AbstractContextLow-dose sulfonylureas (SUs) have been found to augment the classical incretin effect, increase glucose sensitivity and late phase incretin potentiation.ObjectiveTo evaluate potential synergy between low-dose SU plus a dipeptidyl peptidase 4 (DPP4) inhibitor.MethodsUnblinded randomized crossover study at the Clinical Research Centre, University of Dundee. Thirty participants with T2DM (HbA1c < 64 mmol/mol) were treated with diet or metformin. Participants completed 4, 14-day blocks in a random order: control, gliclazide 20 mg (SU), sitagliptin 100 mg (DPP4 inhibitor [DPP4i]), or combination (SUDPP4i). A mixed meal test was conducted after each intervention. The primary outcome was the effect of treatment on beta-cell glucose sensitivity. Secondary outcomes included frequency of glucose <3 mmol/L on continuous glucose monitoring, subanalyses by genotype (KNCJ11 E23K), gender, and body mass index.ResultsSU combination with DPP4i showed additive effect on glucose lowering: mean glucose area under the curve (mean 95% CI) (mmol/L) was control 11.5 (10.7-12.3), DPP4i 10.2 (9.4-11.1), SU 9.7 (8.9-10.5), SUDPP4i 8.7 (7.9-9.5) (P < .001). Glucose sensitivity mirrored the additive effect (pmol min−1 m−2 mM−1): control 71.5 (51.1-91.9), DPP4i 75.9 (55.7-96.0), SU 86.3 (66.1-106.4), SUDPP4i 94.1 (73.9-114.3) (P = .04). The additive effect was seen in men but not women. Glucose time in range <3 mmol/L on continuous glucose monitoring (%) was unaffected: control 1 (2-4), DPP4i 2 (3-6), SU 1 (0-4), SUDPP4i 3 (2-7) (P = .65).ConclusionLow-dose sulfonylurea plus DPP4i has a potent glucose-lowering effect through augmentation of beta-cell function. A double-blind randomized controlled trial would formalize efficacy and safety of this combination, which may avoid negative aspects of SU.

01 Jul 2024·Joint Bone Spine

Monosodium urate crystal depletion and bone erosion remodeling during pegloticase treatment in patients with uncontrolled gout: Exploratory dual-energy computed tomography findings from MIRROR RCT

Article

Author: Padnick-Silver, Lissa ; Dalbeth, Nicola ; Botson, John ; Becce, Fabio ; Kumar, Ada ; Saag, Kenneth ; LaMoreaux, Brian

OBJECTIVEMonosodium-urate (MSU) crystal deposits can be visualized and quantified with dual-energy CT (DECT). Pegloticase lowers serum urate (SU) in uncontrolled gout patients, with methotrexate (MTX) co-therapy recommended to increase SU-lowering response rate and decrease infusion reaction risk. The literature on serial DECT-imaging during pegloticase+MTX co-therapy is sparse, with only 2 prior cases of rapid MSU deposition depletion with subsequent bone-erosion remodeling reported from a small open-label trial. Here, we report DECT findings during pegloticase treatment in a larger number of patients from a randomized controlled trial to confirm bone-erosion remodeling that follows MSU depletion with pegloticase. The influence of length-of-therapy is also explored.METHODSPatients received pegloticase (8mg every 2weeks)+MTX (15mg/week orally) or pegloticase+placebo (PBO) during the MIRROR RCT trial. A subset underwent DECT-imaging on Day1 (first pegloticase infusion) and at Weeks 14, 24, and 52. Patients with paired baseline-Week 52 images were included. Imaged regions with baseline MSU-crystal volume (V_MSU)<0.5cm³ were excluded to minimize artifact contributions. V_MSU and bone-erosion remodeling were assessed.RESULTSEight patients (6 MTX, 2 PBO) were included. Included patients had received 52weeks (5 MTX), 42weeks (1 PBO), and 6weeks (1 MTX, 1 PBO) of pegloticase therapy. Patients who prematurely discontinued pegloticase maintained SU<6mg/dL on allopurinol (n=2)/febuxostat (n=1). At Week 52, V_MSU had markedly decreased in both the pegloticase+MTX and pegloticase+PBO treatment groups, with faster depletion during pegloticase therapy. Bone-erosion remodeling was observed in 29/42 (69%) evaluated erosions: 29 (69%) size decrease, 4 (9.5%) recortication, 3 (7.1%) new bone formation.CONCLUSIONRapid V_MSU depletion during pegloticase therapy was observed with concomitant bone remodeling within 1year. Following pegloticase discontinuation, V_MSU reduction slowed or stopped even when SU was maintained<6mg/dL with oral ULT.CLINICAL TRIAL REGISTRATIONNCT03994731.

01 May 2024·AIDS and Behavior

Association Between Substance Abuse and Mental Illness Symptoms Screener (SAMISS) Scores and HIV Care Continuum Outcomes in People Newly Diagnosed with HIV in the US South

Article

Author: Chow, Jeremy Y ; Ahn, Chul ; Nijhawan, Ank E ; Ahmed, Manal ; Gao, Ang

Mental illness (MI) and substance use (SU) are highly prevalent among people with HIV (PWH) and impact care outcomes. The Substance Abuse and Mental Illness Symptoms Screener (SAMISS) is a validated screener for MI and SU, but it is unknown how screening results at entry to care correlate with subsequent HIV outcomes. This is a retrospective chart review of individuals newly diagnosed with HIV between 2016 and 2019 in a Southern US, safety-net clinic. Baseline demographics, HIV risk factors, socioeconomic variables, and SAMISS screening scores were collected. Outcomes included retention in care, achieving virologic suppression (VS), and continuous VS. Data analyses included stepwise Cox and logistic multivariate regression modeling. Among the 544 newly diagnosed PWH, mean age was 35, 76% were male, 46% non-Hispanic Black, 40% Hispanic/other. Overall, 35% screened positive for SU and 41% for MI. A positive SU (odds ratio (OR) 0.66, p = 0.04) or MI (OR 0.65, p = 0.03) SAMISS screening was associated with lower retention in care in univariate analysis, but was not statistically significant after adjusting for other variables. Positive SAMISS screening for SU and MI were both associated with reduced continuous VS in univariate and multivariate analyses (SU: adjusted OR (aOR) 0.67, p = 0.05; MI: aOR 0.66, p = 0.03). SAMISS is a useful tool for prospectively identifying individuals at risk for low retention in care and for not achieving sustained VS. Future interventions guided by SAMISS may improve HIV care continuum outcomes.

100 Deals associated with BCG polysaccharide and nucleic acid(Zhejiang Wansheng Pharmaceutical Co., Ltd.)

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Indication	Country/Location	Organization	Date
Asthma	CN	Zhejiang Sunshine Mandi Pharmaceutical Co.,Ltd.	01 Jan 1996
Bronchitis, Chronic	CN	Zhejiang Sunshine Mandi Pharmaceutical Co.,Ltd.	01 Jan 1996
Common Cold	CN	Zhejiang Sunshine Mandi Pharmaceutical Co.,Ltd.	01 Jan 1996

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ASCO2006	Phase 2	Recurrent Metastatic Gastric Carcinoma	23	P-HDFL	gchmntxkja(luasrkvbjh) = joubjyuyje cuwkctvnjk (rgumllfjhr ) View more	-	20 Jun 2006
				DI	(ntnulpbvnu) = xbsfwabkco fksbicuntc (rxdliwaxiy ) View more

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BCG polysaccharide and nucleic acid(Zhejiang Wansheng Pharmaceutical Co., Ltd.)

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