Nomogram predictive models for adult patients with acute lymphoblastic leukaemia based on real-world treatment outcomes.

This study aimed to analyse the characteristics and treatment outcomes of adult patients with acute lymphoblastic leukaemia (ALL) and construct nomogram predictive models for prognosis prediction. Between January 2017 and June 2022, 462 adult patients with ALL were included in this retrospective analysis. Patients' ages ranged from 14 to 84 years. B-cell origin was observed in 82.7% of these patients, while 17.3% of the cases were of T-cell origin. The BCR/ABL1 fusion gene was detected in 32.9% of those with B-ALL. Complete remission was achieved in 83.7% of the patients after induction chemotherapy. The median disease-free survival (DFS) and overall survival (OS) of patients were 19.0 and 39.1 months, respectively. The 5-year DFS and OS rates were 29.5% and 41.8%, respectively. The BCR/ABL1 fusion gene had a significant adverse impact on DFS and OS when patients were treated with tyrosine kinase inhibitors (TKIs) and chemotherapy; however, this effect was eliminated when patients underwent transplantation. Multivariate analysis identified that age ≥ 35 years, white blood cell count ≥ 30 × 109/L, platelet count < 100 × 109/L, failure to achieve complete remission after induction chemotherapy, positive measurable residual disease (MRD), and absence of transplantation were independent adverse prognostic factors for DFS and/or OS. Nomogram predictive models constructed by the rms package in R software based on these prognostic factors demonstrated precise predictive value. In conclusion, adult patients with ALL experience poor survival. TKIs in combination with transplantation can eliminate the adverse effects of BCR/ABL1 fusion genes on prognosis. Nomogram predictive models were accurate for prognostic prediction and will be useful in clinical practice.

Efficacy and Safety of Belimumab in Patients With Lupus Nephritis: Subgroup Analyses of a Phase 3 Randomized Trial in the East Asian Population.

RATIONALE & OBJECTIVE: Belimumab improved kidney outcomes in patients with active lupus nephritis (LN) in BLISS-LN, leading to its approval in the United States and the European Union. As data on treatment of East Asian patients with LN are limited, we evaluated the efficacy and safety of belimumab in the BLISS-LN East Asian subgroup. STUDY DESIGN: Prespecified subgroup analysis of BLISS-LN, a phase 3, placebo-controlled, randomized 104-week trial. SETTING & PARTICIPANTS: Adults with biopsy-proven, active LN were randomized (1:1) to belimumab or placebo, plus standard therapy. INTERVENTION: Patients were administered intravenous belimumab 10mg/kg, or placebo, plus standard therapy (oral glucocorticoids and either cyclophosphamide for induction followed by azathioprine for maintenance, or mycophenolate mofetil for both induction and maintenance). At the investigator's discretion, 1-3 intravenous pulses of methylprednisolone, 500-1,000mg each, could be administered during induction. OUTCOMES: The primary end point was primary efficacy renal response (PERR; ie, urinary protein-creatinine ratio≤0.7g/g, estimated glomerular filtration rate no more than 20% below preflare value or≥60mL/min/1.73m2, and no treatment failure) at week 104. Key secondary end points included complete renal response (CRR; urinary protein-creatinine ratio<0.5g/g, estimated glomerular filtration rate no more than 10% below preflare value or≥90mL/min/1.73m2, and no treatment failure) at week 104; PERR at week 52; time to kidney-related event or death; and safety. ANALYTICAL APPROACH: PERR and CRR were analyzed using a logistic regression model, and time to a kidney-related event or death was analyzed using a Cox proportional hazards regression model. RESULTS: 142 patients from mainland China, Hong Kong, South Korea, and Taiwan were included (belimumab, n=74; placebo, n=68). At week 104, more belimumab than placebo patients achieved PERR (53% vs 37%; OR, 1.76 [95% CI, 0.88-3.51]) and CRR (35% vs 25%; OR, 1.73 [95% CI, 0.80-3.74]). At week 52, more belimumab than placebo patients achieved PERR (62% vs 37%; OR, 2.74 [95% CI, 1.33-5.64]). Belimumab reduced the risk of a kidney-related event or death compared with placebo at any time (HR, 0.37 [95% CI, 0.15-0.91]). Safety was similar across treatment groups. LIMITATIONS: Small sample size and lack of formal significance testing. CONCLUSIONS: Safety and efficacy profiles were consistent with BLISS-LN overall population, supporting benefits of belimumab treatment in the East Asian subgroup with LN. FUNDING: This study was funded by GSK (GSK study no. BEL114054). TRIAL REGISTRATION: Registered at ClinicalTrials.gov with study number NCT01639339.

Interim Analysis of Pregnancy Outcomes After Exposure to Dimethyl Fumarate in a Prospective International Registry.

BACKGROUND AND OBJECTIVES: Oral delayed-release dimethyl fumarate (DMF) is not recommended during pregnancy and should only be used if the potential benefit justifies the potential fetal risk. Although DMF was well tolerated in clinical trials with consistent safety results in postmarketing surveillance, data are limited in pregnant women. The objective was to provide pregnancy outcomes and DMF exposure information from an interim analysis from a prospective, international registry (TecGistry; NCT01911767). METHODS: Women exposed to DMF from the first day of their last menstrual period before conception or during pregnancy were evaluated. Data were obtained at enrollment; 6-7 months' gestation; 4 weeks after estimated due date; and 4, 12, and 52 weeks after birth. Outcomes included live births, gestational size, pregnancy loss, birth defects, and infant or maternal death after delivery. Outcomes were analyzed cumulatively from October 30, 2013 (the start of TecGistry), to April 8, 2020. RESULTS: Of 345 enrolled patients, median (range) age was 32 (20-43) years. The mean (SD) duration of gestational weeks of DMF exposure was 4.9 (3.8). Most infants were full-term at birth (n = 249/274; 91%) and of average gestational size (n = 190/232; 82%). Of 351 outcomes, 277 were live births; 17 (5%) spontaneous abortions (95% confidence interval [CI] 2.6%-7.1%), including 1 (<1%) molar and 1 (<1%) ectopic pregnancy, were reported. There were 8 (2.9% [95% CI 1.3%-5.6%]) adjudicator-confirmed birth defects among the 277 live births. DISCUSSION: Interim results from this large registry indicate that early DMF exposure was not significantly associated with adverse pregnancy outcomes. Outcomes are consistent with previous smaller reports and with the general population. TRIAL REGISTRATION INFORMATION: TecGistry; clinical trial registration number: NCT01911767.

Focal segmental glomerulosclerosis, excluding atypical lesion, is a predictor of renal outcome in patients with membranous nephropathy: a retrospective analysis of 716 cases.

BACKGROUND: Focal segmental lesions (FSLs) are not uncommon in idiopathic membranous nephropathy (IMN). The reported percentage of IMN patients with focal segmental glomerulosclerosis (FSGS) lesions varies widely between studies. The objective of this study was to differentiate atypical FSL (aFSL) from typical FSGS in IMN and to analyse the clinicopathological predictors of primary outcome of IMN patients. METHODS: A total of 716 patients with biopsy-proven IMN between January 1, 2007 and December 31, 2017 were enrolled in the study. An atypical focal segmental lesion was defined as pure synechia, segmental hyperplasia of podocytes or thickening of the GBM accompanied by proliferation of the mesangial matrix, and absence of typical FSGS. The patients were divided into three groups: patients without FSL (FSL-), patients with typical FSGS (FSGS+), and patients with aFSL (aFSL+).The primary outcome was a 50% decline in the initial estimated glomerular filtration rate or end-stage renal disease (ESRD) incidence. Secondary outcomes included all-cause death and ESRD. RESULTS: FSGS was present in 174 patients, while aFSL was noted in 161 patients. Systolic blood pressure was higher in both aFSL+ group and FSGS+ groups compared with the FSL- group. IMN patients without FSL and with aFSL had lower serum creatinine levels than IMN patients with FSGS. Both the FSGS+ and aFSL+ groups had higher levels of proteinuria and lower albumin levels than the FSL- group. Renal tissue lesions, including tubulointerstitial fibrosis, glomerular obsolescence, and vascular sclerosis were significantly more severe in the FSGS+ group. Cox multivariate analysis showed that older age ≥ 60 years, eGFR< 60 ml/(min·1.73m2), tubulointerstitial fibrosis area ≥ 15% and FSGS at biopsy were independent risk factors for the primary outcome. CONCLUSIONS: No significant difference in outcome was found between the FSL- and aFSL+ groups, although the patients with aFSL had lower levels of serum albumin and eGFR, higher level of urinary protein, more severe renal lesions with proliferation of the mesangial area,tubulointerstitial fibrosis and vascular sclerosis. FSGS, excluding atypical lesions, was an independent predictor of the primary outcome.

Roxadustat for Anemia in Patients with Kidney Disease Not Receiving Dialysis.

BACKGROUND: Roxadustat (FG-4592) is an oral inhibitor of hypoxia-inducible factor (HIF) prolyl hydroxylase that stimulates erythropoiesis and regulates iron metabolism. In phase 2 studies involving patients with chronic kidney disease, roxadustat increased levels of endogenous erythropoietin to within or near the physiologic range, along with increasing hemoglobin levels and improving iron homeostasis. Additional data are needed regarding the efficacy and safety of roxadustat for the treatment of anemia in patients with chronic kidney disease who are not undergoing dialysis. METHODS: In this phase 3 trial conducted at 29 sites in China, we randomly assigned 154 patients with chronic kidney disease in a 2:1 ratio to receive roxadustat or placebo three times a week for 8 weeks in a double-blind manner. All the patients had a hemoglobin level of 7.0 to 10.0 g per deciliter at baseline. The randomized phase of the trial was followed by an 18-week open-label period in which all the patients received roxadustat; parenteral iron was withheld. The primary end point was the mean change from baseline in the hemoglobin level, averaged over weeks 7 through 9. RESULTS: During the primary-analysis period, the mean (±SD) change from baseline in the hemoglobin level was an increase of 1.9±1.2 g per deciliter in the roxadustat group and a decrease of 0.4±0.8 g per deciliter in the placebo group (P<0.001). The mean reduction from baseline in the hepcidin level (associated with greater iron availability) was 56.14±63.40 ng per milliliter in the roxadustat group and 15.10±48.06 ng per milliliter in the placebo group. The reduction from baseline in the total cholesterol level was 40.6 mg per deciliter in the roxadustat group and 7.7 mg per deciliter in the placebo group. Hyperkalemia and metabolic acidosis occurred more frequently in the roxadustat group than in the placebo group. The efficacy of roxadustat in hemoglobin correction and maintenance was maintained during the 18-week open-label period. CONCLUSIONS: In Chinese patients with chronic kidney disease who were not undergoing dialysis, those in the roxadustat group had a higher mean hemoglobin level than those in the placebo group after 8 weeks. During the 18-week open-label phase of the trial, roxadustat was associated with continued efficacy. (Funded by FibroGen and FibroGen [China] Medical Technology Development; ClinicalTrials.gov number, NCT02652819.).

miR-142-3p suppresses uveal melanoma by targeting CDC25C, TGFßR1, GNAQ, WASL, and RAC1.

Purpose: Uveal melanoma (UM) is the most frequent metastatic ocular tumor in adults. Therapeutic intervention remains ineffective since none of the novel procedures used to treat this disease increased survival rates. To deal with this limitation, additional studies are required to clarify its pathogenesis. The current study focused on describing how epigenetic modulation by miR-142-3p affects changes in some cellular functions underlying UM pathogenesis. Methods and results: Microarray analysis identified 374 miRNAs which were differentially expressed between UM cells and uveal melanocytes. miR-142-3p was one of the 10 most downregulated miRNAs. Quantitative RT-PCR analysis confirmed that miR-142-3p expression levels were significantly decreased in both UM cell lines and clinical specimens. The results of the MTS, clone formation, scratch wound, transwell assays, and in vivo biofluorescence imaging showed that miR-142-3p overexpression significantly inhibited cell proliferation, migration, and invasiveness. Nevertheless, miR-142-3p did not affect cell apoptotic activity or sensitivity to doxorubicin. Cell cycle and EdU analysis showed that miR-142-3p overexpression induced G1/G2 cell cycle arrest and reduced DNA synthesis in UM cells. Microarray analysis showed that miR-142-3p mainly regulates the TGFß signaling pathway, and those in which MAPK and PI3K-Akt are constituents. Functional interactions between miR-142-3p and CDC25C, TGFßR1, GNAQ, WASL, and RAC1 target genes were confirmed based on the results of the luciferase reporter assay and Western blot analysis. CDC25C or RAC1 downregulation is in agreement with cell cycle arrest and DNA synthesis disorder induction, while downregulation of TGFßR1, GNAQ, WASL, or RAC1 accounts for declines in cell migration. Conclusion: miR-143-3p is a potential therapeutic target to treat UM since overriding its declines in expression that occur in this disease reversed the pathogenesis of this disease. Such insight reveals novel biomarker for decreasing UM vitality and for improved tracking of tumor progression.

Effect of norcantharidin on the proliferation, apoptosis, and cell cycle of human mesangial cells.

AIMS: Norcantharidin (NCTD) regulates immune system function and reduces proteinuria. We sought to investigate the effect of NCTD on proliferation, apoptosis and cell cycle of cultured human mesangial cells (HMC) in vitro. METHODS: HMC cells were divided into a normal control group, and various concentrations of NCTD group (2.5, 5, 10, 20, or 40 µg/mL). Cell proliferation was determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, apoptosis was detected by Annexin V/propidium iodide (PI) assays, and morphological analysis was performed by Hoechest 33258 staining. Finally, cell cycle was analyzed by flow cytometry. RESULTS: NCTD dose and time dependently inhibits HMC proliferation significantly (p < .05). Apoptosis dose and time dependently increased after NCTD treatment. Cell-cycle analysis revealed that the number of cells in the G2 phase increased significantly, whereas the fraction of cells in the S phase decreased, especially 24 h after 5 µg/ml NCTD treatment. CONCLUSION: NCTD inhibits HMC cell proliferation, induces apoptosis, and affects the cell cycle.

Demographic and Clinical Profiles of Type 2 Diabetes Mellitus Patients Initiating Canagliflozin Versus DPP-4 Inhibitors in a Large U.S. Managed Care Population.

BACKGROUND: Canagliflozin is the first sodium-glucose co-transporter-2 (SGLT-2) inhibitor-a new class of oral antidiabetic (OAD) medication-approved for type 2 diabetes mellitus (T2DM) treatment in the United States. Approved less than 2 years ago, use of canagliflozin is largely uncharacterized. OBJECTIVE: To investigate and compare baseline demographic, clinical, and economic characteristics of patients initiating canagliflozin and dipeptidyl peptidase-4 (DPP-4) inhibitors in the real-world setting. METHODS: Using administrative claims data from a large, geographically diverse U.S. managed care organization, this retrospective study assessed adult T2DM patients (aged ≥ 18 years) initiating treatment with canagli-flozin or DPP-4 agents. Eligible patients had ≥1 medical claim with a T2DM diagnosis and ≥ 1 outpatient pharmacy claim for canagliflozin or a DPP-4 agent between January 1, 2011, and September 30, 2013. Patients with ≥ 1 canagliflozin fill were selected first and assigned to the canagliflozin cohort following a hierarchical approach; the date of the earliest canagliflozin fill was defined as the index date. Remaining patients with DPP-4 fills were then assigned to the DPP-4 cohort, with the index date as the first DPP-4 fill. Only patients with at least 12 months of pre-index (baseline) enrollment were included. Patients with fills for their cohort-defining drug over 3 months before the index date were excluded in order to focus on new initiators. A subset of patients with ≥ 3 months of continuous enrollment following their index dates was used to examine medication patterns after initiation. Patients with hyperglycemia; type 1, gestational, or nonclinical diabetes; or diabetes with hyperosmolar coma were excluded. Demographic, clinical, and economic characteristics were assessed over baseline and compared using two-sample t-tests or chi-square/Fisher's exact tests. Multivariable logistic regression models were built to assess baseline factors associated with initiation of canagliflozin versus DPP-4. RESULTS: Overall, 1,566 patients initiated canagliflozin, and 26,224 patients initiated DPP-4 treatment. Males constituted slightly more than 60% of each treatment group; mean age was approximately 55 years in each cohort. A significantly smaller proportion of canagliflozin patients (41.3%) initiated treatment with endocrinologists compared with DPP-4 patients (69.2%, P less than 0.001), and canagliflozin patients were more likely (29.4%) to initiate treatment with a primary care physician compared with DPP-4 patients (9.9%, P less than 0.001). Comorbidities were present more frequently in canagliflozin initiators: nephropathy (10.6% vs. 7.0%), retinopathy (10.4% vs. 7.5%), dyslipidemia (82.4% vs. 72.2%), and obesity (24.9% vs. 15.6%), respectively (P less than 0.001 for all comparisons). The mean (SD) Quan-Charlson Comorbidity Index score was greater for canagliflozin, 1.05 (1.7), compared with DPP-4 initiators, 0.92 (1.6), P = 0.002. Among the subset of patients with available hemoglobin A1c (A1c) results, a significantly smaller proportion of canagliflozin initiators (16.5%) versus DPP-4 initiators (26.7%) were at the A1c less than 7% treatment goal at baseline (P less than 0.001). Among patients with 3 months follow-up, 89.2% of canagliflozin and 75.1% of DPP-4 initiators had ≥ 1 fill for their index drugs over this time frame. Canagliflozin initiators had significantly greater baseline utilization of office visits, endocrinologist and outpatient services, and more prescription fills. Total diabetes-related medical costs at baseline ($3,025 vs. $3,477 for canagliflozin and DPP-4 initiators) were not significantly different, while mean diabetes-related pharmacy costs were higher in the canagliflozin group ($4,037 vs. $1,411, P less than 0.001). Regression analysis indicated that baseline insulin and glucagon-like peptide-1 use, as well as comorbid dyslipidemia and obesity, were significantly associated with the initiation of canagliflozin versus DPP-4 agents. CONCLUSIONS: In this sample of commercially insured patients within a large managed care plan, canagliflozin was often initiated as second- or third-line therapy, with a relatively high share of patients receiving concomitant antidiabetic injectables, compared with DPP-4 initiators. Canagliflozin initiators had highly elevated A1c levels and were frequently diagnosed with other metabolic conditions. Baseline pharmacy utilization and costs were higher among canagliflozin patients. Future research is needed to assess real-world clinical outcomes after canagliflozin initiation, while taking these baseline differences into account.

Long-term evaluation of opioid treatment in fibromyalgia.

OBJECTIVES: In a 12-month observational study, we evaluated the effect of opioid use on the outcomes in 1700 adult patients with fibromyalgia. METHODS: Data were evaluated using propensity score matching after patients were divided into cohorts based on their baseline medication use: (1) taking an opioid (concurrent use of tramadol was permitted); (2) taking tramadol (but no opioids); and (3) not taking opioids or tramadol. Changes in outcomes were assessed using the Brief Pain Inventory for severity and pain-related interference (BPI-S, BPI-I), Fibromyalgia Impact Questionnaire (FIQ), Patient Health Questionnaire for depression (PHQ-8), Insomnia Severity Index (ISI), Sheehan Disability Scale (SDS), 7-item Generalized Anxiety Disorder Scale (GAD-7), and economic factors. Time-to-opioid or tramadol discontinuation was analyzed using Kaplan-Meier survival analyses. RESULTS: Compared with the opioid cohort, the nonopioid cohort demonstrated significantly greater reductions (P<0.05) in BPI-I, FIQ, PHQ-8, SDS, and ISI; the tramadol cohort compared with the opioid group showed greater reductions on FIQ and ISI. Reductions in BPI-S and GAD-7 did not differ significantly among cohorts. Compared with the opioid cohort, patients in the tramadol cohort had fewer outpatient visits to health care providers. Few significant differences were found between the tramadol and nonopioid cohorts across outcomes. DISCUSSION: Although pain severity was reduced over time in all cohorts, opioid users showed less improvement in pain-related interference with daily living, functioning, depression, and insomnia. Overall, the findings show little support for the long-term use of opioid medications in patients with fibromyalgia given the poorer outcomes across multiple assessment domains associated with this cohort.

Direct medical costs and medication compliance among fibromyalgia patients: duloxetine initiators vs. pregabalin initiators.

OBJECTIVES: To assess and compare direct medical costs and medication compliance between patients with fibromyalgia who initiated duloxetine and patients with fibromyalgia who initiated pregabalin in 2008. METHODS: A retrospective cohort study design was used based on a large US national commercial claims database (2006 to 2009). Patients with fibromyalgia aged 18 to 64 who initiated duloxetine or pregabalin in 2008 and who had continuous health insurance 1 year preceding and 1 year following the initiation were selected into duloxetine cohort or pregabalin cohort based on their initiated agent. Medication compliance was measured by total supply days, medication possession ratio (MPR), and proportion of patients with MPR ≥ 0.8. Direct medical costs were measured by annual costs per patient and compared between the cohorts in the year following the initiation. Propensity score stratification and bootstrapping methods were used to adjust for distribution bias, as well as cross-cohort differences in demographic, clinical and economic characteristics, and medication history prior to the initiation. RESULTS: Both the duloxetine (n = 3,033) and pregabalin (n = 4,838) cohorts had a mean initiation age around 49 years, 89% were women. During the postindex year, compared to the pregabalin cohort, the duloxetine cohort had higher totally annual supply days (273.5 vs. 176.6, P < 0.05), higher MPR (0.7 vs. 0.5, P < 0.05), and more patients with MPR ≥ 0.8 (45.1% vs. 29.4%, P < 0.05). Further, relative to pregabalin cohort, duloxetine cohort had lower inpatient costs ($2,994.9 vs. $4,949.6, P < 0.05), lower outpatient costs ($8,259.6 vs. $10,312.2, P < 0.05), similar medication costs ($5,214.6 vs. $5,290.8, P > 0.05), and lower total medical costs ($16,469.1 vs. $20,552.6, P < 0.05) in the postinitiation year. CONCLUSIONS: In a real-world setting, patients with fibromyalgia who initiated duloxetine in 2008 had better medication compliance and consumed less inpatient, outpatient, and total medical costs than those who initiated pregabalin.

Longitudinal observation of treatment patterns and outcomes for patients with fibromyalgia: 12-month findings from the reflections study.

OBJECTIVE: To describe 12-month treatment patterns and outcomes for patients starting a new medication for fibromyalgia in routine clinical practice. DESIGN AND OUTCOME MEASURES: Data from 1,700 patients were collected at baseline and 1, 3, 6, and 12 months. Repeated measures and Poisson regression models controlling for demographic, clinical, and baseline outcomes were used to assess changes in health outcomes (Brief Pain Inventory severity and interference, Sheehan Disability Scale, Fibromyalgia Impact Questionnaire), satisfaction, and economic factors for patients who initiated on pregabalin (214, 12.6%), duloxetine (264, 15.5%), milnacipran (134, 7.9%), or tricyclic antidepressants (66, 3.9%). Sensitivity analyses were run using propensity-matched cohorts. RESULTS: Patients started on 145 unique drugs for fibromyalgia, and over 75% of patients took two or more medications concurrently for fibromyalgia at each time point assessed. Overall, patients showed improvement on the four health outcomes, with few differences across medication cohorts. At baseline, patients reported annual averages of 20.3 visits for outpatient care, 27.7 missed days of work, and 32.6 days of care by an unpaid caregiver. The duloxetine and milnacipran (vs pregabalin or tricyclic antidepressant) cohorts had fewer outpatient visits during the 12-month study. Patients reported satisfaction with overall treatment and their fibromyalgia medication (46.0% and 42.8%, respectively). CONCLUSIONS: In this real-world setting, patients with fibromyalgia reported modest improvements, high resource, and medication use, and were satisfied with the care they received. Cohort differences were difficult to discern because of the high rates of drug discontinuation and concomitant medication use over the 12-month study period.

Use of select medications prior to duloxetine initiation among commercially-insured patients.

BACKGROUND: The purpose of this study was to assess select medication utilization prior to duloxetine initiation among patients with major depressive disorder, generalized anxiety disorder, diabetic peripheral neuropathic pain, fibromyalgia, and musculoskeletal pain associated with osteoarthritis or low back pain. METHODS: Commercially insured duloxetine initiators between January 1, 2007 and March 31, 2010 were identified from a large US administrative claims database. Disease subgroups were constructed based on diagnosis from medical claims during the 12 months prior to duloxetine initiation. Prior use of antidepressants, anticonvulsants, opioids, nonsteroidal anti-inflammatory drugs, and muscle relaxants was assessed during the 12-month preinitiation period. RESULTS: This study identified 56,845 (2007), 44,838 (2008), and 65,840 (January 2009 to March 2010) duloxetine initiators. Among the 2009 initiators, utilization patterns were similar for patients with major depressive disorder and generalized anxiety disorder, with antidepressants being the most used (84% and 80%, respectively), followed by opioids (58% and 55%, respectively). Patients across pain-related conditions also had similar utilization patterns, with opioid use being the highest (76%-82%), followed by antidepressants (65%-72%). Use of other medication classes was common (29%-63%) but less frequent, and over 50% of the patients used any antidepressants, 70% used any antidepressants or anticonvulsants, and 90% used any antidepressants, anticonvulsants, or opioids. Trends in the use of these select medications were similar between 2007 and 2009. CONCLUSION: Patients used several types of medications over the 12 months prior to initiating duloxetine across disease states, with antidepressants and opioids being the most frequently used medications. Trends of select medication use were similar over time.

[Study of cytochrome P450 1A1 gene 3'-UTR 6235T-C polymorphism and susceptibility to breast cancer with Uighur medicine].

OBJECTIVE: To explore the association between polymorphism of cytochrome P450 1A1 Gene 3'-UTR (3'-untranslated region) 6235T-C and breast cancer with abnormal Hilit in Chinese Han population of Xinjiang. METHODS: The breast cancer patients were divided into four body fluids according to Uighur medical theories. And the technique of polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was employed to detect the genotypic and allelic frequencies of 6235T-C polymorphism situated in 3'-untranslated region of CYP1A1 gene in 137 breast cancer patients with abnormal Hilit and 148 normal control subjects in Han population of Xinjiang province. RESULTS: (1) Significant differences in the genotypic and allelic distribution frequencies of CYP1A1 gene 3'-UTR6235T-C were found between breast cancer patients with abnormal Sapra Hilit and controls (χ(2) = 8.790, P = 0.012; χ(2) = 7.102, P = 0.008). The frequencies of CC genotype and C allele were significantly higher in breast cancer patients with abnormal Sapra Hilit (16.4% vs 39.8%) than in controls (4.7% vs 25.7%). (2) Significant differences in the genotypes and allelic distribution frequencies of CYP1A1 gene 3'-UTR6235T-C were found between breast cancer patients with abnormal Savda Hilit and controls (χ(2) = 6.638, P = 0.036; χ(2) = 5.824, P = 0.016). And the frequencies of TC, CC genotypes and C allele were significantly higher in breast cancer patients with abnormal Savda Hilit (56.9%, 9.8%, 39.2%) than those of the controls (41.9%, 4.7%, 25.7%). CONCLUSION: The CC genotype and C allele of 6235T-C polymorphism of CYP1A1 may be linked with breast cancer with abnormal Sapra Hilit and abnormal savda Hilit in Chinese Han population of Xinjiang province. But they are not correlated with the susceptibility to breast cancer with abnormal Balgham Hilit.

[Relationship between genetic polymorphisms of DAT1 VNTR and cancer with abnormal Hilit].

OBJECTIVE: This study was to investigate the relationship between the 40 bp VNTR polymorphism of dopamine transporter gene (DAT1) and cancer with Uighur medicine abnormal Hilit on Chinese Uighur population of Xinjiang province. METHODS: Divided the cancer patients into four body fluids according to Uighur medicine theory, the polymerase chain reaction and VNTR polymorphism technique was employed to detect genotype and allele frequencies of a 40 bp VNTR polymorphism situated in 3' untranslated region of the DAT1 gene in 47 cancer patients with abnormal black Savda, 26 cancer patients with other abnormal Hilit and 57 normal control subjects in Uighur population of Xinjiang Province. RESULTS: (1) In our sample,the repeat numbers of 40 bp were 6 to 11 (PCR product length of 320 bp to 520 bp) and 10-repeats allele (480 bp) detected was the dominant allele of DAT1 gene polymorphisms with the allele frequency 90.4%. Six kinds of genotype were detected in this study and the genotype 480 bp/480 bp was the most common genotype with genotype frequency 80.7%. (2) The susceptibility to cancer patients with abnormal black Savda among the subjects with 10 repeat (R) allele and 10/10 genotypes and the subjects with non-10 repeat (R) allele and non-10/10 genotypes were similar (P = 0.158, OR = 1.994, 95% CI = 0.754-5.275; P = 0.138, OR = 2.143, 95% CI = 0.772-5.947). No significant differences for the genotype frequency or the allele frequency of the 40 bp VNTR polymorphism of DAT1 were revealed between cancer patients with abnormal black Savda and cancer patients with other abnormal Hilit (P = 0.729, P = 0.782). CONCLUSION: The 40 bp VNTR polymorphism of DAT1 may not be correlated to the susceptibility to cancer with Uighur medicine abnormal Hilit.

[Association analysis between polymorphism of dopamine transporter variable number tandem repeat and breast cancer with abnormal Hilit].

OBJECTIVE: To explore the association between polymorphism of dopamine 1 transporter variable number tandem repeat (DAT1 VNTR) and breast cancer with abnormal Hilit in Chinese Han population from Xinjiang. METHODS: The breast caner patients were divided into four body fluids according to Uighur medicine theory. And polymerase chain reaction and VNTR polymorphism technique were employed to detect genotypic and allelic frequencies of a 40 bp VNTR polymorphism situated in 3' untranslated region of DAT1 gene in 144 breast cancer patients with abnormal Hilit and 104 normal control subjects in Han population of Xinjiang province. RESULTS: In our sample, the repeat numbers of 40 bp were 7 and 9 - 11 (PCR product length of 360 bp and 440 bp to 520 bp) and 10-repeat allele (480 bp) detected was the dominant allele of DAT1 gene polymorphisms with an allelic frequency of 90.9%; Seven kinds of genotype were detected and genotype 10/10 was the most common genotype with a genotypic frequency of 83.1%. The frequency of 10-repeats allele and 10/10 genotype was significantly higher in breast caner patients with abnormal balgham Hilit than in controls (OR = 0.127, 95%CI 0.016 - 0.988, P = 0.026; OR = 0.134, 95%CI 0.018 - 1.016, P = 0.020) and breast caner patients with abnormal Sapra Hilit (OR = 0.132, 95%CI 0.016 - 1.075, P = 0.049; OR = 0.132, 95%CI 0.017 - 1.042, P = 0.033). CONCLUSION: The 10-repeats allele and 10/10 genotype of 40 bp VNTR polymorphism of DAT1 may increase the risk of breast cancer with Uighur medicine abnormal Hilit in Chinese Han population from Xinjiang province and it is not correlated with the susceptibility to breast cancer with Uighur medicine abnormal Sapra Hilit.

[Study of serotonin transporter gene polymorphisms in disease of patients with abnormal black Savda].

OBJECTIVE: To explore the association between patients with abnormal black Savda according to Uighur medicine theory and the serotonin transporter (5-HTT) gene polymorphisms in the promoter (5-HTTLPR) and the variable number tandem repeats (VNTRs) in intron 2 (5-HTTVNTR). METHODS: Divided the patients into four body fluids according to Uighur medicine theory, PCR was used to detect genotype and allele frequencies of 5-HTILPR and 5-HTTVNTR polymorphisms in 66 patients with abnormal black Savda (including 35 cases of hypertension, 19 cases of diabetes, 12 cases of cancer diagnosis) and 45 control subjects. RESULTS: No significant differences for the genotype frequency or the allele frequency of 5-HTTLPR and 5-HTTVNTR were revealed between patients with abnormal black Savda and control subjects. More control subjects tended to be of L/L genotype (15.56%) than hypertension with abnormal black Savda (5.72%). On the contrary, more cancer diagnosis with abnormal black Savda tended to be of L/L genotype (25.00%) and L (54.17%) allele than control subjects L/L genotype (15.56%) and L allele (37.78%). On the other hand, fewer control subjects tended to be of 10/10 genotype (4.45%) than diabetes with abnormal black Savda (10.53%) and cancer diagnosis with abnormal black Savda (8.34%). CONCLUSION: 5-HTTLPR L/L genotype may be a protective factor for hypertension with abnormal black Savda, 5-HTTLPR L/L genotype and L allele may be risk factors for cancer diagnosis with abnormal black Savda, 5-HTTVNTR 10/10 genotype may be risk factors for cancer diagnosis with abnormal black Savda and diabetes with abnormal black Savda.