Reduction In Hemoglobin Research Articles

Abstract 138: Efficacy of oral semaglutide according to race: An exploratory subgroup analysis of the PIONEER trial program

The global PIONEER program investigated the efficacy and safety of oral semaglutide, a glucagon-like peptide-1 receptor agonist. Patients with type 2 diabetes were randomized to once-daily oral semaglutide (3, 7 or 14 mg, or flexibly dosed [flex]), placebo, or active comparator (empagliflozin 25 mg, sitagliptin 100 mg or liraglutide 1.8 mg). This exploratory subgroup analysis evaluated the effect of race on glycated hemoglobin (HbA1c) and body weight (BW) reductions at the end of treatment (week 26, 52 or 78). Data were analyzed from PIONEER 1-5, 7 and 8 by race (White, Asian, Black/African American). Baseline characteristics were generally similar across subgroups except for BW, which was lower in Asian patients. Generally, greater HbA1c reductions were observed with oral semaglutide 14 mg/flex vs. comparators across subgroups [Table 1]. In PIONEER 1, 4 and 8, there was a significant interaction between treatment and race, with greater HbA reductions and estimated treatment differences in Asian patients than in other subgroups [Table 1]. Overall, BW reductions were greater for oral semaglutide vs. comparators, regardless of subgroup and without significant interactions between treatment and race. Our findings in this exploratory subgroup analysis suggest that, in some PIONEER trials, Asian patients achieve greater HbA reductions than other race groups when treated with oral semaglutide.

A patient-centered multidisciplinary cardiac rehabilitation program improves glycemic control and functional outcome in coronary artery disease after percutaneous and surgical revascularization.

BackgroundCardiac rehabilitation (CR) is strongly associated with all-cause mortality reduction in patients with coronary artery disease (CAD). The impact of CR on pathological risk factors, such as impaired glucose tolerance (IGT) and functional recovery remains under debate. The aim of the present study is to determine whether CR had a positive effect beside physical exercise improvement on pathological risk factors in IGT and diabetic patients with CAD.MethodsOne hundred and seventy-one consecutive patients participating in a 3-month CR from January 2014 to June 2015 were enrolled. The primary endpoint was defined as an improvement of peak workload and VO2-peak; glycated hemoglobin (HbA1c) reduction was considered as secondary endpoint.ResultsEuglycemic patients presented a significant improvement in peak workload compared to diabetic patients (from 5.75 ± 1.45 to 6.65 ± 1.84 METs vs. 4.8 ± 0.8 to 4.9 ± 1.4 METs, p = 0.018). VO2-peak improved in euglycemic patients (VO2-peak from 19.3 ± 5.3 to 22.5 ± 5.9 mL/min/kg, p = 0.003), while diabetic patients presented only a statistically significant trend (VO2-peak from 16.9 ± 4.4 to 18.0 ± 3.8 mL/min/kg, p < 0.056). Diabetic patients have benefited more in terms of blood glucose control compared to IGT patients (HbA1c from 7.7 ± 1.0 to 7.4 ± 1.1 compared to 5.6 ± 0.4 to 5.9 ± 0.5, p = 0.02, respectively).ConclusionsA multidisciplinary CR program improves physical functional capacity in CAD setting, particularly in euglycemic patients. IGT patients as well as diabetic patients may benefit from a CR program, but long-term outcome needs to be clarified in larger studies.

A randomised double-blind placebo-controlled clinical trial of oral hydroxyurea for transfusion-dependent \u03b2-thalassaemia

Hydroxyurea is an antimetabolite drug that induces fetal haemoglobin in sickle cell disease. However, its clinical usefulness in β-thalassaemia is unproven. We conducted a randomised, double-blind, placebo-controlled clinical trial to evaluate the efficacy and safety of hydroxyurea in transfusion-dependent β-thalassaemia. Sixty patients were assigned 1:1 to oral hydroxyurea 10–20 mg/kg/day or placebo for 6 months by stratified block randomisation. Hydroxyurea treatment did not alter the blood transfusion volume overall. However, a significantly higher proportion of patients on hydroxyurea showed increases in fetal haemoglobin percentage (89% vs. 59%; p < 0.05) and reductions in erythropoietic stress as measured by soluble transferrin receptor concentration (79% vs. 40%; p < 0.05). Based on fetal haemoglobin induction (> 1.5%), 44% of patients were identified as hydroxyurea-responders. Hydroxyurea-responders, required significantly lower blood volume (77 ± SD27ml/kg) compared to hydroxyurea-non-responders (108 ± SD24ml/kg; p < 0.01) and placebo-receivers (102 ± 28ml/kg; p < 0.05). Response to hydroxyurea was significantly higher in patients with HbE β-thalassaemia genotype (50% vs. 0%; p < 0.01) and Xmn1 polymorphism of the γ-globin gene (67% vs. 27%; p < 0.05). We conclude that oral hydroxyurea increased fetal haemoglobin percentage and reduced erythropoietic stress of ineffective erythropoiesis in patients with transfusion-dependent β-thalassaemia. Hydroxyurea reduced the transfusion burden in approximately 40% of patients. Response to hydroxyurea was higher in patients with HbE β-thalassaemia genotype and Xmn1 polymorphism of the γ-globin gene.

Oral and intravenous tranexamic acid are equivalent at reducing blood loss following shoulder arthroplasty—A multicenter, double-blinded, randomized, placebo-controlled trial

BackgroundTranexamic acid (TXA) has been shown to reduce blood loss significantly in shoulder arthroplasty. Oral TXA is significantly cheaper than intravenous TXA, but there has been no published literature comparing oral and intravenous TXA in shoulder arthroplasty. The purpose of this study was to compare the efficacy and safety of oral versus intravenous TXA in shoulder arthroplasty. We hypothesized that oral and intravenous TXA are equivalent at reducing blood loss following shoulder arthroplasty. MethodsThis study was approved by the New Zealand Health and Disability Ethics Committee (HDEC) and registered with the Australian and New Zealand Clinical Trials Registry (ANZCTR). Patients undergoing elective shoulder arthroplasties were prospectively randomized into one of two groups. In the oral TXA group, 2g of TXA was administered two hours prior to induction of anesthesia, and in the intravenous TXA group, 1.5g of TXA was administered as a bolus following induction of anesthesia. The primary outcome was a reduction in hemoglobin concentration. The secondary outcomes included drain output, number of blood units transfused, length of hospital stay, and complications. ResultsA total of 80 consecutive patients were randomized. The baseline demographics were comparable between the two groups. There was no difference in the primary outcome measure or any of the secondary outcome measures. With regards to the primary outcome measure, using a two one-sided test (TOST) for equivalence, with a P value of < 0.05 demonstrating equivalence, the mean reduction of hemoglobin was 23.30g/L (± 1.62) versus 22.45g/L (± 1.30) for the oral and the intravenous groups, respectively (P < .001). Postoperative drain output was 74.58mLs (± 11.27) versus 90.03mLs (± 14.53) for the oral and the intravenous groups, respectively (P = .41). Furthermore, there was no difference in the number of blood units transfused, length of hospital stay, and complications. DiscussionTo the best of our knowledge, this is the first study in the literature comparing oral and intravenous tranexamic in shoulder arthroplasty, and we found no difference in the efficacy of the two routes of administration. Surgeons should be encouraged to use the less expensive oral form of the medication as a means to minimize overall healthcare expenditure.

Transfusion-Free Survival Predicts Severe Retinopathy in Preterm Neonates.

Repeated red blood cell (RBC) transfusions are thought to increase the risk for retinopathy of prematurity (ROP), likely due to a critical fetal hemoglobin (HbF) reduction. In this study, we investigated if the postmenstrual age (PMA) of neonates at transfusion influences the risk for ROP. We estimated the cumulative transfusion-free survival (TFS) in a series of 100 preterm neonates receiving one or more RBC units. TFS was calculated by censoring patients at first transfusion and expressing the time between birth and transfusion as either PMA or postnatal day. Then, we investigated if TFS predicted the occurrence of severe ROP, defined as ROP stage 3 or higher. We found that neonates with severe ROP displayed a significantly shorter TFS expressed according to their PMA (p = 0.001), with similar TFS according to postnatal days. At receiver operating characteristic (ROC) curve analysis, receiving an RBC unit before week 28 of PMA predicted severe ROP with a sensitivity of 64% and a specificity of 78%. In addition, receiving a second RBC unit before the PMA of 29 weeks predicted severe ROP with a sensitivity of 75% and a specificity of 69%. At multivariate analysis, PMA at the second transfusion was even more informative than at first transfusion and outperformed all other variables in predicting severe ROP, with an odds ratio of 4.554 (95% CI 1.332–15.573, p = 0.016). Since HbF decrease is greater after multiple RBC transfusions, it is conceivable that neonates receiving more than one unit before the PMA of 29 weeks may be exposed to a greater disturbance of retinal vascularization. Any strategy aimed at preventing the critical HbF decrease at this low age might potentially reduce the risk for severe ROP.

Hypotensive Anesthesia Combined with Tranexamic Acid Reduces Perioperative Blood Loss in Simultaneous Bilateral Total Hip Arthroplasty: A Retrospective Cohort Study.

ObjectiveTo assess the efficacy and safety of hypotensive anesthesia (HA) combined with tranexamic acid (TXA) for reducing perioperative blood loss in simultaneous bilateral total hip arthroplasty (SBTHA).MethodsIn this retrospective cohort study, a total of 183 eligible patients (15 females and 168 males, 44.01 ± 9.29 years old) who underwent SBTHA from January 2015 to September 2020 at our medical center were enrolled for analysis. Fifty‐nine patients received standard general anesthesia (Std‐GA group), the other 85 and 39 patients received HA with an intraoperative mean arterial pressure between 70 and 80 mmHg (70–80 HA group) and below 70 mmHg (<70 HA group), respectively. TXA was administrated to all patients. Perioperative blood loss (total, dominant, and hidden), transfusion rate and volume, hemoglobin and hematocrit reduction, duration of operation and anesthesia, length of hospitalization, range of hip motion as well as postoperative complications were collected from hospital's electronic records and compared between groups.ResultsAll patients were followed for more than 3 months. Total blood loss in the two HA groups (1390.25 ± 595.67 ml and 1377.74 ± 423.46 ml, respectively) was significantly reduced compared with that in Std‐GA group (1850.83 ± 800.73 ml, P < 0.001). Both dominant and hidden blood loss were dramatically decreased when HA was applied (both P < 0.001). Accordingly, the transfusion rate along with volume in 70–80 HA group (14.1%, 425.00 ± 128.81 ml) and <70 HA group (12.8%, 340.00 ± 134.16 ml) were reduced in comparison with those in Std‐GA group (37.3%, 690.91 ± 370.21ml; P = 0.001 and P = 0.014, respectively). The maximal hemoglobin and hematocrit reduction in both HA groups were significantly less than those in Std‐GA group (both P < 0.001). Of note, 70–80 and <70 HA groups exhibited comparable efficacy with no significant differences between them. Besides, significant difference in duration of surgery was found among groups (P = 0.044 and P < 0.001), while no differences in anesthesia time and postoperative range of hip motion were observed. Regarding complications, the incidence of both acute kidney injury and postoperative hypotension in <70 HA group was significantly higher than that in 70–80 HA and Std‐GA groups (P = 0.014 and P < 0.001). Incidence of acute myocardial injury was similar among groups (P = 0.099) and no other severe complications or mortality were recorded.ConclusionThe combination of HA with a mean arterial pressure (MAP) of 70–80 mmHg and TXA could significantly reduce blood loss and transfusion during SBTHA, in addition to shortening operation time and length of hospitalization, and with no increase in complications.

A multicenter retrospective study of transurethral prostate split for benign prostate hyperplasia.

BackgroundTransurethral split of the prostate (TUSP) is effective in treating benign prostatic hyperplasia (BPH). However, there is still a lack of research focusing on the optimal target population for TUSP. This study aimed to compare the efficacy of TUSP in patients with different prostate volumes or ages.MethodsThe study was a multicenter retrospective study. The outcomes of TUSP in BPH patients with different prostate volumes or different ages were compared. A total of 439 patients were included in the study. Patients were divided into two groups according to prostate volume, with a cut-off value of 50 mL. Similarly, the cut-off value for the age groups was 70 years. Baseline patient characteristics and perioperative outcomes were recorded. Follow-up was performed at 1, 6, and 12 months after surgery.ResultsThe mean age of the patients was 73.4 years, and the mean prostate volume was 51.2 mL. At 12-month follow-up after TUSP treatment, the patients’ International Prostate Symptom Scores (IPSS), quality of life (QoL) scores, and postvoid residual (PVR) volumes decreased significantly, while peak urinary flow rate (Qmax) increased significantly. Intraoperative hemoglobin (Hb) reduction was significantly lower in the small volume group than in the large volume group. The incidence of postoperative urinary urgency and transient incontinence was lower in the small volume group. IPSS score, PVR, and Qmax in the small volume group showed more remarkable changes at several time points compared to the preoperative period. Postoperative pain scores were higher in the small volume group than in the large volume group. There were no differences between the two groups in terms of long-term complications. The younger group showed greater variation in PVR and Qmax at some time points but less variation in QoL than the older group.ConclusionsTUSP is overall safe and effective in treating BPH. This study showed differences in the outcomes of TUSP in treating different prostate volumes or ages of BPH patients. The optimal surgical approach for BPH patients might be selected clinically based on a combination of prostate volume or patient age.

Interaction of Antioxidant Trace Minerals Affecting Blood Picture Including Antioxidant Profile of Healthy Buffalo (Bubalus bubalis) Calves.

Copper (Cu) and selenium (Se) are antioxidants and essential trace elements that have mutual interaction and are reported to have beneficial effects at supranutritional levels. The experiment was executed to evaluate the individual impact of supranutritional levels of targeted elements with the effect of their interactions in buffalo calves. Twenty male Murrah buffalo calves of about 8-9months (bodyweight 112.1 ± 7.69kg) were distributed into four groups of five calves in each group and fed either a control (C) diet or supplemented with supranutritional levels of Cu (T1), Se (T2), or combination of both (T3) for 120days. Higher (P = 0.015) values of packed cell volume were observed in group T2 at day 120; otherwise, all other hematological parameters remained comparable among groups. Over the period (day 120 vs. day 0), an enhancement in the percentage of lymphocytes (P = 0.006) with a reduction in neutrophils (P = 0.028) and hemoglobin (P = 0.024) values was observed in the control group. An enhancement in the percentage of monocytes (P = 0.031), with a reduced percentage of neutrophils (P = 0.022), was reported in groups T2 and T3, respectively. Interaction of Cu and Se at supranutritional level (T3) dramatically reduced plasma Cu (P = 0.008) level against the control values, with an improvement in Se markers (i.e., plasma Se, P = 0.041 and enzyme glutathione peroxidase, P = 0.057) over the values in calves fed supplemental Se alone (T2). Additionally, Cu (T1 and T3) was forced to decline (P < 0.05) Zn level in the plasma of buffalo calves. Cu (T1, P < 0.05) and Se (T2 and T3, P ≤ 0.01) supplementation was able to improve their respective plasma levels. The interaction of two trace elements at the supranutritional level further helped in reducing the lipid peroxidation (P = 0.01) values as well. Though antioxidant vitamins and cell-mediated immunity remained unaffected, humoral immunity against antigen P. multocida was high (P = 0.005) in the group T2. The conclusion may be drawn that supranutritional Cu and Se were capable to influence certain blood parameters with an additional interaction effect due to simultaneous supplementation in buffalo calves.

Bisphenol A Induces Histopathological, Hematobiochemical Alterations, Oxidative Stress, and Genotoxicity in Common Carp (Cyprinus carpio L.).

Bisphenol A (BPA) is one of the environmental endocrine disrupting toxicants and is widely used in the industry involving plastics, polycarbonate, and epoxy resins. This study was designed to investigate the toxicological effects of BPA on hematology, serum biochemistry, and histopathology of different organs of common carp (Cyprinus carpio). A total of 60 fish were procured and haphazardly divided into four groups. Each experimental group contained 15 fish. The fish retained in group A was kept as the untreated control group. Three levels of BPA 3.0, 4.5, and 6 mg/L were given to groups B, C, and D for 30 days. Result indicated significant reduction in hemoglobin (Hb), lymphocytes, packed cell volume (PCV), red blood cells (RBC), and monocytes in a dose-dependent manner as compared to the control group. However, significantly higher values of leucocytes and neutrophils were observed in the treated groups (P < 0.05). Results on serum biochemistry revealed that the quantity of glucose, cholesterol, triglycerides, urea, and creatinine levels was significantly high (P < 0.05). Our study results showed significantly (P < 0.05) increase level of oxidative stress parameters like reactive oxygen species (ROS) and thiobarbituric acid reactive substances (TBARS) and lower values of antioxidant enzymes (superoxide dismutase (SOD), catalase (CAT), peroxidase (POD) in treated groups (4.5 mg/L and 6 mg/L)) in the brain, liver, gills, and kidneys. Our study depicted significant changes in erythrocytes (pear shaped erythrocytes, leptocytes, microcytes, spherocytes, erythrocytes with broken, lobed, micronucleus, blabbed, vacuolated nucleus, and nuclear remnants) among treated groups (4.5 mg/L and 6 mg/L). Comet assay showed increased genotoxicity in different tissues including the brain, liver, gills, and kidneys in the treated fish group. Based on the results of our experiment, it can be concluded that the BPA exposure to aquatic environment is responsible for deterioration of fish health, performance leading to dysfunction of multiple vital organs.

Проблемні питання диференційної діагностики жовтяниць у дітей. Випадки з практики (клінічна лекція)

Залежно від того, на якому рівні відбулося порушення обміну білірубіну, виділяють такі види жовтяниць: надпечінкова, печінкова, підпечінкова. Для надпечінкової жовтяниці характерне підвищення рівня непрямого білірубіну в крові при нормальній активності печінковоклітинних ферментів, паралельно в крові має місце зниження рівня гемоглобіну, еритроцитів і високий ретикулоцитоз. Характерною лабораторною ознакою печінкової жовтяниці є підвищення рівня загального білірубіну за рахунок прямого й підвищення активності печінковоклітинних ферментів. Підпечінкова жовтяниця виникає при порушенні відтоку жовчі з жовчного міхура і жовчних проток у порожнину тонкої кишки.

Learning curve in aquablation: an international multicenter study.

To describe and analyze the learning curve (LC) of aquablation for the treatment of benign prostatic obstruction and determine the number of cases needed to achieve acceptable surgical safety, efficiency, and efficacy. A retrospective analysis of prospectively maintained aquablation databases from France, Lebanon, and Spain was conducted. The combined LC of three surgeons was defined by trifecta and pentafecta outcomes. Trifecta reflected efficiency and safety: operative time < 60min, hemoglobin reduction ≤ 2mg/dL, and no 90day Clavien-Dindo grade ≥ 2 complications. Pentafecta reflected effectiveness: percent reduction in International Prostate Symptom Score (IPSS) and ejaculation preservation. The combined LC was plotted using a moving average with polynomial fitting. The cohort included 175 consecutive patients. Median (IQR) prostate volume was 70 (50-91) cc, and baseline IPSS was 23 (18-27). The achievement of trifecta exceeded 50% after 4 cases, and 70% after 50 cases. Pentafecta achievement exceeded 50% after 38 cases. Logistic regression showed significant improvement in hemoglobin reduction and ejaculation preservation. Grade ≥ 2 complication was not affected by experience, and neither was 3month %IPSS reduction as 94% of patients showed ≥ 50% symptoms' improvement. Aquablation is associated with a quick learning curve for the defined trifecta and pentafecta outcomes. It provided effective LUTS relief and low complication rates independent of surgeon experience. Hemoglobin drop and ejaculatory function preservation were the two factors influenced by the surgeons' LC. Training to reduce operative time, standardization of hemostasis techniques, and early assistance to improve veru-protection zone planning are keys to quicker learning.

Manual removal of a rare cystic calculus concurrent with recurrent hemorrhagic cystitis in an Arabian mare: A case report

A nine-year-old Arabian mare was presented with symptoms of frequent hematuria, dysuria, pollakiuria and urine dribbling. This report describes a manual removal procedure of a cystic urolith in an Arabian mare. A complete blood count showed a slight reduction in hemoglobin. Renal function tests showed high normal ranges in BUN. The urine sample was very cloudy and had a specific gravity of (1.019) with alkaline pH. The chemical examination showed high hemoglobin concentration with glucose traces. The microscopic examination showed a high number of pus cells and red blood cells with few numbers of rounded epithelial cells. Bacterial culture revealed Klebsiella spp and as a result of the sensitivity test, sensitivity to amoxicillin/ clavulanic acid, amikacin and gentamicin was determined. Cystoscopy revealed a large cystic urolith cranioventrally on the left wall of the urinary bladder. The apex vesicae was inflamed, with blood sludge. The definitive diagnosis was chronic hemorrhagic cystitis caused by a large cystic urolith. As a result, it was concluded that the removal of relatively large calculi through the urethra in the mare, while providing some protection to the bladder neck and urethral mucosa, has been effective with minimal complications.

Evaluation of the Efficacy of Tranexamic Acid in Control of Bleeding in Total Knee Replacement

Introduction: Among the various strategies for in routine total knee replacement (TKR), tranexamic acid (TA) has always been a safer and affordable method. Surgeons have used it in intravenous, intraarticular or in a combined manner to reduce blood loss because it is easily available and has an easy dosing regimen. We aim to find out its efficacy and associated complication when used intravenously. Materials and Methods: This study was done in our institute among 27 cases who was operated for primary TKR. They were distributed into two groups based on the use of TA. Hemodynamic parameters such as blood loss, reduction in hemoglobin (Hb), and blood transfusion were assessed. Student's t-test and ANOVA were utilized for tests of significance. Results: Out of 27 patients, 17 (62.9%) were female and in the age group of 51–60 years. Most 22 (81.5%) had osteoarthritis. The difference in blood loss across various pathologies and comorbidities was statistically insignificant. Average blood loss was 266.2 ml ± 64 ml (Range = 150–406 ml) per TKR in the 1st group. In 2nd, it was 667.5 ± 111.5 ml (Range = 414–860 ml) (P &lt; 0.001). Mean Hb loss was 0.78 ± 0.275 g/dl (Range = 0.1–1.2 g/dl) in Group A. It was statistically significant comparing to Group B where it was 1.86 ± 0.55 g/dl (Range = 1.5–3.7 g/dl). Tourniquet used though decreased blood loss, it was not statistically significant. Conclusion: TA used in intravenously is very effective in decreasing the loss of blood and transfusion requirements in patients of primary TKR.

Acute effects of a typical rhythmic gymnastic training session on physiological parameters in Olympic athletes

The aim of this study was to evaluate the effects of a day with two separate training sessions (morning and afternoon) of rhythmic gymnastics on erythrocytes, leukocytes, muscle damage, oxidative stress, and hydration of Brazilian team [age 17.7 (±1.1) years; body height 165 (±0.5) cm; body mass 49.7 (±4.2) kg]. Heart rate and session-ratings of perceived exertion were used to monitor training intensity. Blood samples were collected immediately before (M1) and after (M2) the training day for analyzing erythrocytes, leukocytes, plasma creatine kinase activity, lactate dehydrogenase, alanine aminotransferase, aspartate aminotransferase, ferric reducing ability plasma, thyroid-stimulating hormone, and free T4. Saliva was collected for cortisol analysis. After 24 hours rest (M3), blood collection was performed to analyze creatine kinase and lactate dehydrogenase. The moderate-intensity training day induced significant elevations of total leukocytes (5,163.3 to 9,617.8), lymphocytes (1,752.7 to 2,729.7), neutrophils (2,873.9 to 6,163.6), monocytes (255.7 to 519.1), platelets (280,000.0 to 300,666.7), aspartate aminotransferase (13.1 to 25.6), lactate dehydrogenase (102.5 to 249.1), thyroid-stimulating hormone (1.0 to 3.2), and ferric reducing ability plasma (136.8 to 165.4), as well as significant reductions in red cells (4,691,111.1 to 4,497,777.8), hematocrit (42.1 to 39.3), and hemoglobin (12.9 to 12.5) at M2. There were also significant increases in creatine kinase (144.2 to 519.3) and lactate dehydrogenase (102.5 to 538.2) at M3. The average dehydration rate was 1.3%. A moderate-intensity day of training in rhythmic gymnastics of 8h21min duration caused hemolysis, leukocytosis, muscle damage, redox status perturbations, and insufficient hydration status. These findings show that athletes are exposed to physiological vulnerabilities that can possibly harm their performance and health.

A Community Health Volunteer Involvement Program for Glycated Hemoglobin Reduction Among Thai Patients With Uncontrolled Type 2 Diabetes: A Mixed-Method Study.

Background:Diabetes mellitus is increasing and a shortage exists of nurses to care for patients. Community health volunteers (CHVs) pose potential supportive networks in assisting patients to perform healthy behaviors.Aim:The study aimed to develop and investigate the effects of a CHV involvement program on reducing glycated hemoglobin (HbA1c) levels among Thai patients with uncontrolled type 2 diabetes.Methods:This sequential mixed-method study was conducted from January to June 2019. Sixty patients with HbA1c exceeding 7% were recruited from 2 communities assigned as the intervention and comparison groups. Using King’s General Systems Framework as a basis to develop the program, the study initially explored the perceptions of diabetes and its management among patients, family members, and CHVs. Then, a quasi-experimental study with 2 groups pretest-posttest design was conducted and compared with usual care. The intervention included educational sessions, home visits, and activities created by CHVs including a campaign, broadcasting, and health food shops. Quantitative data were collected at baseline and 20-week follow-up and analyzed by descriptive statistics, Independent t-test, and paired t-test.Results:The intervention group exhibited a lower mean HbA1c (p < .001) and reported significant, improvement concerning diabetes knowledge, self-efficacy, perceived support, and behavior compared with the comparison group at the end of the study (Cohen’s d > 1.0, effect size large).Conclusion:Applying this framework to develop the program could benefit glycemic control among patients with uncontrolled diabetes residing in communities. Further studies should be conducted on a large sample to demonstrate the efficacy of the program.

Improving packed red blood cell storage with a high-viscosity buffered storage solution

BackgroundMassive transfusion with older packed red blood cells is associated with increased morbidity and mortality. As packed red blood cells age, they undergo biochemical and structural changes known as the storage lesion. We developed a novel solution to increase viscosity in stored packed red blood cells. We hypothesized that packed red blood cell storage in this solution would blunt storage lesion formation and mitigate the inflammatory response after resuscitation. MethodsBlood was obtained from 8- to 10-week-old C57BL/6 male donor mice or human volunteers and stored as packed red blood cell units for 14 days for mice or 42 days for humans in either standard AS-3 storage solution or EAS-1587, the novel packed red blood cell storage solution. Packed red blood cells were analyzed for microvesicles, cell-free hemoglobin, phosphatidylserine, band-3 protein, glucose utilization, and osmotic fragility. Additional mice underwent hemorrhage and resuscitation with packed red blood cells stored in either AS-3 or EAS-1587. Serum was analyzed for inflammatory markers. ResultsMurine packed red blood cells stored in EAS-1587 demonstrated reductions in microvesicle and cell-free hemoglobin accumulation as well as preserved band-3 expression, increase glucose utilization, reductions in phosphatidylserine expression, and susceptibility to osmotic stress. Serum from mice resuscitated with packed red blood cells stored in EAS-1587 demonstrated reduced proinflammatory cytokines. Human packed red blood cells demonstrated a reduction in microvesicle and cell-free hemoglobin as well as an increase in glucose utilization. ConclusionStorage of packed red blood cells in a novel storage solution mitigated many aspects of the red blood cell storage lesion as well as the inflammatory response to resuscitation after hemorrhage. This modified storage solution may lead to improvement of packed red blood cell storage and reduce harm after massive transfusion.

Long-term clinical and cost-effectiveness of collaborative care in people with uncontrolled type 2 diabetes mellitus and polypharmacy: A multicenter randomized controlled trial

AimsThis study examined the effectiveness of a collaborative care model on clinical and humanistic outcomes, medical cost, productivity loss, and its cost-effectiveness in managing uncontrolled Type 2 Diabetes Mellitus (T2DM). MethodsA randomized controlled study was conducted in two outpatient health institutions in Singapore. Patients aged above 21 years with HbA1c > 7% and polypharmacy were included. Eligible patients were randomized into the intervention (collaborative care) and control (usual care) arms. ResultsA total of 255 patients were included in the analysis. Compared to the control arm, the intervention arm achieved significantly greater glycated hemoglobin (HbA1c) reduction (mean difference: 0.25, 95%CI: [0.001, 0.50], p = 0.049) and quality-adjusted life year (QALY) (+0.011, 95%CI: [0.003, 0.019], p = 0.011) at 12 months. The costs per additional HbA1c and QALY improvements over one year were $40.52 and $920.91 respectively. Activity impairment was lower in the intervention group both at 6 months (12.7% vs 19.0%; p = 0.022) and at 12 months (6.7% vs 14.0%; p = 0.008). ConclusionsThe collaborative care model achieved earlier HbA1c reduction and reduced patients’ activity impairment without decreasing work productivity or increasing medical costs. This intervention is cost-effective for improving glycemic control and quality of life in patients with T2DM.

Higher Rates of Persistence and Adherence in Patients with Type 2 Diabetes Initiating Once-Weekly vs Daily Injectable Glucagon-Like Peptide-1 Receptor Agonists in US Clinical Practice (STAY Study).

IntroductionReducing dosing frequency may lower treatment burden and improve persistence and adherence. This retrospective, observational study assessed persistence and adherence in patients with type 2 diabetes (T2D) initiating once-weekly or daily injectable glucagon-like peptide-1 receptor agonists (GLP-1 RAs) in US clinical practice.MethodsThe study used data from adults (≥ 18 years) with T2D who were included in the IBM MarketScan Explorys Claims-EMR Data Set for ≥ 180 days pre-index and ≥ 365 days post-index, were GLP-1 RA and insulin naïve at first claim (index date) for once-weekly or daily injectable GLP-1 RAs (follow-up: index date + 365 days), and were propensity score (PS) matched 1:1 by baseline characteristics. Persistence, defined as the stay time, was assessed using Kaplan–Meier analysis and Cox proportional hazards models. Adherence was defined as a proportion of days covered of 0.8 or greater. To assess whether patients with more advanced disease would benefit from long-acting treatments, patients were matched to the baseline characteristics of basal insulin initiators using inverse probability of treatment weighting (IPTW).ResultsThe PS-matched cohorts (n = 784 each) had similar baseline characteristics. Once-weekly regimens were associated with significantly higher persistence than daily treatments (median stay time: 333 vs 269 days; hazard ratio 0.80 [95% confidence interval 0.71, 0.90]; p < 0.01) and with significantly higher adherence than daily regimens at 6 months and 12 months (p < 0.01 for both). Mean glycated haemoglobin reductions were greater with once-weekly than with daily treatment at 6 months (– 1.1% vs – 0.9%; p < 0.01) and 12 months (– 0.9% vs – 0.7%; p = not significant); adherent patients experienced greater reductions than those with poor adherence. Results were similar in the IPTW-matched analysis.ConclusionIn US clinical practice, once-weekly injectable treatments are associated with better persistence and adherence than daily regimens over 1 year. Once-weekly regimens may also benefit patients with more advanced T2D.Supplementary InformationThe online version contains supplementary material available at 10.1007/s13300-021-01189-6.

Prostate-Specific Membrane Antigen Radioligand Therapy Using 177Lu-PSMA I&T and 177Lu-PSMA-617 in Patients with Metastatic Castration-Resistant Prostate Cancer: Comparison of Safety, Biodistribution, and Dosimetry.

The objective of this study was to determine the safety, kinetics, and dosimetry of the 177Lu-labeled prostate-specific membrane antigen (PSMA) small molecules 177Lu-PSMA I&T and 177Lu-PSMA-617 in a large cohort of patients with metastatic castration-resistant prostate cancer (mCRPC) undergoing PSMA radioligand therapy (PRLT). Methods: In total, 138 patients (mean age, 70 ± 9 y; age range, 46-90 y) with progressive mCRPC and PSMA expression verified by 68Ga-PSMA-11 PET/CT underwent PRLT. Fifty-one patients received 6.1 ± 1.0 GBq (range, 3.4-7.6 GBq) of 177Lu-PSMA I&T, and 87 patients received 6.5 ± 1.1 GBq (range, 3.5-9.0 GBq) of 177Lu-PSMA-617. Dosimetry was performed on all patients using an identical protocol. The mean absorbed doses were estimated with OLINDA software (MIRD Scheme). Treatment-related adverse events were graded according to the Common Terminology Criteria for Adverse Events, version 5.0, of the National Cancer Institute. Results: The whole-body half-lives were shorter for 177Lu-PSMA I&T (35 h) than for 177Lu-PSMA-617 (42 h). The mean whole-body dose of 177Lu-PSMA-617 was higher than that of 177Lu-PSMA I&T (0.04 vs. 0.03 Gy/GBq, P < 0.00001). Despite the longer half-life of 177Lu-PSMA-617, the renal dose was lower for 177Lu-PSMA-617 than for 177Lu-PSMA I&T (0.77 vs. 0.92 Gy/GBq, P = 0.0015). Both PSMA small molecules demonstrated a comparable dose to the parotid glands (0.5 Gy/GBq, P = 0.27). Among all normal organs, the lacrimal glands exhibited the highest mean absorbed doses, 5.1 and 3.7 Gy/GBq, for 177Lu-PSMA-617 and 177Lu-PSMA I&T, respectively. All tumor metastases exhibited a higher initial uptake when using 177Lu-PSMA I&T than when using 177Lu-PSMA-617, as well as a shorter tumor half-life (P < 0.00001). The mean absorbed tumor doses were comparable for both 177Lu-PSMA I&T and 177Lu-PSMA-617 (5.8 vs. 5.9 Gy/GBq, P = 0.96). All patients tolerated the therapy without any acute adverse effects. After 177Lu-PSMA-617 and 177Lu-PSMA I&T, there was a small, statistically significant reduction in hemoglobin, leukocyte counts, and platelet counts that did not need any clinical intervention. No nephrotoxicity was observed after either 177Lu-PSMA I&T or 177Lu-PSMA-617 PRLT. Conclusion: Both 177Lu-PSMA I&T and 177Lu-PSMA-617 PRLT demonstrated favorable safety in mCRPC patients. The highest absorbed doses among healthy organs were in the lacrimal and parotid glands-not, however, resulting in any significant clinical sequel. 177Lu-PSMA-617 demonstrated a higher absorbed dose to the whole-body and lacrimal glands but a lower renal dose than did 177Lu-PSMA I&T. The mean absorbed tumor doses were comparable for both 177Lu-PSMA I&T and 177Lu-PSMA-617. There was a large interpatient variability in the dosimetry parameters. Therefore, individual patient-based dosimetry seems favorable for personalized PRLT.

Plasma biomarkers of hemoglobin loss in Plasmodium falciparum–infected children identified by quantitative proteomics

AbstractAnemia is common among young children infected with Plasmodium falciparum and severe malarial anemia (SMA) is a major cause of their mortality. Two major mechanisms cause malarial anemia: hemolysis of uninfected as well as infected erythrocytes and insufficient erythropoiesis. In a longitudinal birth cohort in Mali, we commonly observed marked hemoglobin reductions during P falciparum infections with a small proportion that progressed to SMA. We sought biomarkers of these processes using quantitative proteomic analysis on plasma samples from 9 P falciparum-infected children, comparing those with reduced hemoglobin (with or without SMA) vs those with stable hemoglobin. We identified higher plasma levels of circulating 20S proteasome and lower insulin-like growth factor-1 (IGF-1) levels in children with reduced hemoglobin. We confirmed these findings in independent enzyme-linked immunosorbent assay-based validation studies of subsets of children from the same cohort (20S proteasome, N = 71; IGF-1, N = 78). We speculate that circulating 20S proteasome plays a role in digesting erythrocyte membrane proteins modified by oxidative stress, resulting in hemolysis, whereas decreased IGF-1, a critical factor for erythroid maturation, might contribute to insufficient erythropoiesis. Quantitative plasma proteomics identified soluble mediators that may contribute to the major mechanisms underlying malarial anemia. This study was registered at www.clinicaltrials.gov as #NCT01168271.