Prevalence Of Pts Research Articles

Incidence of second primary malignancies (SPMs) in patients with multiple myeloma (MM) receiving anti-CD38 monoclonal antibodies (mAbs): A systematic review and meta-analysis.

e24078 Background: The addition of anti-CD38 mAbs, daratumumab and isatuximab, to standard anti-myeloma regimens have drawn scrutiny towards long-term safety concerns, including the risk of SPMs. ICARIA-MM study reported SPMs in 3.9% patients (pts.) in the Isatuximab, pomalidomide and dexamethasone (Isa-Pd) arm compared to 0.7% in the Pd arm. We hypothesized that exposure to anti-CD38 mAbs could potentially increase risk of SPMs due to prolonged immunosuppression. An assessment of this association is warranted, given the improved life expectancy and growing prevalence of pts. with MM. Methods: We performed a meta-analysis on data obtained from RCTs published between January 2005 and April 2022 that compared anti-CD38 mAb-based regimens to other standard anti-myeloma regimens (control) in pts. with newly diagnosed or relapsed/refractory (r/r) MM. Total number of SPMs (including categories) were extracted for pts. in both groups. Malignant melanomas were included under solid SPM category. Binary outcome data were analyzed using fixed-effect Peto method. Treatment effect estimates were expressed as odds ratio (OR) and 95% confidence interval (CI). I2 > 50% indicated substantial heterogeneity. Results: 10 RCTs involving 4980 pts. were included, with 2824 (57%) and 2156 (43%) pts. randomized to the anti-CD38 mAb and control arms, respectively (Table). Overall, 191 and 112 SPMs were reported in the anti-CD38 mAb and control arms, respectively. At a median follow-up of 35.3 months, anti-CD38 mAb exposure was associated with an increased risk of developing SPMs compared to control (6.8% vs. 5.2%; OR: 1.53 [95% CI: 1.20-1.95]; I2= 0%). Non-melanoma cutaneous cancers were the most common, and higher in the anti-CD38 mAb vs. control arms (92 versus 47; OR: 1.77 [95% CI: 1.25-2.51]; I2= 0%). The increase in solid cancers (including melanoma) (OR: 1.28 [95% CI: 0.85-1.95]) and hematologic SPMs (OR: 1.86; [95% CI: 0.81-4.27] was not significant. On sensitivity analysis, the total number of SPMs were higher in the anti-CD38 mAb arm vs. control arm, regardless of the presence of immunomodulatory drugs in combination regimen. Conclusions: This meta-analysis shows an increased risk of SPMs in pts. with MM exposed to daratumumab or isatuximab, particularly that of non-invasive cutaneous tumors. This association should be further investigated in real-world settings using large databases. [Table: see text]

Strategic management to optimize response to cardiac resynchronization therapy registry

Abstract Background Cardiac resynchronization therapy (CRT) is guideline-recommended for the treatment of symptomatic heart failure (HF) in patients (pts) with reduced LVEF and prolonged QRS. Clinical trials report Clinical Composite Score (CCS) response rates from 60 to 75%. However, patients with common comorbidities, such as atrial fibrillation, are often under-represented in clinical trials. The Strategic MAnagement to optimize response to cardiac Resynchronization Therapy (SMART) Registry (NCT03075215) was designed to examine outcomes in CRT patients in the real world. Methods The SMART Registry was a global, multicenter, prospective, clinical registry that enrolled subjects undergoing a de novo CRT-D implant or upgrade from pacemaker to CRT-D using a quadripolar LV lead. CCS was assessed at 12 months post-implant. Results For study design and CCS outcomes see Figure 1. CCS at 12 months showed that 58.8% of pts improved and 20.1% stabilized. Of the 21.1% of pts that worsened, 8.4% were due to death, 7.8% non-fatal heart failure event, and 5% worsening of NYHA or patient global assessment. Notably, this registry had a high prevalence of pts with NYHA I/II (51%), Non-LBBB (50%), AF (37%), diabetes (35%), and bradycardia (31%) at baseline. Age (>65), diabetes, ischemia, non-LBBB, atrial fibrillation (AF) and renal dysfunction correlated with worsened CCS outcomes. NYHA III/IV patients had significantly higher HF hospitalization (HFH) rates than NYHA I/II (P-value <0.001) (Figure 2a) and patients with AF had higher HFH rates than those without (P-value <0.001) (Figure 2b). Similar effects of NYHA score and AF were seen on mortality. The use of ACE/ARB, or ARNI, and MRA correlated with better outcomes, whereas diuretics and anticoagulants correlated with poorer outcomes. Conclusions In this large registry, clinical outcomes across important sub-populations are in line with expectations, with older age, ischemia, renal dysfunction, AF, non-LBBB, and diabetes associated with a lower likelihood of response to CRT. By including these patients, this study provides a clearer picture of the effectiveness of CRT in the real world. Future studies should examine optimization approaches to facilitate CRT effectiveness in these under studied patient populations. Funding Acknowledgement Type of funding sources: Private company. Main funding source(s): This registry was funded by Boston Scientific (BSC)

Postthrombotic syndrome and quality of life after deep vein thrombosis in patients treated with edoxaban versus warfarin

BackgroundPostthrombotic syndrome (PTS) is a long‐term complication after deep vein thrombosis (DVT) and can affect quality of life (QoL). Pathogenesis is not fully understood but inadequate anticoagulant therapy with vitamin K antagonists is a known risk factor for the development of PTS. ObjectivesTo compare the prevalence of PTS after acute DVT and the long‐term QoL following DVT between patients treated with edoxaban or warfarin. MethodsWe performed a long‐term follow‐up study in a subset of patients with DVT who participated in the Hokusai‐VTE trial between 2010 and 2012 (NCT00986154). Primary outcome was the prevalence of PTS, defined by the Villalta score. The secondary outcome was QoL, assessed by validated disease‐specific (VEINES‐QOL) and generic health‐related (SF‐36) questionnaires. ResultsBetween 2017 and 2020, 316 patients were enrolled in 26 centers in eight countries, of which 168 (53%) patients had been assigned to edoxaban and 148 (47%) to warfarin during the Hokusai‐VTE trial. Clinical, demographic, and thrombus‐specific characteristics were comparable for both groups. Mean (SD) time since randomization in the Hokusai‐VTE trial was 7.0 (1.0) years. PTS was diagnosed in 85 (51%) patients treated with edoxaban and 62 (42%) patients treated with warfarin (adjusted odds ratio 1.6, 95% CI 1.0–2.6). Mean differences in QoL scores between treatment groups were not clinically relevant. ConclusionContrary to our hypothesis, the prevalence of PTS tended to be higher in patients treated with edoxaban compared with warfarin. No differences in QoL were observed. Further research is warranted to unravel the role of anticoagulant therapy on development of PTS.

Abstract 437: Comprehensive genomic profiling (CGP) in breast cancer (BC): Patterns and results from a clinico-genomic database

Abstract Genomic testing is an important part of personalized oncology. This study explored testing patterns and results, as well as patient (pt) characteristics, in the BC setting. Data from the nationwide, de-identified Flatiron Health (FH)-Foundation Medicine, Inc. (FMI) BC clinico-genomic database were included; pts had to have been treated in a FH network oncology practice and tested with a FMI CGP test. Pts were >18 years old and had a primary or metastatic BC (mBC) diagnosis between 1/1/2011 and 3/30/2020. Only pts with solid-tumor tissue of origin and solid-tumor assay tests were considered; pts whose tests occurred >120 days after their last visit (based on report date) were excluded. Pt cohorts were classified by timing of test result receipt: cohort 1, between primary diagnosis and <60 days after primary surgery, or <120 days post-diagnosis if no surgery recorded; cohort 2, between 60 days post-primary surgery and 60 days prior to mBC diagnosis, or >120 days post-diagnosis if no surgery recorded; cohort 3a, within 60 days prior to/after mBC diagnosis; and cohort 3b, >60 days after mBC diagnosis. Pt characteristics and actionable mutations according to the FMI report only (associated with sensitivity or resistance to ≥1 therapy) were described by cohort and BC subtype, defined at primary diagnosis for cohorts 1/2 and at mBC diagnosis for cohorts 3a/3b. Pt characteristics were compared with those of the FH cohort (not tested with next-generation sequencing or received other next-generation sequencing tests). Overall, 4183 pts were included: 285 in cohort 1, 412 in cohort 2, and 3486 in cohorts 3a/3b. There was an overrepresentation of triple-negative BC (TNBC) among pts tested in the early setting (cohorts 1/2) vs the underlying population (33%/32% vs 10%), and an underrepresentation of hormone receptor (HR)-positive/HER2-negative BC (45%/48% vs 71%). TNBC remained overrepresented among pts tested at mBC diagnosis (cohort 3a; 30% vs 11%), but not during mBC follow-up (cohort 3b; 14% vs 11%), which followed the underlying FH distribution. The majority of patients were tested using samples collected within their respective test windows: 100% in cohort 1, 63% in cohort 2, and 78% and 46% in cohorts 3a/3b. For pts tested in the mBC setting, 22% and 15% in cohorts 3a and 3b, respectively, were tested using tissue collected >60 days prior to mBC diagnosis. Percentages of pts with at least one FMI-report-actionable alteration ranged from 94% (n = 601) in HER2-positive samples to 75% (n = 668) in pts with TNBC. Among this BC cohort, FMI-CGP predominantly occurred in the mBC setting, and use of archival tissue for CGP occurred in later lines of treatment. Testing, in particular prior to mBC diagnosis, reflected a disproportionately higher prevalence of pts with TNBC, potentially due to there being fewer satisfactory treatment options in this setting. The distribution of actionable alterations varied by HER2 and HR status. Citation Format: Achim Rody, Nayan Chaudhary, Christopher Craggs, Marcio Debiasi, Gilles Erb, Virginia Fisher, Margaret McCusker, Tamara Snow, Maria Vidal Losada, Patricia Luhn. Comprehensive genomic profiling (CGP) in breast cancer (BC): Patterns and results from a clinico-genomic database [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 437.

OP07.10: Artificial intelligence weights the importance of clinical and sonographic factors predicting nodal metastasis in endometrial cancer

To determine whether artificial intelligence might be useful in weighting the importance of clinical and sonographic (US) preoperative variables predicting the risk of lymph node metastases in patients (pts) undergoing surgery for endometrial cancer. Retrospective study evaluating the last 100 consecutive endometrial cancer pts undergoing US examination before surgery between 2017 and 2019 at National Cancer Institute of Milan. Using artificial neuronal network (ANN) analysis we estimated the importance of different variables predicting the risk of nodal involvement. Clinical, histological (at pre-operative endometrial biopsy) and US variables were evaluated. ANN simulates a biological neuronal system and similarly to neurons, ANN acquires knowledge through a learning-phase process allowing weighting the importance of covariates, thus establishing how much a variable influences a multifactorial phenomenon. The prevalence of pts diagnosed with nodal disease at surgical staging was 16%. Using ANN we observed that the three main US factors predicting nodal metastasis were: myometrial invasion at US (importance: 0.212), echogenicity of the tumour at US defined as uniform or not-uniform (importance: 0.131) and histology at pre-operative biopsy defined as endometrioid or not (importance: 0.099). Overall, 79% (79/100) of pts had endometrial endometrioid tumour detected at pre-operative biopsy; among this subgroup of pts the main factors predicting nodal spread were: myometrial invasion at US (importance 0.218), echogenicity of the tumour (importance 0.170) and cervical invasion at US (importance 0.147). According to our results, myometrial invasion at US and echogenicity of the tumour should be considered the most important factors predicting nodal involvement in endometrial cancer patients. These data are confirmed in the subgroup analysis of endometrioid tumours only. Further studies are needed to estimate the clinical utility of AI in providing help in decision-making processes. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.

Preventing complications: Hepatitis B screening in cancer patients undergoing systemic therapy.

237 Background: Chemotherapy is a risk factor for HBV reactivation in pts with cancer and chronic HBV. Anti-viral prophylaxis can prevent reactivation but requires identification of infected pts. Many guidelines recommend universal HBV screening prior to cytotoxic/immunosuppressive-therapy, but lack of screening is common globally. A serious safety event and high prevalence of pts from HBV endemic regions receiving treatment at our institution led to a quality improvement project to increase HBV screening prior to chemotherapy. We aimed to increase HBV screening in pts starting systemic therapy at Princess Margaret by 100% by February 28, 2019. Methods: Starting April 2017, an interrupted time series study was undertaken. Baseline HBV screening rate was 43%. Diagnostics including interviews, process mapping and root cause analysis were performed. Interventions to address identified root causes were implemented including specifying required HBV tests, tips for ordering HBV tests, provision of electronic Hepatology referral form, a safety alert email, grand rounds presentation of serious safety event, including HBV screening rate in departmental monthly quality emails and Divisional meetings and adding positive HBV results to the laboratory alerting system. The main outcome measure was the proportion of pts starting systemic therapy screened for HBV. Process measures included correct test ordering, number of Hepatology referrals was a balancing measure. Results were analysed with statistical process control charts. Results: From April 2017-Feb 2019, 5604 pts commenced systemic therapy. Interventions were modified iteratively as the project progressed. HBV screening rate improved from 43 to 79% (84% improvement). Incidence of chronic HBV was routinely above the Canadian average ( > 2%). The percent of correctly ordered screening tests fell from 48 to 33% (31% worsening), while the volume of Hepatology referrals remained manageable (1.5 pts/week). Conclusions: Our Quality Improvement project led to a significant improvement in HBV screening prior to systemic therapy. Further interventions are planned to achieve our target improvement of 100%.

PB2221 OVEREXPRESSION OF PRV1 GENE IN MYELOID NEOLASMS AND ASSOCIATION WITH OTHER MOELCUALR ABNORMALITIES

Background:The polycythemia rubra vera 1 gene(PRV1) gene encodes a cell surface glycoprotein that plays a role in neutrophil activation and transmigration. PRV1 overexpression was found in significant proportion of patients(pts) with BCR‐ABL1‐negative myeloproloferative neoplasms(MPN). In the pre‐JAK2 mutation era testing of PRV1expression was recommented to differentiate polycythemia vera(PV) and essential thrombocytemia(ET) from secondary erythrocytosis or thombocytosis, respectively. The available data concerning the incidence of PRV1 overexpression, as well as its association with JAK2 gene mutation status is highly variable.Aims:To determine the incidence of PRV1 overexpression in different myeloid neoplasms and its association with other molecular abnormalities.Methods:Overall 167 pts with MPN were included in this study:43 with ET; 30 – PV; 15 ‐ primary myelofibrosis(PMF); 22 ‐ unspecified MPN(uPMN), 53 ‐ chronic myeloid leukemia(CML), including 18 pts at diagnosis and 35 pts on therapy with TKI; 4 pts with chronic myelomonocytic leukemia(CMML). PRV1 expression level was evaluated by reverse‐transcription polymerase chain reaction(RT‐PCR), with co‐amplification of b‐actin RNA as an internal control using total RNA from peripheral blood mononuclear cells. Semi‐quantitative characterization of PRV1 expression was done using 3grade score system: negative (‐): no product of PRV1 amplification; moderately elevated expression (+): PRV1 product with lower intensity than b‐actin product; strong overexpression(++): product of PRV1 amplification with intensity equivalent or higher than that of the b‐actin. To determine the association of PRV1 expression with JAK2 mutation status PRV1 expression was assessed in serial dilutions of homozygous JAK2V617F RNA in JAK2 wild type RNA. The PRV1 expression was clearly visible in up to 25% JAK2V617F mutation load. All pts were tested for the presence of BCR‐ABL1, JAK2V617F, and some cases for CALR and/or MPL W515L/K mutations.Results:Overall, PRV1 overexpression was found in 80.5% of pts with MPN (Table 1): 83.6%(n = 36) in ET; 93.3%(n = 28) in PV; 73.3%(n = 11) in PMF; 61.1%(n = 11) in CML(including 1 pt with co‐expression of BCR‐ABL1 and JAK2V617F); 95.5%(n = 21) in uMPN. PRV1 overexpression was significantly associated with JAK2V617F (+) status in BCR‐ABL1(‐) MPN with frequency of ranging between 73.3% and 95.5%. Interestingly, 3 JAK2V617F (‐) pts with PMF and PRV1 overexpression were found positive for CALR(n = 2) or MPL(n = 1) mutations.It was found higher prevalence of pts with strong overexpression PRV1(++) ‐ 67.9%(n = 19) in PV, 71.4%(n = 15) in uMPN, 77.8%(n = 7/9) in CML, with highest value in PMF ‐ 81.8%(n = 9). In contrast, in ET only 58.3%(n = 21) were PRV1(++). In CMML 1 pt was PRV1(++) and the second was PRV1(+). Strong PRV1 expression clearly correlated with JAK2V617F mutation load: PRV1(++) was found 24/28(85.7%) of homozygous pts, compared to 20/46 (43.5%) in heterozygous pts and 21/38 (55.3%) in JAK2 V617F(‐) pts. In CML pts on TKI therapy, PRV1 overexpression was found in 6/35 (17.1%) ‐ cases without any molecular response.Summary/Conclusion:PRV1 overexpression was found in a significant proportion of pts with BCR‐ABL1‐pos and BCR‐ABL1‐neg MPN, with highest frequency in PV and lowest in CML. Despite the clear association of PRV1 overexpression and JAK2V617F status, overexpression was also found in the absence of mutation suggesting alternative underlying mechanisms of activation of PRV1.image

Early incidence of immune-related adverse events (irAEs) predicts efficacy in patients (pts) with solid tumors treated with immune-checkpoint inhibitors (ICIs).

2563 Background: Treatment with ICIs can manifest immune-related adverse events (irAEs), which have correlated with clinical outcomes in certain tumors. However, timing of these events and how early irAEs correlate with outcomes is unclear. We assessed whether early occurring irAEs could predict survival in pts treated with durvalumab (D), an anti-PDL1 and combined with tremelimumab (D+T), an anti-CTLA4 in two clinical studies. Methods: Two phase 2 non-randomized clinical trials evaluating D (D4190C00001 (1108), N=756; available data per internal data re-use policy) or D+T (D4190C00010 (C10), N=327; expansion and ICI naïve cohorts) in multiple solid tumor types were analyzed. Prevalence of pts experiencing irAEs, regardless of grade was 30% and 59% in studies 1108 and C10, respectively, with most frequent including dermatitis/rash (25%), thyroid (15%), diarrhea/colitis (14%), and pancreatic enzyme elevation (5%). Overall survival (OS) was correlated with irAE timing prior to 6, 8, 12, 16, 20 and 24 weeks following D or D+T treatment. Kaplan Meier and log-rank analyses were used. Results: In both studies, pts who experienced at least one irAE by study completion had improved median OS (mOS, 1108: 23.1 mos [18.2, 26.9]; C10: 16.3 mos [12.5, 31.4]) relative to those who experienced none (1108: 6.3 mos [5.4, 7.3]; C10 4.6 mos [3.3, 6.1]). Median time (weeks) to first and second irAE occurred earlier in C10 compared to 1108, 3.9 vs. 5.6 and 6.9 vs. 10.1, respectively. When associating timing of irAEs with survival, there was a significant differential in mOS at each time interval evaluated between pts with at least one irAE and those with none, with differentiation at 6 weeks and maximal survival benefit at 24 weeks following treatment with D or D+T (Table). Conclusions: Early occurrence of irAEs may be predictive of survival benefit in pts treated with D or D+T. OS by 1+ or no irAE(s) occurring up to 6 or 24 weeks post treatment. [Table: see text]

Abstract P4-01-02: Prospective characterization of HER2-positive circulating tumor cells in patients with HER2-negative metastatic breast cancer

Abstract Background: We have previously shown feasibility by CLIA validation of HER2 FISH on circulating tumor cells (CTCs). Several small retrospective studies have identified HER2 amplification in CTCs in a subset of patients (pts) with clinically HER2 negative metastatic breast cancer (MBC). While these findings potentially have profound implications for CTCs as a predictive biomarker, prospective validation and functional characterization of this subgroup is necessary. Methods: We enrolled a prospective cohort of pts with MBC that was HER2 negative by IHC and/or FISH on all available primary and metastatic biopsies. Pts had ≥1 line of prior chemotherapy for MBC. Blood samples were collected at study entry. CTCs were enumerated based on standard criteria (Cytokeratin (CK)+/CD45- staining) as well as by FISH for HER2 using the OncoCEE-BR™ CTC test (Biocept, Incorporated). This test employs a proprietary antibody cocktail for capture followed by CK/CD45 staining, and FISH analysis directly within a microfluidic device. Samples were reported as positive if the HER2/CEP17 ratio was ≥ 2.0. HER2+ CTCs were classified into two categories: CK+/CD45-/HER2+ and CK-/CD45-/HER2- Results: CTCs were observed in 208 out of 323 pts (64%). Median number of CTCs was 10 (range 1 to > 34195). 75 pts (23%) had HER2+ CTCs, with a median number of 3 HER2+ CTCs (range 1 to 21). 36% (27/75) of these pts had CK+/HER2+ CTCs and 43% (32/75) of pts had only CK-/HER2+ CTCs. The remaining pts (21%) had both CK+/HER2+ and CK-/HER2+ CTCs present. Conclusion: HER2 amplified CTCs are present in a subset (23%) of pts with clinically HER2-negative breast cancers. Interestingly, we observed a high prevalence of pts with only CK-/HER2 amplified CTCs (32 out of 323; 10%). The unique multi-antibody CTC capture method used here thus allows for detection of a prevalent population of CK-/HER2+ CTCs that may be largely undetected by other current adopted technologies. The functional significance of CK-/HER2+ and CK+/HER2+ CTCs in patients with clinically HER2 negative breast cancer is currently being evaluated in a prospective study with HER2-directed therapy. Citation Format: Ian E Krop, Erin Macrae, Sarah R Galler, Farideh Bischoff, Romeo Fauni, Edgar Sales, Lan Huynh, Christine Mitchell, Trisky Clarin-Tamayo, Mark Anderson, Leslie Abad, Eric Winer. Prospective characterization of HER2-positive circulating tumor cells in patients with HER2-negative metastatic breast cancer [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P4-01-02.

Prévention secondaire après syndrome coronarien aigu : évolution des recommandations et niveaux d’atteinte des objectifs

Background Secondary prevention is a key strategy for reducing levels of coronary heart disease, but a gap between guidelines and practice remains. Objectives The aim of this double-part survey was to evaluate the improvement in secondary prevention one year after acute coronary syndrome (ACS) in real life, between 1999 and 2005, with respect to the change in guidelines. Methods Two surveys of almost similar design were performed in 1999 and 2005–2006. In each survey, unselected consecutive patients suffering from ACS ( n = 112 hospitalized in 1998, and n = 110 in 2004) were evaluated at admission, and one year after hospitalization, for the risk factors, lifestyle, and achievement of therapeutic goals recommended by the most recent guidelines. Follow-up (FU) data were obtained by mail and phone contact with patient, general practitioner and cardiologist, and medical laboratory when appropriate. Results At 1-year FU ( n = 192 survivors with FU), smoking cessation (87% in 1999 versus 89% in 2005) and obesity (13% versus 19%, respectively) did not vary significantly. Blood pressure was controlled (< 140/90 mmHg, excepted in diabetics in 2005 with less than 130/80 mmHg) in 65% versus 80% ( p < 0.03). The rate of patients with no or controlled diabetes mellitus decreased from 1999 to 2005 (90% versus 76%), despite more intensive treatment (insuline in 1% versus 20%).The goals for LDL cholesterol were achieved in 47% of patients in 1999 (< 3.4 mmol/L) and in 76% in 2005 (< 2.6 mmol/L) ( p < 0.0001). Goals for triglycerides were achieved in 86% in 1999 (< 2 g/L), and in 80% in 2005 (< 1.5 g/L) (NS). Besides, 63% of patients received an hypolipemic drug in 1999 (a statin in 59%) and 91% in 2005 (a statin in 88%). Mean number of controlled risk factors was 3.96 ± 1.52 in 1999 versus 4.94 ± 1.83 in 2005, and prevalence of pts with more than five controlled risk factors at one year FU increased from 15 to 44% ( p < 0.0001). Conclusions These results, drawn from unselected consecutive patients managed in real life, demonstrate an improvement in secondary prevention one year after ACS, between 1999 and 2005, despite strengthened guidelines for blood pressure, triglycerides and LDL cholesterol levels. Control of obesity and diabetes remains unoptimal.