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PloS One 2024The objective of this study was to estimate the associations of jail-initiated medication for opioid use disorder (MOUD) and patient navigation (PN) with opioid use... (Randomized Controlled Trial)
Randomized Controlled Trial
The objective of this study was to estimate the associations of jail-initiated medication for opioid use disorder (MOUD) and patient navigation (PN) with opioid use disorder (OUD) at 6 months post-release. Three randomized trials (combined N = 330) were combined to assess whether MOUD (extended-release naltrexone or interim methadone) initiated prior to release from jail with or without PN would reduce the likelihood of a DSM-5 diagnosis of OUD 6 months post-release relative to enhanced treatment-as-usual (ETAU). Across the three studies, assignment to MOUD compared to ETAU was not associated with an OUD diagnosis at 6 months post-release (69% vs. 75%, respectively, OR = 0.67, 95% CI: 0.42 to 1.20). Similarly, PN compared to MOUD without PN was not associated with an OUD diagnosis (63% vs 77%, respectively, OR = 0.61, 95% CI: 0.27 to 1.53). Results underscore the need to further optimize the effectiveness of MOUD for patients initiating treatment in jail, beginning with an emphasis on post-release treatment adherence.
Topics: Humans; Opioid-Related Disorders; Male; Naltrexone; Female; Adult; Methadone; Jails; Opiate Substitution Treatment; Middle Aged; Narcotic Antagonists; Prisoners
PubMed: 38885220
DOI: 10.1371/journal.pone.0305165 -
Scientific Reports Jun 2024This study aimed to compare tumor lesion detectability and diagnostic accuracy of whole-body magnetic resonance imaging (WB-MRI) and radioiodine-labeled... (Comparative Study)
Comparative Study
This study aimed to compare tumor lesion detectability and diagnostic accuracy of whole-body magnetic resonance imaging (WB-MRI) and radioiodine-labeled meta-iodo-benzylguanidine (mIBG) imaging techniques in patients with metastatic pheochromocytoma and paraganglioma (PPGL). This retrospective study included 13 patients had pheochromocytoma and 5 had paraganglioma, who were all suspected of having metastatic tumors. Each patient underwent WB-MRI and I-mIBG as a pretreatment screening for I-mIBG therapy. Two expert reviewers evaluated WB-MRI, I-mIBG images, and post-therapy I-mIBG images for the presence of metastatic lesions in the lungs, bones, liver, lymph nodes, and other organs. Diagnostic measures for detecting metastatic lesions, including sensitivity, specificity, accuracy, positive predictive value (PPV), negative predictive value (NPV), and receiver operating characteristics (ROC)-area under the curve (AUC), were calculated for each imaging technique. We analyzed WB-MRI images for detecting metastatic lesions, which demonstrated sensitivity, specificity, accuracy, PPV, NPV, and AUC of 82%, 97%, 90%, 96%, 86%, and 0.92, respectively. These values were 83%, 95%, 89%, 94%, 86%, and 0.90 in I-mIBG images and 85%, 92%, 89%, 91%, 87%, and 0.91 in post-therapy I-mIBG images, respectively. Our results reveal the comparable diagnostic accuracy of WB-MRI to one of the mIBG images.
Topics: Humans; Pheochromocytoma; 3-Iodobenzylguanidine; Paraganglioma; Female; Male; Magnetic Resonance Imaging; Middle Aged; Adult; Whole Body Imaging; Adrenal Gland Neoplasms; Retrospective Studies; Iodine Radioisotopes; Aged; Neoplasm Metastasis; Radiopharmaceuticals; Sensitivity and Specificity; Young Adult
PubMed: 38879654
DOI: 10.1038/s41598-024-64607-2 -
Canadian Journal of Psychiatry. Revue... Jun 2024Capacity to consent to treatment of substance use disorders at Ontario's Consent and Capacity Board: A review of past reported decisions.
Capacity to consent to treatment of substance use disorders at Ontario's Consent and Capacity Board: A review of past reported decisions.
PubMed: 38872386
DOI: 10.1177/07067437241261488 -
Systematic Reviews Jun 2024Due to increasing life expectancy, almost half of people with type 2 diabetes are aged 65 years or over worldwide. When metformin alone does not control blood sugar,...
The optimal second-line therapy for older adults with type 2 diabetes mellitus: protocol for a systematic review and network meta-analysis using individual participant data (IPD).
BACKGROUND
Due to increasing life expectancy, almost half of people with type 2 diabetes are aged 65 years or over worldwide. When metformin alone does not control blood sugar, the choice of which second-line therapy to prescribe next is not clear from currently available evidence. The existence of frailty and comorbidities in older adults further increases the complexity of medical decision-making. As only a relatively small proportion of trials report results separately for older adults, the relative efficacy and safety of second-line therapies in older adults with type 2 diabetes mellitus are unknown and require further investigation. This individual participant data (IPD) network meta-analysis evaluates the relative efficacy and safety of second-line therapies on their own or in combination in older adults with type 2 diabetes mellitus.
METHODS
All relevant published and unpublished trials will be identified. Studies published prior to 2015 will be identified from two previous comprehensive aggregate data network meta-analyses. Searches will be conducted in CENTRAL, MEDLINE, and EMBASE from 1st January 2015 onwards, and in clinicaltrials.gov from inception. Randomised controlled trials with at least 100 estimated older adults (≥ 65 years) receiving at least 24 weeks of intervention that assess the effects of glucose-lowering drugs on mortality, glycemia, vascular and other comorbidities outcomes, and quality of life will be eligible. The screening and data extraction process will be conducted independently by two researchers. The quality of studies will be assessed using the Cochrane risk of bias tool 2. Anonymised IPD of all eligible trials will be requested via clinical trial portals or by contacting the principal investigators or sponsors. Received data will be reanalysed where necessary to standardise outcome metrics. Network meta-analyses will be performed to determine the relative effectiveness of therapies.
DISCUSSION
With the increasing number of older adults with type 2 diabetes worldwide, an IPD network meta-analysis using data from all eligible trials will provide new insights into the optimal choices of second-line antidiabetic drugs to improve patient management and reduce unnecessary adverse events and the subsequent risk of comorbidities in older adults.
SYSTEMATIC REVIEW REGISTRATION
PROSPERO CRD42021272686.
Topics: Humans; Diabetes Mellitus, Type 2; Systematic Reviews as Topic; Aged; Hypoglycemic Agents; Network Meta-Analysis; Metformin; Research Design
PubMed: 38872216
DOI: 10.1186/s13643-024-02558-5 -
PloS One 2024Previous experimental and clinical studies suggested a beneficial effect of statins, metformin, angiotensin-converting-enzyme inhibitors and angiotensin II receptor...
BACKGROUND
Previous experimental and clinical studies suggested a beneficial effect of statins, metformin, angiotensin-converting-enzyme inhibitors and angiotensin II receptor blockers (RASi) on portal hypertension. Still, their effects on hard cirrhosis-related clinical endpoints, such as variceal bleeding and bleeding-related mortality, remain to be investigated.
METHODS
Thus, we recorded the use of statins, metformin and RASi in a large cohort of cirrhotic patients undergoing endoscopic band ligation (EBL) for primary (PP, n = 440) and secondary bleeding prophylaxis (SP, n = 480) between 01/2000 and 05/2020. Variceal (re-) bleeding and survival rates were compared between patients with vs. without these co-medications.
RESULTS
A total of 920 cirrhotic patients with varices were included. At first EBL, median MELD was 13 and 515 (56%) patients showed ascites. Statins, metformin and RASi were used by 49 (5.3%), 74 (8%), and 91 (9.9%) patients, respectively. MELD and platelet counts were similar in patients with and without the co-medications of interest. Rates of first variceal bleeding and variceal rebleeding at 2 years were 5.2% and 11.7%, respectively. Neither of the co-medications were associated with decreased first bleeding rates (log-rank tests in PP: statins p = 0.813, metformin p = 0.862, RASi p = 0.919) nor rebleeding rates (log-rank tests in SP: statin p = 0.113, metformin p = 0.348, RASi p = 0.273). Similar mortality rates were documented in patients with and without co-medications for PP (log-rank tests: statins p = 0.630, metformin p = 0.591, RASi p = 0.064) and for SP (statins p = 0.720, metformin p = 0.584, RASi p = 0.118).
CONCLUSION
In clinical practice, variceal bleeding and mortality rates of cirrhotic patients were not reduced by co-medication with statins, metformin or RASi. Nevertheless, we recommend the use of these co-medications by indication, as they may still exert beneficial effects on non-bleeding complications in patients with liver cirrhosis.
Topics: Humans; Metformin; Male; Female; Middle Aged; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Liver Cirrhosis; Gastrointestinal Hemorrhage; Esophageal and Gastric Varices; Aged; Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Cohort Studies
PubMed: 38870117
DOI: 10.1371/journal.pone.0302811 -
Amino Acids Jun 2024Creatine is a natural nitrogenous organic acid that is integral to energy metabolism and crucial for proper cell functioning. The kidneys are involved in the first step... (Comparative Study)
Comparative Study
Creatine is a natural nitrogenous organic acid that is integral to energy metabolism and crucial for proper cell functioning. The kidneys are involved in the first step of creatine production. With kidney transplantation being the gold-standard treatment for end-stage kidney disease, kidney transplant recipients (KTR) may be at risk of impaired creatine synthesis. We aimed to compare creatine homeostasis between KTR and controls. Plasma and urine concentrations of arginine, glycine, guanidinoacetate, creatine and creatinine were measured in 553 KTR and 168 healthy controls. Creatine intake was assessed using food frequency questionnaires. Iothalamate-measured GFR data were available in subsets of 157 KTR and 167 controls. KTR and controls had comparable body weight, height and creatine intake (all P > 0.05). However, the total creatine pool was 14% lower in KTR as compared to controls (651 ± 178 vs. 753 ± 239 mmol, P < 0.001). The endogenous creatine synthesis rate was 22% lower in KTR as compared to controls (7.8 ± 3.0 vs. 10.0 ± 4.1 mmol per day, P < 0.001). Despite lower GFR, the plasma guanidinoacetate and creatine concentrations were 21% and 41% lower in KTR as compared to controls (both P < 0.001). Urinary excretion of guanidinoacetate and creatine were 66% and 59% lower in KTR as compared to controls (both P < 0.001). In KTR, but not in controls, a higher measured GFR was associated with a higher endogenous creatine synthesis rate (std. beta: 0.21, 95% CI: 0.08; 0.33; P = 0.002), as well as a higher total creatine pool (std. beta: 0.22, 95% CI: 0.11; 0.33; P < 0.001). These associations were fully mediated (93% and 95%; P < 0.001) by urinary guanidinoacetate excretion which is consistent with production of the creatine precursor guanidinoacetate as rate-limiting factor. Our findings highlight that KTR have a disturbed creatine homeostasis as compared to controls. Given the direct relationship of measured GFR with endogenous creatine synthesis rate and the total creatine pool, creatine supplementation might be beneficial in KTR with low kidney function.Trial registration ID: NCT02811835.Trial registration URL: https://clinicaltrials.gov/ct2/show/NCT02811835 .
Topics: Humans; Creatine; Kidney Transplantation; Male; Female; Middle Aged; Homeostasis; Adult; Kidney; Glycine; Glomerular Filtration Rate; Transplant Recipients; Case-Control Studies; Creatinine
PubMed: 38869518
DOI: 10.1007/s00726-024-03401-w -
Gut Microbes 2024Metformin is widely used for treating type 2 diabetes mellitus (T2D). However, the efficacy of metformin monotherapy is highly variable within the human population....
Metformin is widely used for treating type 2 diabetes mellitus (T2D). However, the efficacy of metformin monotherapy is highly variable within the human population. Understanding the potential indirect or synergistic effects of metformin on gut microbiota composition and encoded functions could potentially offer new insights into predicting treatment efficacy and designing more personalized treatments in the future. We combined targeted metabolomics and metagenomic profiling of gut microbiomes in newly diagnosed T2D patients before and after metformin therapy to identify potential pre-treatment biomarkers and functional signatures for metformin efficacy and induced changes in metformin therapy responders. Our sequencing data were largely corroborated by our metabolic profiling and identified that pre-treatment enrichment of gut microbial functions encoding purine degradation and glutamate biosynthesis was associated with good therapy response. Furthermore, we identified changes in glutamine-associated amino acid (arginine, ornithine, putrescine) metabolism that characterize differences in metformin efficacy before and after the therapy. Moreover, metformin Responders' microbiota displayed a shifted balance between bacterial lipidA synthesis and degradation as well as alterations in glutamate-dependent metabolism of N-acetyl-galactosamine and its derivatives (e.g. CMP-pseudaminate) which suggest potential modulation of bacterial cell walls and human gut barrier, thus mediating changes in microbiome composition. Together, our data suggest that glutamine and associated amino acid metabolism as well as purine degradation products may potentially condition metformin activity via its multiple effects on microbiome functional composition and therefore serve as important biomarkers for predicting metformin efficacy.
Topics: Humans; Metformin; Gastrointestinal Microbiome; Diabetes Mellitus, Type 2; Amino Acids; Male; Middle Aged; Female; Purines; Bacteria; Biomarkers; Hypoglycemic Agents; Aged; Adult; Treatment Outcome; Metabolomics
PubMed: 38868903
DOI: 10.1080/19490976.2024.2361491 -
Frontiers in Endocrinology 2024Polycystic ovary syndrome (PCOS) and thyroid disorders have both been linked to adverse pregnancy and neonatal outcomes. Even small variations in thyroid function within... (Randomized Controlled Trial)
Randomized Controlled Trial
OBJECTIVES
Polycystic ovary syndrome (PCOS) and thyroid disorders have both been linked to adverse pregnancy and neonatal outcomes. Even small variations in thyroid function within the normal range may influence fetal growth. Our aim was to investigate whether maternal thyroid function is associated with newborn anthropometrics in PCOS and explore the potential modifying effect of metformin.
METHODS
analyses of two RCTs in which pregnant women with PCOS were randomized to metformin or placebo, from first trimester to delivery. Maternal serum levels of thyroid stimulating hormone (TSH) and free thyroxine (fT4) were measured at gestational weeks (gw) 5-12, 19, 32 and 36 in 309 singleton pregnancies. The mean z-scores of birthweight, birth length, and head circumference were estimated in the offspring. Associations of maternal thyroid parameters with offspring anthropometrics and the outcomes large for gestational age (LGA) and small for gestational age (SGA) were studied using linear and logistic regression models, with adjustment for body mass index (BMI) when relevant.
RESULTS
Maternal fT4 at baseline was negatively associated with birth length (b= -0.09, p=0.048). Furthermore, ΔfT4 during pregnancy correlated positively to z-score of both birth weight and length (b=0.10, p=0.017 and b=0.10, p=0.047 respectively), independently of treatment group. TSH at baseline and gw19 was inversely associated with LGA (OR 0.47, p=0.012 and OR 0.58, p=0.042), while ΔTSH was positively associated with LGA (OR 1.99, p=0.023). There were inverse associations between TSH at baseline and SGA (OR 0.32, p=0.005) and between ΔfT4 and SGA (OR 0.59, p=0.005) in the metformin group only. There were no associations between maternal thyroid function and head circumference of the newborns.
CONCLUSION
In women with PCOS, a higher maternal fT4 in early pregnancy and a greater decrease in fT4 during pregnancy was associated with a lower offspring birthweight and shorter birth length. Higher TSH by mid-gestation and smaller increase in TSH during pregnancy was associated with less risk of LGA. Subclinical variations in maternal thyroid function might play a role for birth anthropometrics of PCOS offspring.
Topics: Humans; Female; Polycystic Ovary Syndrome; Pregnancy; Adult; Infant, Newborn; Birth Weight; Metformin; Thyrotropin; Thyroid Gland; Thyroid Function Tests; Pregnancy Complications; Thyroxine; Infant, Small for Gestational Age; Pregnancy Outcome; Anthropometry; Hypoglycemic Agents; Male
PubMed: 38868742
DOI: 10.3389/fendo.2024.1388473 -
Cardiovascular Diabetology Jun 2024Metformin and sodium-glucose-cotransporter-2 inhibitors (SGLT2i) are cornerstone therapies for managing hyperglycemia in diabetes. However, their detailed impacts on...
BACKGROUND
Metformin and sodium-glucose-cotransporter-2 inhibitors (SGLT2i) are cornerstone therapies for managing hyperglycemia in diabetes. However, their detailed impacts on metabolic processes, particularly within the citric acid (TCA) cycle and its anaplerotic pathways, remain unclear. This study investigates the tissue-specific metabolic effects of metformin, both as a monotherapy and in combination with SGLT2i, on the TCA cycle and associated anaplerotic reactions in both mice and humans.
METHODS
Metformin-specific metabolic changes were initially identified by comparing metformin-treated diabetic mice (MET) with vehicle-treated db/db mice (VG). These findings were then assessed in two human cohorts (KORA and QBB) and a longitudinal KORA study of metformin-naïve patients with Type 2 Diabetes (T2D). We also compared MET with db/db mice on combination therapy (SGLT2i + MET). Metabolic profiling analyzed 716 metabolites from plasma, liver, and kidney tissues post-treatment, using linear regression and Bonferroni correction for statistical analysis, complemented by pathway analyses to explore the pathophysiological implications.
RESULTS
Metformin monotherapy significantly upregulated TCA cycle intermediates such as malate, fumarate, and α-ketoglutarate (α-KG) in plasma, and anaplerotic substrates including hepatic glutamate and renal 2-hydroxyglutarate (2-HG) in diabetic mice. Downregulated hepatic taurine was also observed. The addition of SGLT2i, however, reversed these effects, such as downregulating circulating malate and α-KG, and hepatic glutamate and renal 2-HG, but upregulated hepatic taurine. In human T2D patients on metformin therapy, significant systemic alterations in metabolites were observed, including increased malate but decreased citrulline. The bidirectional modulation of TCA cycle intermediates in mice influenced key anaplerotic pathways linked to glutaminolysis, tumorigenesis, immune regulation, and antioxidative responses.
CONCLUSION
This study elucidates the specific metabolic consequences of metformin and SGLT2i on the TCA cycle, reflecting potential impacts on the immune system. Metformin shows promise for its anti-inflammatory properties, while the addition of SGLT2i may provide liver protection in conditions like metabolic dysfunction-associated steatotic liver disease (MASLD). These observations underscore the importance of personalized treatment strategies.
Topics: Metformin; Animals; Citric Acid Cycle; Sodium-Glucose Transporter 2 Inhibitors; Humans; Hypoglycemic Agents; Diabetes Mellitus, Type 2; Male; Liver; Kidney; Female; Drug Therapy, Combination; Mice, Inbred C57BL; Metabolomics; Biomarkers; Middle Aged; Blood Glucose; Longitudinal Studies; Mice; Aged; Treatment Outcome
PubMed: 38867314
DOI: 10.1186/s12933-024-02288-x