Progression-Free Survival of Daratumumab Versus Bortezomib Triplet Combination With Lenalidomide and Dexamethasone in Transplant Ineligible Patients With Newly Diagnosed Multiple Myeloma: TAURUS Chart Review Study.

BACKGROUND: Daratumumab, lenalidomide and dexamethasone (DRd) and bortezomib, lenalidomide and dexamethasone (VRd) are preferred regimens for transplant ineligible (TIE) patients with newly diagnosed multiple myeloma (NDMM). Both DRd and VRd demonstrated superior efficacy versus Rd in the MAIA and SWOG S0777 trials, respectively, but there is no head-to-head (H2H) clinical trial comparing their efficacy. Differing populations in the MAIA and S0777 trials make an unadjusted comparison of outcomes challenging and biased. The current TAURUS study is the first real-world H2H study comparing progression-free survival (PFS) among TIE NDMM patients treated with DRd or VRd as first-line (1L) in similar clinical settings. MATERIALS AND METHODS: A multicenter chart review study was conducted at nine sites across the United States. All TIE patients treated with DRd and a randomly selected population of VRd patients were included. TIE NDMM patients aged ≥65 were included if they initiated 1L DRd/VRd between January 2019 and September 2021. PFS was defined as the time from DRd/VRd initiation until disease progression or death. A doubly-robust multivariable Cox regression model combined with inverse probability of treatment weighting (IPTW) methodology was used to compare PFS between cohorts. RESULTS: Weighted cohorts comprised 91 DRd and 87 VRd patients. Thirteen DRd and 24 VRd patients experienced progression/death. Patients treated with DRd had a lower risk of progression/death versus VRd (adjusted hazard ratio: 0.35, 95% confidence interval: [0.17; 0.73]). CONCLUSION: DRd is associated with a significantly lower risk of disease progression or death compared to VRd as 1L treatment for TIE NDMM patients.

Survey of patients and physicians on shared decision-making in treatment selection in relapsed/refractory multiple myeloma.

Shared decision-making (SDM) is a key component of patient-centered healthcare. SDM is particularly pertinent in the relapsed and/or refractory multiple myeloma (RRMM) setting, in which numerous treatment options can present challenges for identifying optimal care. However, few studies have assessed the extent and relevance of SDM and patient-centered communication (PCC) in RRMM. To describe treatment decision-making patterns between physicians and patients in the RRMM setting, we conducted online surveys of patients and physicians in the USA to compare their perspectives on the process of treatment decision-making. We analyzed the surveys descriptively. Two hundred hematologists/oncologists and 200 patients with RRMM receiving second-line (n = 89), third-line (n = 65), and fourth-line (n = 46) therapy participated. Top treatment goals for physicians and patients included extending overall survival (among 76% and 83% of physicians and patients, respectively) and progression-free survival (among 54% and 77% of physicians and patients, respectively), regardless of the number of prior relapses. Thirty percent of physicians believed patients preferred a shared approach to treatment decision-making, while 40% of patients reported most often preferring a shared role in treatment decision-making. One-fourth of patients most often preferred physicians to make the final treatment decision after seriously considering their opinion. Thirty-two percent of physicians and 16% of patients recalled ≥3 treatment options presented at first relapse. Efficacy was a primary treatment goal for patients and physicians. Discrepancies in their perceptions during RRMM treatment decision-making exist, indicating that communication tools are needed to facilitate SDM and PCC.

Shared decision-making (SDM) is an important facet of patient-centered healthcare. Multiple myeloma (MM) is a cancer of the bone marrow that can return (relapse) after treatment. SDM may be especially pertinent for relapsed MM as there is no uniform standard of care and treatment selection can be complex. Few studies have examined the extent and relevance of SDM and patient-centered communication (PCC) in this relapsed and/or refractory (RRMM) setting. We conducted online surveys of 200 patients who had received 1­3 previous therapies and 200 physicians to compare treatment decision-making patterns in RRMM in the USA. Both physicians and patients felt that extending patient survival was a top treatment goal, regardless of the number of prior relapses. A lower percentage of physicians believed patients preferred a shared approach to treatment decision-making than patients who reported preferring such a shared role. Twice as many physicians than patients recalled ≥3 treatment options presented at first relapse. In conclusion, while improving survival was an important treatment goal for physicians and patients, there are discrepancies in physician and patient perceptions during RRMM treatment decision-making. Thus, communication tools are needed to facilitate SDM and PCC.

Patient characteristics associated with dose modifications for VRd among newly diagnosed multiple myeloma patients.

Aim: To evaluate among multiple myeloma (MM) patients, the proportions with first-line bortezomib/lenalidomide/dexamethasone (VRd) dose modifications and the associated baseline patient characteristics. Patients & methods: Adult MM patients treated with first-line VRd were selected from the Optum claims database. VRd dose modifications were defined based on lenalidomide dose. Results: Among 1497 MM patients, 33% received VRd lite and 22% VRd reduced. Compared with VRd regular, VRd lite usage was more likely to be associated with patients aged ≥75 years and female sex; VRd reduced usage was more likely to be associated with female sex and frailty. Conclusion: A large proportion of MM patients received VRd dose modifications in the real-world, which could potentially result in reduced effectiveness of VRd.

Real-world patient characteristics and treatment outcomes among nontransplanted multiple myeloma patients who received Bortezomib in combination with Lenalidomide and Dexamethasone as first line of therapy in the United States.

BACKGROUND: There is limited real-world evidence that describes patients with newly diagnosed multiple myeloma (NDMM) treated with the bortezomib, lenalidomide, and dexamethasone (VRd) triplet regimen. We evaluated patient characteristics and treatment outcomes among nontransplanted NDMM patients who received VRd as their first line of therapy (LOT) in US oncology practice settings. METHODS: This retrospective observational cohort study evaluated patients from the Flatiron MM Core Registry who received VRd as first LOT between November 1, 2015, and February 28, 2021. Progression-free survival (PFS) was analyzed using the Kaplan-Meier method. Associations between patient demographic and clinical characteristics and PFS were evaluated using a multivariable Cox proportional hazards model. RESULTS: A total of 2342 eligible patients with VRd as first LOT were identified (mean age, 67.0 years). Among all identified patients, 64.3% were ≥ 65 years of age, 25.5% were elderly (≥75 years), and 47.9% were frail. Among patients with available data, 21.2% had high-risk cytogenetics, and the majority had International Staging System (ISS) stage I/II disease (71.8%), and Eastern Cooperative Oncology Group performance status (ECOG PS) score 0/1 (81.2%). Median duration of therapy was 5.5 months. With median follow-up of 21.0 months, median PFS and time-to-next-treatment were 26.5 and 16.1 months, respectively. Higher risk of disease progression or death was seen in patients categorized as elderly (hazard ratio [HR] = 1.37; 95% confidence interval [CI]: 1.13-1.66 vs patients < 65 years), having high-risk cytogenetics (HR = 1.44; 95% CI: 1.19-1.75 vs standard risk), having ISS disease stages II and III (HR = 1.31; 95% CI: 1.06-1.63 and HR = 1.37; 95% CI: 1.10-1.70 versus stage I, respectively), and having worse ECOG PS score (≥2) (HR = 1.49; 95% CI: 1.22-1.81 versus functionally active patients). CONCLUSIONS: The majority of patients treated with VRd in this study were ≥ 65 years of age, were ISS stage I/II, had an ECOG PS score of 0/1, and had standard cytogenetic risk. Median PFS observed in real-world practice was notably shorter than that observed in the SWOG S0777 clinical trial. In nontransplanted patients treated with VRd as first LOT, a higher risk of disease progression or death was associated with older age, having high-risk cytogenetics, worse disease stage, and worse ECOG PS score.

Daratumumab Improves Depth of Response and Progression-free Survival in Transplant-ineligible, High-risk, Newly Diagnosed Multiple Myeloma.

BACKGROUND: Patients with high-risk, newly diagnosed multiple myeloma (HR-NDMM) who are ineligible for autologous stem cell transplant (ASCT) have limited first-line treatment options. Recent meta-analyses evaluating the impact of incorporating daratumumab in the backbone regimen on progression-free survival (PFS) have found mixed results in these patients. MATERIALS AND METHODS: A pooled analysis of patient-level data for ASCT-ineligible patients with HR-NDMM [ie, del(17p), t(4;14), t(14;16)] from the MAIA and ALCYONE trials; stratified by study identifier and adjusting for cytogenetic abnormality subtype, baseline performance status, International Staging System stage, myeloma type, and renal impairment; was conducted. Impact of daratumumab on PFS and rates of complete response or better (≥CR), minimal residual disease (MRD)-negative CR, very good partial response or better (≥VGPR), and overall response (ORR) was compared to control. RESULTS: Among 101 patients in the daratumumab and 89 patients in the control cohort, median follow-up was 43.7 months. Daratumumab reduced the risk of progression or death by 41% (adjusted hazard ratio for PFS [95% confidence interval (CI)] = 0.59 [0.41-0.85]) versus control. At 36 months, the estimated proportion of patients who did not progress and were still alive was 41.3% in the daratumumab and 19.9% in the control cohort. Rates of ≥CR (41.6% vs. 22.5%), MRD-negative CR (24.8% vs. 5.6%), ≥VGPR (75.2% vs. 46.1%), and ORR (92.1% vs. 74.2%) were higher for daratumumab versus control. CONCLUSION: These findings demonstrate that incorporation of daratumumab in frontline treatment regimens reduced the risk of progression or death and improved response rates among ASCT-ineligible HR-NDMM patients.

Real-world evidence for carfilzomib dosing intensity on overall survival and treatment progression in multiple myeloma patients.

INTRODUCTION: Carfilzomib dosing as a single agent or in combination with dexamethasone (Kd) has evolved from the initial 27 mg/m2 twice-weekly (legacy dose), to more recently approved doses of 56 mg/m2 twice-weekly and 70 mg/m2 once-weekly (optimized doses). The objective of this study was to evaluate the overall survival (OS), and time to next treatment (TTNT) among multiple myeloma patients treated with Kd optimized vs legacy doses. METHODS: A retrospective analysis of patients receiving Kd between 01/01/2013-07/31/2017 was conducted using IQVIA's oncology electronic medical records database. Kd dose was estimated based on body surface area. OS was measured from the Kd-initiation date until death. TTNT was defined as the time from Kd-initiation until the start of subsequent treatment. Kaplan-Meier analysis and Cox models were used to evaluate OS and TTNT. RESULTS: Of the 1,469 patients evaluated, 129 (8.8%) received optimized dose and 1,340 (91.2%) received legacy dose. Risk of mortality was 64% lower for patients receiving the optimized doses (HR: 0.36, 95% CI: 0.178-0.745). Patients receiving the optimized doses had significantly longer TTNT compared to patients receiving the legacy dose (median TTNT: 17.5 months [95% CI: 14.8-NE] and 13.2 months, [95% CI: 12.4-14.4], respectively; p = 0.023), and 33% lower risk of progressing to the subsequent treatment (HR: 0.67, 95% CI: 0.48-0.93). CONCLUSIONS: Patient outcomes could be improved if eligible MM patients are treated with the optimized, recently approved Kd doses (56 mg/m2 twice-weekly and 70 mg/m2 once-weekly).

Health-related quality of life outcomes from the CANDOR study in patients with relapsed or refractory multiple myeloma.

CANDOR (NCT03158688) compared carfilzomib, dexamethasone, and daratumumab (KdD) to carfilzomib and dexamethasone (Kd) in patients with relapsed/refractory multiple myeloma (RRMM). A secondary objective of CANDOR was to evaluate health-related quality of life (HRQoL) scores using the Global Health Status (GHS)/Quality of Life (QoL) domain of the EORTC QLQ-C30. Scores were compared between KdD and Kd using a restricted maximum likelihood-based mixed effects model for repeated measures. GHS/QoL completion rates were >81% for both arms. Higher GHS/QoL scores were observed with KdD versus Kd from Cycle 7-26. The overall least squares mean estimate (95% CI) of the difference between treatment arms was 0.06 (-2.39 to 2.50; p = 0.96). In an exploratory analysis, 55.5% in the KdD arm and 43.0% in the Kd arm improved ≥10 points in GHS/QoL score from baseline. HRQoL was maintained with KdD, consistent with superior clinical benefit observed with KdD versus Kd in patients with RRMM.

Cost-effectiveness of once weekly carfilzomib 70 mg/m2 plus dexamethasone in patients with relapsed and refractory multiple myeloma in the United States.

BACKGROUND: In the US, carfilzomib 70 mg/m2 once-weekly plus dexamethasone (Kd70 QW) was recently indicated for relapsed and/or refractory multiple myeloma. In current US clinical practice, most patients treated with Kd receive carfilzomib at a previously approved dose of 27 mg/m2 twice-weekly (Kd27 BIW). This analysis assessed the cost-effectiveness (CE) of Kd70 QW vs Kd27 BIW regimens which were compared in the randomized phase 3 ARROW trial. METHODS: Based on clinical outcomes (overall survival and utilities) from ARROW, a partitioned survival model was developed to estimate life years (LYs) and quality-adjusted life years (QALYs). Long-term survival was extrapolated using SEER registry data matched to ARROW patients. Costs were estimated using a US healthcare payer perspective. RESULTS: The analysis estimated that treatment with Kd70 QW vs Kd27 BIW resulted in an increase of 1.10 LYs, 0.91 QALYs, and additional lifetime costs of $74,858, yielding an incremental CE ratio (ratio of incremental costs to QALYs) of $82,257 per QALY gained. Results were robust to sensitivity and subgroup analyses. CONCLUSIONS: When compared with Kd27 BIW, Kd70 QW is the optimal dose that represents a cost-effective utilization of health care budget with incremental CE ratios well below the accepted willingness-to-pay thresholds in the US.

Healthcare resource utilization and costs in patients with multiple myeloma with and without skeletal-related events.

AIM: To compare healthcare resource use and costs between newly diagnosed multiple myeloma (NDMM) patients with and without skeletal-related events (SREs). METHODS: Adults newly diagnosed with MM (1 January 2006 and 30 June 2017) with at least 12 months continuous health coverage prior to diagnosis were identified using the IBM MarketScan administrative claims. To control for baseline differences, NDMM patients with SREs were propensity score matched to NDMM patients without SREs. Outcomes included annual HRU and costs during follow-up along with number and type of SREs (SRE cohort only). Patients with SREs were stratified by number of SREs, and annual SRE-related costs were reported. Student's t test and Chi-squared test were used to compare outcomes. RESULTS: Before matching, the 6648 patients in the SRE cohort had more comorbidities, were more likely to have MM treatment, and had higher pre-index healthcare costs than the 7458 patients in the non-SRE cohort. After matching, cohorts of 3432 patients were well balanced on baseline characteristics. Patients with SREs (vs. without SREs) had significantly higher inpatient, outpatient, and pharmacy HRU. Patients with SREs had significantly higher mean annual all-cause healthcare costs ($213,361 vs. $94,896, p < 0.001) with hospitalization being the leading driver of increased costs (38.7% of total). Among 6648 patients with SREs, the mean annual SRE-related healthcare costs were $39,603, $45,463, and $50,111 for patients with one, two, and three or more events, respectively. CONCLUSIONS: NDMM patients with SREs have more than twice the all-cause healthcare costs than matched patients without SREs. Costs increase with the number of SRE events.

Letter--Value-Driven Treatment Decisions: Need of the Hour for Relapsed/Refractory Multiple Myeloma.

DISCLOSURES: No funding was involved in the writing of this letter. Medhekar, Sapra, Majer, Harrison, and Tekle are employees of and stockholders in Amgen.

A real-world comparative analysis of carfilzomib and other systemic multiple myeloma chemotherapies in a US community oncology setting.

BACKGROUND: Most multiple myeloma (MM) patients ultimately progress, with remission duration decreasing after first relapse. Recently, novel agents have been approved for the treatment of relapsed MM. There is a paucity of real-world data on these treatments. We sought to compare time to next treatment (TTNT) in MM patients in their second line of therapy (LOT2), treated with common proteasome inhibitor (PI)-based triplets. METHODS: Adult MM patients who received carfilzomib (K) between 1 November 2013 and 29 February 2016 at US Oncology Network (USON) clinics utilizing iKnowMed™ electronic health records (EHRs) were identified. Patients were included if they were ⩾18 years of age, not enrolled in clinical trials, had ⩾2 visits at a USON clinic and received LOT2 regimens consisting of: K+lenalidomide with steroid (KRd), bortezomib+lenalidomide with steroid (VRd), or bortezomib+cyclophosphamide with steroid (VCyd). TTNT was estimated from LOT2 initiation to LOT3 initiation using the Kaplan-Meier method, and hazard ratios (HRs) were estimated using Cox modeling. RESULTS: A total of 718 patients received a K-containing regimen sometime during their MM treatment (LOT1 to LOT5). Of these, 156 patients received: KRd (n = 112; 71.8%), VRd (n =27; 17.3%), or VCyd (n = 17; 10.9%). Baseline characteristics were similar between groups (mean age: 64.8 years; 58% male). Median TTNT was longest for KRd [25.3 months; 95% confidence interval (CI): 19.71-NR], versus VRd or VCyd (VRd median TTNT: 10.2 months, 95% CI: 4.24-12.71; VCyd: 6.5 months, 95% CI: 3.02-12.78; log-rank p < 0.0001). The adjusted HR for KRd was 0.19 (95% CI: 0.11-0.37), compared with VRd. CONCLUSIONS: Considering the real-world nature of these data, the median TTNT observed with KRd was relatively consistent, with progression-free survival (PFS) for KRd observed in the phase III ASPIRE trial (median PFS: ITT population = 26.3 months; LOT2 = 29.6 months). Patients who received KRd at first relapse had significantly longer TTNT, compared with those on VRd or VCyd, confirming the value of KRd as an important treatment option for relapsed MM.

Risk factors of psychotropic polypharmacy in the treatment of children and adolescents with psychiatric disorders.

OBJECTIVE: To examine patient and provider characteristics associated with the use of pediatric psychotropic polypharmacy. METHODS: A retrospective study was conducted on children with psychiatric disorder diagnosis and treatment using the 2013-2015 claims data from a Pediatric Medicaid Managed Care Plan. Psychotropic polypharmacy was defined as the receipt of ≥2 psychotropic medications from different drug classes concurrently for ≥60 days. Stratified logistic regression analyses based on the number of prescribers involved in the treatment, i.e. single prescriber (SP) and multiple prescribers (MP) were conducted to determine the risk factors associated with multiclass psychotropic polypharmacy. The Fairlie decomposition method was used to test the difference in receipt of psychotropic polypharmacy between patients with and without a psychiatrist visit. RESULTS: A total of 24,147 children and adolescents met the inclusion criteria. The prevalence of psychotropic polypharmacy was 20.09%. In addition to patients' demographics, diagnoses, number of comorbid psychiatric disorders (MP only), and the number of prescribers involved in the treatment (MP only), patients with a psychiatrist involved in the treatment had 5.3 times and 3.6 times higher odds of receiving psychotropic polypharmacy in SP and MP groups respectively (SP: OR = 5.32; 95% CI 4.62-6.14 & MP: OR = 3.57; 95% CI 3.20-3.99). Only a quarter of the prescribing practice variation between psychiatrists and PCPs was explained by the observed need factors. CONCLUSIONS: Pediatric psychotropic polypharmacy may be necessary and justified as it is mainly prescribed by the best-trained providers.

Physician Care Coordination and the Use of Psychotropic Polypharmacy in the Management of Pediatric Mental Disorders.

BACKGROUND: Psychotropic polypharmacy is a concern in the management of pediatric mental disorders due to the lack of pediatric data to support the practice. Although seeing multiple providers has been identified as an important predictor of polypharmacy, no study has yet assessed the effect of care coordination between providers on receipt of psychotropic polypharmacy. OBJECTIVE: To examine the association between the intensity of care coordination within a patient's care team and the likelihood of the patient receiving multiclass psychotropic polypharmacy. METHODS: A retrospective study was conducted using the 2013-2015 administrative claims data from a Medicaid managed care organization (Texas Children's Health Plan). Children and adolescents aged 18 years or younger with a diagnosis of a mental/behavioral disorder and receipt of psychotropic prescriptions from multiple prescribers were included in the study. Psychotropic polypharmacy was defined as the receipt of 2 or more psychotropic medications from different drug classes concurrently for 60 days or more. Care coordination was measured using social network analysis (SNA), a new technique included in the Agency for Healthcare Research and Quality Care Coordination Measures Atlas. Care density, an SNA surrogate for care coordination, was calculated as the ratio of the sum of patients shared by physician pairs within a patient's care team to the total number of physician pairs. The Andersen behavioral model was used to guide multivariate logistic regression analyses conducted to assess the association between care density and the likelihood of patients receiving psychotropic polypharmacy after controlling for predisposing and need factors. RESULTS: A total of 24,147 children and adolescents diagnosed with a mental/behavioral disorder were identified. About 34.0% (n = 8,092) of these individuals received psychotropic medications from multiple prescribers who were either primary care physicians (PCPs) or specialists. Logistic regression analysis showed a significant association between care density and the use of psychotropic polypharmacy. However, the direction of this relationship varied depending on the composition of the patient's care team. Among patients with only PCPs involved in their care team, patients in the higher care-density group were 28% less likely to receive psychotropic polypharmacy (OR = 0.72; 95% CI = 0.62-0.96) than those in the lower care-density group. In contrast, among patients who had both PCPs and specialists involved in their care team, those in the higher care-density group were 2 times more likely to experience psychotropic polypharmacy (OR = 2.01; 95% CI = 1.68-2.40). Care density was not significantly associated with the receipt of psychotropic polypharmacy in the specialist-only group. CONCLUSIONS: This study found significant associations between care density and prescription of psychotropic polypharmacy. This relationship varied depending on the patient's diagnosis, disease complexity, and composition of the patient's care team. DISCLOSURES: No outside funding supported this study. The authors do not have any financial relationships or potential conflicts of interest relevant to this article to disclose. The abstract for part of this study, titled "Association Between Physician Care Coordination and the Use of Psychotropic Polypharmacy in the Management of Pediatric Mental Disorders," was selected as a silver medal abstract and was presented at the AMCP Managed Care & Specialty Pharmacy Annual Meeting 2017; March 27-30, 2017; Denver, CO.

Effect of Psychopharmacotherapy on Body Mass Index Among Children and Adolescents with Bipolar Disorders.

OBJECTIVE: To assess the long-term effect of all treatment options for pediatric bipolar disorders on body mass index (BMI) and to explore individual characteristics associated with less BMI increase during psychotropic medication exposures. METHODS: A retrospective cohort study was conducted by using the 1995 to 2010 General Electric Electronic Medical Record database. Individuals aged 18 years or younger who had a new bipolar disorder episode were identified. Treatment exposure was defined based on the medication regimens patients received, which include atypical antipsychotic (AT) monotherapy, mood stabilizer (MS) monotherapy, antidepressant (AD) monotherapy, AT+MS polytherapy, AT+AD polytherapy, MS+AD polytherapy, and no treatment. Both treatment exposure and BMI were coded as time varying, which could change from month to month. According to the duration of treatment and the availability of BMI measures, individuals were followed for up to 3, 6, 9, and 12 months since the treatment initiation. Repeated-measures mixed models were applied to compare the impact of different medication regimens and the length of drug exposure on BMI after adjusting for the baseline BMI, sociodemographic factors, comorbidities, and psychotherapy. RESULTS: A total of 2299 treated and 4544 untreated children and adolescents who met the inclusion criteria were identified. Analysis using repeated-measures mixed models showed that those on AT monotherapy (the reference group) had a gradually diminished, but statistically significant, monthly increase in BMI during all durations of drug exposure (3 months: 0.36 kg/m2, 6 months: 0.20 kg/m2, 9 months: 0.17 kg/m2, and 12 months: 0.16 kg/m2). As compared with AT monotherapy, the magnitude of increase in BMI associated with MS, AD monotherapy, and no treatment was significantly less at all time points, indicating less steep slopes of BMI change over time compared with AT monotherapy, especially during the short-term exposure. The combinations of AT with other psychotropic medications (ATMS, ATAD) were associated with a similar BMI increase as AT monotherapy. Individual characteristics found to be associated with a less increase in BMI during psychotropic medication exposure were being younger and having a higher baseline BMI. CONCLUSION: The long-term use of atypical antipsychotics, both as monotherapy or in combination with other psychotropic medications in children and adolescents with bipolar disorder, was associated with a steady and cumulative increase in BMI.

Care Provision and Prescribing Practices of Physicians Treating Children and Adolescents With ADHD.

OBJECTIVE: Care provision and prescribing practices of physicians treating children with attention-deficit hyperactivity disorder (ADHD) were compared. METHODS: A retrospective cohort study was conducted with the 1995-2010 General Electric Centricity Electronic Medical Record database. The sample included children (≤18 years) with newly diagnosed ADHD (ICD-9-CM code 314.XX) who received a prescription for a stimulant or atomoxetine. Identification of comorbid psychiatric disorders, duration from initial ADHD diagnosis to treatment, prescription of other psychotropic medications, and follow-up care during the ten months after the ADHD treatment initiation were compared across provider type (primary care physicians [PCPs], child psychiatrists, and physicians with an unknown specialty). The associations between provider type and practice variations were further determined by multivariate logistic regression accounting for patient demographic characteristics, region, insurance type, and prior mental health care utilizations. RESULTS: Of the 66,719 children identified, 75.8% were diagnosed by PCPs, 2.6% by child psychiatrists, and 21.6% by physicians whose specialty was unknown. Child psychiatrists were less likely than PCPs to initiate ADHD medication immediately after the diagnosis. However, once the ADHD treatment was initiated, they were more likely to prescribe psychotropic polytherapy even after analyses accounted for the comorbid psychiatric disorders identified. Only one-third of ADHD cases identified by both PCPs and child psychiatrists have met the HEDIS quality measure for ADHD medication-related follow-up visits. CONCLUSIONS: Differences were found by physician type in care of children with ADHD. Additional studies are needed to understand clinical consequences of these differences and the implications for care coordination across provider specialties.

The risk of febrile neutropenia and need for G-CSF primary prophylaxis with the docetaxel and cyclophosphamide regimen in early-stage breast cancer patients: a meta-analysis.

The febrile neutropenia (FN) rates reported with the docetaxel 75 mg/m(2) plus cyclophosphamide 600 mg/m(2) (TC) regimen given every 3 weeks vary from 4 to 69 % in early-stage breast cancer (ESBC) patients. This creates uncertainty as to whether patients receiving the TC regimen should also receive granulocyte colony-stimulating factor primary prophylaxis (G-CSFpp), which is recommended when chemotherapy regimens have ≥20 % FN rate. We conducted a meta-analysis of published studies to determine FN rate with the TC regimen, its dependence on patients' age, and the efficacy of G-CSFpp in reducing it in ESBC patients. We systematically searched the literature via PUBMED using the following terms: 'docetaxel', 'cyclophosphamide', 'febrile neutropenia', and 'breast cancer'. Inclusion criteria were full text peer-reviewed clinical studies in English reporting FN rates with TC regimen in relationship to G-CSFpp. Comprehensive meta-analysis software was used for all statistical analyses. Eight studies (N = 1542 patients) were included in our meta-analysis. The pooled mean FN rate was 23.2 % (95 % confidence interval (CI) 6.9-55.2 %; Q = 218.17, I (2) = 97.7). The FN risk in <65 years old patients was lower by 67.7 % compared to that in patients ≥65 years old (pooled odds ratio (OR) 0.323; 95 % CI 0.127-0.820; P = 0.017). The FN risk was reduced by 92.3 % with G-CSFpp (pooled OR 0.077; 95 % CI 0.013-0.460; P = 0.005). Our meta-analysis demonstrated that TC regimen was associated with ≥20 % FN risk, which was significantly higher in patients ≥65 years old and improved with G-CSFpp. G-CSFpp should be considered for all ESBC patients receiving TC regimen, especially those ≥65 years old.