With the increasing utilization of medications worldwide, coupled with the increasing availability of long-term data, there is a growing opportunity and need for robust studies evaluating drug-cancer associations. One methodology of importance in such studies is the application of lag…
Fracture and osteoporosis are known side effects of aromatase inhibitors (AIs) for postmenopausal hormone receptor positive (HR+) breast cancer (BC) patients. How modifiable lifestyle factors impact fracture risk in these patients is relatively unknown. We conducted a prospective cohort study…
Many asthma patients remain uncontrolled on inhaled corticosteroids (ICS) and long-acting beta agonists (LABAs), but guidance for selecting add-on therapies, including long-acting muscarinic antagonists (LAMAs) or biologics, is limited. We describe how prescribing practices for add-on LAMA and biologic therapy…
The overall objective of the Cholesterol Lowering via Bempedoic Acid/Ezetimibe, an ACL-Inhibiting Regimen in Acute Coronary Syndrome ACS (CLEAR ACS) study is to determine the efficacy, safety, and tolerability of bempedoic acid/ezetimibe (BA/E) in a contemporary and real-world population, enriched…
Inhaled corticosteroids (ICS) are a cornerstone of asthma treatment. However, their efficacy is characterized by wide variability in individual responses. We investigated the association between genetic variants and risk of exacerbations in adults with asthma and how this association is…
We compared the efficacy of the antiviral agent, remdesivir, versus standard-of-care treatment in adults with severe coronavirus disease 2019 (COVID-19) using data from a phase 3 remdesivir trial and a retrospective cohort of patients with severe COVID-19 treated with standard…
This project will establish a prospective cohort of white and Black cancer patients treated with immune checkpoint inhibitors, leveraging the NCI Community Oncology Research Program network infrastructure, to investigate racial differences in immune-related adverse events and their predictors, treatment delay…
This study will use rigorous methods and rich health care data from a diverse, multi-site study population to study psychotherapy and antidepressant treatments for new episodes of depression during pregnancy. Analyses will include examination of infant outcomes and breastfeeding.
This career development award project will compare the effectiveness of pharmacological therapy for lower urinary tract symptoms secondary to benign prostatic hyperplasia in preventing long-term disease progression; and develop and validate predictive models using demographic, clinical, and laboratory data available…
This randomized controlled trial study is testing an intervention to reduce unsafe medication use in patients aged 75 years and older. The intervention uses collaborative drug therapy management between physicians and pharmacists, standard-of-care treatment protocols, shared decision-making, and the CEASE deprescribing protocol…
Treatment options for patients with venous thromboembolism (VTE) include warfarin and direct oral anticoagulants (DOACs). Although DOACs are easier to administer than warfarin and do not require routine laboratory monitoring, few studies have directly assessed whether patients are more satisfied…
Integrase strand transfer inhibitor (InSTI)-based regimens are now recommended as first-line antiretroviral therapy (ART) for adults with human immunodeficiency virus, but evidence on long-term clinical effectiveness of InSTI-based regimens remains limited. We examined whether InSTI-based regimens improved longer-term clinical outcomes…
Hydrochlorothiazide (HCTZ), a common diuretic known to be photosensitizing and previously associated with non-melanoma skin cancer, was recently reported to be associated with two melanoma subtypes, nodular and lentigo, among residents of Denmark. Our goal was to examine whether Danish…
Atypical femur fracture (AFF) is an uncommon complication of long-term bisphosphonate use, but the risk declines substantially after treatment cessation. We report a case of a 70-year-old woman with osteopenia treated with alendronate for 9 years who presented with right…
This study is designed to help patients with type 2 diabetes and their clinicians identify which glucose-lowering medications among SGLT2 inhibitors, GLP-1 receptor agonists, DPP4 inhibitors, or Sulfonylureas have the most favorable effects on heart health and other patient-important outcomes;…
To estimate the association of cefuroxime and moxifloxacin in relation to the occurrence of endophthalmitis following phacoemulsification cataract surgery. Retrospective clinical cohort study. We studied patients with noncomplex phacoemulsification cataract surgery in Kaiser Permanente Northern California during 2014-2019. Data were…
It has been shown that racial/ethnic disparities exist with regard to initiation of and adherence to adjuvant endocrine therapy (AET). However, the relationship among American Indian/Alaska Native (AIAN) individuals is poorly understood, particularly among those who reside in urban areas…
Persons living with human immunodeficiency virus (HIV; PLWH) experience a high burden of cancer. It remains unknown which cancer types are reduced in PLWH with earlier initiation of antiretroviral therapy (ART). We evaluated AIDS-free, ART-naive PLWH during 1996-2014 from 22…
To examine the effects of prescription sleep medications on patient-reported sleep disturbances. Retrospective cohort. Longitudinal cohort of community-dwelling women in the USA. Racially and ethnically diverse middle-aged women who reported a sleep disturbance. New users of prescription sleep medications propensity…
This statement summarizes evidence that adverse pregnancy outcomes (APOs) such as hypertensive disorders of pregnancy, preterm delivery, gestational diabetes, small-for-gestational-age delivery, placental abruption, and pregnancy loss increase a woman's risk of developing cardiovascular disease (CVD) risk factors and of developing…
Pregnant women with lupus are at high risk to develop preeclampsia and preterm delivery. This work leverages three large population-based databases with detailed prescription and clinical data to determine whether use of hydroxychloroquine during pregnancy among women with lupus reduces…
Large observational study to evaluate the effects of initiating buprenorphine treatment on subsequent suicidal behavior among people with opioid use disorder.
Hostility is a complex personality trait associated with many cardiovascular risk factor phenotypes. Although magnesium intake has been related to mood and cardio-metabolic disease, its relation with hostility remains unclear. We hypothesize that high total magnesium intake is associated with…
DISCLOSURES: No funding was received for the writing of this letter. All authors were members of the National Academies study committee to which this letter refers, with Shortliffe as the chair. All committee members who contributed to the report were…
The MITIGATE study aims to evaluate the real-world clinical effectiveness of pre-treatment with icosapent ethyl (IPE), compared with usual care, on laboratory-confirmed viral upper respiratory infection (URI)-related morbidity and mortality in adults with established atherosclerotic cardiovascular disease (ASCVD). IPE is…
Phacoemulsification has been linked to lowered intraocular pressure (IOP) in patients with glaucoma, ocular hypertension, anatomic narrow angles, and in glaucoma suspects, but the magnitude of change has varied. Retrospective cohort study. Patients with glaucoma treated from June 2010 through…
Hepatitis C and HIV are associated with opioid use disorders (OUD) and injection drug use. Medications for OUD can prevent the spread of HCV and HIV. To describe the prevalence of documented OUD, as well as receipt of office-based medication…
The aim of the RAAS-COVID-19 randomized control trial is to evaluate whether an upfront strategy of temporary discontinuation of renin angiotensin aldosterone system (RAAS) inhibition versus continuation of RAAS inhibition among patients admitted with established COVID-19 infection has an impact…
This clinical trial will evaluate treatment with IV administered remdesivir in an outpatient setting in patients with COVID-19 who are at risk for disease progression.
This virtual, pragmatic randomized clinical trial will evaluate whether rivaroxaban reduces the risk of a composite endpoint of major venous and arterial thrombotic events, all-cause hospitalization, and all-cause mortality compared with placebo in outpatients with acute, symptomatic COVID-19 infection.
In pharmacogenomic studies of quantitative change, any association between genetic variants and the pretreatment (baseline) measurement can bias the estimate of effect between those variants and drug response. A putative solution is to adjust for baseline. We conducted a series…
Mail order pharmacy (MOP) use has been linked to improved medication adherence and health outcomes among patients with diabetes. However, no large-scale intervention studies have assessed the effect of encouraging MOP use on medication adherence. To assess an intervention to…
The study will assess the effects of statin treatment on risk of Alzheimer's disease and related dementias, controlling for potential confounding and examining potential mediating factors among Kaiser Permanente Northern California members during the years 1996 to 2020. A second…
To describe the safety and tolerability profiles of prophylactic BNT162 vaccines in healthy adults after 1 or 2 doses
This study will test the hypothesis that the underlying prenatal depression and use of SSRIs are independent risk factors for adverse neurodevelopmental outcomes. The aims of this study are: 1) evaluate the effect of untreated prenatal depression, compared to no…
This study compared the efficacy and safety of sacubitril/valsartan to enalapril in Black and non-Black Americans with acute decompensated heart failure (ADHF). Black patients have a different response to treatment with angiotensin-converting enzyme inhibitors compared with other racial and ethnic…
The PARADIGM-HF (Prospective Comparison of Angiotensin II Receptor Blocker Neprilysin Inhibitor With Angiotensin-Converting Enzyme Inhibitor to Determine Impact on Global Mortality and Morbidity in Heart Failure) trial reported that sacubitril/valsartan (S/V), an angiotensin receptor-neprilysin inhibitor, significantly reduced mortality and heart failure…
There are few descriptions of virologic failure (VF) and acquired drug resistance (HIVDR) in large cohorts initiating contemporary antiretroviral therapy (ART). We studied all persons with HIV (PWH) in a California clinic population initiating ART between 2010 and 2017. VF…
Clinical practice guidelines recommend routine kidney function and serum potassium testing within 30 days of initiating ACE (angiotensin-converting enzyme) inhibitor or angiotensin II receptor blocker therapy. However, evidence is lacking about whether follow-up testing reduces therapy-related adverse outcomes. We conducted…
In large artery occlusion stroke, both intravenous (IV) tPA (tissue-type plasminogen activator) and endovascular stroke treatment (EST) are standard-of-care. It is unknown how often tPA causes distal embolization, in which a procedurally accessible large artery occlusion is converted to a…
The PIONEER-HF (comParIson Of sacubitril/valsartaN versus Enalapril on Effect on nt-pRo-bnp in patients stabilized from an acute Heart Failure episode) trial demonstrated the efficacy and safety of sacubitril/valsartan (S/V) in stabilized patients with acute decompensated heart failure (HF) and reduced ejection…
The study will examine patient knowledge and experience in a Value-based insurance designs plan by surveying 1,000 patients newly enrolling in a VBID plan. The survey will collect patient knowledge of their plan, patient-reported medication behavior (including specific cost barriers…
Recent clinical trials have evaluated angiotensin-converting enzyme (ACE) inhibitors (ACEis), angiotensin receptor blockers (ARBs), and beta blockers (BBs) in relation to cardiotoxicity in patients with cancer, typically defined by ejection fraction declines. However, these trials have not examined long-term, hard…
This multi-center, multi-country retrospective cohort study will assess the clinical course and outcome of adults with severe COVID-19 not treated with remdesivir using a 7-point ordinal scale for clinical outcomes on Day 14 and all-cause mortality at Day 28 after…
The MITIGATE Study will evaluate the real-world clinical effectiveness of icosapent ethyl (Vascepa®) compared to usual care in patients with established atherosclerotic cardiovascular disease. The study will evaluate whether the drug, which is used to reduce the risk of heart…
Infants with Neonatal Opioid Withdrawal Syndrome (NOWS) are often treated with prolonged opioid-replacement pharmacotherapy. Whether opioid exposure in-utero or significant opioid exposure used to treat withdrawal symptoms impacts neurodevelopmental outcomes is unknown. Our aim is to evaluate neurodevelopmental outcomes at…
MMR II (M-M-R II [Merck & Co, Inc.]) is currently the only measles, mumps, and rubella (MMR) vaccine licensed in the United States. A second MMR vaccine would mitigate the potential risk of vaccine supply shortage or delay. In this…
The Menopause Strategies: Finding Lasting Answers for Symptoms and Health clinical trials network was funded by the National Institutes of Health to find new ways to alleviate the most common, bothersome menopausal symptoms by designing and conducting multiple concurrent clinical…
The reported association between maternal antibiotic use and childhood obesity, if true, could change obstetric practice. However, it is unclear whether the reported association was due to antibiotics, or underlying infection or both. To examine the independent contributions of maternal…
People living with human immunodeficiency virus (HIV; PLWH) have a markedly elevated anal cancer risk, largely due to loss of immunoregulatory control of oncogenic human papillomavirus infection. To better understand anal cancer development and prevention, we determined whether recent, past,…
The impact of atrial fibrillation (AF) catheter ablation versus chronic antiarrhythmic therapy alone on clinical outcomes such as death and stroke remains unclear. We compared adverse outcomes for AF ablation versus chronic antiarrhythmic therapy in 1,070 adults with AF treated…
The association between statins and diabetes mellitus (DM) remains controversial. The Kaiser Permanente CHAMP Study identified adults without DM who had cardiovascular (CV) risk factors and no previous lipid lowering therapy (LLT) between 2008 and 2010. The CV risk factors…
Reports suggest that up to 50% of women with hormone receptor-positive (HR+) breast cancer (BC) do not complete the recommended 5Â years of adjuvant endocrine therapy (AET). We examined the impact of an outreach program at Kaiser Permanente Northern California (KPNC)…
The U.S. experienced nearly 48,000 opioid overdose deaths in 2017. Treatment of opioid use disorder (OUD) with buprenorphine is a recommended part of primary care, yet little is known about current U.S. practices in this setting. This observational study reports…
In PIONEER-HF, among stabilized patients with acute decompensated heart failure (ADHF), the in-hospital initiation of sacubitril/valsartan was well tolerated and led to improved outcomes compared with enalapril. However, there are limited data comparing the strategies of in-hospital vs postdischarge initiation…
Although most chemotherapies are dosed on body surface area or weight, body composition (ie, the amount and distribution of muscle and adipose tissues) is thought to be associated with chemotherapy tolerance and adherence. To evaluate whether body composition is associated…
The relationship between achieved low-density lipoprotein cholesterol (LDL-C) levels and risk of incident atherosclerotic cardiovascular disease events among patients with diabetes and metabolic dyslipidemia has not been well described. We conducted an observational cohort study of statin-treated adults (ages 21-90…
The overall goal of this project is to demonstrate that the newly FDA-approved Airwave Oscillometry System (tremoFlo c-100, Thorasys) can be used to reliably and easily obtain lung function measurements in ECHO cohorts and that these oscillometry measures of respiratory…
The goals of this study are to (1) examine temporal trends in early hospital antibiotic prescribing patterns over the past 5 years, to assess for unintended consequences associated with earlier antibiotics in severe sepsis/septic shock; (2) quantify the patient-level harm…
How to best medically manage patients who survived hospitalized AKI is unclear. Use of renin-angiotensin system blockers in this setting may increase risk of recurrent AKI. This is a cohort study of 10,242 members of an integrated health care delivery…
In pharmacogenomic studies of quantitative change, any association between genetic variants and the pretreatment (baseline) measurement can bias the estimate of effect between those variants and drug response. A putative solution is to adjust for baseline. We conducted a series…
The objective was to examine the association between sleep quality and global and domain-specific cognitive function among older individuals with type 1 diabetes (T1D). We evaluated 695 individuals with T1D aged 60 years or above who participated in the baseline…
Improvements in life expectancy among people living with human immunodeficiency virus (PLWH) receiving antiretroviral treatment in the United States and Canada might differ among key populations. Given the difference in substance use among key populations and the current opioid epidemic,…
Background Despite the success of current cardiovascular disease (CVD) management programs, many patients do not achieve optimal control of CVD-related risk factors. New strategies are needed to better activate and engage these patients. Methods and Results We conducted a parallel,…
Concomitant excessive alcohol consumption and benzodiazepine use is associated with adverse health outcomes. We examined associations of unhealthy alcohol use and other patient characteristics with benzodiazepine use. A cross-sectional analysis of 2,089,525 Kaiser Permanente of Northern California outpatients screened for…
In a northern California population of older women who were treated with oral bisphosphonate drugs, the incidence of atypical femur fracture, a rare complication of treatment, increased with longer duration of bisphosphonate exposure. These findings align with those previously reported…
To lower risk from cardiovascular disease (CVD), national guidelines recommend lifestyle changes followed by use of lipid-lowering medications when appropriate. Previous studies have questioned whether individuals taking these medications are less likely to modify their dietary intake and physical activity,…
Few studies describe both inpatient and outpatient treatment and outcomes of patients with acute venous thromboembolism in the United States. A multi-institutional cohort of patients diagnosed with confirmed pulmonary embolism or deep venous thrombosis during the years 2004 through 2010…
The antipsychotic drug haloperidol has antiproliferative and growth-inhibiting properties on prostate cancer cell lines in vitro by binding the sigma 1 protein. Evidence is needed regarding a possible preventive association in men. To examine whether our epidemiologic data support an…
The aims of this study are to 1) Assess the relationship between untreated prenatal depression and the risk of speech and language disorders of offspring; 2) Compare the effectiveness of treatment of prenatal depression on speech and language disorders of…
Aim 1: Identify patient-level predictors of metformin treatment during the year following type 2 diabetes diagnosis. Examined factors will include: demographics, such as age, race/ethnicity, gender, and rural versus urban; clinical characteristics, such as A1c at diagnosis, diabetes-related comorbidities (hypertension,…
Evidence suggests use of proton pump inhibitors (PPIs) and H2 blockers may provoke disease flares in individuals with established inflammatory bowel disease (IBD); however, there are no studies investigating the relationship of these medications with risk of developing pediatric IBD…
To assess the impact of CYP2C9 variation on phenytoin patient response and clinician prescribing practice where genotype was unknown during treatment. A retrospective analysis of Resource on Genetic Epidemiology Research on Adult Health and Aging cohort participants who filled a…
We validated an algorithm to detect frequency errors in computerized healthcare data and estimated the incidence of these errors in an integrated healthcare system. We applied Sentinel System analytic tools on the electronic health records of Kaiser Permanente, Northern California,…
Hydroxychloroquine (HCQ) is a cornerstone to managing systemic lupus erythematosus (SLE), yet adherence to medication is poor. We sought to measure the association of adherence with 5 "dimensions of adherence" as articulated by the World Health Organization for chronic conditions:…
This study will provide a comprehensive program of infrastructure development, methods development, and innovative research to generate real-world evidence addressing critical gaps in the regulation of medical products. We will explore four related issues: Potential for existing medical products to…
To evaluate implementation of an enhanced recovery after surgery (ERAS) program for patients undergoing elective cesarean delivery by comparing opioid exposure, multimodal analgesia use, and other process and outcome measures before and after implementation. An ERAS program was implemented among…
To assess fracture risk among women with depot medroxyprogesterone acetate (DMPA), oral contraceptive pill (OCP), and intrauterine device (IUD) use. A retrospective cohort study of 308,876 women age 12-45 years who initiated DMPA, combined or progestin-only OCPs, and copper and…
This study evaluates the safety and efficacy in reducing recurrence of Clostridium difficile infection in adults who had a recurrence within 8 weeks of receiving CP101 or placebo in PRISM3. Subjects who are experiencing recurrent Clostridium difficile infection will undergo…
To evaluate the efficacy of two common interventions for bothersome postmenopausal vaginal symptoms on improving sexual frequency and pain. This is a post-hoc analysis of data from a 12-week double-blind placebo-controlled trial that randomized postmenopausal women (ages 45-70 years) with…
The quadrivalent meningococcal conjugate vaccine MenACWY-CRM has been shown to be immunogenic and well-tolerated in infants and toddlers. We evaluated antibody persistence for up to 4 years after vaccination with MenACWY-CRM in the first years of life and response to a…
Depression strongly predicts stroke incidence, suggesting that treating depression may reduce stroke risk. Antidepressant medications, however, may increase stroke risk via direct pathways. Previous evidence on antidepressant medication and stroke incidence is mixed. We evaluated associations between antidepressant use and…
Janus kinase (JAK) inhibitors represent a novel therapeutic class for treatment of inflammatory bowel disease. To determine the efficacy and safety of JAK inhibitors compared to placebo for the treatment of Crohn's disease (CD) and ulcerative colitis (UC). PubMed, Embase…
We examined the fracture risk after initiation of blood pressure-lowering drugs compared with initiation of antidepressants. Multivariable regression models demonstrated an increased risk of fracture among women initiating a blood pressure-lowering medication (HR 1.73, 95% CI 1.02-2.95). This is likely…
Medication non-adherence is a major contributor to poor outcomes in diabetes. Previous research has shown an association between use of mail order pharmacy delivery and better medication adherence, but little is known about the barriers and facilitators to mail order…
Assigning drug exposure is a necessary first step in examining bisphosphonate (BP) treatment in observational studies using pharmacy data. To determine whether the choice of adherence level using the proportion of days covered (PDC) affected BP exposure assignment. 10,381 female…
This study develops generalized per-protocol analyses based on Inverse Probability Weighting and Targeted Learning to control for or evaluate the effect of medication nonadherence in observational studies that use electronic health databases to inform the management of chronic conditions. Unlike…
Background Patient satisfaction with therapy is an important metric of care quality and has been associated with greater medication persistence. We evaluated the association of patient satisfaction with warfarin therapy to other metrics of anticoagulation care quality and clinical outcomes…
Epidural steroid injections may offer little-to-no short-term benefit in the overall population of patients with symptomatic spinal stenosis compared with lidocaine alone. We investigated whether imaging could identify subgroups of patients who might benefit most. A secondary analysis of the…
Surgical clinic and perioperative settings are critical touchpoints for treating smoking, yet health care systems have not typically prioritized smoking cessation among surgical patients. We evaluated the implementation of a pilot smoking cessation intervention integrated into standard perioperative care. English-speaking…
Barriers to HIV preexposure prophylaxis (PrEP) use have not been well-characterized in people who became HIV-infected, all of whom could have benefited from PrEP. We invited Kaiser Permanente Northern California members diagnosed with HIV during 2014-2016, following a negative HIV…
Pharmacists are an expensive and limited resource in the hospital and outpatient setting. A pharmacist can spend up to 25% of their day planning. Time spent planning is time not spent delivering an intervention. A readmission risk adjustment model has…
The effectiveness of 5-fluorouracil compared with that of imiquimod for preventing keratinocyte carcinoma is unknown. To compare the effectiveness of 5-fluorouracil and that of imiquimod in preventing keratinocyte carcinoma in a real-world practice setting. We identified 5700 subjects who filled…
Allopurinol, which lowers uric acid (UA) concentration, is increasingly being recognized for its benefits in cardiovascular and renal disease. However, response to allopurinol is variable. We gathered samples from 4,446 multiethnic subjects for a genome-wide association study of allopurinol response…
The objectives of this Phase 2 study are to evaluate the safety and tolerability of CP101 treatment compared to placebo in adults with previously treated, recurrent Clostridium difficile infection, and to evaluate the efficacy of CP101 treatment relative to placebo…
The risk of acute thrombotic events such as venous thromboembolism (VTE) and ischemic stroke in transgender women receiving hormone therapy was addressed in our longitudinal Study of Transition, Outcomes & Gender (STRONG), supported by the Patient-Centered Outcomes Research Institute. STRONG…
Current World Health Organization guidelines for conducting anti-malarial drug efficacy clinical trials recommend genotyping Plasmodium falciparum genes msp1 and msp2 to distinguish recrudescence from reinfection. A more recently developed potential alternative to this method is a molecular genotyping assay based…
Atrial fibrillation (AF) patients are routinely prescribed medications to prevent and treat complications, including those from common co-occurring comorbidities. However, adherence to such medications may be suboptimal. Therefore, we sought to identify risk factors for general medication non-adherence in a…
Acute decompensated heart failure accounts for more than 1 million hospitalizations in the United States annually. Whether the initiation of sacubitril-valsartan therapy is safe and effective among patients who are hospitalized for acute decompensated heart failure is unknown. We enrolled…
Henry Ford Health System, Kaiser Permanente Colorado, Kaiser Permanente Northern California, Kaiser Permanente Northwest, and Kaiser Permanente Southern California are implementing the National Zero Suicide Model (NZSM), and have received funding from the National Institute of Mental Health to evaluate…
The primary objective of this study is to evaluate the safety and tolerability of V114 with respect to the proportion of participants with adverse events. Secondary objectives are: 1) To evaluate the anti-pneumococcal polysaccharide serotype-specific Immunoglobulin Geometric Mean Concentrations at…
In the United States whites are more likely to misuse opioid pain relievers (OPRs) than blacks, and blacks are less likely to be prescribed OPRs than whites. Our objective is to determine whether racial discrimination in medical settings is protective…
Epidemiologic analyses of gabapentin use and cancer risk in Kaiser Permanente Northern California were previously carried out in a collaborative study and independently evaluated in a UK database. To update these epidemiologic analyses with 7.5 more years of follow-up. Case-control…
In Kaiser Permanente Northern California (KPNC), members had similar access to care and a very high overall rate of hypertension control. However, blacks had poorer blood pressure (BP) control than whites. The Shake Rattle & Roll (SRR) trial aimed to…
Opioid use during pregnancy is associated with suboptimal pregnancy outcomes. Little is known about child neurodevelopmental outcomes. We examined associations between maternal opioid prescriptions preconception to delivery (peri-pregnancy) and child's risk of ASD, developmental delay/disorder (DD) with no ASD features,…
The risk of acute thrombotic events such as venous thromboembolism (VTE) and ischemic stroke in transgender women receiving hormone therapy was addressed in our longitudinal Study of Transition, Outcomes and Gender (STRONG). STRONG is a cohort of transgender people enrolled…
To investigate the implications of a cancer diagnosis on medication adherence for pre-existing comorbid conditions, we explored statin adherence patterns prior to and following a new diagnosis of breast, colorectal, or prostate cancer among a multi-ethnic cohort. We identified adults…
Marijuana use is clinically problematic in depression, and non-medical and medical use may both contribute to barriers to care in this population. Among outpatients with depression, we examined the differential impact of medical or non-medical marijuana use, relative to no-use,…
Findings on maternal 25-hydroxyvitamin D (25[OH]D) and neonatal anthropometry are inconsistent, and may at least be partly due to variations in gestational week (GW) of 25(OH)D measurement and the lack of longitudinal 25(OH)D measurements across gestation. The aim of the…
​Cardiotoxicity of commonly prescribed medications, typically assessed by electrocardiographic features such as prolongation of the QT interval, has regulatory effects and is associated with potentially fatal outcomes. This project aims to advance understanding of the genetic basis for drug cardiotoxicity…
Kaiser Permanente Mid-Atlantic States (KPMAS) members are increasingly utilizing electronic encounter types, such as telephone appointments and secure messaging for healthcare purposes, although their impact on health outcomes is unknown. We evaluated whether use of alternative encounters by adult human…
To determine the efficacy and safety of statins for primary prevention of atherosclerotic cardiovascular disease (ASCVD) events in older adults, especially those aged 80 and older and with multimorbidity. The National Institute on Aging and the National Heart, Lung and…
Discontinuation of hormone replacement therapy (HRT) is much more common than what is reported in randomized, double-blind clinical trials. Our purpose in this retrospective study, using a prescription database, was to compare the continuation rate among women who took cyclic…
Stroke rates in patients with nonvalvular atrial fibrillation (AF) who are not receiving anticoagulant therapy vary widely across published studies; the resulting effect on the net clinical benefit of anticoagulation in AF is unknown. To determine the effect of variation…
Anticoagulation is highly effective for the prevention of stroke in patients with atrial fibrillation (AF) but it is dependent on patients continuing therapy. While studies have demonstrated suboptimal therapeutic persistence on warfarin, few have studied persistence rates with non vitamin…
Many antihypertensive drugs (ADs) are photosensitizing, heightening reactivity of the skin to sunlight. Photosensitizing ADs have been associated with lip cancer, but whether they impact the risk of cutaneous squamous cell carcinoma (cSCC) is unknown. To examine the association between…
​Building on past research, this project will establish the infrastructure to expand a prescription opioid registry across diverse health systems in the Addiction Research Network. Harmonized electronic health record data elements will be used to examine how changes in opioid…
This study employs a cluster randomization design to examine the vaccine effectiveness of Flublok relative to that of other flu vaccines used at Kaiser Permanente Northern California over two influenza seasons (2018 to 2019 and 2019 to 2020), in Kaiser…
The purpose of this project is, first, to estimate the proportion of the population under study receiving one and two doses of recombinant zoster vaccine (RZV). Second, among live zoster vaccine (ZVL)-naive persons, this study aims to: 1) estimate the…
​The goal of this project is to address the following research question: Does the use of antidepressant treatment, specifically, selective serotonin reuptake inhibitors (SSRIs) and serotonin and norepinephrine reuptake inhibitors (SNRIs), reduce the risk of primary open angle glaucoma?
Risk of community-acquired Clostridium difficile infection (CA-CDI) following antibiotic treatment specifically for urinary tract infection (UTI) has not been evaluated. We conducted a nested case-control study at Kaiser Permanente Northern California, 2007-2010, to assess antibiotic prescribing and other factors in…
Nontuberculous mycobacterial (NTM) pulmonary disease prevalence is increasing. To determine the association between the use of inhaled corticosteroids and the likelihood of NTM pulmonary infection among individuals with treated airway disease. We conducted a case-control study of subjects with airway…
Prediabetes is prevalent and significantly increases lifetime risk of progression to type 2 diabetes. This review summarizes the evidence surrounding metformin use for type 2 diabetes prevention. Articles published between 1998 and 2017 examining metformin use for the primary indication…
Background Chronic kidney disease ( CKD ) is a common comorbidity in patients with atrial fibrillation. The presence of CKD complicates drug selection for stroke prevention and rhythm control. Methods and Results Patients enrolled in ORBIT AF (Outcomes Registry for…
Possibly through its effects on glia, the peroxisome proliferator-activated gamma receptor (PPARÎł) agonist pioglitazone (PIO) has been shown to alter the effects of heroin in preclinical models. Until now, these results have not been assessed in humans. Heroin-dependent participants were…
With few notable exceptions, drug development for heart failure (HF) has become progressively more challenging, and there remain no definitively proven therapies for patients with acute HF or HF with preserved ejection fraction. Inspection of temporal trends suggests an increasing…
Low-density lipoprotein cholesterol (LDL-C) response to statin therapy has not been fully elucidated in real-world populations. The primary objective of this study was to characterize statin LDL-C dose-response and its heritability in a large, multiethnic population of statin users. We…
The relevance of low-density lipoprotein cholesterol (LDL-C) or non-high-density lipoprotein cholesterol (non-HDL-C) goals for primary prevention of atherosclerotic cardiovascular disease (ASCVD) among patients with diabetes was assessed. This retrospective cohort study included patients with type 2 diabetes, age 21 to…
To compare the risk of mortality among men treated for benign prostatic hyperplasia (BPH) with 5 alpha-reductase inhibitors (5ARI) to those treated with alpha-blockers (AB) in community practice settings. We employed a retrospective matched cohort study in 4 regions of…
Nonsteroidal antiinflammatory drugs are among the medications most widely used by pregnant women, and previous studies have reported an increased risk of miscarriage that is associated with nonsteroidal antiinflammatory drug use during pregnancy. Although the findings have not always been…
Bleeding is commonly cited as a reason for stopping oral anticoagulants (OACs). Whether minor bleeding events (nuisance bleeding, NB) in patients with atrial fibrillation on OACs are associated with OAC discontinuation, major bleeding, and stroke/systemic embolism (SSE) is unknown. Within…
Background Current American College of Cardiology/American Heart Association guidelines suggest that for patients with atrial fibrillation who are at low risk for stroke (CHA2DS2VASc=1) (or women with CHA2DS2VASc=2) a variety of treatment strategies may be considered. However, in clinical practice,…
Venous thromboembolism (VTE), ischemic stroke, and myocardial infarction in transgender persons may be related to hormone use. To examine the incidence of these events in a cohort of transgender persons. Electronic medical record-based cohort study of transgender members of integrated…
AIMS: Obesity is present in up to 45% of patients with heart failure (HF). Liraglutide, a glucagon-like peptide-1 (GLP-1) receptor antagonist, facilitates weight loss in obese patients. The efficacy of liraglutide as a weight loss agent among patients with HF…
Cutaneous melanoma incidence may be modestly elevated in people with HIV (PWH) vs. people without HIV. However, little is known about the relationship of immunosuppression, HIV replication, and antiretroviral therapy (ART) with melanoma risk. PWH of white race in the…
Androgen deprivation therapy (ADT), used increasingly in the treatment of localized prostate cancer, is associated with substantial long-term adverse consequences, including incident diabetes. While previous studies have suggested that ADT negatively influences glycemic control in existing diabetes, its association with…
The National Institute of Diabetes and Digestive and Kidney Diseases convened a workshop on research gaps in gestational diabetes mellitus (GDM) with a focus on 1) early pregnancy diagnosis and treatment and 2) pharmacologic treatment strategies. This article summarizes the…
Background: Some prior studies have reported reduced colorectal cancer risk among individuals using antidepressant medications, especially selective serotonin reuptake inhibitors (SSRIs). Yet most studies have not considered the potential role of depression or other confounders in their analyses.Methods: We utilized…
Patients with heart failure will be randomized 1:1 to either oral torsemide or oral furosemide prior to hospital discharge. The primary endpoint will be all-cause mortality over the follow-up period. Secondary endpoints are hospitalizations, quality of life, and depression.
This project will identify all patients who have a laboratory-confirmed diagnosis of Hepatitis C. The intervention group will be those who had a prescription filled for a new antiviral medication after October 10, 2014, and who were naive to treatment…
Although the benefits of combination antiretroviral therapy (ART) for reducing HIV-related morbidity and mortality are well-recognized, toxicity from some ART may potentially contribute to excess age-related comorbidities. Certain antiretrovirals, including tenofovir, have known renal toxicity, but recent formulations may be…
The purpose of this project is to assess the variation and impact of oral anticoagulant prescribing in the emergency department in order to inform development of interventions to improve acute atrial fibrillation and flutter management. A longitudinal database will be…
In clinical trials of patients with type 2 diabetes, long-acting insulin analogs modestly reduced the risk of nocturnal hypoglycemia compared with human neutral protamine Hagedorn (NPH) insulin, but cost 2 to 10 times more. Outcomes in clinical practice may differ…
Atrial fibrillation is a potent risk factor for stroke, but whether the burden of atrial fibrillation in patients with paroxysmal atrial fibrillation independently influences the risk of thromboembolism remains controversial. To determine if the burden of atrial fibrillation characterized using…
Metformin is the first-line treatment for type 2 diabetes (T2D). Although widely prescribed, the glucose-lowering mechanism for metformin is incompletely understood. Here, we used a genome-wide association approach in a diverse group of individuals with T2D from the Action to…
Nonadherence to controller and overuse of reliever asthma medications are associated with exacerbations. We aimed to determine patterns of seasonal asthma medication use and to identify time period(s) during which interventions to improve medication adherence could reduce asthma morbidity. We…
Nonsteroidal anti-inflammatory drugs (NSAIDs) use has consistently been associated with lower risk of colorectal cancer (CRC); however, studies showed inconsistent results on which cohort of individuals may benefit most. We performed multivariable logistic regression analysis to systematically test for the…
Secondary prevention after an acute coronary syndrome (ACS) hospitalization is critical to prevent additional morbidity and mortality. While poor adherence to prescribed cardio-protective medications is a known problem;1;2 it is unknown whether an ACS event might motivate patients to achieve…
This study aims to employ machine learning methods to develop predictive models for adverse drug events, or ADEs, that result in patients using the emergency department and/or being hospitalized (non-nosocomial ADEs, NNADEs). Based on work with a pharmacist expert panel…
In individuals with diabetes, the comparative effectiveness of add-on antihypertensive medications added to an angiotensin-converting enzyme inhibitor or angiotensin II receptor blocker on the risk of significant kidney events is unknown. We used an observational, multicenter cohort of 21,897 individuals…
Emergency department (ED) patients with acute pulmonary embolism (PE) despite therapeutic anticoagulation at the time of diagnosis are uncommonly encountered and present a diagnostic and management challenge. Their characterization and outcomes are poorly described. We sought to describe the prevalence…
There is persistent confusion as to whether abacavir (ABC) increases the risk of myocardial infarction (MI), and whether such risk differs by type 1 (T1MI) or 2 (T2MI) MI in adults with HIV. Incident MIs in North American Cohort Collaboration…
This analysis of the lumbar epidural steroid injections for spinal stenosis multicenter randomized controlled trial data identifies the degree of and risk factors for cortisol suppression after epidural steroid injections in older adults with spinal stenosis. Four hundred patients aged…
Strategies are needed to identify at-risk patients for adverse events associated with prescription opioids. This study identified prescription opioid misuse in an integrated health system using electronic health record (EHR) data, and examined predictors of misuse and overdose. The sample…
Anxiety and depression are associated with worse outcomes in several cardiovascular conditions, but it is unclear whether they affect outcomes in atrial fibrillation (AF). In a large diverse population of adults with AF, we evaluated the association of diagnosed anxiety…
Mineralocorticoid receptor antagonist (MRA) therapy may be beneficial to patients with atrial fibrillation (AF), but little is known about their use in patients with AF and subsequent outcomes. In order to better understand MRA use and subsequent outcomes, we performed…
Kaiser Permanente Northern California has recently collaborated with Pfizer in identifying invasive and noninvasive group B streptococcus (GBS) disease burden in adults during a seven-year time period spanning 2007 to 2014. In Phase 1 of this research collaboration, comorbid medical…
We assessed bone mineral density (BMD) change with aromatase inhibitor (AI) treatment in a contemporary cohort of women with breast cancer treated in Kaiser Permanente Northern California. Percent and estimated annual percent changes in BMD at the total hip and…
To describe the relationship between the incidence of age-related macular degeneration (AMD) and nonsteroidal anti-inflammatory drug (NSAIDs) use. Prospective cohort study. This study consisted of participants in the California Men's Health Study. Those who completed surveys in 2002-2003 and 2006…
The objective of this study was to compare outcomes and health care utilization of older patients who did versus did not fill opioid prescriptions within 90 days of initiating care for low back pain. For patients ≥65 years with new…
To estimate the effect of out-of-pocket (OOP) cost on nonadherence to classes of cardiometabolic medications among patients with diabetes. Electronic health records from a large, health care delivery system for 223,730 patients with diabetes prescribed 842,899 new cardiometabolic medications during…
We investigated the effect of inflammatory biomarkers (neutrophil, platelet, and lymphocyte counts) on risk of progression in patients with metastatic melanoma treated with an immune checkpoint inhibitor targeting programmed cell death protein-1 (PD-1). This retrospective cohort study included 108 patients…
With stroke treatment, there is a general belief that "time is brain." However, there has been no published data examining specifically the association between door-to-needle times for acute treatment with intravenous alteplase in stroke patients and 90-day outcomes. In 2016,…
The US Food and Drug Administration's Sentinel system developed tools for sequential surveillance. In patients with non-valvular atrial fibrillation, we sequentially compared outcomes for new users of rivaroxaban versus warfarin, employing propensity score matching and Cox regression. A total of…
Although traditional renin-angiotensin system antagonists including angiotensin-converting enzyme inhibitors and angiotensin receptor blockers have revolutionized the treatment of cardiovascular disease (CVD), the pivotal PARADIGM-HF trial demonstrated that sacubitril/valsartan, an angiotensin receptor-neprilysin inhibitor (ARNI), was superior to an angiotensin-converting enzyme inhibitor…
OBJECTIVE: The objective is to assess the safety, tolerability, and efficacy of sacubitril/valsartan compared with enalapril in patients with heart failure (HF) with a reduced ejection fraction (EF) stabilized during hospitalization for acute decompensated HF.BACKGROUND: Sacubitril/valsartan, a first-in-class angiotensin receptor-neprilysin…
For adults aged 40 to 75 years, randomized trials provide conclusive evidence that statins reduce the risk of initial and secondary cardiovascular disease (CVD) events. However, there is limited evidence that statins reduce CVD events in individuals over the age…
Comparative safety studies typically use hierarchical treatment categories that lump monotherapy and combination therapy. The consequence of this approach on study results is not clear. For example, studies of tumor necrosis factor inhibitors usually lump users regardless of whether they…
Studies suggest that ACE-inhibitors (ACE-I) and angiotensin receptor blockers (ARBs) may preserve skeletal muscle with aging. We evaluated longitudinal differences in lean body mass (LBM) among women diagnosed with hypertension and classified as ACE-I/ARB users and nonusers among Women's Health…
The cardiovascular safety of saxagliptin, a dipeptidyl-peptidase 4 inhibitor, compared with other antihyperglycemic treatments is not well understood. We prospectively examined the association between saxagliptin use and acute myocardial infarction (AMI). We identified patients aged ≥18 years, starting from the…
BACKGROUND: The opioid epidemic in the US is affecting pregnant women and their offspring, with rising numbers of maternal and neonatal treatment episodes. The aim of this study was to characterize pregnant drug users in order to inform intervention strategies…
The most widely used topical agents for the field-based treatment of multiple actinic keratoses (AKs) are 5-fluorouracil and imiquimod, but their comparative effectiveness has not been assessed in a real-world setting. We compared the effectiveness of 5-fluorouracil and imiquimod in…
Dabigatran (150 mg twice daily) has been associated with lower rates of stroke than warfarin in trials of atrial fibrillation, but large-scale evaluations in clinical practice are limited. To compare incidence of stroke, bleeding, and myocardial infarction in patients receiving…
In the setting of changing temporal trends in the management of osteoporosis, we examined how select characteristics of new oral bisphosphonate (BP) initiators changed over time among 94,073 women within a large, integrated healthcare organization during the period 2004 to…
Statin therapy is highly efficacious in the prevention of fatal and nonfatal atherosclerotic events in persons at increased cardiovascular risk. However, its long-term effectiveness in practice depends on a high level of medication adherence by patients. We identified nondiabetic adults…
This study will survey a sample of patients with pain about their use of medical marijuana. The goal is to describe patterns of use, mode, medical conditions, or symptoms for which medical marijuana is used, as well as perceived benefits,…
National guidelines encourage counseling high-risk women about pharmacologic breast cancer risk reduction. We evaluated the use of integrated health care data to identify and characterize breast cancer chemoprevention use. Chemoprevention included US Food and Drug Administration-approved use of tamoxifen and…
Acute heart failure (HF) is a global pandemic with more than one million admissions to hospital annually in the US and millions more worldwide. Post-discharge mortality and readmission rates remain unchanged and unacceptably high. Although recent drug development programmes have…
Possibly through their actions upon glia, peroxisome proliferator-activated receptor agonists (PPAR) have been shown to alter the abuse potential of addictive drugs in several preclinical models. The current study extends this research into the human laboratory as the first clinical…
The diuretic hydrochlorothiazide is amongst the most frequently prescribed drugs in the United States and Western Europe, but there is suggestive evidence that hydrochlorothiazide use increases the risk of lip cancer. To study the association between use of hydrochlorothiazide and…
Little is known about the use of ibutilide for cardioversion in atrial fibrillation and flutter outside of clinical trials. We seek to describe patient characteristics, ibutilide administration patterns, cardioversion rates, and adverse outcomes in the community emergency department (ED) setting…
To assess the clinical effectiveness of beta-blocker therapy in individuals with heart failure (HF) and chronic lung disease and of angiotensin-converting enzyme inhibitors (ACE-Is) and angiotensin II receptor blockers (ARBs) in individuals with HF and chronic kidney disease. Retrospective cohort…
Minority variant human immunodeficiency virus type 1 (HIV-1) nonnucleoside reverse transcriptase inhibitor (NNRTI) resistance mutations are associated with an increased risk of virological failure during treatment with NNRTI-containing regimens. To determine whether individuals to whom variants with isolated NNRTI-associated drug…
Animal and human data suggest statins may be protective against developing multiple myeloma; however, findings may be biased by the interrelationship with lipid levels. We investigated the association between statin use and risk of multiple myeloma in a large US…
BACKGROUND: This study sought to determine the relative importance of a range of Bup/Nx doses compared to Bup alone in producing subjective and reinforcing effects.METHODS: Heroin-using volunteers (n=13) were transitioned onto daily oral hydromorphone (40mg). Laboratory sessions assessed the reinforcing…
RATIONALE, AIMS, AND OBJECTIVES: Prolongation of the corrected QT (QTc) interval is associated with increased morbidity and mortality. The association between QTc interval-prolonging medications (QTPMs) and risk factors with magnitude of QTc interval lengthening is unknown. We examined the contribution…
Therapeutic response to metformin, a first-line drug for type 2 diabetes (T2D), is highly variable, in part likely due to genetic factors. To date, metformin pharmacogenetic studies have mainly focused on the impact of variants in metformin transporter genes, with…
BACKGROUND:Ofatumumab (Arzerra®, Novartis) is a treatment for chronic lymphocytic leukemia refractory to fludarabine and alemtuzumab [double refractory (DR-CLL)]. Ofatumumab was licensed on the basis of an uncontrolled Phase II study, Hx-CD20-406, in which patients receiving ofatumumab survived for a median…
To establish a prescription opioid registry protocol in a large health system and to describe algorithms to characterize individuals using prescription opioids, opioid use episodes, and concurrent use of sedative/hypnotics. Protocol development and retrospective cohort study. Using Kaiser Permanente Northern…
Seven-year surveillance study (2005-2011) to evaluate race/ethnic differences in the trends in rates of severe hypoglycemia (SH) in a population of insured, at-risk adults with diabetes. SH events were identified via any primary or principal diagnosis from emergency department or…
EXCELS, a postmarketing observational cohort study, was a commitment to the US Food and Drug Administration to assess the long-term safety of omalizumab in an observational setting, focusing predominantly on malignancies. The aim of this study was to examine a…
Ibudilast, a nonselective phosphodiesterase inhibitor, is used clinically in Asia for the treatment of asthma and poststroke dizziness. Recent preclinical studies have suggested that it also inhibits glial cell activation in rodents, and may alter opioid-mediated effects, including analgesia and…
Examining drug exposure is essential to pharmacovigilance, especially for bisphosphonate (BP) therapy. To examine differences in 4 measures of oral BP exposure: treatment discontinuation, adherence, persistence, and nonpersistence. Among women aged ≥ 50 years who initiated oral BP therapy during…
The objectives of this study are: 1) To measure the association between in utero exposure to prescription opioids during early pregnancy and primary neurulation defects. 2) To evaluate whether the risk of primary neurulation defects (i.e., craniorachischisis, anencephalus, and myelomeningocele)…
INTRODUCTION: Some fear that distribution of naloxone to persons at risk of experiencing an opioid overdose may reduce the perceived negative consequences of drug use, leading to riskier patterns of use. This study assessed whether participation in naloxone/overdose training altered…
Proton pump inhibitors (PPIs) and histamine-2 receptor antagonists (H2RAs) suppress gastric acid production, which can inhibit iron absorption. However, few data exist regarding whether these medications increase the risk of clinical iron deficiency. A community-based case-control study evaluated the association…
Preclinical studies suggest that angiotensin system inhibitors (ASI) and bevacizumab improve tumor perfusion and chemotherapy efficacy. We performed a retrospective study to examine whether concomitant ASI use during carboplatin and paclitaxel (CP) without or with bevacizumab (CPB) was associated with…
Antihypertensive medication use may vary by race and ethnicity. Longitudinal antihypertensive medication use patterns are not well described in women. Participants from the Study of Women's Health Across the Nation (SWAN), a prospective cohort of women (n=3302, aged 42-52), who…
To conduct a feasibility study to see if topiramate use during pregnancy increases the risk of cleft palates.
The prevalence of Autism Spectrum Disorders (ASD) has increased rapidly over recent decades. Among many environmental exposures that have also increased in frequency is the use of anti-depressant medications during pregnancy. Approximately 10% of pregnant women are prescribed selective seratonin…
This is the Administrative Coordination Hub for the Pharmacogenomics Research Network (PGRN). The main areas of responsibility include meetings support, communications and coordination of nascent network collaborations.
This study continues surveillance of more than 200 of the most commonly prescribed drugs for carcinogenicity, and examines selected drug-cancer associations of potential importance.
The primary goal of this multi-site study is to identify genetic variants that impact response to metformin in patients with diabetes from multiple ethnic groups in the U.S. and Europe
In collaboration with KPNC clinicians and investigators, Stanford performs research investigations regarding the relationship of HIV resistance, antiretroviral therapy and clinical outcomes, including CD4 and HIV RNA response.
This study will recruit statin users with: 1) a major acute coronary event (n=150), 2) new onset type 2 diabetes (n=150), 3) statin-induced myopathy (n=150), and controls free of all 3 conditions (n=300). We will then conduct genetic, transcriptomic, proteomic…
This study will explore the feasibility of accessing information on the nature and extent of prenatal pharmaceutical usage in the late 1950s through the 1970s.
This randomized trial is based in primary care and focuses on management of prescription opioids among chronic pain patients. The intervention uses a patient activation approach to self-management for these patients and to link them to existing health plan resources.
In clinical practice, bisphosphonate drugs are considered one of the main therapies for osteoporosis, based on strong clinical evidence of significant reduction in risk of hip, vertebral and non-vertebral fractures during the first 3-5 years of therapy. However, concerns have…
This contract agreement with the FDA covers epidemiologic studies of drug safety questions identified by the FDA and led by KP researchers in Northern and Southern California. Examples of current studies include the cardiovascular safety of psychostimulant medications used for…
To conduct a feasibility study to see if topiramate use during pregnancy increases the risk of cleft palates.
The FDA requires the ability to quantify product risks and test hypotheses based on signals of possible drug safety problems originating from adverse reaction reports received by the FDA, the medical literature, or from other sources. In addition, the FDA…
This long term surveillance study has three primary goals: 1) to establish algorithms and identify women with postmenopausal osteoporosis; 2) to establish algorithms and identify the occurrence of adverse events of special interest, including osteonecrosis of the jaw, atypical fracture,…
This cohort study examines the possible association of pioglitazone use with the incidence of new bladder cancer in the Kaiser Permanente Northern California Diabetes Registry .
The objective of this study is to determine if there is an increased risk of cancer with pantoprazole (Protonix®), relative to other proton pump inhibitors.
The objective of this study is to conduct exploratory analysis of the potential association between treatment with pioglitazone and risk of cancer at sites other than bladder using information available from a variety of KPNC electronic data sources.
Among adults with diabetes, depression is associated with poorer adherence to cardiometabolic medications in ongoing users; however, it is unknown whether this extends to early adherence among patients newly prescribed these medications. This study examined whether depressive symptoms among adults…
The risk of hepatotoxicity with antiretroviral therapy (ART) remains unknown. We determined the comparative risk of acute liver injury (ALI) for antiretroviral drugs, classes, and regimens, by viral hepatitis status. We followed a cohort of 10 083 human immunodeficiency virus…
To provide greater understanding of the "real world" effect of anticoagulation on stroke risk over several years. Cohort study. Anticoagulation and Risk Factors in Atrial Fibrillation Study community-based cohort. Adults with nonvalvular atrial fibrillation (AF) between 1996 and 2003 (13,559)…
To assess changes in medication use after a diagnosis of dementia in individuals with type 2 diabetes mellitus. Difference-in-differences analysis of changes in the number of dispensed chronic medications between individuals with and without newly diagnosed dementia. Integrated healthcare delivery…
To determine the association between the use of preoperative antibiotics and the risk of postoperative infection after simple knee arthroscopy. The electronic medical records of a large integrated health care organization were used to identify patients who underwent simple knee…
Placebo-controlled and open-label studies have demonstrated the safety and efficacy of daily oral preexposure prophylaxis (PrEP) in preventing HIV infection, but data are limited on real-world PrEP use. We conducted a cohort study from July 2012 through June 2015 of…
To compare the risk of prostate cancer mortality among men treated with 5- alpha reductase inhibitors (5-ARIs) with those treated with alpha-adrenergic blockers (ABs) in community practice settings. A retrospective matched cohort (N=174,895) and nested case-control study (N=18,311) were conducted…
Regular use of nonsteroidal anti-inflammatory drugs (NSAIDs) is associated with a reduced risk of esophageal adenocarcinoma. Epidemiological studies examining the association between NSAID use and the risk of the precursor lesion, Barrett's esophagus, have been inconclusive. We analyzed pooled individual-level…
AIMS: Change in NT-proBNP level is a common surrogate endpoint in early phase heart failure (HF) trials, but whether this endpoint is influenced by atrial fibrillation/flutter (AFF) is unclear.METHODS AND RESULTS: This analysis included 1358 patients from the ASTRONAUT trial,…
A negative association of statin use with liver cancer risk has been reported frequently. We added laboratory measurements, to our knowledge not included in previous investigations, to a case-control analysis of 2877 case patients and 142 850 matched control subjects…
Phosphodiesterase 5A inhibitors (PDEIs), a common treatment for erectile dysfunction, were recently linked to an increased risk of melanoma. We conducted two parallel case-control studies, using the Danish Nationwide Health Registries (DNHR) and the Kaiser Permanente Northern California (KPNC) electronic…
To compare serious infection risk for systemic lupus erythematosus (SLE) patients starting glucocorticoids (GC), antimalarials (AM), or their combination. We conducted a new-user, historical cohort study, Kaiser Permanente Northern California, 1997-2013. Cox proportional hazards analysis was used to calculate adjusted…
Statin administration early in ischemic stroke may influence outcomes. Our aim was to determine the clinical impact of increasing statin administration early in ischemic stroke hospitalization. This is a retrospective analysis of a multicenter electronic medical record (EMR) intervention to…
OBJECTIVE: To determine possible differences in the rate at which hormone replacement therapy (HRT) is continued among postmenopausal women treated initially with transdermal estradiol versus those treated initially with oral conjugated estrogens. DESIGN: A retrospective database search for prescription use…
OBJECTIVE: The purpose of this study was to examine age-related differences in reasons that postmenopausal women began and stopped hormone replacement therapy (HRT). DESIGN: Two identical telephone surveys were conducted of women members of Kaiser Foundation Health Plan who had…
The aim of the study was to describe initiation of osteoporosis drug therapy after bone mineral density (BMD) testing and to determine any association with BMD test results obtained, physician factors, or both. The setting was the Kaiser Foundation Health…
INTRODUCTION: The purpose of this study was to evaluate outcomes of a disease-management program designed to increase rates of bone-mineral-density (BMD) testing and initiation of osteoporosis medication among patients with a recent osteoporotic fracture. STUDY DESIGN: We identified 744 consecutive…
Warfarin reduces ischemic stroke risk in atrial fibrillation (AF) but increases bleeding risk. Novel anticoagulants challenge warfarin as stroke-preventive therapy for AF. They are available at fixed doses but are more costly. Warfarin anticoagulation at a time in therapeutic range…
For many women with non-metastatic breast cancer, adjuvant chemotherapy prevents recurrence and extends survival. Women who discontinue chemotherapy early may reduce those benefits, but little is known about what predicts early discontinuation. We sought to determine prospectively the rate and…
We sought to develop and validate an instrument that can enable providers to identify young women who may be at risk of contraceptive non-adherence. Item response theory based methods were used to evaluate the psychometric properties of the Contraceptive Intent…
The role of triple antithrombotic therapy vs dual antithrombotic therapy in patients with both atrial fibrillation and coronary artery disease remains unclear. This study explores the differences in treatment practices and outcomes between triple antithrombotic therapy and dual antithrombotic therapy…
We present a systematic screening for identifying associations between prescribed drugs and cancer risk using the high quality Danish nationwide health registries. We identified all patients (cases) with incident cancer in Denmark during 2000-2012 (n=278,485) and matched each case to…
Online patient portals are being widely implemented; however, no studies have examined whether portals influence health behaviors or outcomes similarly across patient racial/ethnic subgroups. We evaluated longitudinal changes in statin adherence to determine whether racial/ethnic minorities initiating use of the…
Several epidemiologic studies suggest that compared to white women, Asians have a greater propensity to suffer an atypical femur fracture (AFF) while taking bisphosphonate therapy. This study examines the relative risk of AFF following bisphosphonate initiation for Asian compared to…
The objective of this study was to evaluate regression, matching, and stratification on propensity score (PS) or disease risk score (DRS) in a setting of sequential analyses where statistical hypotheses are tested multiple times. In a setting of sequential analyses,…
OBJECTIVES: The aim of this study was to characterize the association between decongestion therapy and 30-day outcomes in patients hospitalized for heart failure (HF).BACKGROUND: Loop diuretic agents are commonly prescribed for the treatment of symptomatic congestion in patients hospitalized for…
Reports on associations between azole antifungal medications and acute liver injury are inconsistent and have not been based on liver-related laboratory tests. We evaluated incidence rates of acute liver injury associated with oral azole antifungals. We conducted a cohort study…
Among patients with diabetes, racial differences in cardiometabolic risk factor control are common. The extent to which differences in medication adherence contribute to such disparities is not known. We examined whether medication adherence, controlling for treatment intensification, could explain differences…
Intracameral injection is an effective method for preventing infection, but no controlled study has been published in the United States. We conducted an observational, longitudinal cohort study to examine the effect of topical and injected antibiotics on risk of endophthalmitis…
Sulfonamide antibacterials are widely used in pregnancy, but evidence about their safety is mixed. The objective of this study was to assess the association between first-trimester sulfonamide exposure and risk of specific congenital malformations. Mother-infant pairs were selected from a…
In patients with hypogammaglobulinemia secondary to chronic lymphocytic leukemia (CLL) or multiple myeloma (MM), intravenous immune globulin (IVIg) may be administered to reduce the risk of infection. Since 2013, IVIg products have carried a boxed safety warning about the risk…
Studies suggest that dexmedetomidine-an intravenous central-acting ?2-adrenergic agonist that effectively reduces anxiety among critically ill patients-is being used in patients with severe alcohol withdrawal. However, evidence supporting its use is limited, and it is not approved for this indication. To…
Proton pump inhibitors (PPIs) have been shown to be carcinogenic in rodent studies. As part of a long-term post-marketing surveillance study requested by the US Food and Drug Administration, to compare incidence rates of gastric and other cancers after sustained…
Whether there is a kidney function threshold to statin effectiveness in patients with acute myocardial infarction is poorly understood. Our study sought to help fill this gap in clinical knowledge. We undertook a new-user cohort study of the effectiveness of…
AIMS: Activation of PPARÎł by pioglitazone (PIO) has shown some efficacy in attenuating addictive-like responses in laboratory animals. The ability of PIO to alter the effects of opioids in humans has not been characterized in a controlled laboratory setting. The…
BACKGROUND: Decisions regarding how to treat patients who have 1 to 3 brain metastases require important tradeoffs between controlling recurrences, side effects, and costs. In this analysis, the authors compared novel treatments versus usual care to determine the incremental cost-effectiveness…
Little is known regarding toxicities and hospitalizations in community-based settings for patients with advanced non-small-cell lung cancer (NSCLC) who received commonly prescribed carboplatin-paclitaxel (CP) or carboplatin-paclitaxel-bevacizumab (CPB) chemotherapy. Patients with stages IIIB-IV NSCLC age ? 21 years diagnosed between 2005…
Identifying patients who are medication nonpersistent (fail to refill in a timely manner) is important for healthcare operations and research. However, consistent methods to detect nonpersistence using electronic pharmacy records are presently lacking. We developed and validated a nonpersistence algorithm…
Little is known about the use of sirolimus for primary prevention of cutaneous squamous cell carcinoma (SCC) among solid organ transplant recipients (SOTRs). We examined the association between sirolimus exposure and incident SCC risk among SOTRs within Kaiser Permanente Northern…
To describe the effects of six interventions for menopausal vasomotor symptoms relative to control in a pooled analysis, facilitating translation of the results for clinicians and symptomatic women. The Menopause Strategies: Finding Lasting Answers for Symptoms and Health network tested…
Studies suggest pioglitazone use may increase risk of cancers. To examine whether pioglitazone use for diabetes is associated with risk of bladder and 10 additional cancers. Cohort and nested case-control analyses among persons with diabetes. A bladder cancer cohort followed…
​OBJECTIVES:Pharmacogenetic testing is projected to improve health outcomes and reduce the cost of care by increasing therapeutic efficacy and minimizing drug toxicity. American Indian and Alaska Native (AI/AN) people historically have been excluded from pharmacogenetic research and its potential benefits,…
Time in therapeutic range (TTR) of international normalized ratio (INR) of 2.0 to 3.0 is important for the safety and effectiveness of warfarin anticoagulation. There are few data on TTR among patients with atrial fibrillation (AF) in community-based clinical practice…
Although digoxin has long been used to treat atrial fibrillation (AF) and heart failure (HF), its safety remains controversial. This study sought to describe digoxin use over time in patients with AF who were stratified by the presence or absence…
This study aims to evaluate the effects of low-dose estradiol (E2) or venlafaxine on menopause-related quality of life and associated symptoms in healthy perimenopausal and postmenopausal women with hot flashes. A double-blind, placebo-controlled, randomized trial of low-dose oral 17?-E2 0.5…
Increasing attention has focused on the prevalence and outcomes of hyperthyroidism in pregnancy, given concerns for hepatotoxicity and embryopathy associated with antithyroid drugs (ATDs). In an integrated health care delivery system, we examined the prevalence of thyrotoxicosis and gestational ATD…
In 2009, the US Food and Drug Administration (FDA) mandated a label change for leukotriene inhibitors (LTIs) to include neuropsychiatric adverse events (eg, depression and suicidality) as a precaution. This study investigated how this label change affected the use of…
Adults with diabetes typically take multiple medications for hyperglycemia, diabetes-associated conditions, and other comorbidities. Medication adherence is associated with improved outcomes, including reduced health care costs, hospitalization, and mortality. We conducted a retrospective analysis of a large pharmacy claims database…
The Centers for Medicare and Medicaid Services provide significant incentives to health plans that score well on Medicare STAR metrics for cardiovascular disease risk factor medication adherence. Information on modifiable health system-level predictors of adherence can help clinicians and health…
We measured birth prevalence of major congenital malformations (MCMs) after topiramate use during pregnancy to screen for a possible signal of increased risk. Using four healthcare databases, we identified three cohorts of pregnant women: cohort 1, used topiramate during the…
To investigate the prevalence, predictors, and costs associated with unused results from self-monitoring of blood glucose (SMBG). Observational cohort study. We studied 7320 patients with type 2 diabetes mellitus who were not prescribed insulin and who reported SMBG. Patients reported…
The use of aspirin and nonsteroidal anti-inflammatory drugs (NSAIDs) may decrease the risk of esophageal adenocarcinoma; however, it is unknown where these agents may act in the proposed pathway from normal mucosa to Barrett's esophagus to esophageal adenocarcinoma. The aim…
Digoxin remains commonly used for rate control in atrial fibrillation, but limited data exist supporting this practice and some studies have shown an association with adverse outcomes. We examined the independent association between digoxin and risks of death and hospitalization…
To assess the effects of depression and antidepressant medication use during pregnancy on the risk of preeclampsia. We conducted a retrospective, population-based cohort study that linked automated clinical and pharmacy databases including comprehensive electronic medical records of 21,589 pregnant Kaiser…
Methodologic biases may explain why observational studies examining metformin use in relation to lung cancer risk have produced inconsistent results. We conducted a cohort study to further investigate this relationship, accounting for potential biases. For 47,351 patients with diabetes ages…
Breast cancer chemotherapy toxicity is not well documented outside of randomized trials. We developed and conducted preliminary evaluation of an algorithm to detect grade 3 and 4 toxicities using electronic data from a large integrated managed care organization. The algorithm…
Standard Medicare Part D prescription drug benefits include substantial and complex cost-sharing. Many beneficiaries also have functional limitations that could affect self-care capabilities, including managing medications, but also have varying levels of social support to help with these activities. We…
The association between oral bisphosphonate use and upper gastrointestinal cancer has been controversial. Therefore, we examined the association with esophageal and gastric cancer within the Kaiser Permanente, Northern California population. A total of 1,011 cases of esophageal (squamous cell carcinoma…
Genome-wide association studies have uncovered a large number of genetic variants associated with type 2 diabetes or related phenotypes. In many cases the causal gene or polymorphism has not been identified, and its impact on response to anti-hyperglycemic medications is…
To date, there have been few studies evaluating outcomes of patients with atrial fibrillation (AF) who have experienced gastrointestinal (GI) hemorrhages. We examined short- and long-term mortality of major GI hemorrhage in patients with AF on and off warfarin in…
In 2011, the FDA approved telaprevir (TVR) and boceprevir (BOC) for use with pegylated interferon and ribavirin to treat hepatitis C virus (HCV) genotype 1. We aimed to evaluate the real-world application, tolerability, and effectiveness of TVR- and BOC-based HCV…
Statin use during hospitalization is associated with improved survival and a better discharge disposition among patients with ischemic stroke. It is unclear whether inpatient statin use has a similar effect among patients with intracerebral hemorrhage (ICH). To determine whether inpatient…
One year of trastuzumab therapy is recommended for women with HER2-positive breast cancer ? 1.0 cm in size to increase survival and is considered for women with tumors 0.5-0.9 cm in size. We analyzed compliance with trastuzumab among women with…
To describe availability and frequency of use of local snack-food outlets and determine whether reported use of these outlets was associated with dietary intakes. Data were cross-sectional. Availability and frequency of use of three types of local snack-food outlets were…
First marketed in the USA in 1996, topiramate (TPM) is an antiepileptic drug later approved for migraine prophylaxis, and in 2012 for weight loss in combination with phentermine. Some studies indicate an elevated prevalence of oral cleft (OC) in infants…
Psoriasis may predispose to cardiovascular disease and diabetes. However, the role of tumor necrosis factor (TNF) inhibitor in mediating this risk is controversial. To assess this relationship, we estimated change in metabolic physiologic measures before and after initiation of TNF…
AIM: The objective of this study was to evaluate the clinical presentation, inpatient management, and in-hospital outcome of patients hospitalized for acute heart failure syndromes (AHFS) and classified as pulmonary edema (PE).METHODS: The Romanian Acute Heart Failure Syndromes (RO-AHFS) study…
The Epidemiologic Study of Xolair (omalizumab): Evaluating Clinical Effectiveness and Long-term Safety in Patients with Moderate-to-Severe Asthma (EXCELS) assessed the long-term safety of omalizumab in a clinical practice setting as part of a phase IV US Food and Drug Administration…
Based on results of clinical trials, inhaled corticosteroids (ICS) are the most-effective controller medications for preventing asthma-related exacerbations, yet few studies in real-life populations have evaluated the comparative effectiveness of ICS. To determine the likelihood of asthma exacerbations among children…
One-third of type 2 diabetes patients do not respond to metformin. Genetic variants in metformin transporters have been extensively studied as a likely contributor to this high failure rate. Here, we investigate, for the first time, the effect of genetic…
Selective serotonin reuptake inhibitor (SSRI) medications have been linked to increased bleeding risk; however, the actual association among warfarin, SSRI exposure, and bleeding risk has not been well-established. We studied the AnTicoagulation and Risk factors In Atrial fibrillation cohort of…
Depression and adherence to antidepressant treatment are important clinical concerns in diabetes care. While patient-provider communication patterns have been associated with adherence for cardiometabolic medications, it is unknown whether interpersonal aspects of care impact antidepressant medication adherence. To determine whether…
This study examines incident treatment patterns for attention-deficit/hyperactivity disorder (ADHD) in children seen in eight integrated healthcare delivery systems and identifies factors associated with adherence to Healthcare Effectiveness Data and Information Set (HEDIS) quality measures developed by the National Committee…
Recent clinical trials have demonstrated the safety and efficacy of several non-vitamin K oral anticoagulants (NOACs) for the treatment of atrial fibrillation (AF). However, there are limited data on their use and outcomes in routine clinical practice, particularly among patients…
In spite of the clinical utility of buprenorphine, parenteral abuse of this medication has been reported in several laboratory investigations and in the real world. Studies have demonstrated lower abuse liability of the buprenorphine/naloxone combination relative to buprenorphine alone. However,…
The effectiveness of beta-blockers for preventing cardiac events has been questioned for patients who have coronary heart disease (CHD) without a prior myocardial infarction (MI). The purpose of this study was to assess the association of beta-blockers with outcomes among…
This double-blind, placebo-controlled study investigated the effects of oral morphine (0, 45, 135 mg/70 kg) and oral oxycodone (0, 15, 45 mg/70 kg) on buprenorphine-maintained opioid addicts. As a 3: 1 morphine : oxycodone oral dose ratio yielded equivalent subjective…
The study addressed recent concerns regarding increasing prescription of antidepressant drugs to patients with no recorded psychiatric diagnosis. Records from ten large integrated health systems in the Mental Health Research Network were used to examine diagnoses received by 1,011,946 health…
To understand the burden of medication use for patients with newly diagnosed diabetes both before and after diabetes diagnosis and to identify subpopulations of patients with newly diagnosed diabetes who face a relatively high drug burden. Retrospective cohort study. 11…
Antihyperglycemic medication intensification practices among patients with incident diabetes are incompletely understood. We characterized the first intensification the year after oral antihyperglycemic medication initiation among incident diabetes patients. This retrospective cohort study across 11 US health systems included adults identified…
To compare length of hospital stay for minilaparotomy vs laparoscopic hysterectomy. Retrospective cohort study (Canadian Task Force classification II-2). Kaiser Permanente Northern California, a large integrated health care delivery system. Women >18 years of age undergoing laparoscopic or minilaparotomy hysterectomy…
Estrogen therapy is the gold standard treatment for hot flashes and night sweats, but some women are unable or unwilling to use it because of associated risks. The serotonin-norepinephrine reuptake inhibitor venlafaxine hydrochloride is used widely as a nonhormonal treatment…
This study sought to examine the effectiveness of clopidogrel in real-world, medically managed patients with unstable angina (UA) or non-ST-segment elevation myocardial infarction (NSTEMI). Although clinical trials have demonstrated the efficacy of clopidogrel to reduce cardiovascular (CV) morbidity and mortality…
Lower gastrointestinal bleeding is a frequent cause of hospitalization, particularly in the elderly, and its incidence appears to be on the rise. Colonic diverticular bleeding is the most common form of lower gastrointestinal bleeding and is responsible for 30-40 %…
The purpose of this study was to examine the relationship between the presence of clinical depression and persistence to drug therapy treatment for depression with early nonpersistence to antihypertensive therapies in a large, diverse cohort of newly treated hypertension patients…
Pregnant women and their infants are vulnerable to severe disease and secondary complications from influenza infection. For this reason, annual influenza vaccination is recommended for all pregnant women in the United States. Women frequently cite concerns about vaccine safety as…
Recent international phase III clinical trials of novel therapies for hospitalized heart failure (HHF) have failed to improve the unacceptably high postdischarge event rate. These large studies have demonstrated notable geographic and site-specific variation in patient profiles and enrollment. Possible…
Social risk factors for hypoglycemia are not well understood. Cross-sectional analysis from the DISTANCE study, a multi-language, ethnically-stratified random sample of adults in the Kaiser Permanente Northern California diabetes registry, conducted in 2005-2006 (response rate 62%). Exposures were income and…
Bevacizumab plus carboplatin-paclitaxel (BCP) chemotherapy has Food and Drug Administration approval for advanced nonsquamous, non-small-cell lung cancer based upon improved survival in a clinical trial. However, subgroup analyses of this and other studies have suggested variable results by age and…
The objective of this study was to examine the effect of maternal antidepressant exposure on first- and second-trimester maternal serum markers for aneuploidy. We conducted a 10-year retrospective cohort study within a large health care organization. Pregnant women diagnosed with…
Lower serum lipid levels are paradoxically predictive of poor clinical outcomes in hospitalized and ambulatory patients with heart failure (HF). In large randomized controlled trials, statins did not demonstrate an overall mortality benefit in chronic HF patients. We currently lack…
Digoxin is the oldest cardiac drug still in contemporary use, yet its role in the management of patients with heart failure (HF) remains controversial. A purified cardiac glycoside derived from the foxglove plant, digoxin increases ejection fraction, augments cardiac output,…
In January 2006 insurance coverage for medications shifted from Medicaid to Medicare Part D private drug plans for the six million individuals enrolled in both programs. Dual beneficiaries faced new formularies and utilization management policies. It is unclear whether Part…
To determine patient characteristics associated with achieving and sustaining blood pressure (BP) targets in the Adherence and Intensification of Medications program, a program led by pharmacists trained in motivational interviewing and authorized to make BP medication changes. We conducted a…
Qualified physicians may prescribe buprenorphine to treat opioid dependence, but medication use remains controversial. We examined adoption of buprenorphine in two not-for-profit integrated health plans, over time, completing 101 semi-structured interviews with clinicians and clinician-administrators from primary and specialty care…
Online patient portals are being widely implemented, but their impact on health behaviors are not well-studied. To determine whether statin adherence improved after initiating use of the portal refill function. Observational cohort study within an integrated health care delivery system…
To assess the risk of adverse fetal outcomes following exposure to individual immunosuppressive drugs in pregnant women with chronic immune-mediated diseases. Health plan data were obtained from the Tennessee Medicaid and Kaiser Permanente Northern California and Southern California claims databases,…
Telemedicine is one approach to managing patients with chronic illness. Several telephone-based monitoring studies of diabetes patients have shown improved glycosylated hemoglobin (HbA1c), blood pressure (BP), and low-density lipoprotein (LDL) levels. The purpose of this study was to evaluate an…
The purpose of this review was to compare the efficacy and safety of biologics, immunomodulators, corticosteroids, and aminosalicylates in the treatment of Crohn's disease. We searched MEDLINE(®) (1966 through June 2011), Embase(®) (1974 through June 2011), and the Cochrane Central…
Re-examine association of fluoxetine and paroxetine with risk of testicular cancer noted in drug screening, with 4 years more follow-up and expanded study of these and other antidepressant drugs. In the Kaiser Permanente Medical Care Program in Northern California, 906…
To investigate if the widely publicized warnings in 2003 from the US Food and Drug Administration about a possible increased risk of suicidality with antidepressant use in young people were associated with changes in antidepressant use, suicide attempts, and completed…
To evaluate the prevalence, trends, timing and duration of exposure to antiviral medications during pregnancy within a US cohort of pregnant women and to evaluate the proportion of deliveries with a viral infection diagnosis among women given antiviral medication during…
To examine whether use of insulin glargine, compared with another long-acting insulin, is associated with risk of breast, prostate, colorectal cancer, or all cancers combined. Computerized health records from Kaiser Permanente Northern and Southern California regions starting in 2001 and…
Recent reports of antipsychotic medication use in pediatric populations describe large increases in rates of use. Much interest in the increasing use has focused on potentially inappropriate prescribing for non-Food and Drug Administration-approved uses and use amongst youth with no…
Elevated circulating levels of branched chain and aromatic amino acids (BCAA/AAAs) are associated with insulin resistance and incident type 2 diabetes (T2D). BCAA/AAAs decrease acutely during an oral glucose tolerance test (OGTT), a diagnostic test for T2D. It is unknown…
Asthma is one of the most common chronic diseases in women of reproductive age, occurring in up to 8Â % of pregnancies. The objective of this study is to assess the prevalence of asthma medication use during pregnancy in a large…
We examined the association between HbA1c level and self-reported severe hypoglycemia in patients with type 2 diabetes. Type 2 diabetic patients in a large, integrated healthcare system, who were 30-77 years of age and treated with glucose-lowering therapy, were asked…
Although research suggests that mail order pharmacy use is associated with greater medication adherence and cardiovascular disease risk factor control, no research has examined the potential impact of mail order pharmacy use on patient safety and utilization. To compare safety…
Aldosterone receptor antagonists have been shown in randomized trials to reduce morbidity and mortality in adults with symptomatic systolic heart failure. We studied the effectiveness and safety of spironolactone in adults with newly diagnosed systolic heart failure in clinical practice…
Statins, or HMG-CoA reductase inhibitors, may aid in the treatment of asthma through their pleiotropic antiinflammatory effects. To examine the effect of statin therapy on asthma-related exacerbations using a large population-based cohort. Statin users aged 31 years or greater with…
The purpose of this study was to ascertain, in the context of an integrated health care delivery system, the association between a comprehensive list of drugs known to have potential QT liability and QT prolongation or shortening. By using a…
There is limited information on the protective value of Medicare Part D low-income subsidies (LIS). We compared responses to drug costs for LIS recipients with near-poor (?200 percent of the Federal Poverty Level) and higher income beneficiaries without the LIS…
Among adults with incident diabetes, data are lacking about first antihyperglycemic initiation and whether medication choice aligns with recommendations. To identify predictors of initiating any antihyperglycemic, and specifically sulfonylurea versus metformin. This retrospective cohort study included 241 327 patients from…
Clinical guidelines recommend digoxin for patients with symptomatic systolic heart failure (HF) receiving optimal medical therapy, but this recommendation is based on limited, older trial data. We evaluated the effectiveness and safety of digoxin in a contemporary cohort of patients…
OBJECTIVE: To propose a unifying set of definitions for prescription adherence research utilizing electronic health record prescribing databases, prescription dispensing databases, and pharmacy claims databases and to provide a conceptual framework to operationalize these definitions consistently across studies. METHODS: We…
OBJECTIVE: We tested the hypothesis that initiation of tumor necrosis factor alpha (TNFalpha) antagonists reduced the risk of fractures compared to nonbiologic comparators in patients with autoimmune diseases. METHODS: Using 4 large administrative databases, we assembled retrospective cohorts of patients…
Patients with atrial fibrillation (AF) at the highest stroke risk derive the largest benefit from oral anticoagulation (OAC). Those with the highest stroke risk have been paradoxically less likely to receive OAC. This study assessed the association between stroke and…
PURPOSE: This study describes practical considerations for implementation of near real-time medical product safety surveillance in a distributed health data network. METHODS: We conducted pilot active safety surveillance comparing generic divalproex sodium to historical branded product at four health plans…
PURPOSE: In post-marketing drug safety surveillance, data mining can potentially detect rare but serious adverse events. Assessing an entire collection of drug-event pairs is traditionally performed on a predefined level of granularity. It is unknown a priori whether a drug…
Limited data exist describing the differences in the medical treatment of patients with heart failure with preserved ejection fraction (HF-PEF) from those with heart failure with reduced ejection fraction (HF-REF) in more generalizable population-based cohorts. We studied patients with incident…
This study aims to estimate the prevalence of and temporal trends in prenatal antipsychotic medication use within a cohort of pregnant women in the U.S. We identified live born deliveries to women aged 15-45 years in 2001-2007 from 11 U.S…
BACKGROUND: Anti-tumor necrosis factor-alpha (TNF-alpha) agents have been hypothesized to increase the risk of interstitial lung disease (ILD), including its most severe manifestation, pulmonary fibrosis. METHODS: We conducted a cohort study among autoimmune disease patients who were members of Kaiser…
Previous studies have reported that health literacy limitations are associated with poorer disease control for chronic conditions, but have not evaluated potential associations with medication adherence. To determine whether health literacy limitations are associated with poorer antidepressant medication adherence. Observational…
IMPORTANCE: Herpes zoster reactivation disproportionately affects patients with rheumatoid arthritis (RA). It is unclear whether anti-tumor necrosis factor (anti-TNF) therapy elevates herpes zoster risk. OBJECTIVES: To ascertain whether initiation of anti-TNF therapy compared with nonbiologic comparators is associated with increased…
Establishing medication effectiveness outside of a randomized trial requires careful study design to mitigate selection bias. Previous observational studies of ?-blockers in patients with chronic kidney disease and heart failure have had methodologic limitations that may have introduced bias. We…
OBJECTIVE: Kaiser Permanente Northern California is a large integrated health care delivery system in the United States that has guidelines for referring women with newly diagnosed BRCA1-and BRCA2-associated cancers for genetic counseling. This study assesses adherence to genetic counseling referral…
BACKGROUND: Poor medication refill adherence contributes to poor cardiometabolic control and diabetes outcomes. Studies linking communication between patients and health care providers to adherence often use self-reported adherence and have not explored differences across communication domains or therapeutic indications. METHODS:…
AIM: To examine the association of in-hospital diabetes regimen intensification with subsequent 30-day risk for unplanned readmission/emergency department admission. METHODS: We retrospectively studied 1949 adults with Type 2 diabetes receiving primary care within an academic health network admitted to the…
OBJECTIVES: This study sought to compare use of evidence-based secondary preventive medications after coronary bypass surgery (CABG) and percutaneous coronary intervention (PCI). BACKGROUND: Use of cardioprotective medication after coronary revascularization has been inconsistent and relatively low in older studies. METHODS:…
Hospitalization for heart failure (HF) is a clinical entity associated with high postdischarge morbidity and mortality, yet few therapies are available to improve outcomes in patients with this condition. In the past decade, large phase III studies of HF treatments…
PURPOSE: To evaluate the validity of health plan and birth certificate data for pregnancy research. METHODS: A retrospective study was conducted using administrative and claims data from 11 U.S. health plans and corresponding birth certificate data from state health departments…
BACKGROUND: Combined hormonal contraceptives (CHCs) place women at increased risk of venous thromboembolic events (VTEs) and arterial thrombotic events (ATEs), including acute myocardial infarction and ischemic stroke. There is concern that three recent CHC preparations [drospirenone-containing pills (DRSPs), the norelgestromin-containing…
OBJECTIVE:: To describe the prevalence, trends, and patterns in use of antidiabetic medications to treat hyperglycemia and insulin resistance before and during pregnancy in a large U.S. cohort of insured pregnant women. METHODS:: Pregnancies resulting in live births were identified…
OBJECTIVE: In North America, tuberculosis and nontuberculous mycobacterial (NTM) disease rates associated with antitumour necrosis factor alpha (anti-TNFalpha) therapy are unknown. METHODS: At Kaiser Permanente Northern California, the authors searched automated pharmacy records to identify inflammatory disease patients who received…
PURPOSE: To evaluate the incidence of optic neuritis (ON) in patients using anti-tumor necrosis factor (TNF) alpha therapy. DESIGN: Retrospective, population-based cohort study. METHODS: We identified new users of anti-TNF therapy (etanercept, infliximab, or adalimumab) or nonbiologic disease-modifying antirheumatic drugs…
Background: Drug adverse event (AE) signal detection using the Gamma Poisson Shrinker (GPS) is commonly applied in spontaneous reporting. AE signal detection using large observational health plan databases can expand medication safety surveillance. Methods: Using data from nine health plans,…
PURPOSE: To evaluate post-cataract-surgery endophthalmitis rates in relation to changing practice patterns in antibiotic administration. SETTING: Kaiser Permanente, Diablo Service Area, California. DESIGN: Ecological time-trend study. METHODS: During 2007 through 2011, 3 time periods were identified based on increasing adoption…
OBJECTIVE: To compare the incidence of cancer following tumor necrosis factor alpha (TNFalpha) inhibitor therapy to that with commonly used alternative therapies across multiple immune-mediated diseases. METHODS: The Safety Assessment of Biological Therapeutics study used data from 4 sources: national…
BACKGROUND: Arginine vasopressin (AVP) levels are elevated in proportion to heart failure severity and are associated with higher cardiovascular mortality in ambulatory patients. However, the relationship between baseline and trends in AVP with outcomes in patients hospitalized for worsening heart…
PURPOSE: To compare mortality among patients with selected autoimmune diseases treated with anti-tumor necrosis factor alpha (TNF-alpha) agents with similar patients treated with non-biologic therapies. METHODS: Cohort study set within several large health care programs, 1998-2007. Autoimmune disease patients were…
BACKGROUND: Little is known about the extent of antiepileptic drug (AED) use in pregnancy, particularly for newer agents. Our objective was to assess whether AED use has increased among pregnant women in the US, 2001-2007. METHODS: We analysed data from…
PURPOSE: For some women, adjuvant chemotherapy for nonmetastatic breast cancer decreases recurrences and increases survival; however, patient-physician decisions regarding chemotherapy receipt can be influenced by medical and nonmedical factors. PATIENTS AND METHODS: We used a prospective cohort design and multivariate…
BACKGROUND: In screening pharmaceuticals for possible carcinogenic effects we noted an association between lip cancer risk and the photosensitizing antihypertensive drugs hydrochlorothiazide and nifedipine. In this study, we further characterized the risk of lip cancer associated with these and other…
BACKGROUND: Clinical trials demonstrated that women treated for breast cancer with anthracycline or trastuzumab are at increased risk for heart failure and/or cardiomyopathy (HF/CM), but the generalizability of these findings is unknown. We estimated real-world adjuvant anthracycline and trastuzumab use…
BACKGROUND: In the United States, 5-year breast cancer survival is highest among Asian American women, followed by non-Hispanic white, Hispanic, and African American women. Breast cancer treatment disparities may play a role. We examined racial/ethnic differences in adjuvant hormonal therapy…
PURPOSE: Atypical femur fractures represent a potential complication of chronic oral bisphosphonate therapy in women with osteoporosis, but the risk of atypical femur fractures among cancer patients receiving intravenous bisphosphonates at higher cumulative doses remains unclear. We examined femur fractures…
OBJECTIVE: To determine the effects of a personal health record (PHR)-linked medications module on medication accuracy and safety. DESIGN: From September 2005 to March 2007, we conducted an on-treatment sub-study within a cluster-randomized trial involving 11 primary care practices that…
BACKGROUND: There are limited data regarding national patterns of pharmacotherapy for atrial fibrillation (AF) among older patients. Drug exposure data are now captured for Medicare beneficiaries enrolled in prescription drug plans. OBJECTIVE: To describe pharmacotherapy for AF among Medicare beneficiaries…
PURPOSE: American Joint Committee on Cancer (AJCC) Tumor (T), Nodal (N), and Metastatic (M) staging is commonly used in clinical practice for treatment decisions, yet before 2004, Surveillance Epidemiology and End Results (SEER)-affiliated cancer registries did not routinely include TNM…
BACKGROUND: In the past decade, increasing attention has focused on identification and treatment of vitamin D deficiency although repletion outcomes of pharmacologic vitamin D therapy have not been examined at a population level. OBJECTIVE: To investigate population trends and outcomes…
Five patients with primary colorectal adenocarcinoma or anal squamous cell carcinoma were started on a 2-weeks-on, 1-week-off capecitabine dosing regimen in addition to other chemotherapeutic agents and/or radiation. Within the first few doses, patients experienced chest pain and/or dyspnea at…
OBJECTIVE: The aim of this study was to determine the effect of escitalopram on insomnia symptoms and subjective sleep quality in healthy perimenopausal and postmenopausal women with hot flashes. METHODS: A randomized, blinded, multicenter, placebo-controlled parallel-group 8-week trial with 205…
PURPOSE: To characterize the spectrum and outcomes of bisphosphonate-related osteonecrosis of the jaw (BRONJ) occurring with oral bisphosphonate therapy. MATERIALS AND METHODS: We assembled a retrospective cohort of patients who had developed oral BRONJ according to the 2009 American Association…
Patients with resistant hypertension are at risk for poor outcomes. Medication adherence and intensification improve blood pressure (BP) control; however, little is known about these processes or their association with outcomes in resistant hypertension. This retrospective study included patients from…
Adjuvant hormonal therapy for non-metastatic hormone receptor (HR)-positive breast cancer decreases risk of breast cancer recurrence and increases survival. However, some women do not initiate this life-saving treatment. We used a prospective cohort design to investigate factors related to non-initiation…
BACKGROUND: Reports of atypical femur fracture in bisphosphonate-exposed women have prompted interest in characterizing the clinical profiles of these patients. METHODS: Among women age >/=60 years with hip or femur fracture during 2007-2008, we identified 79 with low-trauma subtrochanteric or…
Study Type - Symptom prevalence (population cohort). Level of Evidence 1b. What's known on the subject? and What does the study add? It is known that medical conditions such as diabetes, high blood pressure, high cholesterol, smoking and prescribed medications…
BACKGROUND AND PURPOSE: Prescribing warfarin for atrial fibrillation depends in large part on the expected reduction in ischemic stroke risk versus the expected increased risk of intracranial hemorrhage (ICH). However, the anticoagulation decision also depends on the relative severity of…
BACKGROUND: Even in high-performing health systems, some patients with diabetes mellitus have poor blood pressure (BP) control because of poor medication adherence and lack of medication intensification. We examined whether the Adherence and Intensification of Medications intervention, a pharmacist-led intervention…
Hospitalization for worsening chronic heart failure results in high post-discharge mortality, morbidity, and cost. However, thorough characterization, soon after discharge of patients with early post-discharge events has not been previously performed. The objectives of this study were to describe the…
AIMS: Abnormal liver function tests (LFTs) are common in ambulatory heart failure (HF). The aim of this study was to characterize abnormal LFTs during index hospitalization.METHODS AND RESULTS: A post-hoc analysis was carried out of the placebo group of the…
BACKGROUND: B-type natriuretic peptide (BNP) levels provide diagnostic and prognostic information in heart failure. This study determined the frequency of BNP assessment and analyzed demographic characteristics, clinical variables and the utilization of guideline-recommended heart failure therapies by BNP level in…
In oncology, quality of care is a major issue for patients and providers. Significant variations in care, including nonreceipt of adjuvant systemic therapy, nonadherence to therapy, and/or early discontinuation of therapy, occur frequently and may impact survival. Reasons for these…
PURPOSE: Infliximab, a chimeric monoclonal anti-TNFalpha antibody, has been found to increase the risk of serious infections compared with the TNF receptor fusion protein etanercept in some studies. It is unclear whether the risk varies by patient characteristics. We conducted…
BACKGROUND: Medication adherence and treatment intensification have been advocated as performance measures to assess the quality of care provided. Whereas previous studies have shown that adherence and treatment intensification (TI) of antihypertensive medications is associated with blood pressure (BP) control…
BACKGROUND & AIMS: Regular use of aspirin and other nonsteroidal anti-inflammatory drugs (NSAIDs) has been reported to reduce risks of esophageal adenocarcinoma (EAC) and esophagogastric junctional adenocarcinoma (EGJA). However, individual studies have been too small to accurately assess the effects…
PURPOSE: Use of non-steroidal anti-inflammatory drugs (NSAIDs) may reduce the incidence of several cancers. A recent meta-analysis of randomized trials of aspirin reported a reduction in cancer mortality; however, few studies have investigated whether aspirin or other NSAIDs reduce overall…
PURPOSE: The aim of this study was to determine whether the presence of symptoms would aid in the detection of valvular heart disease (VHD) in those exposed to pergolide. METHODS: Utilizing a prospective, cross-sectional study design, patients with an exposure…
PURPOSE: High doses of gabapentin were associated with pancreatic acinar cell tumors in male Wistar rats, but there is little published epidemiological data regarding gabapentin and carcinogenicity. We explored the association between gabapentin and cancer in a US medical care…
PURPOSE: To describe a protocol for active surveillance of acute myocardial infarction (AMI) in users of a recently approved oral antidiabetic medication, saxagliptin, and to provide the rationale for decisions made in drafting the protocol. METHODS: A new-user cohort design…
PURPOSE: Many challenges arise when conducting a sequentially monitored medical product safety surveillance evaluation using observational electronic data captured during routine care. We review existing sequential approaches for potential use in this setting, including a continuous sequential testing method that…
Active medical product monitoring systems, such as the Sentinel System, will utilize electronic healthcare data captured during routine health care. Safety signals that arise from these data may be spurious because of chance or bias, particularly confounding bias, given the…
PURPOSE: The purpose of this cross-sectional study is to explore primary care providers' (PCPs) perceptions about barriers to initiating insulin among patients. Studies suggest that many patients with poorly controlled type 2 diabetes do not receive insulin initiation by PCPs.METHODS:…
PURPOSE: To assess case-only designs for surveillance with administrative databases. METHODS: We reviewed literature on two designs that are observational analogs to crossover experiments: the self-controlled case series (SCCS) and the case-crossover (CCO) design. RESULTS: SCCS views the 'experiment' prospectively,…
The US Food and Drug Administration's Mini-Sentinel pilot program is developing an organizational structure as well as principles and policies to govern its operations. These will inform the structure and function of the eventual Sentinel System. Mini-Sentinel is a collaboration…
BACKGROUND: Evidence-based treatment guidelines recommend low molecular weight heparin (LMWH) monotherapy for cancer-associated venous thromboembolism (VTE). This analysis assessed the first-line treatment strategies for VTE in patients with advanced solid tumors. METHODS: Using administrative data from advanced lung, prostate, colon,…
CONTEXT: More than 1.5 million US adults use stimulants and other medications labeled for treatment of attention-deficit/hyperactivity disorder (ADHD). These agents can increase heart rate and blood pressure, raising concerns about their cardiovascular safety. OBJECTIVE: To examine whether current use…
BACKGROUND: The benefits of some second-generation antipsychotics (SGAs) must be weighed against the increased risk for diabetes mellitus. This study examines whether the association between SGAs and diabetes differs by dose. METHODS: Patients were >/=18 years of age from three…
CONTEXT: Although tumor necrosis factor (TNF)-alpha antagonists are increasingly used in place of nonbiologic comparator medications, their safety profile remains incomplete. OBJECTIVES: To determine whether initiation of TNF-alpha antagonists compared with nonbiologic comparators is associated with an increased risk of…
BACKGROUND: Preventing fetal exposure to isotretinoin is widely acknowledged as an important safety issue. The iPLEDGE program is the latest in a series of Food and Drug Administration-mandated risk management programs designed to prevent pregnancies in female patients of childbearing…
OBJECTIVE: To assess whether the risk of incident diabetes was increased with the use of second-generation antipsychotics (SGAs) in a large diverse cohort of children. METHODS: A retrospective study was conducted by using the administrative databases of 3 health plans…
OBJECTIVES: The objective of this study was to assess inflammatory bowel disease (IBD) medications in relation to lymphoma risk. METHODS: Information on IBD and relevant medications and other utilization was obtained from the Kaiser Permanente IBD Registry, 1996-2009. Lymphoma cases…
BACKGROUND: Mail order pharmacies are commonly used to deliver CVD risk factor medications. Previous studies have shown that mail order pharmacy use is associated with greater medication adherence; however, no studies have examined whether mail order pharmacy use is related…
BACKGROUND: Adverse-event reports from North America have raised concern that the use of drugs for attention deficit-hyperactivity disorder (ADHD) increases the risk of serious cardiovascular events. METHODS: We conducted a retrospective cohort study with automated data from four health plans…
BACKGROUND: Although biologic treatments have excellent efficacy for many autoimmune diseases, safety concerns persist. Understanding the absolute and comparative risks of adverse events in patient and disease subpopulations is critical for optimal prescribing of biologics. PURPOSE: The Safety Assessment of…
Objective. We hypothesized that initiation of a new disease-modifying antirheumatic drug (DMARD) for treatment of rheumatoid arthritis (RA) would decrease the use of corticosteroids, nonsteroidal antiinflammatory drugs (NSAIDs), and narcotics.Methods. Using administrative databases, we assembled 4 retrospective cohorts of RA…
BACKGROUND: Racial/ethnic minority patients are more likely to report experiences with discrimination in the healthcare setting, potentially leading to reduced access to appropriate care; however, few studies evaluate reports of discrimination with objectively measured quality of care indicators. OBJECTIVE: To…
CONTEXT: The full effect of Medicare Part D, after the initial policy transition period and across the United States Medicare population, remains unclear. OBJECTIVE: To estimate nationally representative changes in prescription drug use and out-of-pocket drug costs 2 years after…
OBJECTIVES: To determine whether atrial fibrillation (AF) patients with mental health conditions (MHCs) were less likely than AF patients without MHCs to be prescribed warfarin and, if receiving warfarin, to maintain an International Normalized Ratio (INR) within the therapeutic range…
BACKGROUND: The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure recommends that clinicians consider the use of multidrug therapy to increase likelihood of achieving blood pressure goal. Little is known about…
OBJECTIVES: The purpose of this study was to develop a risk stratification score to predict warfarin-associated hemorrhage. BACKGROUND: Optimal decision making regarding warfarin use for atrial fibrillation requires estimation of hemorrhage risk. METHODS: We followed up 9,186 patients with atrial…
BACKGROUND:In a phase III trial of women with HER2+ metastatic breast cancer (MBC) previously treated with trastuzumab, an anthracycline, and taxanes (EGF100151), lapatinib plus capecitabine (L+C) improved time to progression (TTP) versus capecitabine monotherapy (C-only). In a trial including HER2+…
The US Centers for Disease Control and Prevention is conducting an observational study of 300-500 women infected with influenza during pregnancy. Women are being recruited from members of the Kaiser Permanente health plan in 2 metropolitan areas before and during…
OBJECTIVE: To identify the range of glycemic levels associated with the lowest rates of complications and mortality in older diabetic patients. RESEARCH DESIGN AND METHODS: We conducted a retrospective cohort study (2004-2008) of 71,092 patients with type 2 diabetes, aged…
BACKGROUND: Patients who speak Spanish and/or have low socioeconomic status are at greater risk of suboptimal glycemic control. Inadequate intensification of anti-glycemic medications may partially explain this disparity. OBJECTIVE: To examine the associations between primary language, income, and medication intensification…
OBJECTIVES: To estimate rates and predictors of clinical laboratory test completion by patients with diabetes after provider referral. STUDY DESIGN: Prospective cohort study. METHODS: Among 186,306 adult members with diabetes in Kaiser Permanente Northern California, we searched the electronic medical…
Recent reports of bisphosphonate-related osteonecrosis of the jaw (BRONJ) have increased awareness of oral health in patients receiving osteoporosis therapy. This study describes the demographic, oral health, and clinical characteristics of a contemporary population of women aged 50 and older…
PURPOSE: Previous data suggest a potential relationship between inflammation and erectile dysfunction. If it is causal, nonsteroidal anti-inflammatory drug use should be inversely associated with erectile dysfunction. To this end we examined the association between nonsteroidal anti-inflammatory drug use and…
We observed an independent association between vitamin D insufficiency and higher carotid intima-media thickness in a cross-sectional analysis of 139 HIV-infected persons. If confirmed, these findings support a clinical trial of vitamin D supplementation to reduce cardiovascular events in HIV-infected…
OBJECTIVE: Some preclinical in vivo studies and limited human data suggest a possible increased risk of bladder cancer with pioglitazone therapy. This is an interim report of an ongoing cohort study examining the association between pioglitazone therapy and the risk…
OBJECTIVE: To explore whether treatment with pioglitazone was associated with risk of incident cancer at the 10 most common sites (prostate, female breast, lung/bronchus, endometrial, colon, non-Hodgkin lymphoma [NHL], pancreas, kidney/renal pelvis, rectal, and melanoma). RESEARCH DESIGN AND METHODS: A…
OBJECTIVE: Ethnic minorities with diabetes typically have lower rates of cardiovascular outcomes and higher rates of end-stage renal disease (ESRD) compared with whites. Diabetes outcomes among Asian and Pacific Islander subgroups have not been disaggregated. RESEARCH DESIGN AND METHODS: We…
Despite the benefit of adjuvant hormonal therapy (HT) on mortality among women with breast cancer (BC), many women are non-adherent with its use. We investigated the effects of early discontinuation and non-adherence to HT on mortality in women enrolled in…
INTRODUCTION: It has been > 25 years since it was first discovered that arginine vasopressin levels are elevated in heart failure and this elevation is proportional to the severity of heart failure. Tolvaptan is an oral nonpeptide Vâ‚‚-selective antagonist and…
PURPOSE: Anti-tumor necrosis factor-alpha (anti-TNF) therapies are associated with severe mycobacterial infections in rheumatoid arthritis patients. We developed and validated electronic record search algorithms for these serious infections. METHODS: The study used electronic clinical, microbiologic, and pharmacy records from Kaiser…
STUDY OBJECTIVE: To determine if the concomitant use of nelfinavir and proton pump inhibitors (PPIs) in patients with human immunodeficiency virus (HIV) infection results in the loss of virologic control. DESIGN: Retrospective cohort study. DATA SOURCE: Pharmacy, laboratory, and administrative…
BACKGROUND: Warfarin reduces the risk for ischemic stroke in patients with atrial fibrillation (AF) but increases the risk for hemorrhage. Dabigatran is a fixed-dose, oral direct thrombin inhibitor with similar or reduced rates of ischemic stroke and intracranial hemorrhage in…
BACKGROUND: Patients with chronic kidney disease (CKD) are less likely to receive cardiovascular medications. It is unclear whether differential cardiovascular drug use explains, in part, the excess risk of cardiovascular events and death in patients with CKD and coronary heart…
OBJECTIVE: To examine a reported association between use of angiotensin converting enzyme (ACE) inhibitors during the first trimester and risk of malformations in offspring. DESIGN: A population based, retrospective cohort study linking automated clinical and pharmacy databases including comprehensive electronic…
PURPOSE: Because second generation antipsychotics (SGA) might affect the risk of suicide, systematic assessment of suicide risk associated with SGA in the postmarketing setting is important and of interest to regulatory authorities. To fulfill a postmarketing request, our objective was…
BACKGROUND: Although warfarin is widely recommended to prevent atrial fibrillation-related thromboembolism, many eligible patients do not take warfarin. The objective of this study was to describe factors associated with warfarin discontinuation in patients newly starting warfarin for atrial fibrillation. METHODS…
BACKGROUND/AIMS: Statins are widely used and of high interest as potential chemopreventive agents for cancer. Preclinical studies suggest that lipophilic statins have anticancer properties targeting hormone receptor (HR)-negative breast cancer. Few epidemiologic studies have investigated the relationship between lipophilic statin…
BACKGROUND: Thiazolidinedione (TZD) treatment has been associated with fractures. The purpose of this study was to examine the association between TZD treatment and fractures in type 2 diabetic patients. METHODS: Using data from Translating Research into Action for Diabetes, a…
BACKGROUND: Trials comparing hypertension monotherapies have found either no difference or modest differences in blood pressure (BP) and cardiovascular events. However, no trial has assessed the comparative effectiveness of 2nd-line therapy in patients whose BP was not controlled with a…
PURPOSE: Radiographic features in patients with bisphosphonate-related osteonecrosis of the jaw (BRONJ) are well described, but less is known in bisphosphonate-exposed individuals with stage 0 disease (clinical symptoms without exposed necrotic bone) considered at risk for BRONJ. We sought to…
BACKGROUND: Studies have associated thiazolidinedione (TZD) treatment with cardiovascular disease (CVD) and questioned whether the two available TZDs, rosiglitazone and pioglitazone, have different CVD risks. We compared CVD incidence, cardiovascular (CV), and all-cause mortality in type 2 diabetic patients treated…
BACKGROUND & AIMS: Drugs that inhibit gastric acid might increase the risk of hip fracture. However, little long-term exposure data exist and no large studies have been conducted in the United States. METHODS: We conducted a case-control study using data…
BACKGROUND: Studies suggest that extended clopidogrel use after drug-eluting stent (DES) implantation may decrease the risk of myocardial infarction (MI) and death. Little is known about the competing risk of bleeding from clopidogrel in 'real world' clinical practice. METHODS AND…
INTRODUCTION: A large study on the safety of biologics required pooling of data from multiple data sources, but while extensive confounder adjustment was necessary, private, individual-level covariate information could not be shared. OBJECTIVES: To describe the methods of pooling data…
BACKGROUND: Some Medicare Part D enrollees whose drug expenditures exceed a threshold enter a coverage gap with full cost-sharing, increasing their risk for reduced adherence and adverse outcomes. OBJECTIVE: To examine comorbidities and demographic characteristics associated with gap entry and…
BACKGROUND: Adjuvant clopidogrel therapy is essential after drug-eluting stent (DES) implantation. The frequency with which patients delay filling a clopidogrel prescription after DES implantation and the association of this delay with adverse outcomes is unknown. METHODS AND RESULTS: This was…
