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JAMA Network Open Jun 2024Varenicline is the most effective sole pharmacotherapy for smoking cessation. If used in combination with nicotine replacement therapy (NRT), cessation rates may be... (Randomized Controlled Trial)
Randomized Controlled Trial
IMPORTANCE
Varenicline is the most effective sole pharmacotherapy for smoking cessation. If used in combination with nicotine replacement therapy (NRT), cessation rates may be further improved, but the efficacy and safety of the combination need to be evaluated.
OBJECTIVE
To examine whether hospitalized smokers treated with varenicline and NRT lozenges achieve higher prolonged smoking abstinence rates compared with those treated with varenicline alone.
DESIGN, SETTING, AND PARTICIPANTS
A double-blind, placebo-controlled randomized clinical trial was conducted in adult medical or surgical inpatients of 5 Australian public hospitals with a history of smoking 10 cigarettes or more per day, interested in quitting, and available for 12-month follow-up between May 1, 2019, and May 1, 2021 (final 12-month data collection in May 2022). Data analysis was performed from June 1 to August 30, 2023.
INTERVENTIONS
A 12-week varenicline regimen was initiated during hospitalization at standard doses in all participants. Participants were randomized to additionally use NRT (2 mg) or placebo lozenges if there was an urge to smoke. Behavioral support (Quitline) was offered to all participants.
MAIN OUTCOMES AND MEASURES
The primary outcome was biochemically verified sustained abstinence at 6 months. Secondary outcomes included self-reported prolonged abstinence, 7-day point prevalence abstinence (3, 6, and 12 months), and medicine-related adverse events.
RESULTS
A total of 320 participants (mean [SD] age, 52.5 [12.1] years; 183 [57.2%] male) were randomized. The conduct of biochemical verification was affected by COVID-19 restrictions; consequently, the biochemically verified abstinence in the intervention vs control arms (18 [11.4%] vs 16 [10.1%]; odds ratio [OR], 1.14; 95% CI, 0.56-2.33) did not support the combination therapy. The secondary outcomes in the intervention vs control arms of 7-day point prevalence abstinence at 6 months (54 [34.2%] vs 37 [23.4%]; OR, 1.71; 95% CI, 1.04-2.80), prolonged abstinence at 12 months (47 [29.9%] vs 30 [19.1%]; OR, 1.77; 95% CI, 1.05-3.00), and 7-day point prevalence abstinence at 12-months (48 [30.6%] vs 31 [19.7%]; OR, 1.79; 95% CI, 1.07-2.99) significantly improved with the combination therapy. The self-reported 6-month prolonged abstinence (61 [38.6%] vs 47 [29.7%]; OR, 1.49; 95% CI, 0.93-2.39) favored the combination therapy but was not statistically significant. Medicine-related adverse events were similar in the 2 groups (102 [74.5%] in the intervention group vs 86 [68.3%] in the control group).
CONCLUSIONS AND RELEVANCE
In this randomized clinical trial of the combination of varenicline and NRT lozenges in hospitalized adult daily smokers, the combination treatment improved self-reported abstinence compared with varenicline alone, without compromising safety, but it did not improve biochemically validated abstinence.
TRIAL REGISTRATION
anzctr.org.au Identifier: ACTRN12618001792213.
Topics: Humans; Varenicline; Male; Female; Smoking Cessation; Tobacco Use Cessation Devices; Middle Aged; Double-Blind Method; Adult; Smoking Cessation Agents; Australia; Hospitalization; Smokers; Aged; Treatment Outcome; Nicotine Replacement Therapy
PubMed: 38935378
DOI: 10.1001/jamanetworkopen.2024.18120 -
Endocrine Jun 2024We recently demonstrated an additional oxytocin (OT) deficiency in patients with arginine vasopressin (AVP) deficiency (central diabetes insipidus) by using...
PURPOSE
We recently demonstrated an additional oxytocin (OT) deficiency in patients with arginine vasopressin (AVP) deficiency (central diabetes insipidus) by using 3,4-methylenedioxy-methamphetamine (MDMA) as a novel provocation test. However, the implication of the MDMA provocation test in clinical practice might be challenging. Glucagon effectively stimulates vasopressinergic neurons with a strong increase in plasma copeptin. We therefore hypothesized that this provocation test might also stimulate OT.
METHODS
This is a predefined secondary analysis of a prospective double-blind, randomised, placebo-controlled cross-over trial involving ten patients with AVP deficiency and ten sex- and body-mass index-matched healthy participants at the University Hospital Basel, Switzerland. Each participant underwent the glucagon test (s.c. injection of 1 mg glucagon) and placebo test (s.c. injection of 0.9% normal saline). Plasma OT levels were measured at baseline, 60, 120 and 180 min after injection. The primary objective was to determine whether glucagon stimulates OT and whether OT levels differ between patients with AVP deficiency and healthy participants. The primary outcome (maximum change in OT within 180 min) was compared between groups and conditions using a linear mixed effects model.
RESULTS
In healthy participants, the median OT at baseline was 82.7 pg/ml [62.3-94.3] and slightly increased to a maximum of 93.3 pg/ml [87.2-121.1] after injection of glucagon, resulting in a change increase of 24.9 pg/ml [5.1-27.8]. Similarly, in patients with AVP deficiency, the median OT at baseline was 73.9 pg/ml [65.3-81.6] and slightly increased after glucagon injection to 114.9 pg/ml [70.9-140.9], resulting in a change increase of 36.8 pg/ml [-2.2 to 51.2]. The results from the mixed model showed no effect between glucagon compared to placebo on OT (difference: -0.5 pg/ml; 95%-CI [-25, 24]; p = 0.97) and no significant treatment-by-group interaction effect between patients compared to healthy participants (interaction: 28 pg/ml; 95%-CI [-7, 62]; p = 0.13).
CONCLUSION
We found no effect of glucagon on plasma OT levels and no difference between patients with AVP deficiency and healthy participants.
PubMed: 38935296
DOI: 10.1007/s12020-024-03920-2 -
Journal of Perianesthesia Nursing :... Jun 2024The perioperative use of gabapentin has been suggested to reduce postoperative pain and opioid consumption. However, there is a variation in clinical practice, the type...
PURPOSE
The perioperative use of gabapentin has been suggested to reduce postoperative pain and opioid consumption. However, there is a variation in clinical practice, the type of surgery and the administration time seem to be distinct between the available studies. We assess whether gabapentin administered before surgery reduces postoperative pain in patients who have undergone inguinal hernioplasty.
DESIGN
This is a double-blind, randomized, and placebo-controlled trial.
METHODS
Seventy-seven patients scheduled for inguinal hernioplasty were randomized in two groups to receive gabapentin (900 mg) or placebo in the perioperative period. The primary outcome was analgesia measured by visual analog scale up to 30 days after surgery. The secondary outcomes such as morphine consumption, nausea, headache, and sedation have been also described.
FINDINGS
Patients who received gabapentin had lower postoperative pain scores compared to the control group, P < .001. The postoperative morphine use was significantly lower in the gabapentin (5.3%) versus placebo group (74.4%), P < .001. No significant difference between groups was observed for the occurrence of adverse events.
CONCLUSIONS
The perioperative administration of gabapentin was effective in reducing postoperative pain and had an important effect in decreasing morphine use. Together, our data reveal a long-lasting opioid-sparing effect of gabapentin in patients who underwent inguinal hernioplasty.
PubMed: 38935013
DOI: 10.1016/j.jopan.2024.01.018 -
Experimental and Clinical... Jun 2024Intranasal oxytocin (INOT) has received attention as a treatment for substance use disorders including tobacco dependence. However, it is unclear whether INOT-related...
Intranasal oxytocin (INOT) has received attention as a treatment for substance use disorders including tobacco dependence. However, it is unclear whether INOT-related effects differ by sex and social functioning traits. This study examined the influence of sex and two trait social functioning measures (hostility and rejection sensitivity) on INOT effects on abstinence-related subjective measures and smoking lapse. Adults who smoked cigarettes daily ( = 64; 21-40 years; 39% female) completed trait hostility and rejection sensitivity surveys at baseline followed by three experimental sessions following 12-hr smoking abstinence. Each session, participants received a single INOT dose (placebo, 20, 40 international units [IU]) in counterbalanced order, completed withdrawal, smoking urges and affect questionnaires, and a smoking lapse analog task. Interactive effects between INOT and sex, hostility, or rejection sensitivity on all outcomes were analyzed. INOT produced differential effects as a function of sex, trait hostility, and rejection sensitivity. The 20 IU dose worsened abstinence-related subjective effects for individuals with high trait hostility. Both INOT doses decreased smoking urges for high rejection sensitivity, and the 20 IU dose increased smoking urges for low rejection sensitivity. INOT increased withdrawal symptoms, smoking urges, and feelings of anger in females but not males. INOT did not improve withdrawal symptoms during abstinence and did not affect smoking lapse. While INOT produced some beneficial effects for a subset of participants with high rejection sensitivity, it worsened abstinence-related symptoms for others. Our results suggest that sex and social functioning should be considered when examining the therapeutic potential of INOT for smoking cessation in future research. (PsycInfo Database Record (c) 2024 APA, all rights reserved).
PubMed: 38934915
DOI: 10.1037/pha0000733 -
Journal of Pediatric Hematology/oncology Jun 2024There are conflicting results in preventing catheter-related thrombosis (CRT). Continuing infusion of unfractionated heparin (UFH) was a potential option for CRT. This...
A Randomized, Controlled Trial of Continuous Heparin Infusion to Prevent Asymptomatic Catheter-Related Thrombosis at Discharge in Infants After Cardiac Surgery: The CHIP-CRT Trial.
OBJECTIVES
There are conflicting results in preventing catheter-related thrombosis (CRT). Continuing infusion of unfractionated heparin (UFH) was a potential option for CRT. This study was to determine the effect of continuous UFH infusion on asymptomatic CRT at discharge in infants after cardiac surgery.
STUDY DESIGN
This study was a randomized, placebo-controlled, clinical trial at a single center. All infants with central venous catheters after cardiac surgery, below 3 months of age, were eligible. Stratified by CRT, infants were randomly assigned to the UFH group or the normal saline group. UFH was initiated at a speed of 10 to 15 units/kg/h for infants with CRT and 2 to 3 units/kg/h without CRT. The primary outcome was to determine the rate of CRT at discharge. The secondary outcomes included thrombosis 6 months after surgery, adverse events of UFH, and post-thrombotic symptoms.
RESULTS
Due to slow recruitment during the COVID-19 pandemic, this trial was prematurely stopped. Only 35 infants were randomly assigned to the UFH or control groups. There was no statistically significant difference in CRT rate at discharge (P=0.429) and 6 months after surgery (P=1.000) between groups. All CRTs except one disappeared at discharge. No thrombosis or post-thrombotic symptom was reported at follow-up evaluation. There was no difference between groups in duration of thrombus (P=0.088), D dimer (P=0.412), catheter in situ days (P=0.281), and post-thrombotic syndrome (P=1.000), except for activated partial thromboplastin time (P=0.001).
CONCLUSIONS
With the early stop of this trial and limited data, it is difficult to draw a definitive conclusion about the efficacy of UFH on CRT. Meanwhile, considering the data from 6 months follow-up, in this population, asymptomatic CRT might resolve with no intervention.
PubMed: 38934602
DOI: 10.1097/MPH.0000000000002905 -
BMJ Open Sport & Exercise Medicine 2024No study has evaluated the effects of dry needling on Paralympic athletes. Therefore, in this study, we will evaluate the effect of dry needling on lower limb spasticity...
No study has evaluated the effects of dry needling on Paralympic athletes. Therefore, in this study, we will evaluate the effect of dry needling on lower limb spasticity and motor performance, as well as the range of motion of Paralympic athletes. The study will be a triple-blinded, randomised controlled trial. Twenty-four athletes aged 18-45 in T35-T38 groups of the International Paralympic Committee classification will be included in the study. Twelve participants will receive dry needling of the quadriceps and gastrocnemius muscles, and 12 will receive placebo treatment with sham needles at similar points. We will assess the spasticity of the quadriceps and gastrocnemius muscles using the Modified Ashworth Scale, evaluate motor function using the Selective Control Assessment of the Lower Extremity Scale and measure ankle range of motion (ROM) with a goniometer. Considering our hypothesis, the athletes who will undergo the dry needling are supposed to achieve better improvements in spasticity, ROM and motor performance. This study can provide useful information to help better decide on managing complications in Paralympics and its long-term outcomes, to cover the current lack in the literature.
PubMed: 38933371
DOI: 10.1136/bmjsem-2024-002096 -
Journal of Diabetes and Metabolic... Jun 2024Excess body fat, insulin resistance, and abnormal lipid levels signal type 2 diabetes mellitus (DM2). Globally, 536.6 million people suffer from DM2, projected to rise...
Evaluating the effectiveness and safety of various Tirzepatide dosages in the management of Type 2 diabetes mellitus: a network meta-analysis of randomized controlled trials.
PURPOSE
Excess body fat, insulin resistance, and abnormal lipid levels signal type 2 diabetes mellitus (DM2). Globally, 536.6 million people suffer from DM2, projected to rise to 783.2 million by 2045. Obesity fuels insulin resistance and DM2 development, with weight loss significantly improving glycemic control. Titrzepatide (TZP), a dual GIP and GLP-1 receptor agonist, proves highly effective in controlling hyperglycemia, stimulating insulin secretion, and promoting weight loss. TZP, holds promise as a treatment for DM2, surpassing insulin and GLP-1. The study aimed to meticulously assess the safety and efficacy of various doses, offering insights into optimal therapeutic strategies for managing DM2.
METHODS
This study aimed to comprehensively evaluate the safety and efficacy of TZP in treating DM2. The primary focus of the inclusion criteria was on trials comparing TZP with a placebo until November 23, 2023, excluding patients with certain comorbidities. Data extraction included key parameters, and outcomes were assessed for HbA1c levels, weight changes, fasting serum glucose levels, and various adverse events. Quality assessment utilized the Cochrane Collaboration's risk-of-bias tool, and a network meta-analysis explored outcomes across different TZP dosages.
RESULTS
This meta-analysis systematically reviewed ten studies on TZP for DM2. Results revealed significant reductions in HbA1c with TZP 10 mg (19%) and TZP 15 mg (31%) compared to TZP 5 mg (MD: -0.19 and MD: -0.32, respectively). Additionally, weight reduction was notable for TZP 10 mg (MD: -1.96) and TZP 15 mg (MD: -3.31). Fasting serum glucose showed improvement with TZP 15 mg (MD:-6.71). Gastrointestinal events increased with higher doses, yet without statistical significance. Death, nausea, diarrhea, vomiting, dyspepsia, decreased appetite, injection site reaction, hypoglycemia, treatment discontinuation, and serious adverse events showed no significant differences across doses.
CONCLUSION
TZP effectively lowers HbA1c and induces weight loss across its three doses for type 2 diabetes management. The higher dose (15 mg) significantly reduces fasting serum glucose, with increased adverse events observed at higher doses. Dose-specific patterns for adverse effects emphasize the need to balance therapeutic benefits and risks. Further research is crucial for refining clinical applications and understanding TZP's role in DM2 management across doses.
SUPPLEMENTARY INFORMATION
The online version contains supplementary material available at 10.1007/s40200-024-01412-8.
PubMed: 38932909
DOI: 10.1007/s40200-024-01412-8 -
Journal of Diabetes and Metabolic... Jun 2024Although several randomized clinical trials have tested the effect of prenatal dietary supplements on plasma glucose and lipid levels in non-pharmacologically managed...
The dietary supplements effect on metabolic markers in non-pharmacologically managed gestational diabetes mellitus patients: a systematic review and meta-analysis and meta-regression of randomized controlled trials.
BACKGROUND
Although several randomized clinical trials have tested the effect of prenatal dietary supplements on plasma glucose and lipid levels in non-pharmacologically managed gestational diabetes mellitus patients (GDM), a rigorous meta-analytic compendium lacks in the context. Therefore, this study aims to address this evidence gap.
METHOD
Eligible trials retrieved from searches in the PubMed, Embase, and Scopus databases were appraised using the Revised Cochrane risk-of-bias tool for randomized trials (RoB 2). The weighted mean differences (WMD) between dietary supplements and placebo were estimated using random-effect meta-analysis models for plasma glycemic and lipid markers. Meta-regression analysis ensued for effect modifier identification. The statistical significance estimation happened at < 0.05 (95% confidence interval).
RESULTS
This review included 19 trials (mostly Iranian and of low risk of bias primarily) of > 8000 GDM patients. Meta-analysis showed favorable effects of dietary supplementation on fasting plasma glucose (WMD: -5.42 mg/dL, p < 0.001), homeostasis model assessment indexes- insulin resistance (HOMA-IR; WMD: -1.02, p < 0.001), quantitative insulin sensitivity check index (WMD: 0.01, p < 0.001), total cholesterol (TC; WMD: -7.70 mg/dL, = 0.006), triglycerides (WMD: -10.23 mg/dL, = 0.0083), TC/high-density lipoprotein (WMD: -0.31 mg/dL, < 0.001), low-density lipoprotein (WMD: -5.79 mg/dL; < 0.001) and very-low-density lipoprotein (WMD: -5.67 mg/dL, < 0.001) levels. However, the HOMA- ß-cell function didn't increase (WMD: -17.91, < 0.001). Baseline maternal age ( = 0.28, = 0.014) and GDM diagnostic criteria ( = 0.90, = 0.012) were effect moderators of HOMA-IR and body mass index (BMI) ( = 6.07, = 0.022) and supplement type (solo versus combined) ( = 14.99, = 0.006) were effect moderators of triglyceride levels.
CONCLUSION
Altogether, antenatal dietary supplements achieved control over plasma glycemic and lipid profiles in non-pharmacologically treated GDM patients. Maternal age and GDM diagnostic criteria moderated HOMA-IR levels. BMI and supplement-type moderated triglyceride levels.
SUPPLEMENTARY INFORMATION
The online version contains supplementary material available at 10.1007/s40200-023-01369-0.
PubMed: 38932907
DOI: 10.1007/s40200-023-01369-0 -
Journal of Diabetes and Metabolic... Jun 2024Efpeglenatide, a novel GLP-1 receptor agonist, has shown promise in improving glycemic control and inducing weight loss in individuals with type 2 diabetes (T2DM). This... (Review)
Review
BACKGROUND
Efpeglenatide, a novel GLP-1 receptor agonist, has shown promise in improving glycemic control and inducing weight loss in individuals with type 2 diabetes (T2DM). This meta-analysis assessed its therapeutic potential and safety profile.
METHODS
A literature search was conducted on PubMed, SCOPUS, and Cochrane Central from inception until September 2023. We selected patients with T2DM and identified and compared those receiving efpeglenatide to placebo. Outcomes assessed included fasting plasma glucose (FPG), HbA1c, body weight, BMI, and cardiometabolic parameters. Data were analyzed using a random-effects model, with results presented as mean differences (MD) for continuous outcomes and risk ratios (RR) for safety analysis, along with their respective 95% confidence intervals. Quality assessment was conducted using the Cochrane risk of bias tool.
RESULTS
We included 11 studies in our analysis. Efpeglenatide demonstrated significant reductions in FPG (MD = -1.53 mmol/L, 95% CI = [-2.86, -0.66], < 0.01), HbA1c (MD = -0.84, 95% CI= [-1.08, -0.60], < 0.01), body weight (MD = -2.24 kg, 95% CI = [-4.20, -2.00], < 0.01), and BMI (MD = -1.61 kg/m, 95% CI= [-2.12, -1.09], < 0.01). However, efpeglenatide was associated with a moderate increase in the risk of gastrointestinal adverse events, nausea, diarrhea, and vomiting. There was a non-significant elevated risk of hypoglycemia.
CONCLUSIONS
Efpeglenatide significantly improves glycemic outcomes and promotes weight loss in individuals with diabetes. However, it is associated with moderate adverse effects related to the gastrointestinal system. Thus, further trials are warranted to comprehensively assess its safety and efficacy to derive a robust conclusion.
SUPPLEMENTARY INFORMATION
The online version contains supplementary material available at 10.1007/s40200-024-01409-3.
PubMed: 38932865
DOI: 10.1007/s40200-024-01409-3 -
Journal of Diabetes and Metabolic... Jun 2024Regarding the importance of obesity concerns and trying to help obese individuals, we planned to develop an effective probiotic formula for weight control. So, this...
PURPOSE
Regarding the importance of obesity concerns and trying to help obese individuals, we planned to develop an effective probiotic formula for weight control. So, this double-blind randomized clinical trial study investigated the impact of probiotics supplementation on anthropometric and biochemical parameters in obese adults.
METHODS
In this study, 66 obese patients with BMI in the range of 30-40 kg/m2, were enrolled and randomly assigned to either the probiotic or placebo group. They all received advice to maintain a reduction in daily caloric intake and for 3 months received two unlabeled placebo or probiotic (, , ) capsules per day. For each participant demographic and medical history questionnaire, semi-quantitative food frequency questionnaire (FFQ), and modifiable activity questionnaire (MAQ) were completed at the beginning of the study and anthropometric and biochemical measurements were done before and after intervention.
RESULTS
At the end of the trial 25 subjects in the probiotic group and 26 subjects in the placebo group were analyzed. After the intervention, in the probiotic group, the level of fasting insulin was reduced significantly ( < 0.05). Weight, body mass index, waist circumference, and hip circumference decreased within both groups. This reduction amount's mean was higher in the probiotic group. Also, total cholesterol, triglycerides, and LDL levels were decreased, but not statistically significant.
CONCLUSION
This study may suggest the potential of this combined probiotic supplement for treating obesity and related metabolic disorders. However, further researches are warranted for a definitive determination of its properties.
PubMed: 38932862
DOI: 10.1007/s40200-024-01400-y