Adverse events and costs among non-metastatic castration-resistant prostate cancer patients.

BACKGROUND: Limited real-world evidence exists on the economic burden of adverse events (AEs) to the healthcare system among patients with non-metastatic castration-resistant prostate cancer (nmCRPC) treated with second-generation androgen receptor antagonists (ARAs). Current data is needed to understand real-world clinical event rates among ARAs and the cost of these events. OBJECTIVES: Describe the incidence of non-central nervous system (CNS)-related AEs and CNS-related AEs among nmCRPC patients treated in the United States with second-generation ARAs (apalutamide and enzalutamide) and evaluate healthcare resource utilization (HCRU) and costs for these patients. METHODS AND STUDY DESIGN: This was a retrospective observational cohort study using claims data from Optum Clinformatics Data Mart to identify adult males with prostate cancer, castration, no metastases, and >1 claim for apalutamide or enzalutamide. The study was conducted from January 2017 to March 2020, with a patient index identification period from January 2018 to December 2019. AEs were classified as CNS-related or non-CNS-related. RESULTS: Of 605 patients (156 apalutamide and 449 enzalutamide), most were ≥65 years (94%) and had ≥1 non-CNS-related AE (55%). Many had ≥1 CNS-related AE (32%). Pain (12%) and arthralgia (11%) were the most frequently reported non-CNS-related AEs. Fatigue/asthenia (14%) and dizziness (7%) were the most frequently reported CNS-related AEs. Among patients with versus without non-CNS-related AEs, 34% versus 8% had emergency room (ER) events, and 25% versus 2% had inpatient events. Among patients with versus without CNS-related AEs, 41% versus 14% had ER events, and 38% versus 4% had inpatient events. Adjusted per-patient per-year cost (in 2020 USD) differences were significant between patients with and without non-CNS-related AEs ($30,765, p = 0.0018) and between patients with and without CNS-related AEs ($40,689, p = 0.0017). CONCLUSION: There is significant HCRU and cost burden among nmCRPC patients treated with ARAs developing AEs, highlighting the need for treatments with improved tolerability. Additional studies are warranted to include recently approved agents.

Low-dose intravenous plus inhaled versus intravenous polymyxin B for the treatment of extensive drug-resistant Gram-negative ventilator-associated pneumonia in the critical illnesses: a multi-center matched case-control study.

BACKGROUND: The mortality of extensively drug-resistant Gram-negative (XDR GN) bacilli-induced ventilator-associated pneumonia (VAP) is extremely high. The purpose of this study was to compare the efficacy and safety of inhaled (IH) plus intravenous (IV) polymyxin B versus IV polymyxin B in XDR GN bacilli VAP patients. METHODS: A retrospective multi-center observational cohort study was performed at eight ICUs between January 1st 2018, and January 1st 2020 in China. Data from all patients treated with polymyxin B for a microbiologically confirmed VAP were analyzed. The primary endpoint was the clinical cure of VAP. The favorable clinical outcome, microbiological outcome, VAP-related mortality and all-cause mortality during hospitalization, and side effects related with polymyxin B were secondary endpoints. Favorable clinical outcome included clinical cure or clinical improvement. RESULTS: 151 patients and 46 patients were treated with IV polymyxin B and IH plus IV polymyxin B, respectively. XDR Klebsiella pneumoniae was the main isolated pathogen (n = 83, 42.1%). After matching on age (± 5 years), gender, septic shock, and Apache II score (± 4 points) when polymyxin B was started, 132 patients were included. 44 patients received simultaneous IH plus IV polymyxin B and 88 patients received IV polymyxin B. The rates of clinical cure (43.2% vs 27.3%, p = 0.066), bacterial eradication (36.4% vs 23.9%, p = 0.132) as well as VAP-related mortality (27.3% vs 34.1%, p = 0.428), all-cause mortality (34.1% vs 42.0%, p = 0.378) did not show any significant difference between the two groups. However, IH plus IV polymyxin B therapy was associated with improved favorable clinical outcome (77.3% vs 58.0%, p = 0.029). Patients in the different subgroups (admitted with medical etiology, infected with XDR K. pneumoniae, without bacteremia, with immunosuppressive status) were with odd ratios (ORs) in favor of the combined therapy. No patient required polymyxin B discontinuation due to adverse events. Additional use of IH polymyxin B (aOR 2.63, 95% CI 1.06, 6.66, p = 0.037) was an independent factor associated with favorable clinical outcome. CONCLUSIONS: The addition of low-dose IH polymyxin B to low-dose IV polymyxin B did not provide efficient clinical cure and bacterial eradication in VAP caused by XDR GN bacilli. Keypoints Additional use of IH polymyxin B was the sole independent risk factor of favorable clinical outcome. Patients in the different subgroups were with HRs substantially favoring additional use of IH polymyxin B. No patients required polymyxin B discontinuation due to adverse events.

Surfactant protein D (SP-D) gene polymorphism rs721917 is an independent predictor of acute kidney injury development in sepsis patients: a prospective cohort study.

BACKGROUND: Currently, there are no reliable predictors of risk of development and severity of acute kidney injury (AKI) in septic patients. The surfactant protein D (SP-D) polymorphism rs721917C/T is associated with a greater susceptibility to AKI in the Chinese population. Our aim was to evaluate the value of SP-D polymorphisms rs721917C/T and of plasma SP-D levels to predict the risk of development of AKI (defined with KDIGO criterion) in septic patients. METHODS: The study enrolled septic patients admitted to the Critical Care Department of two tertiary care hospitals. SP-D rs721917C/T polymorphisms were determined using the PCR-SSP method. Plasma SP-D and urine NGAL contents were measured using commercially available ELISA kits. RESULTS: 330 septic patients were included. Their SOFA scores were 12 ± 3. Patients with AKI (n = 156) had higher plasma SP-D levels (median: 153 ng/mL, range 111-198 ng/mL) and urinary NGAL levels (median: 575 ng/mL, range 423-727 ng/mL) than those without AKI (SP-D median: 124 ng/mL, range 81-159 ng/mL, P = 0.001; NGAL median: 484 ng/mL, range 429-573 ng/mL). Plasma SP-D levels of AKI patients were correlated with urinary NGAL contents (r = 0.853). In 32 patients receiving continuous renal replacement therapy (CRRT), plasma SP-D levels correlated with duration of CRRT (r = 0.448). The area under the receiver operating characteristic curve for plasma SP-D levels to predict AKI was 0.84. Patients with AKI had a higher rate of rs721917 CC genotype (AKI: 35% vs. non-AKI: 20%; P = 0.012), but a significantly lower rate of TT genotype (AKI: 19% vs. non-AKI: 26%; P = 0.005). SP-D rs721917 CC genotype was an independent predictor of AKI (P = 0.044) and mortality (P = 0.014). CONCLUSION: Our study showed that increased plasma SP-D level is associated with a higher risk of AKI in patients with sepsis. The SP-D rs721917CC genotype is an independent and significant predictor of AKI development and mortality of septic patients. The SP-D rs721917C/T polymorphisms should be further studied as diagnostic and prognostic biomarkers to facilitate early recognition of AKI.

Evaluation of Treatment Patterns and Costs in Patients with Prostate Cancer and Bone Metastases.

BACKGROUND: There are a lack of guideline recommendations for patients with metastatic castration-resistant prostate cancer (mCRPC) undergoing treatment progression and sequencing. Understanding treatment patterns and associated utilization and costs may help inform stakeholders and guide decision making. OBJECTIVE: To describe treatment patterns and health care costs in prostate cancer (PC) patients with bone metastases treated with agents approved by the FDA for mCRPC. METHODS: 2 large integrated claims databases (MarketScan and PharMetrics) were used to identify males aged ≥ 18 years who were diagnosed and treated for PC (ICD-9-CM code 185.xx or 233.4) with bone metastases (ICD-9-CM code 198.5) from June 2013 to September 2014. Patients were required to be continuously enrolled for ≥ 6 months before and after initiation of treatment with abiraterone, cabazitaxel, docetaxel, enzalutamide, mitoxantrone, radium-223, sipuleucel-T, or other chemotherapy. Study endpoints included lines of therapy, health care resource utilization per patient per month (PPPM), PPPM costs, and mortality rate. Descriptive analysis was completed for the study sample, and survival function was calculated via Kaplan-Meier estimates. RESULTS: There were 953 patients meeting all inclusion criteria in the MarketScan database and 565 patients in the PharMetrics database. The median follow-up time was 18 months (interquartile range [IQR] = 14-23) for MarketScan and 14 months (IQR = 11-18) for PharMetrics. Mean age (SD) was 71 (± 10.7) and 66 (± 9.3) years, respectively. Before mCRPC treatment initiation, patients received palliative radiation therapy and bone antiresorptive therapy. For MarketScan and PharMetrics, respectively, 14.0% and 18.2% of patients received radiation therapy, 36.1% and 40.0% received denosumab; 16.5% and 16.8% received zoledronic acid; and 0.2% and 0.8% received pamidronate. Across both databases, abiraterone was the most commonly received bone metastasis treatment agent across all lines of therapy, except fourth line. Radium-223, cabazitaxel, and mitoxantrone were the least utilized therapies. The median cost PPPM during the post-index period was $10,916 (IQR=$5,334-$13,457) in MarketScan and $10,292 (IQR = $7,245-$14,699) in PharMetrics. The cost PPPM during the 6-month pre-index period was $2,643 (IQR = $850-$4,357) in MarketScan and $2,742 (IQR = $1,484-$4,730) in PharMetrics. CONCLUSIONS: Patients were treated mainly with abiraterone across most lines of care, with radium-223, cabazitaxel, and mitoxantrone as the least utilized therapies. Median costs PPPM increased by approximately $8,900 after initiation of FDA-approved agents for mCRPC, with the largest increase in cost stemming from oral medications. DISCLOSURES: Funding for this study was provided by Bayer HealthCare Pharmaceuticals. All authors were employees at Bayer HealthCare Pharmaceuticals at the time this study was conducted. This study was presented as a poster at the 2017 American Society of Clinical Oncology (ASCO) Genitourinary Cancers Symposium; February 16-18, 2017; Orlando, FL.

Economic Evaluation of Treating Skeletal-Related Events among Prostate Cancer Patients.

OBJECTIVES: To evaluate the economic burden of treating skeletal-related events (SREs) in prostate cancer (PC) patients with bone metastasis from an insurer perspective. METHODS: We conducted a retrospective cohort analysis using claims data. PC patients with bone metastasis were identified in the MarketScan Databases between January 1, 2004, and March 1, 2014. The propensity score matching approach was used to match patients with SREs to those without SREs. A pseudo-SRE date was assigned to the control group. We compared 6-month and 12-month total costs of patients between two groups after the SRE or pseudo-SRE date. All costs were adjusted to 2014 US$. RESULTS: We identified 4083 PC men with bone metastasis, from which 787 patients with SREs were matched (1:1) to those without SREs. On average, the total 6-month cost of treating patients with SREs was $43,746 compared with $25,956 in the matched control cohort (P < 0.05). The largest proportion of differences in costs between the two groups was incurred in the first month after the SRE index date or the pseudo-SRE date ($14,979 vs. $4,849; P < 0.05) and was mostly attributable to outpatient visits (43.4%; P < 0.05) and inpatient hospitalization (33.1%; P < 0.05). The total cost per patient over the 12-month period was $22,171 higher among patients with SREs than among patients without SREs (P < 0.05). CONCLUSIONS: Our findings suggest that SREs impose considerable burden on health resource utilization for payers. Costs attributable to SREs were substantial. Most costs were incurred in the first month after the occurrence of SREs. Although costs decreased thereafter, they remained significantly higher for patients with SREs in subsequent months compared with patients without SREs.

Occurrence of Chronic Pelvic Pain, Abnormal Uterine Bleeding, and Hysterectomy Post-procedure among Women Who Have Undergone Female Sterilization Procedures: A Retrospective Claims Analysis of Commercially Insured Women in the US.

STUDY OBJECTIVE: To evaluate the frequency of chronic pelvic pain (CPP), abnormal uterine bleeding (AUB), and hysterectomy after hysteroscopic sterilization (HS) or laparoscopic sterilization (LS) in the United States. DESIGN: Retrospective cohort study (Canadian Task Force classification II-2). SETTING: Commercially insured women. PATIENTS: Women (aged 18-49 years) with claims for HS or LS from January 1, 2010 to December 31, 2012 were identified from the MarketScan Commercial database. Women were required to have 6 months of continuous coverage before (baseline) and 24 months after (follow-up) the procedure date. Women with ≥1 diagnosis for a pain condition (pain in pelvis/lower abdomen, low back pain, chronic headache, fibromyalgia) and/or AUB (excessive/frequent menstruation, irregular menstrual cycle, metorrhagia) during baseline were identified with International Classification of Diseases, Ninth Revision, Clinical Modification codes. INTERVENTIONS: HS/LS. MEASUREMENTS AND MAIN RESULTS: Outcome measurements were proportions of women with CPP, AUB, and hysterectomy during follow-up. Among the study population 10 224 women underwent HS, whereas 8051 underwent LS. During baseline 23.3% and 26.9% of women with HS and LS, respectively, had a pre-existing pain diagnosis. Among both HS and LS study cohorts, greater proportions of women with a pre-existing pain condition versus those without had CPP in the 24 months afterward (HS cohort: 19.8% vs 9.3%, p < .001; LS cohort: 23.8% vs 11.4%, p < .001). During baseline 11.7% and 6.4% of women with HS and LS, respectively, had pre-existing AUB. Among cohorts, greater proportions of women with pre-existing AUB versus those without had AUB in the 24 months afterward (HS cohort: 21.2% vs 7.3%, p < .001; LS cohort: 15.9% vs 6.4%, p < .001). Among women who underwent HS and LS, pre-existing pain and AUB were associated with higher rates of hysterectomy postprocedure. Multivariable regression results showed similar direction of findings. CONCLUSION: Among women who underwent HS and LS, pre-existing pain conditions and AUB were associated with higher rates of CPP and AUB postprocedure, respectively, and both pre-existing conditions were associated with a greater frequency of subsequent hysterectomy.

Comparison of Healthcare Costs Among Commercially Insured Women in the United States Who Underwent Hysteroscopic Sterilization Versus Laparoscopic Bilateral Tubal Ligation Sterilization.

BACKGROUND: This study evaluated healthcare costs of index procedures and during a 6-month follow-up of women who had hysteroscopic sterilization (HS) versus laparoscopic bilateral tubal ligation (LBTL). MATERIALS AND METHODS: Women (18-49 years) with claims for HS and LBTL procedures were identified from the MarketScan commercial claims database (January 1, 2010, to December 31, 2012) and placed into separate cohorts. Demographics, characteristics, index procedure costs, and 6-month total healthcare costs and sterilization procedure-related costs were compared. Multivariable regression analyses were used to examine the impact of HS versus LBTL on costs. RESULTS: Among the study population, 12,031 had HS (mean age: 37.0 years) and 7286 had LBTL (mean age: 35.8 years). The majority (80.9%) who had HS underwent the procedure in a physician's office setting. Fewer women who had HS versus LBTL received the procedure in an inpatient setting (0.5% vs. 2.1%), an ambulatory surgical center setting (5.0% vs. 23.8%), or a hospital outpatient setting (13.4% vs. 71.9%). Mean total cost for the index sterilization procedure was lower for HS than for LBTL ($3964 vs. $5163, p < 0.0001). During the 6-month follow-up, total medical and prescription costs for all causes ($7093 vs. $7568, p < 0.0001) and sterilization procedure-related costs ($4971 vs. $5407, p < 0.0001) were lower for women who had HS versus LBTL. Multivariable regression results confirmed that costs were lower for women who had HS versus LBTL. CONCLUSIONS: Among commercially insured women in the United States, HS versus LBTL is associated with lower average costs for the index procedure and lower total healthcare and procedure-related costs during 6 months after the sterilization procedure.

Greater adherence to diabetes drugs is linked to less hospital use and could save nearly $5 billion annually.

Improving adherence to medication offers the possibility of both reducing costs and improving care for patients with chronic illness. We examined a national sample of diabetes patients from 2005 to 2008 and found that improved adherence to diabetes medications was associated with 13 percent lower odds of subsequent hospitalizations or emergency department visits. Similarly, losing adherence was associated with 15 percent higher odds of these outcomes. Based on these and other effects, we project that improved adherence to diabetes medication could avert 699,000 emergency department visits and 341,000 hospitalizations annually, for a saving of $4.7 billion. Eliminating the loss of adherence (which occurred in one out of every four patients in our sample) would lead to another $3.6 billion in savings, for a combined potential savings of $8.3 billion. These benefits were particularly pronounced among poor and minority patients. Our analysis suggests that improved adherence among patients with diabetes should be a key goal for the health care system and policy makers. Strategies might include reducing copayments for certain medications or providing feedback about adherence to patients and providers through electronic health records.

Impact of proton pump inhibitors on the effectiveness of clopidogrel after coronary stent placement: the clopidogrel Medco outcomes study.

STUDY OBJECTIVE: To investigate the potential impact of proton pump inhibitors (PPIs) on the effectiveness of clopidogrel in preventing recurrent ischemic events after percutaneous coronary intervention (PCI) with stent placement. DESIGN: Population-based, retrospective cohort study. DATA SOURCE: National medical and pharmacy benefit claims database comprising approximately 19 million members. PATIENTS: A total of 16,690 patients who had undergone PCI with stent placement and who were highly adherent to clopidogrel therapy alone (9862 patients) or to clopidogrel with a PPI (6828 patients) between October 1, 2005, and September 30, 2006. MEASUREMENTS AND MAIN RESULTS: The primary end point was the occurrence of a major adverse cardiovascular event during the 12 months after stent placement. These events were defined as hospitalization for a cerebrovascular event (stroke or transient ischemic attack), an acute coronary syndrome (myocardial infarction or unstable angina), coronary revascularization (PCI or coronary artery bypass graft), or cardiovascular death. A composite event rate was compared between patients who received clopidogrel alone and those who received concomitant clopidogrel-PPI therapy. Baseline differences in covariates were adjusted by using Cox proportional hazards models. In the 9862 patients receiving clopidogrel alone, 1766 (17.9%) experienced a major adverse cardiovascular event compared with 1710 patients (25.0%) who received concomitant clopidogrel-PPI therapy (adjusted hazard ratio 1.51, 95% confidence interval 1.39-1.64, p<0.0001). Similar associations of increased risk were observed for each PPI studied (omeprazole, esomeprazole, pantoprazole, and lansoprazole). CONCLUSION: Concomitant use of a PPI and clopidogrel compared with clopidogrel alone was associated with a higher rate of major adverse cardiovascular events within 1 year after coronary stent placement.

Is there a relationship between early statin compliance and a reduction in healthcare utilization?

OBJECTIVE: To investigate whether compliance during the first 2 years of statin therapy is associated with reduced hospitalization rates and direct medical costs during year 3. STUDY DESIGN: An integrated pharmacy and medical claims database was used to identify adult patients with a new statin prescription between July 1, 2001, and June 30, 2002. The study tracked statin prescription refills during the first 2 years after the initial statin claim and tracked hospitalizations and direct medical costs during the first 3 years. METHODS: Patients were stratified according to compliance in the first 2 years using the medication possession ratio, where 80% or higher is compliant and less than 80% is noncompliant. The relationship between compliance rates and direct medical costs was evaluated using a generalized linear model. Adjusting for covariates that may affect cardiovascular risk, the relationship between compliance and the likelihood of hospitalization was assessed using logistic regression models. RESULTS: The 2-year medication possession ratio was 80% or higher in 3512 patients (compliant) and was less than 80% in 6715 patients (noncompliant). Compared with the noncompliant patients, the compliant patients during year 3 had significantly fewer hospitalizations (16% vs 19%) and lower total direct medical costs (excluding the cost of statin therapy) ($4040 vs $4908 per patient) (P <.01 for both). CONCLUSION: Compliance with statin therapy in the first 2 years of use may reduce hospitalization rates and direct medical costs in the subsequent year.

Oseltamivir prescribing in pharmacy-benefits database, United States, 2004-2005.

We reviewed information from a US pharmacy benefits manager database from 2004 through 2005 during periods with little influenza activity. We calculated rates of oseltamivir prescriptions to enrollees. Prescription rates increased significantly from 27.3/100,000 in 2004 to 134/100,000 in 2005 (p<0.05), which suggested that personal stockpiling of oseltamivir occurred.

Frequency of follow-up care for adult and pediatric patients during initiation of antidepressant therapy.

OBJECTIVES: To measure the timing and frequency of follow-up care during the initiation phase of antidepressant therapy, and to compare the typical pattern of care with current product guidelines. STUDY DESIGN: Retrospective cohort study. METHODS: The study included 84514 adult and pediatric patients who started a new course of antidepressant therapy for any indication between July 2001 and September 2003. Patients were members of a large managed care organization in the northeastern United States. Ambulatory visits during the first 12 weeks of treatment were identified using medical claims data. Outcome measures were time to first follow-up visit, frequency of follow-up visits, and percentage of patients receiving recommended levels of care. RESULTS: During the first 4 weeks of treatment with antidepressants, only 55.0% of patients saw a healthcare provider for any purpose, and only 17.7% saw a provider for mental healthcare. Ambulatory visit rates during the first 4, 8, and 12 weeks were significantly lower than the minimum levels recommended in product labeling (P <.0001). Only 14.9% of patients received the Food and Drug Administration-recommended level of follow-up care during the first 4 weeks, 18.1% at 8 weeks, and 22.6% at 12 weeks. CONCLUSIONS: Adults and children who begin a new course of antidepressant therapy tend to receive far less monitoring than is recommended in current product labeling. Given safety concerns during the initiation phase, earlier and more frequent follow-up care appears desirable. Further research is needed to identify the most cost-effective schedule of care.