Sanmateo, California

Comparison of Type 2 Diabetes Pharmacotherapy Regimens

The study will conduct head-to-head comparisons of type 2 diabetes mellitus (T2DM) treatment strategies using observational data from real-world clinical settings to assess cardiovascular disease (CVD) outcomes and other patient-centered outcomes in T2DM patients with moderate baseline CVD risk who are treated with each of these four classes of glucose-lowering medications known as SGLT2, GLP-1RA, DPP4, and SU. To mitigate bias concerns related to confounding and informative loss to follow-up, analyses will be based on modern causal inference methods combined with machine learning that emulate intention-to-treat (ITT) and per-protocol (PP) analyses of pragmatic randomized trials with active comparators to provide the most robust and precise estimates of relative and absolute effects we would expect in usual care settings. Specific Aims and Hypotheses: Aim 1. Compare the effect off SGLT21, GLP-1RA, DPP4, and SU on each study outcome in adults with T2DM when each type of medication is (a) initiated as second-line therapy after metformin, and (b) initiated as first-, second-, or third-line therapy, or after any history of glucose-lowering therapy independent of prior metformin use. Aim 2. Compare the effect on each study outcome of earlier versus later initiation of SGLT2i, GLP-1RA, DPP4, SU as first-, or second-, or third-line therapy, or after any history of glucose-lowering therapy triggered by various changes in A1C, or CVD risk, or other patient characteristics. Aim 3. Assess in each of the prior analyses whether the treatment effects on study outcomes vary across categories of baseline CVD risk and CVD event history, renal function, congestive heart failure status, age, sex and race/ethnicity, or other patient characteristics. Aim 4. Evaluate trends in new pharmacy dispensing of SGLT2i and GLP1-RA between 2014 and 2021, in aggregate and by age, sex, race and ethnicity and concurrent T2DM drug use Aim 5. Evaluate trends in new pharmacy dispensing of SGLT2i and GLP1-RA between 2014 and 2021, by baseline ASCVD, heart failure and diabetic kidney disease. Aim 6. Describe primary adherence, secondary adherence, and persistence for diabetes medication Aim 7. Compare rates of primary non-adherence, secondary adherence, and medication persistence for brand name and generic medications for type 2 diabetes in specific subgroups of patients Aim 8. Examine trends in medication possession for brand name medications over the course of the calendar year Glucose-lowering medications will be compared at both the class and agent level. The key outcomes that will be considered are MACE 3-point, Myocardial Infarction, Stroke, Heart Failure, Hospitalization, Coronary or Carotid Artery Stent or Bypass Procedure, CVD Mortality, Overall Mortality. Additional patient-centered outcomes will be specified based on insights from stakeholder members of the research team.

A Comparison of TULSA Procedure vs. Radical Prostatectomy in Participants With Localized Prostate Cancer

The typical standard of care for patients with localized, intermediate risk prostate cancer is radical prostatectomy, which involves the surgical removal of the prostate. Although radical prostatectomy is effective in terms of controlling the cancer, it may leave men with significant long-term effects in urinary, sexual function like erectile dysfunction and/or incontinence (loss of bladder control), thus reducing quality of life. Preservation of continence (ability to control your bladder) and potency (ability to achieve erection and/or ejaculation) may be significant concerns for men. Targeted ablation of localized prostate cancer using MRI-guided technology is becoming a favorable option for many men who wish to have their cancer treated but do not wish to compromise their urinary and sexual functions. The TULSA Procedure is a new, minimally-invasive technique that uses real-time MRI-guided technology to guide the delivery of high-energy ultrasound to precisely, and in a customized fashion specific to you, heat and kill the prostate cancer tissue while protecting important surrounding body parts that are important for preserving urinary and sexual function. Minimally invasive here means that the procedure is performed through natural openings in your body (the urethra) instead of creating larger openings like traditional surgery or minimally invasive surgery. The purpose of this research study is to: - Test whether the TULSA Study Procedure preserves or improves your quality of life (urinary, bowel and sexual functions) at 12 months post-study treatment compared to standard of care (radical prostatectomy). - Test how many subjects who undergo the TULSA Study Procedure are free from treatment failure by 3 years post-study treatment compared to subjects who undergo the standard of care (radical prostatectomy). Treatment failure is defined as undergoing other additional prostate cancer treatments, spreading of cancer or death caused by cancer. About 201 subjects will participate in this study with 67 randomly assigned to the radical prostatectomy group and 134 randomly assigned to the TULSA procedure group. Patients will have a 1 in 3 chance of being assigned to the radical prostatectomy group and a 2 in 3 chance of being assigned to the TULSA group. Following treatment, patients will be followed up for 10 years.

A Study of Nipocalimab Administered to Adults With Generalized Myasthenia Gravis

FOOD PRESCRIPTION APP

We are specifically planning app to create meal plans that are affordable, meet the recommended dietary allowances (RDAs) and adhere to sustainability guidelines to reduce the food-related carbon footprint. The app will enable participants to customize their weekly meal plans. We hypothesize that having the ability to customize the weekly menus through a FoodRx app will improve outcomes, as the lack of customization appeared to be a barrier for some families to improve their diet quality and achieve weight loss goals. (eg, some families did not like tofu or oatmeal, and would have preferred a substitute). We will be able to test the impact of the Food Rx app by comparing participants who use it to our control group that does not currently have access to the standard menus/grocery delivery or FoodRx app.

Food Prescriptions to Promote Affordable Diets

FoodRx will test the effects of a culturally sensitive meal planning and affordable grocery delivery service in a randomized controlled trial to improve diet quality, weight control and chronic disease risk among multi-generational Latino households. This will be the first study to test the effectiveness of food prescriptions and home delivery on BMI and diet quality among Latino families. Food prescriptions will meet the EAT-Lancet sustainability guidelines and achieve at least 90% of the recommended dietary allowances (RDAs) for 23 critical nutrients for all family members at a cost not exceeding $680/month, the current CalFresh [California's Supplemental Nutrition Assistance Program (SNAP)] budget allocated for a family of four. Investigators will include tailored directions on portion size based on age, sex, activity level and weight goals. Investigators will develop and validate our menus and test logistics with focus groups of Latino adults with overweight or obesity [Body mass index (BMI) >25 kg/m2]. Thereafter, 180 Latino households of 3-5 people (n=720) from Kaiser Permanente members with at least two individuals with overweight or obese and at least 1 child aged 5-10 years will participate in a 6-month randomized trial with a wait-list cross-over design. Based on the weekly menu plan, a grocery list will be generated, and items delivered to the home. Anthropometric measurements, blood pressure, and dietary intake and blood samples will be collected at baseline, 6, and 12 months. Each family will be expected to pay for the majority of grocery costs, with the amount above this covered as an incentive for participation. Specific aims are: 1. To develop an affordable and culturally sensitive meal-planning and grocery delivery intervention for Latino households. 2) To determine the impact of food prescriptions and grocery delivery on parental health and diet quality. 3) To determine the impact of food prescriptions and grocery delivery on child health and diet quality. In a cross-center aim, data from this Project will be combined with Projects 1 and 2 to examine 1) the multi-level determinants of chronic disease risk in Latino children and 2) the effects of different types of interventions and how social and environmental factors in Latino affect the response to intervention. Measure include BMI for adults and BMI z-score (primary outcome) for children, dietary quality, cognitive function in children, blood pressure, HbA1C, blood lipids and liver function (ALT/AST) (secondary outcomes) and compare intervention with wait-list control participants. If the approach proves effective, food prescriptions could provide a scalable and sustainable model to improve the diet, health, and well-being of Latino families.

To Evaluate Efficacy and Safety of Serplulimab + Chemotherapy (Carboplatin- Etoposide) in US Patients With ES-SCLC

Provider Recommendation and HPV Vaccination

US teens remain at risk of developing human papillomavirus (HPV)-related cancers due to inadequate HPV vaccine uptake, despite strong endorsement in clinical guidelines and substantial intervention efforts by healthcare providers and public health entities. A strong recommendation from a clinician has been identified as the most powerful facilitator of HPV vaccine uptake, yet less than half of parents of pre-teens for whom routine HPV vaccination is recommended by the CDC's Advisory Committee on Immunization Practices receive an HPV vaccine recommendation from their providers. Unfortunately, training clinicians in effective HPV vaccine communication alone produces only a small improvement in vaccination rates. In order to develop effective interventions for improving HPV vaccine uptake, there is a critical need to understand the full range of multilevel factors influencing providers' likelihood and effectiveness in a strong recommendation (secondary outcome). Previous studies have demonstrated the complexity of barriers to HPV vaccination, including their multilevel, multi-factorial nature and heterogeneity across communities and practice settings; as reflected in our and others' data. However, most intervention studies display two limitations: 1) many are single level and single component (e.g., parent education only), leaving many barriers unaddressed; and 2) most address pre-selected barriers using pre-specified interventions that are fixed for all sites. This "prescribed" approach ignores differences in barriers across sites (due to varying context, culture, etc.), and likely leaves key local barriers unaddressed. These interventions have mostly shown modest and inconsistent success. Current thinking in implementation science suggests that significant improvement in HPV vaccination rates will require synergistic, multi-level, multi-component interventions tailored to the local context and barriers. The study goal is to evaluate the effectiveness of three implementation strategies (local-tailored, prescribed strategy, and usual care) to improve HPV vaccination rates among children 9-12 years old. Study Aims A1) Examine baseline associations between patient-, provider-, and clinic-level factors and variations in (a) HPV vaccination rates; (b) the quality of the provider recommendation; and (c) the impact of provider recommendation on vaccine uptake. A2) Conduct a cluster RCT comparing the effectiveness of a "tailored" multilevel implementation strategy to a "prescribed" multilevel implementation strategy and to usual care in improving HPV vaccination rates (primary outcome) and strengthening the provider recommendation (secondary outcome). Sub-aim: Conduct cost-effectiveness analyses of the implementation strategies based on the RCT results. A3) Study mechanisms of the effect of the implementation strategies to understand the interaction between the intervention, local context, and participant experience combined with quantitative measures. Study Descriptions: In this study, we are using a 3-arm cluster randomized controlled trial (RCT) to compare: (1) An innovative "local-tailored" implementation strategy, engaging local care teams, using local barrier assessment and barrier-driven local tailoring of interventions versus (2) A "prescribed" strategy, that involves pre-specified interventions addressing pre-selected vaccination barriers, guided by the 4 Pillars for Practice Transformation Program versus (3) Usual care - there are no research-led activities. This study will examine two theses: (a) interventions need to be multilevel and multi-component, and (b) local barrier assessment and intervention tailoring with the engagement of local teams (who are familiar with the local context) are needed to increase the uptake of the HPV vaccine. Clinics will be randomized into one of the three groups. Prior to randomization, clinics will be matched in triads on key attributes that may be associated with implementation success (e.g. geographic location, Consolidated Framework for Implementation Research (CFIR) constructs, membership, race/ethnicity, and baseline HPV vaccine coverage) using a SAS algorithm. The three clinics matched in a triad will be most like each other in these attributes. Within each triad, the three clinics will then be randomized to determine which receives the local-tailored strategy ( 20 clinics) vs prescribed ( 20 clinics) vs usual care (20 clinics). The study subjects will include pediatric physicians, nurses, and other clinical staff. We will also include other non-clinical individuals, such as department administrators. The outcome of interest is: improving HPV vaccination rates (primary outcome) and strengthening provider recommendations (secondary outcome). We will also examine assess other outcome measures such as HPV vaccine series completion rate in children 9-12 years, time taken to recommend the HPV vaccine (provider-centered outcome); perceived comfort/distress in discussing HPV vaccination with parents (provider-centered outcome), parent satisfaction with HPV vaccine communication (parent-centered outcome) and sustainment of interventions (system-centered outcomes). Study data will be obtained through collection electronic medical record extraction, patient surveys, and semi-structured interviews. The analysis will follow an intent-to-treat (ITT) strategy using a log-binomial or Robust Poisson model. Content analysis will be used to evaluate the qualitative data collected. We will use the Consolidated Framework for Implementation Research (CFIR) and the Multilevel Influences on the Cancer Care Continuum (MICC) to inform our overall study approach and provide rigor and structure to our analyses.

Motivational Wellness Coaching to Reduce Childhood Obesity in Families and Kids

Rates of childhood obesity in the United States (US) remain at historic highs. Before the age of 11 years, 18% of all children in the US are already obese; 26% of Hispanic and 24% of Black children are obese. Pediatric primary care settings are underutilized in preventing and treating childhood obesity. An evidence-based method for treatment of childhood obesity to help engage and motivate patients is Motivational Interviewing (MI). One recent successful study, BMI2 (for Brief Motivational Interviewing to Reduce Child Body Mass Index) directed at the parents of children in pediatric care practices lowered body mass index (BMI) significantly. MI-based approaches have been particularly successful for racial/ethnic minorities and low-income populations. However, the targeted MI dose of BMI2 requires significant resources, with MI sessions administered by the PCP and a registered dietician. It is unclear whether the impressive results of BMI2 can be replicated in a health care system with real-world conditions. It is challenging to find an effective intervention that is feasible and sustainable without requiring significant resources. Our overall goal is to reduce excess body weight in children in primary care. The investigators will conduct a cluster-randomized pragmatic trial in 49 pediatric clinics in Kaiser Permanente Southern California (KPSC) to test the effectiveness of a modified version of BMI2 intervention in pediatric clinics (24 intervention, 25 usual care with attention control, = 6,600 children). The clinics serve over 45,000 children aged 2-8 yrs who are overweight or obese with high racial/ethnic and socioeconomic diversity (53% Hispanic; 23% state-subsidized insurance). Using MI techniques, primary care providers (PCPs) will initiate and maintain discussion about weight management with parent (6 x 20 min) and refer patients electronically to experienced and MI-trained lifestyle coaches. With full access to the electronic medical record (EMR), coaches will call referred families (child's BMI-for-age ≥85th percentile) and deliver intervention via telephonic MI counseling over two years (6 x 45 min). Usual care clinics with attention control will include regular encounters and educational videos as attention control. Primary Aim: Determine the effectiveness and dose-response relationship of a pragmatic, system-integrated childhood obesity intervention using mBMI2Kids (a modified BMI2 approach) on BMI at 2-yr follow-up. Secondary Aim: Investigate how patient characteristics such as minority or low-income background and parental obesity modify the effect of the mBMI2Kids intervention (Heterogeneity of effects). IMPACT: This study has the potential for a highly significant shift in pediatric primary care practices. Our results will provide valuable guidance to providers and health care systems to help them effectively halt and reverse the childhood obesity epidemic. Our results can be quickly translated into other clinical care settings and endorse the meaningful use of EMR systems to support providers using tools and centralized approaches that make interventions scalable.