (PV) for patients aged 65 years and older (treatment effect: 4.3%, P < 0.05) and PV for high-risk patients (eg, with immunocompromising conditions) aged 19-64 years (2.7%, P < 0.001). Significant effects were also observed for PV for at-risk patients (eg, with diabetes) aged 19-64 years (1.7%, P < 0.05). Individual health systems demonstrated even greater improvements (eg, greater increase in PV rates for patients aged 65 years and older), with treatment effects as high as 20.4% (P < 0.05). A learning collaborative approach was demonstrated to be an effective approach to improve adult vaccination rates among participating integrated delivery systems and medical groups. Factors associated with success included organization type (ie, integrated delivery systems) and systems characterized by a positive learning climate and collaborative culture.

Metabolic syndrome appears early after hematopoietic cell transplantation.

BACKGROUND: Improved survival after allogeneic hematopoietic cell transplantation (allo-HCT) enables us to learn more about potential late complications after HCT, one of which is metabolic syndrome. There are no studies investigating the prevalence or development of metabolic syndrome within the first year post-HCT in adult myeloablative transplant recipients. METHODS: In this retrospective study, we evaluated the prevalence of and risk factors associated with metabolic syndrome early post-HCT in human subjects. Due to lack of complete information regarding all the factors that define metabolic syndrome, we evaluated metabolic characteristics using available objective data referred to as modified metabolic syndrome (MMS). The cohort included 785 patients. RESULTS: We demonstrated that the incidence of MMS was 34% pre-HCT, 48% at day 80 post-HCT, and 40% at 1 year post-HCT. MMS at day 80 post-HCT was predictive of having MMS at 1 year post-HCT. CONCLUSION: These results support the need for nutrition and lifestyle intervention to prevent and treat metabolic abnormalities among patients who survive the acute transplant period.

The need for office systems to improve colorectal cancer screening.

UNLABELLED: Patients generally access colorectal cancer (CRC) screening through primary care physicians. National guidelines recommend CRC screening for adults beginning at age 50, yet one-third of Americans are not up to date. METHODS: A self-administered questionnaire was administered to family physicians from 16 practices in a Midwestern state who attended an information session for a randomized study to improve CRC screening. The questionnaire assessed CRC screening practices, knowledge of CRC screening guidelines, and office strategies for improving screening. RESULTS: Of 131 health care providers, 85 (65%) completed the questionnaire. Two-thirds were aware of the CRC screening guidelines; 91% knew that the follow-up interval for screening depends on the test chosen. Twenty-five percent incorrectly stated that a single-sample in-office fecal occult blood test is an acceptable screening test. Only 8% had a written policy regarding CRC screening; 18% had offices that used chart reminders; and 32% had charts organized to easily identify patient screening status. Regarding perceptions, those who agreed that they encourage their office staff to participate in screening estimated that they offer screening to more patients than those who disagreed (82.8% vs 70.2%, P < .0001); in addition, those who agreed with and tried to follow the guidelines estimated that they offer screening to more patients than those who disagreed (77.4% vs 60.5%, P = .004). CONCLUSION: Although physicians were knowledgeable about CRC screening guidelines, 25% mistakenly believed that single-sample in-office fecal testing was appropriate. There was a striking lack of office systems for identifying eligible patients and facilitating CRC screening.

Splicing and splice factor SRp55 participate in the response to DNA damage by changing isoform ratios of target genes.

Alternative splicing is an important source of protein diversity, and is an established but not yet fully understood mechanism for gene regulation in higher eukaryotes. Its regulation is governed by a variety of mechanisms, including variation in the expression levels of splicing factors engaged in spliceosome formation. SRp55 is one of the most ubiquitous splicing factors and one that can be up-regulated by DNA damage in the absence of p53, and we had previously found that depletion of its activity increased resistance to DNA damage in p53-dependant manner. To assess its influence on the splicing patterns of genes involved in apoptosis, we performed splice-specific microarray analysis of cells treated with siRNA specific for this gene. This analysis, backed by RT-PCR verification, identified three genes, KSR1, ZAK and mda7/IL24, which are sensitive to SRp55 depletion. We also analyzed the splice patterns of apoptosis-related genes in p53-deficient U2OS cells following treatment with the genotoxic drug mitomycin C. This analysis revealed that DNA damage resulted in changes in splicing activity that modified the splicing pattern of Fas, a key pro-apoptotic, p53-inducible death receptor. Interestingly, this modification led to an enrichment of the anti-apoptotic soluble Fas isoform, and this secreted isoform was detected in the media surrounding cells subjected to DNA damage. These findings show that modulation of splicing activity in p53-deficient cells during the early response to sub-lethal DNA damage results in a change in the splicing of target genes, thus modifying the cellular response to genotoxic agents.

Orphanin FQ/nociceptin is a physiological regulator of prolactin secretion in female rats.

Orphanin FQ/nociceptin (OFQ/N), the most recently identified endogenous opioid peptide, stimulates prolactin secretion in both male and female rats. OFQ/N, however, did not elicit this stimulatory effect through the mu-, delta-, or kappa-opiate receptor subtype. The role OFQ/N plays in prolactin regulation under physiological conditions and its mechanism of action are not known. The purpose of these studies was to determine the physiological significance and pharmacological specificity of the prolactin secretory response to OFQ/N. In addition, the role of the tuberoinfundibular dopaminergic (TIDA) neurons in mediating this response was examined. Opioid receptor-like-1 (ORL-1) receptors were blocked by pretreatment with compound B (Comp B), a purported OFQ/N antagonist, or receptor synthesis was disrupted by pretreatment with ORL-1 receptor antisense oligonucleotides. The prolactin secretory response to OFQ/N administration in diestrous females was measured. Furthermore, the suckling-induced prolactin response was also determined after Comp B pretreatment. TIDA neuronal activity was quantified in diestrous female rats to determine whether OFQ/N stimulates prolactin release by inhibiting TIDA neurons. OFQ/N significantly inhibited the TIDA neurons by 1 min, preceding the prolactin secretory response. Both Comp B and antisense pretreatment blocked the stimulatory effects of OFQ/N on prolactin release, and Comp B abolished the suckling-induced prolactin response. These studies indicate that OFQ/N is a potent stimulus for prolactin secretion in female rats and that it mediates this effect by rapid and transient inhibition of TIDA neuronal activity. Furthermore, OFQ/N plays a physiologically significant role in the regulation of prolactin secretion during lactation, and it mediates its effects via actions at the ORL-1 receptor subtype.

Activation of long-term synaptic plasticity causes suppression of epileptiform activity in rat hippocampal slices.

Electrical stimulation of cerebral targets for the treatment of epilepsy is an area under active investigation. Recent studies have shown that chronic stimulation of the subthalamic nucleus, fornix, or hippocampus may be effective in attenuating seizure frequency in animal models and in patients with intractable epilepsy. However, many questions exist, such as what are the specific electrical parameters, target sites, and mechanisms, etc., which should be investigated in animal studies before considering the routine use of chronic stimulation in epileptic patients. It is also important to understand what happens to neural activity during repetitive pulse stimulation as well as after stimulation. To this end, we hypothesized: (1) activation of synaptic plasticity suppresses epileptiform activity and (2) low frequency stimulation is an effective stimulation protocol for reducing seizure intensity and frequency. We used rat hippocampal brain slices to study how electrical stimulation affects spontaneous and evoked epileptiform activity. Further, we compared low (1 Hz) versus high (100 Hz) frequency stimulation in the same preparation. We found that orthodromic stimulation of the Schaffer collaterals for 10 min reduces the amplitude of normal responses and diminishes epileptiform activity. The onset of suppression by 1 Hz stimulation was gradual, but persistent, whereas the onset of suppression by 100 Hz was rapid; however, the effects of 100 Hz stimulation were transient. Finally, the NMDA antagonist, AP5 reversed the antiepileptic effects achieved by 1 Hz stimulation. Collectively, these data suggest that using different stimulation parameters prolonged electrical stimulation in the hippocampus may be effective in reducing seizure frequency in patients with epilepsy and that suppression by low frequency stimulation may be mediated by long-term depression (LTD).