GLP-1 Receptor Agonist Discontinuation Among Patients With Obesity and/or Type 2 Diabetes.

This cohort study examines the prevalence of and factors associated with glucagon-like peptide 1 agonist discontinuation among new users.

Disease-Modifying Medications in Patients with Rheumatoid Arthritis in the USA: Trends from 2016 to 2021.

BACKGROUND: Disease-modifying anti-rheumatic drugs (DMARDs), since their introduction in 1990, have revolutionized the management of rheumatoid arthritis. Newer DMARDs have recently been approved, influencing treatment patterns and clinical guidelines. OBJECTIVE: To update the current prescribing patterns of DMARDs in the pharmacotherapy of rheumatoid arthritis (RA) to include the pandemic era. METHODS: This was a retrospective cross-sectional multi-year study. Using Optum's Clinformatics® Data Mart Database, we summarized trends in the prevalence of DMARD use in the USA from 2016 to 2021 by year for adult patients ≥ 18 years old with at least one medical RA claim and one pharmacy/medical claim of a DMARD medication. Trends included type of DMARD, class of DMARD (conventional (csDMARDs), biologics [tumor necrosis factor (TNFi) and Non-TNFi), and Janus kinase inhibitors (JAKs)], and triple therapy [methotrexate (MTX), hydroxychloroquine (HCQ), sulfasalazine (SUL)] used. RESULTS: The total sample from 2016 to 2021 was 670,679 commercially insured patients. The average age was 63.7 years (SD 13.6), and 76.7% were female and 70% were White. csDMARDs remain the most prescribed (ranging from 77.2 to 79.2%). Although JAKs were the least prescribed DMARD class, their proportion more than doubled from 2016 (1.5%) to 2021 (4%). MTX utilization declined from 40% in 2016 to 34% in 2021. In contrast, HCQ use increased during the pandemic era from < 25% in 2018 to 30% in 2021. Although there is evidence of the therapeutic benefit of triple therapy, its use was very low (~ 1%) compared to biologics only (~ 17%) or biologics+MTX (~ 10%). CONCLUSION: About half of patients with RA were on DMARDs. As expected, csDMARDs were highly used consistently. The COVID-19 pandemic might have influenced the use of HCQ and infusion DMARDs. Triple therapy use remains low.

Prevalence and Predictors of Multimodal Treatment Among U.S. Adults Newly Diagnosed With ADHD.

INTRODUCTION: Although a combined treatment of prescription medication and psychotherapy provides long-term benefits for adults with attention deficit/hyperactivity disorder (ADHD), little is known about the prevalence of receiving such multimodal treatment. This study investigated trends in the prevalence and correlates of multimodal treatment among U.S.-insured adults newly diagnosed with ADHD. METHODS: 495,180 U.S. adults from the Komodo Healthcare Map with newly diagnosed ADHD in 2017-2021 were included. Descriptive statistics were used to estimate trends in the prevalence of treatment (no treatment, prescription-only, psychotherapy-only, or both) within 3 months from the index ADHD diagnosis. Multinomial logistic regression was used to examine patient and provider characteristics associated with ADHD treatment. Analysis was conducted in May 2023. RESULTS: From 2017 to 2021, the prevalence of newly diagnosed ADHD adults receiving multimodal, prescription-only, and psychotherapy-only treatment within 3 months following their first diagnosis increased from 12.9% to 21.4%, 30.2% to 33.3%, and 18.4% to 20.4%, respectively. Over the same period, the prevalence of newly diagnosed ADHD adults receiving no treatment declined from 38.5% to 25%. Relative to their counterparts, the odds of receiving multimodal ADHD treatment were significantly lower (p<0.05) for men, older adults, adults with multiple co-existing conditions, Medicaid and Medicare beneficiaries, and those living in socially disadvantaged areas. Furthermore, the odds of receiving multimodal treatment were higher (p<0.05) for adults who saw a nurse practitioner, physician assistant, or behavioral care (non-physician) provider on their first visit with an ADHD diagnosis, compared to those who saw a physician. CONCLUSIONS: 25% of newly diagnosed ADHD adults received no treatment in 2021 and 53.7% only received a single-modality treatment-raising concerns about the potential implications of untreated ADHD or insufficient treatment on the persistence of ADHD-related impairments, morbidity, productivity, and downstream healthcare cost. The study also highlighted potential sociodemographic, clinical, and provider disparities in ADHD treatment.

PROTAC chemical probes for histone deacetylase enzymes.

Over the past three decades, we have witnessed the progression of small molecule chemical probes designed to inhibit the catalytic active site of histone deacetylase (HDAC) enzymes into FDA approved drugs. However, it is only in the past five years we have witnessed the emergence of proteolysis targeting chimeras (PROTACs) capable of promoting the proteasome mediated degradation of HDACs. This is a field still in its infancy, however given the current progress of PROTACs in clinical trials and the fact that FDA approved HDAC drugs are already in the clinic, there is significant potential in developing PROTACs to target HDACs as therapeutics. Beyond therapeutics, PROTACs also serve important applications as chemical probes to interrogate fundamental biology related to HDACs via their unique degradation mode of action. In this review, we highlight some of the key findings to date in the discovery of PROTACs targeting HDACs by HDAC class and HDAC isoenzyme, current gaps in PROTACs to target HDACs and future outlooks.

Association of PCSK9 Inhibitor Initiation on Statin Adherence and Discontinuation.

Background PCSK9is (proprotein convertase subtilisin/kexin type 9 inhibitors) are well tolerated, potently lower cholesterol, and decrease cardiovascular events when added to statins. However, statin adherence may decrease after PCSK9i initiation and alter clinical outcomes. We evaluate the association of PCSK9i initiation on statin discontinuation and adherence. Methods and Results In this retrospective pre-post difference-in-difference analysis, new PCSK9i claims were propensity matched with statin-alone users (April 2017-September 2019). The primary outcomes were statin adherence (proportion of days covered) and statin discontinuation (absence of statin coverage for at least 60 days) 12 months following PCSK9i initiation. Secondary outcomes included low-density lipoprotein cholesterol levels after 1 year. A total of 220 538 statin users and 700 PCSK9i users were identified, from which 178 on PCSK9i were included and matched to 712 on statins alone. At 12 months, mean statin proportion of days covered decreased from 67% to 48% in the PCSK9i group but increased from 68% to 86% in the statin-alone groups (P<0.0001). Statin discontinuation rates increased from 11% to 39% in the PCSK9i group and from 7% to 9% in the statin-alone group (P=0.0041). Patients with low-density lipoprotein cholesterol <70 mg/dL increased from 5% to 68% with PCSK9i but increased from 16% to 24% with statins alone (P<0.0001). Changes in hospitalization rates were similar between both groups during the follow-up period. Conclusions PCSK9i initiation was associated with decreased low-density lipoprotein cholesterol, higher statin discontinuation, and reduced statin adherence.

Medicaid Costs and Utilization of Collaborative Versus Colocation Care for Patients With Depression.

OBJECTIVE: The authors examined cost and utilization metrics for racially diverse Medicaid primary care patients with depression receiving care through either a collaborative care model (CoCM) of integration or the standard colocation model. METHODS: Data from a retrospective cohort of Medicaid patients screening positive for clinically significant depression during January 2016-December 2017 were analyzed to assess health care costs and selected utilization measures. Seven primary care clinics providing CoCM were compared with 16 clinics providing colocated behavioral health care. Data for the first year and second year after a patient received an initial Patient Health Questionnaire-9 score ≥10 were analyzed. RESULTS: In the first year, compared with patients receiving colocated care (N=3,061), CoCM patients (N=4,315) had significantly lower odds of emergency department (ED) visits (OR=0.95) and medical specialty office visits (OR=0.92), with slightly higher odds of primary care provider (PCP) visits (OR=1.03) and behavioral health office visits (OR=1.03). In year 2, CoCM patients (N=2,623) had significantly lower odds of inpatient medical admissions (OR=0.87), ED visits (OR=0.84), medical specialty office visits (OR=0.89), and PCP visits (OR=0.94) than the colocated care patients (N=1,838). The two groups did not significantly differ in total cost in both years. CONCLUSIONS: Access to CoCM treatment in primary care for racially diverse Medicaid patients with depression was associated with more positive health care utilization outcomes than for those accessing colocated treatment. As organizations continue to seek opportunities to integrate behavioral health care into primary care, consideration of health care costs and utilization may be helpful in the selection and implementation of integration models.

Impact of New York State's Health Home Model on Health Care Utilization.

The Affordable Care Act established Medicaid health homes to provide care management and coordination for high-need individuals, including many with serious mental illness. The authors used data from the Medicaid Data Warehouse to examine health care utilization over 3 years among 10,193 individuals who enrolled in a New York State health home and had at least one outpatient mental health visit during the year prior to enrollment. Results for postenrollment year 2 indicated a 43% decrease in inpatient mental health discharges, a 38% decrease in substance use discharges, and a 7% reduction in general medical discharges, whereas mental health outpatient treatment and behavioral and nonbehavioral medication utilization increased. Further research is needed to determine the effectiveness of health home care management for individuals with serious mental illness.

Severe Acute Respiratory Syndrome Coronavirus 2 Receptor (Human Angiotensin-Converting Enzyme 2) Binding Inhibition Assay: A Rapid, High-Throughput Assay Useful for Vaccine Immunogenicity Evaluation.

Emerging variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) show immune evasion of vaccine-derived immunity, highlighting the need for better clinical immunogenicity biomarkers. To address this need, an enzyme-linked immunosorbent assay-based, human angiotensin-converting enzyme 2 (hACE2) binding inhibition assay was developed to measure antibodies against the ancestral strain of SARS-CoV-2 and was validated for precision, specificity, linearity, and other parameters. This assay measures the inhibition of SARS-CoV-2 spike (S) protein binding to the receptor, hACE2, by serum from vaccine clinical trials. Inter- and intra-assay precision, specificity, linearity, lower limit of quantitation, and assay robustness parameters successfully met the acceptance criteria. Heme and lipid matrix effects showed minimal interference on the assay. Samples were stable for testing in the assay even with 8 freeze/thaws and up to 24 months in -80 °C storage. The assay was also adapted for variants (Delta and Omicron BA.1/BA.5), with similar validation results. The hACE2 assay showed significant correlation with anti-recombinant S immunoglobulin G levels and neutralizing antibody titers. This assay provides a rapid, high-throughput option to evaluate vaccine immunogenicity. Along with other clinical biomarkers, it can provide valuable insights into immune evasion and correlates of protection and enable vaccine development against emerging COVID-19 variants.

Association of the Chantix Recall With US Prescribing of Varenicline and Other Medications for Nicotine Dependence.

This cross-sectional study evaluates the association between the 2021 varenicline tartrate recall and prescribing of varenicline and other medications for nicotine dependence in a large US national patient cohort.

Collaborative Care for Low-Income Patients From Racial-Ethnic Minority Groups in Primary Care: Engagement and Clinical Outcomes.

OBJECTIVE: To assess model impact and opportunities for improvement, this study examined collaborative care model (CoCM) engagement and clinical outcomes among low-income patients from racial-ethnic minority groups with depression and anxiety. METHODS: Starting in 2015, the CoCM was implemented in seven primary care practices of an urban academic medical center serving patients from racial-ethnic minority backgrounds, predominantly Medicaid beneficiaries. Eligible individuals scored positive for depressive or anxiety symptoms (or both) on the Patient Health Questionnaire-2 (PHQ-2) and PHQ-9 and the Generalized Anxiety Disorder Scale-2 (GAD-2) and GAD-7 during systematic screening in primary care settings. Screening rates and yield, patient characteristics, and CoCM engagement and outcomes were examined. Clinical improvement was measured by the difference in PHQ-9 and GAD-7 scores at baseline and at 10-to-14-week follow-up. RESULTS: High rates of screening (87%, N=88,236 of 101,091) and identification of individuals with depression or anxiety (13%, N=11,886) were observed, and 58% of 3,957 patients who engaged in minimally adequate CoCM treatment had significant clinical improvement. Nevertheless, only 56% of eligible patients engaged in the model, and 25% of those individuals did not return for at least one follow-up appointment. Being female with clinically significant comorbid anxiety and depressive symptoms and having Medicaid or commercial insurance increased the likelihood of CoCM engagement. CONCLUSIONS: CoCM can help engage vulnerable patients in behavioral health care and improve clinical symptoms. However, significant opportunity exists to advance the model's impact in treating depressive and anxiety disorders and decreasing health disparities by addressing engagement barriers.

Real-world insights from launching remote peer-to-peer mentoring in a safety net healthcare delivery setting.

Peer mentors have been proven to improve diabetes outcomes, especially among diverse patients. Delivering peer mentoring via remote strategies (phone, text, mobile applications) is critical, especially in light of the recent pandemic. We conducted a real-world evaluation of a remote diabetes intervention in a safety-net delivery system in New York. We summarized the uptake, content, and pre-post clinical effectiveness for English- and Spanish-speaking participants. Of patients who could be reached, 71% (n = 690/974) were enrolled, and 90% of those (n = 618/690) participated in coaching. Patients and mentors had a mean of 32 check-ins, and each patient set an average of 10 goals. 29% of the participants accessed the program via the smartphone application. Among participants with complete hemoglobin A1c data (n = 179), there was an absolute 1.71% reduction (P < .01). There are multiple lessons for successful implementation of remote peer coaching into settings serving diverse patients, including meaningful patient-mentor matching and addressing social determinants.

Enhancing the scalability of the collaborative care model for depression using mobile technology.

The collaborative care model (CoCM) has substantial support for improving behavioral health care in primary care. However, large-scale CoCM adoption relies on addressing operational and financial implementation challenges across health care settings with varying resources. An academic medical center serving socioeconomically and racially diverse patients implemented the CoCM in seven practices. A smartphone application was introduced to facilitate CoCM care management during depression treatment (app-augmented CoCM). App features included secure texting, goal/appointment reminders, symptom monitoring, and health education material. A nonrandomized convenience patient sample (N = 807) was enrolled in app-augmented CoCM and compared with patients in standard CoCM (N = 3,975). Data were collected on clinical contact frequency, engagement, and clinical outcomes. App-augmented CoCM patients received more health care team contacts (7.9 vs. 4.9, p < .001) and shorter time to follow up compared with the standard CoCM sample (mean = 11 vs. 19 days, p < .001). App-augmented CoCM patients had clinical outcomes similar to the standard CoCM group (47% vs. 46% with ≥50% depression improvement or score <10), despite app-augmented patients having more prior depression treatment episodes. Further, the app-augmented group with greater app engagement demonstrated increased behavioral health appointment compliance, including more completed appointments and fewer no shows, and greater depression symptom improvement than those with less app engagement. App-augmented CoCM may improve patient engagement in treatment and provide opportunities to implement key CoCM elements without overburdening practice resources. CoCM sustainability and scalability in primary care may be enhanced by using this technology.

Treatment of Serious Mental Illness in Medical and Mental Health Settings.

OBJECTIVE: This study investigated service use by individuals with serious and nonserious mental illness receiving mental health care in medical and mental health settings. METHODS: Claims data from the New York State Medicaid Data Warehouse were examined for 8,988 patients who received at least one mental health service at an urban academic medical center during 2017 at a mental health setting, a medical setting, or both. RESULTS: Most patients (59%) received all of their mental health care in medical settings and from unaffiliated providers, including a large portion (16%) with serious mental illness. Despite the availability of integrated care in the medical setting and use of unaffiliated mental health providers, rates of mental health inpatient admissions were high among all patients in this setting (including those with serious and with nonserious mental illness), considerably higher than for patients treated in a mental health clinic within the system. Rates of medical and substance abuse inpatient admissions were also much higher for patients treated in the medical setting and by unaffiliated providers, compared with those treated in the system's mental health clinics. CONCLUSIONS: Findings suggest that when mental health services are available in medical and mental health settings within the same system, either patients with more severe physical illnesses are more likely to receive their mental health care in medical settings and from unaffiliated providers and thus have more hospitalizations of all types or affiliated mental health settings more effectively address clinical needs and thus reduce hospitalizations.

Comparison of Collaborative Care and Colocation Treatment for Patients With Clinically Significant Depression Symptoms in Primary Care.

OBJECTIVE: The study compared clinical outcomes of depression treatment in primary care with a colocation model versus a collaborative care model (CoCM). METHODS: Patients (N=240) with Patient Health Questionnaire-9 (PHQ-9) scores of ≥10 treated for clinically significant depression symptoms in primary care sites implementing the CoCM or a colocation model were compared. PHQ-9 scores were collected at baseline and 12 weeks. RESULTS: From baseline to follow-up, reductions in PHQ-9 scores were 33% for the CoCM sites and 14% for the colocation sites, with an unadjusted mean difference in scores of 2.81 (p=.001). CONCLUSIONS: More patients treated in sites that used the CoCM experienced a significantly greater reduction in depression symptoms, compared with patients in sites with the colocation model. As greater adoption of integration models in primary care occurs, it will be important to consider potential implications of these results for promoting adoption of CoCM elements. Further replication of these findings is warranted.

Horizon's patient-centered medical home program shows practices need much more than payment changes to transform.

Skyrocketing costs and the uneven quality of patient care challenge the US health care system. Some health insurance companies are exploring patient-centered medical homes as a way to change incentives and transform the health care delivery system by increasing primary care providers' accountability for care coordination and outcomes. Horizon Healthcare Services, Inc., New Jersey's oldest and largest health insurance company, developed medical home programs that include financial incentives with essential support tools. Our experience in implementing and evaluating various approaches indicates that medical homes require intensive and targeted patient care coordination supported by committed primary care leadership, as well as new payment structures that include a monthly care coordination fee and outcome-based payments. Our experience also indicates that considerable nonmonetary support-such as an education program for population care coordinators, a medical home guide that offers effective ways to transform a practice into a medical home, and useful data sharing-are needed to improve the quality of care and reduce costs.

The impact of the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) on prescribing practices: an analysis of data from a large midwestern state.

BACKGROUND: The Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) was a series of effectiveness trials. The results of these trials began publication in September 2005. Among other findings, these studies were interpreted to suggest that (1) second-generation antipsychotics might have fewer advantages over first-generation antipsychotics than had been generally thought; (2) among the agents assessed, olanzapine had the best efficacy outcome; and (3) after treatment failure with a second-generation antipsychotic, the most efficacious second-line medication is clozapine. To examine the actual impact on practice of these publications, we looked at change in physician prescribing behavior based on these 3 conclusions before and after publication of CATIE. METHOD: Rates of antipsychotic medication prescriptions to 51,459 patients with an ICD-9 code of 295 for schizophrenia were extracted from a Missouri Medicaid claims database. χ² Tests were used to compare the rates of prescribing antipsychotic medications before and after each of 3 key CATIE publications (time 1 was September 2005, time 2 was December 2006, and time 3 was April 2006). RESULTS: At all time points, we demonstrated a decrease in prescriptions by all prescribers for olanzapine (P < .0001). One year after time 1, we found an increase in prescriptions by all prescribers for aripiprazole (P < .0001). No statistically significant increases in clozapine prescribing were observed. Also, a small but statistically significant increase was seen in prescriptions of perphenazine (P < .02 at time 3). However, this increase occurred only for prescriptions written by psychiatrists and not other prescribers. CONCLUSIONS: We found some evidence in our sample that the publication of the results from CATIE had a small but statistically significant effect on prescribing habits of psychiatrists but not other physicians in our sample population. However, larger changes occurred in prescribing behavior that were largely unrelated to the CATIE trial. We propose a hypothesis to explain the direction of observed changes.

An attempt to improve antipsychotic medication adherence by feedback of medication possession ratio scores to prescribers.

Poor medication adherence is well documented for patients with severe and persistent mental illness. The State of Missouri implemented an early alert system to notify caregivers when patients fail to refill essential prescriptions in a timely manner and as an educational resource for providers on best practices for improving treatment adherence. Missouri Medicaid patients who were prescribed at least 1 of 9 orally-administered antipsychotic medications and who had at least 1 medication possession ratio (MPR) score below 0.8 were included in the adherence intervention group. Their prescribing clinicians and case managers were messaged electronically 2 times per week at the point that failure to refill the targeted prescription was identified. Notification occurred when the prescription had lapsed at 7 days, 30 days, and 45 days, and occurred in real time. In addition, MPR scores were provided monthly for the most recent 6-month period. Change in MPR scores was measured for the intervention group and for a matched control group. Trends in MPR scores were analyzed for both groups pre, during, and post intervention. In both the intervention and postintervention periods, there was a significant difference in the MPR scores between the two groups. The intervention group had a significantly greater increase in MPR score between preintervention and intervention periods. After the conclusion of the intervention, the MPR score decreased somewhat but was still higher than during the preintervention period. Results suggest that clinicians and patients need specific data about adherence in order to address the issue.

Evaluation of chronic disease management on outcomes and cost of care for Medicaid beneficiaries.

OBJECTIVES: To evaluate the impacts of the chronic disease management program on the outcomes and cost of care for Virginia Medicaid beneficiaries. METHODS: A total of 35,628 patients and their physicians and pharmacists received interventions for five chronic diseases and comorbidities from 1999 to 2001. Comparisons of medical utilization and clinical outcomes between experimental groups and control group were conducted using ANOVA and ANCOVA analyses. RESULTS: Findings indicate that the disease state management (DSM) program statistically significantly improved patient's drug compliance and quality of life while reducing (ER), hospital, and physician office visits and adverse events. The average cost per hospitalization would have been $42 higher without the interventions. CONCLUSIONS: A coordinated disease management program designed for Medicaid patients experiencing significant chronic diseases can substantially improve clinical outcomes and reduce unnecessary medical utilization, while lowering costs, although these results were not observed across all disease groups. The DSM model may be potentially useful for Medicaid programs in states or other countries. If the adoption of the DSM model is to be promoted, evidence of its effectiveness should be tested in broader settings and best practice standards are expected.

GCP-WD is a gamma-tubulin targeting factor required for centrosomal and chromatin-mediated microtubule nucleation.

The gamma-tubulin ring complex (gammaTuRC) is a large multi-protein complex that is required for microtubule nucleation from the centrosome. Here, we show that the GCP-WD protein (originally named NEDD1) is the orthologue of the Drosophila Dgrip71WD protein, and is a subunit of the human gammaTuRC. GCP-WD has the properties of an attachment factor for the gammaTuRC: depletion or inhibition of GCP-WD results in loss of the gammaTuRC from the centrosome, abolishing centrosomal microtubule nucleation, although the gammaTuRC is intact and able to bind to microtubules. GCP-WD depletion also blocks mitotic chromatin-mediated microtubule nucleation, resulting in failure of spindle assembly. Mitotic phosphorylation of GCP-WD is required for association of gamma-tubulin with the spindle, separately from association with the centrosome. Our results indicate that GCP-WD broadly mediates targeting of the gammaTuRC to sites of microtubule nucleation and to the mitotic spindle, which is essential for spindle formation.