-
1.
Comparative safety of different sodium-glucose transporter 2 inhibitors in patients with type 2 diabetes: a systematic review and network meta-analysis of randomized controlled trials.
Li, CX, Liu, LY, Zhang, CX, Geng, XH, Gu, SM, Wang, YQ, Liu, H, Xie, Q, Liang, S
Frontiers in endocrinology. 2023;:1238399
Abstract
BACKGROUNDS The safety of different sodium-glucose transporter 2 (SGLT-2) inhibitors remains uncertain due to the lack of head-to-head comparisons. METHODS This network meta-analysis (NMA) was performed to compare the safety of nine SGLT-2 inhibitors in patients with type 2 diabetes (T2DM). PubMed, Embase, Cochrane Central Register of Controlled Trials and ClinicalTrials.gov were searched for studies published in English before August 30, 2022. Published and unpublished randomized controlled trials (RCTs) comparing the safety of individual SGLT-2 inhibitors in patients with T2DM were included. A Bayesian NMA with random effects model was applied. Subgroup and sensitivity analyses were performed. The quality of the evidence was evaluated using the Confidence in Network Meta-Analysis framework. RESULTS Nine SGLT-2 inhibitors were evaluated in 113 RCTs (12 registries) involving 105,293 adult patients. Reproductive tract infections (RTIs) were reported in 1,967 (4.51%) and 276 (1.01%) patients in the SGLT-2 inhibitor and placebo groups, respectively. Furthermore, pollakiuria was reported in 233 (2.66%) and 45 (0.84%) patients, respectively. Compared to placebo, a significantly higher risk of RTIs was observed with canagliflozin, ertugliflozin, empagliflozin, remogliflozin, dapagliflozin, and sotagliflozin, but not with luseogliflozin and ipragliflozin, regardless of gender. An increased risk of pollakiuria was observed with dapagliflozin [odds ratio (OR) 10.40, 95% confidence interval (CI) 1.60-157.94) and empagliflozin (OR 5.81, 95%CI 1.79-32.97). Remogliflozin (OR 6.45, 95%CI 2.18-27.79) and dapagliflozin (OR 1.33, 95%CI 1.10-1.62) were associated with an increased risk of urinary tract infections (UTIs). Instead, the included SGLT-2 inhibitors had a protective effect against acute kidney injury (AKI). No significant differences were found for hypovolemia, renal impairment or failure, fracture, diabetic ketoacidosis (DKA), amputation, and severe hypoglycemia between the SGLT-2 inhibitor and the placebo groups. CONCLUSION In patients with T2DM, dapagliflozin was associated with an increased risk of RTIs, pollakiuria, and UTIs. Empagliflozin increased the risk of RTIs and pollakiuria. Remogliflozin increased the risk of UTIs. None of the SGLT-2 inhibitors showed a significant difference from the placebo for hypovolemia, renal impairment or failure, fracture, DKA, amputation, and severe hypoglycemia. The findings guide the selection of SGLT-2 inhibitors for patients with T2DM based on the patient's profiles to maximize safety. SYSTEMATIC REVIEW REGISTRATION https://www.crd.york.ac.uk/prospero, identifier CRD42022334644.
-
2.
Bioequivalence Study of Two Formulations of Mifepristone Tablets in Healthy Chinese Subjects Under Fasting Conditions.
Li, M, Yi, X, Fan, L, Yang, L, Xie, S, Shentu, J
Clinical pharmacology in drug development. 2023;(9):874-880
Abstract
A single-dose, open-label, randomized, two-period crossover-design study was conducted to evaluate the bioequivalence of the reference and test formulations of mifepristone tablets. Each subject was randomized at the beginning to receive a 25-mg tablet of the test or the reference mifepristone under fasting conditions during the first period, then received the alternate formulation during the second period following a 2-week washout period. A validated high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) method was used to determine the plasma concentrations of mifepristone and its two metabolites (RU42633 and RU42698). Fifty-two healthy subjects were enrolled in this trial, 50 of whom completed the study. The 90% confidence intervals for the log-transformed Cmax , AUC0-t , and AUC0-∞ fell within the accepted 80%-125% range. Throughout the study period, a total of 58 treatment-emergent adverse events were reported. No serious adverse event was observed. In conclusion, the test and reference mifepristone were bioequivalent and well tolerated under fasting conditions.
-
3.
Automated Insulin Delivery in Women with Pregnancy Complicated by Type 1 Diabetes.
Lee, TTM, Collett, C, Bergford, S, Hartnell, S, Scott, EM, Lindsay, RS, Hunt, KF, McCance, DR, Barnard-Kelly, K, Rankin, D, et al
The New England journal of medicine. 2023;(17):1566-1578
Abstract
BACKGROUND Hybrid closed-loop insulin therapy has shown promise for management of type 1 diabetes during pregnancy; however, its efficacy is unclear. METHODS In this multicenter, controlled trial, we randomly assigned pregnant women with type 1 diabetes and a glycated hemoglobin level of at least 6.5% at nine sites in the United Kingdom to receive standard insulin therapy or hybrid closed-loop therapy, with both groups using continuous glucose monitoring. The primary outcome was the percentage of time in the pregnancy-specific target glucose range (63 to 140 mg per deciliter [3.5 to 7.8 mmol per liter]) as measured by continuous glucose monitoring from 16 weeks' gestation until delivery. Analyses were performed according to the intention-to-treat principle. Key secondary outcomes were the percentage of time spent in a hyperglycemic state (glucose level >140 mg per deciliter), overnight time in the target range, the glycated hemoglobin level, and safety events. RESULTS A total of 124 participants with a mean (±SD) age of 31.1±5.3 years and a mean baseline glycated hemoglobin level of 7.7±1.2% underwent randomization. The mean percentage of time that the maternal glucose level was in the target range was 68.2±10.5% in the closed-loop group and 55.6±12.5% in the standard-care group (mean adjusted difference, 10.5 percentage points; 95% confidence interval [CI], 7.0 to 14.0; P<0.001). Results for the secondary outcomes were consistent with those of the primary outcome; participants in the closed-loop group spent less time in a hyperglycemic state than those in the standard-care group (difference, -10.2 percentage points; 95% CI, -13.8 to -6.6); had more overnight time in the target range (difference, 12.3 percentage points; 95% CI, 8.3 to 16.2), and had lower glycated hemoglobin levels (difference, -0.31 percentage points; 95% CI, -0.50 to -0.12). Little time was spent in a hypoglycemic state. No unanticipated safety problems associated with the use of closed-loop therapy during pregnancy occurred (6 instances of severe hypoglycemia, vs. 5 in the standard-care group; 1 instance of diabetic ketoacidosis in each group; and 12 device-related adverse events in the closed-loop group, 7 related to closed-loop therapy). CONCLUSIONS Hybrid closed-loop therapy significantly improved maternal glycemic control during pregnancy complicated by type 1 diabetes. (Funded by the Efficacy and Mechanism Evaluation Program; AiDAPT ISRCTN Registry number, ISRCTN56898625.).
-
4.
Early Extracorporeal CPR for Refractory Out-of-Hospital Cardiac Arrest.
Suverein, MM, Delnoij, TSR, Lorusso, R, Brandon Bravo Bruinsma, GJ, Otterspoor, L, Elzo Kraemer, CV, Vlaar, APJ, van der Heijden, JJ, Scholten, E, den Uil, C, et al
The New England journal of medicine. 2023;(4):299-309
Abstract
BACKGROUND Extracorporeal cardiopulmonary resuscitation (CPR) restores perfusion and oxygenation in a patient who does not have spontaneous circulation. The evidence with regard to the effect of extracorporeal CPR on survival with a favorable neurologic outcome in refractory out-of-hospital cardiac arrest is inconclusive. METHODS In this multicenter, randomized, controlled trial conducted in the Netherlands, we assigned patients with an out-of-hospital cardiac arrest to receive extracorporeal CPR or conventional CPR (standard advanced cardiac life support). Eligible patients were between 18 and 70 years of age, had received bystander CPR, had an initial ventricular arrhythmia, and did not have a return of spontaneous circulation within 15 minutes after CPR had been initiated. The primary outcome was survival with a favorable neurologic outcome, defined as a Cerebral Performance Category score of 1 or 2 (range, 1 to 5, with higher scores indicating more severe disability) at 30 days. Analyses were performed on an intention-to-treat basis. RESULTS Of the 160 patients who underwent randomization, 70 were assigned to receive extracorporeal CPR and 64 to receive conventional CPR; 26 patients who did not meet the inclusion criteria at hospital admission were excluded. At 30 days, 14 patients (20%) in the extracorporeal-CPR group were alive with a favorable neurologic outcome, as compared with 10 patients (16%) in the conventional-CPR group (odds ratio, 1.4; 95% confidence interval, 0.5 to 3.5; P = 0.52). The number of serious adverse events per patient was similar in the two groups. CONCLUSIONS In patients with refractory out-of-hospital cardiac arrest, extracorporeal CPR and conventional CPR had similar effects on survival with a favorable neurologic outcome. (Funded by the Netherlands Organization for Health Research and Development and Maquet Cardiopulmonary [Getinge]; INCEPTION ClinicalTrials.gov number, NCT03101787.).
-
5.
Preoperative Treatment of Locally Advanced Rectal Cancer.
Schrag, D, Shi, Q, Weiser, MR, Gollub, MJ, Saltz, LB, Musher, BL, Goldberg, J, Al Baghdadi, T, Goodman, KA, McWilliams, RR, et al
The New England journal of medicine. 2023;(4):322-334
-
-
Free full text
-
Abstract
BACKGROUND Pelvic radiation plus sensitizing chemotherapy with a fluoropyrimidine (chemoradiotherapy) before surgery is standard care for locally advanced rectal cancer in North America. Whether neoadjuvant chemotherapy with fluorouracil, leucovorin, and oxaliplatin (FOLFOX) can be used in lieu of chemoradiotherapy is uncertain. METHODS We conducted a multicenter, unblinded, noninferiority, randomized trial of neoadjuvant FOLFOX (with chemoradiotherapy given only if the primary tumor decreased in size by <20% or if FOLFOX was discontinued because of side effects) as compared with chemoradiotherapy. Adults with rectal cancer that had been clinically staged as T2 node-positive, T3 node-negative, or T3 node-positive who were candidates for sphincter-sparing surgery were eligible to participate. The primary end point was disease-free survival. Noninferiority would be claimed if the upper limit of the two-sided 90.2% confidence interval of the hazard ratio for disease recurrence or death did not exceed 1.29. Secondary end points included overall survival, local recurrence (in a time-to-event analysis), complete pathological resection, complete response, and toxic effects. RESULTS From June 2012 through December 2018, a total of 1194 patients underwent randomization and 1128 started treatment; among those who started treatment, 585 were in the FOLFOX group and 543 in the chemoradiotherapy group. At a median follow-up of 58 months, FOLFOX was noninferior to chemoradiotherapy for disease-free survival (hazard ratio for disease recurrence or death, 0.92; 90.2% confidence interval [CI], 0.74 to 1.14; P = 0.005 for noninferiority). Five-year disease-free survival was 80.8% (95% CI, 77.9 to 83.7) in the FOLFOX group and 78.6% (95% CI, 75.4 to 81.8) in the chemoradiotherapy group. The groups were similar with respect to overall survival (hazard ratio for death, 1.04; 95% CI, 0.74 to 1.44) and local recurrence (hazard ratio, 1.18; 95% CI, 0.44 to 3.16). In the FOLFOX group, 53 patients (9.1%) received preoperative chemoradiotherapy and 8 (1.4%) received postoperative chemoradiotherapy. CONCLUSIONS In patients with locally advanced rectal cancer who were eligible for sphincter-sparing surgery, preoperative FOLFOX was noninferior to preoperative chemoradiotherapy with respect to disease-free survival. (Funded by the National Cancer Institute; PROSPECT ClinicalTrials.gov number, NCT01515787.).
-
6.
Head-to-head comparison of FOLFIRINOX versus gemcitabine plus nab-paclitaxel in advanced pancreatic cancer: a target trial emulation using real-world data.
Boyne, DJ, Brenner, DR, Gupta, A, Mackay, E, Arora, P, Wasiak, R, Cheung, WY, Hernán, MA
Annals of epidemiology. 2023;:28-34
Abstract
PURPOSE To emulate a hypothetical target trial assessing the effect of initiating 5-fluorouracil, folinic acid, irinotecan, and oxaliplatin (FOLFIRINOX) versus gemcitabine plus nab-paclitaxel (GN) within 8 weeks of diagnosis on overall survival. METHODS An observational cohort study was conducted using population-level data from Alberta, Canada. Individuals diagnosed with advanced pancreatic cancer between April 2015 and December 2019 were identified through the provincial cancer registry and followed until March 2021. Records were linked to other administrative databases containing information on relevant variables. Individuals were excluded if they did not have adequate hemoglobin, platelet, white blood cell, and serum creatinine measures or if they received prior therapy. The observational analog of the per-protocol effect was estimated using inverse probability weighted Kaplan-Meier curves with bootstrapped 95% confidence intervals. RESULTS Four hundred seven individuals were eligible. The weighted median overall survival was 8.3 months (95% CI, 5.7-11.9) for FOLFIRINOX and 5.1 months (95% CI: 4.3 to 5.8) for GN. The adjusted difference in median overall survival was 3.2 months (95% CI, 1.1-7.4) and the mortality hazard ratio was 0.78 (95% CI, 0.61-0.97). CONCLUSIONS Our estimates favored the initiation of FOLFIRINOX over GN with respect to overall survival.
-
7.
Comparative efficacy of glucagon-like peptide 1 (GLP-1) receptor agonists, pioglitazone and vitamin E for liver histology among patients with nonalcoholic fatty liver disease: systematic review and pilot network meta-analysis of randomized controlled trials.
Gu, Y, Sun, L, He, Y, Yang, L, Deng, C, Zhou, R, Kong, T, Zhang, W, Chen, Y, Li, J, et al
Expert review of gastroenterology & hepatology. 2023;(3):273-282
Abstract
INTRODUCTION There is no conclusive evidence comparing the efficacy of glucagon-like peptide 1 (GLP-1) receptor agonists to the other guidelines recommended pharmacotherapy for nonalcoholic fatty liver disease (NAFLD). Therefore, we aim to compare the effects of GLP-1 receptor agonists, pioglitazone and vitamin E in patients with NAFLD. METHODS We searched PubMed, Embase, Web of Science and Cochrane Library up to 11 April 2022. Randomized clinical trials (RCTs) comparing GLP-1 receptor agonists, pioglitazone and vitamin E against placebo or other active controls in patients with NAFLD were included. RESULTS Nine RCTs including 1482 patients proved eligible. GLP-1 receptor agonists ranked first in steatosis, ballooning necrosis, γ-glutamyl transferase, body weight, body mass index, and triglycerides. Administration of GLP-1 receptor agonists, as compared with placebo, was associated with improvement in liver histology [steatosis (OR = 4.11, 95% CI: 2.83, 5.96), ballooning necrosis (OR = 3.07, 95% CI: 2.14, 4.41), lobular inflammation (OR = 1.86, 95% CI: 1.29, 2.68), fibrosis (OR = 1.52, 95% CI: 1.06, 2.20)]. CONCLUSIONS GLP-1 receptor agonists were as effective as pioglitazone and vitamin E for liver histology among patients with NAFLD. GLP-1 receptor agonists might be considered as an alternative or complementary treatment in the future clinical practice. [Figure: see text].
-
8.
A comparison of observed feeding practices of infants and young children aged 6-23 months to national responsive feeding recommendations in Sri Lanka.
Schwendler, TR, Rowel, D, Abdulloeva, S, Jayawickrama, H, de Silva, C, Romano, O, Senarath, U, Kodish, SR
Maternal & child nutrition. 2023;(3):e13522
-
-
Free full text
-
Abstract
To describe the extent to which Sri Lankan caregivers follow current national responsive feeding recommendations and the factors limiting and enabling those behaviours. Study design. This ethnographic substudy was conducted using a four-phase, mixed methods formative research design across rural, estate and urban sectors of Sri Lanka. Data collection methods. Data were collected using direct meal observations and semistructured interviews. Participants including infants and young children aged 6-23 months (n = 72), community leaders (n = 10), caregivers (n = 58) and community members (n = 37) were purposefully sampled to participate in this study. Data analysis. Observational data were summarized using descriptive statistics while textual data were analysed thematically using Dedoose. Findings were then interpreted vis-à-vis six national responsive feeding recommendations. During observed feeding episodes, caregivers were responsive to nearly all food requests (87.2% [34/39]) made by infants and young children. Many caregivers (61.1% [44/72]) also positively encouraged their infant and young child during feeding. Despite some responsive feeding practices being observed, 36.1% (22/61) of caregivers across sectors used forceful feeding practices if their infant or young child refused to eat. Interviews data indicated that force-feeding practices were used because caregivers wanted their infants and young children to maintain adequate weight gain for fear of reprimand from Public Health Midwives. Despite overall high caregiver knowledge of national responsive feeding recommendations in Sri Lanka, direct observations revealed suboptimal responsive feeding practices, suggesting that other factors in the knowledge-behaviour gap may need to be addressed.
-
9.
Comparative Evaluation of a Low-Carbohydrate Diet and a Mediterranean Diet in Overweight/Obese Patients with Type 2 Diabetes Mellitus: A 16-Week Intervention Study.
Currenti, W, Losavio, F, Quiete, S, Alanazi, AM, Messina, G, Polito, R, Ciolli, F, Zappalà, RS, Galvano, F, Cincione, RI
Nutrients. 2023;(1)
Abstract
INTRODUCTION The worldwide prevalence of type 2 diabetes mellitus (T2DM) and obesity has been steadily increasing over the past four decades, with projections indicating a significant rise in the number of affected individuals by 2045. Therapeutic interventions in T2DM aim to control blood glucose levels and reduce the risk of complications. Dietary and lifestyle modifications play a crucial role in the management of T2DM and obesity. While conventional medical nutritional therapy (MNT) often promotes a high-carbohydrate, low-fat Mediterranean diet as an elective treatment, low-carbohydrate diets (LCDs), specifically those restricting carbohydrate intake to less than 130 g/day, have gained popularity due to their multifaceted benefits. Scientific research supports the efficacy of LCDs in improving glycemic control, weight loss, blood pressure, lipid profiles, and overall quality of life. However, sustaining these benefits over the long term remains challenging. This trial aimed to compare the effects of a Mediterranean diet vs. a low-carbohydrate diet (carbohydrate intake < 130 g/day) on overweight/obese patients with T2DM over a 16-week period. The study will evaluate the differential effects of these diets on glycemic regulation, weight reduction, lipid profile, and cardiovascular risk factors. METHODS The study population comprises 100 overweight/obese patients with poorly controlled T2DM. Anthropometric measurements, bioimpedance analysis, and blood chemistry assessments will be conducted at baseline and after the 16-week intervention period. Both dietary interventions were hypocaloric, with a focus on maintaining a 500 kcal/day energy deficit. RESULTS After 16 weeks, both diets had positive effects on various parameters, including weight loss, blood pressure, glucose control, lipid profile, and renal function. However, the low-carbohydrate diet appears to result in a greater reduction in BMI, blood pressure, waist circumference, glucose levels, lipid profiles, cardiovascular risk, renal markers, and overall metabolic parameters compared to the Mediterranean diet at the 16-week follow up. CONCLUSIONS These findings suggest that a low-carbohydrate diet may be more effective than a Mediterranean diet in promoting weight loss and improving various metabolic and cardiovascular risk factors in overweight/obese patients with T2DM. However, it is important to note that further research is needed to understand the clinical implications and long-term sustainability of these findings.
-
10.
Efficacy and safety of iodized lecithin tablets versus spironolactone in alleviating central serous retinopathy among Chinese patients with uncontrolled diabetes.
Gu, H, Pu, L, Yu, S
Pakistan journal of pharmaceutical sciences. 2023;(2(Special)):595-599
Abstract
To compare the effectiveness and safety of spironolactone versus lecithin-bound iodine in patients with central serous retinopathy (CSR). Chinese diabetes patients aged>18 years with CSR with persistent increased level of subretinal fluid (SRF) were enrolled. Subjects were randomized to receive either oral lecithin-bound iodine (390µg/kg/day) or oral spironolactone (50mg/day) for 6 months. A total of 200 patients were randomized and completed the study. Compared to spironolactone group, patients treated with lecithin-bound iodine had greater proportion of eye with complete resolution (87% vs 81%, p>0.005). Higher improvement in height of SRF was observed in lecithin-bound iodine-treated patients as compared with Spironolactone-treated patients (91.2[87.5] vs 142.5 [121.1]; p>0.005). However, no statistically significant difference was observed on none of comparisons. Compared to Spironolactone, the patients treated with lecithin-bound iodine had greater improvement in lesion size, central macular thickness and best-corrected visual acuity. However, no statistically significant difference was observed in any of parameter assessed. (p>0.005). The results of the present study suggested that the lecithin-bound iodine was found more effective (nnumerically) than spironolactone in Chinese diabetes patients with CSR.