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Global prevalence of antibiotic consumption during pregnancy: A systematic review and meta-analysis.The Journal of Infection Jun 2024Antibiotic use during pregnancy is widespread with notable variations across regions.
BACKGROUND
Antibiotic use during pregnancy is widespread with notable variations across regions.
METHODS
This systematic review and meta-analysis (Prospero protocol CRD42023418979) examines the prevalence and variability of antibiotic use in pregnancy globally and regionally, considering different methodologies and maternal characteristics. We searched Embase, PubMed, and Web of Science for observational studies published in English from the year 2000 and onwards. Random-effect meta-analyses were used to pool the prevalence of antibiotic consumption during pregnancy, presented as percentages with 95% confidence intervals (CI). Joanna Briggs Institute Critical appraisal checklist for prevalence studies was used for bias assessment.
FINDINGS
Overall, 116 studies (14 from Africa, 24 from the Americas, six from Eastern Mediterranean, 57 from Europe, four from South-East Asia and 11 from Western Pacific) were included (33,821,194 pregnancies). The majority of studies (84.5%) were appraised with a low risk of bias. The prevalence of antibiotic consumption during pregnancy ranged between 0.04 to 90%, with a pooled estimate of 23.6% (95% CI: 20.1-27.5, I =100%). Low-income countries had the highest pooled prevalence (45.3%, 95% CI: 15.4-79.1, I =99.6%). Regionally, the Western Pacific had the highest pooled prevalence (34.4%, 95% CI: 13.4-64.1, I =100%). The prevalence of antibiotic consumption during pregnancy increased over time in the Americas and Western Pacific. The studies exhibited considerable heterogeneity (I >95%), and the trim-and-fill method estimated a potential 10% underestimation of the overall pooled prevalence, suggesting publication bias.
INTERPRETATION
This meta-analysis suggests that about 1/4 of women worldwide use antibiotics during pregnancy. This study suggests a high prevalence of antibiotic consumption during pregnancy with disparities according to region and level of country income, ethnicity and whether antibiotics were prescribed or self-medicated. There was a variability in reported findings across age categories, potential bias from small sample sizes, and language bias from including only studies published in English.
PubMed: 38844084
DOI: 10.1016/j.jinf.2024.106189 -
Diabetes & Metabolic Syndrome Jun 2024The implication of intermediately elevated fasting plasma glucose (FPG) in the first trimester of pregnancy is uncertain.
First-trimester fasting plasma glucose as a predictor of subsequent gestational diabetes mellitus and adverse fetomaternal outcomes: A systematic review and meta-analysis.
BACKGROUND
The implication of intermediately elevated fasting plasma glucose (FPG) in the first trimester of pregnancy is uncertain.
PURPOSE
The primary outcome of the meta-analysis was to analyze if intermediately elevated first-trimester FPG could predict development of GDM at 24-28 weeks. The secondary outcomes were to determine if the commonly used FPG cut-offs 5.1 mmol/L (92 mg/dL), 5.6 mmol/L (100 mg/dL), and 6.1 mmol/L (110 mg/dL) correlated with adverse pregnancy events.
DATA SOURCES
Databases were searched for articles published from 2010 onwards for studies examining the relationship between first-trimester FPG and adverse fetomaternal outcomes.
STUDY SELECTION
A total of sixteen studies involving 115,899 pregnancies satisfied the inclusion criteria.
DATA EXTRACTION AND DATA SYNTHESIS
Women who developed GDM had a significantly higher first-trimester FPG than those who did not [MD 0.29 mmoL/l (5 mg/dL); 95 % CI: 0.21-0.38; P < 0.00001]. First-trimester FPG ≥5.1 mmol/L (92 mg/dL) predicted the development of GDM at 24-28 weeks [RR 3.93 (95 % CI: 2.67-5.77); P < 0.0000], pre-eclampsia [RR 1.55 (95%CI:1.14-2.12); P = 0.006], gestational hypertension [RR1.47 (95%CI:1.20-1.79); P = 0.0001], large-for-gestational-age (LGA) [RR 1.32 (95%CI:1.13-1.54); P = 0.0004], and macrosomia [RR1.29 (95%CI:1.15-1.44); P < 0.001]. However, at the above threshold, the rates of preterm delivery, lower-segment cesarean section (LSCS), small-for gestational age (SGA), and neonatal hypoglycemia were not significantly higher. First-trimester FPG ≥5.6 mmol/L (100 mg/dL) correlated with occurrence of macrosomia [RR1.47 (95 % CI:1.22-1.79); P < 0.0001], LGA [RR 1.43 (95%CI:1.24-1.65); P < 0.00001], and preterm delivery [RR1.51 (95%CI:1.15-1.98); P = 0.003], but not SGA and LSCS.
LIMITATIONS
Only one study reported outcomes at first-trimester FPG of 6.1 mmol/L (110 mg/dL), and hence was not analyzed.
CONCLUSION
The risk of development of GDM at 24-28 weeks increased linearly with higher first-trimester FPG. First trimester FPG cut-offs of 5.1 mmol/L (92 mg/dL) and 5.6 mmol/L (100 mg/dL) predicted several adverse pregnancy outcomes.
PubMed: 38843646
DOI: 10.1016/j.dsx.2024.103051 -
Frontiers in Immunology 2024According to the PRISMA criteria, a systematic review has been conducted to investigate the clinical relevance between patients with severe congenital neutropenia (SCN)...
INTRODUCTION
According to the PRISMA criteria, a systematic review has been conducted to investigate the clinical relevance between patients with severe congenital neutropenia (SCN) and cyclic congenital neutropenia (CyN) induced by ELANE mutations.
METHODS
We have searched PubMed, EMBASE, Web of Science, Scopus, Cochrane, CNKI, Wanfang Medicine, and VIP for ELANE mutation related literature published from 1997 to 2022. Using Microsoft Excel collect and organize data, SPSS 25, GraphPad Prism 8.0.1, and Omap analyze and plot statistical. Compare the gender, age, geography, mutation sites, infection characteristics, treatment, and other factors of SCN and CyN patients induced by ELANE mutations, with a focus on exploring the relationship between genotype and clinical characteristics, genotype and prognosis.
RESULTS
This study has included a total of 467 patients with SCN and 90 patients with CyN. The onset age of SCN and CyN are both less than 1 year old, and the onset and diagnosis age of SCN are both younger than CyN. The mutation of ELANE gene is mainly missense mutation, and hot spot mutations include S126L, P139L, G214R, c.597+1G>A. The high-frequency mutations with severe outcomes are A57V, L121H, L121P, c.597+1G>A, c.597+1G>T, S126L, C151Y, C151S, G214R, C223X. Respiratory tract, skin and mucosa are the most common infection sites, Staphylococcus aureus, Pseudomonas aeruginosa and Escherichia coli are the most common.
DISCUSSION
Patients with refractory G-CSF are more likely to develop severe outcomes. The commonly used pre-treatment schemes for transplantation are Bu-Cy-ATG and Flu-Bu-ATG. The prognosis of transplantation is mostly good, but the risk of GVHD is high.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/PROSPERO/. PROSPERO, identifier CRD42023434656.
Topics: Humans; Neutropenia; Mutation; Congenital Bone Marrow Failure Syndromes; Prognosis; Male; Female; Clinical Relevance
PubMed: 38840904
DOI: 10.3389/fimmu.2024.1349919 -
International Journal of Radiation... Jun 2024This systematic review provides an overview of literature on the impact of MR-guided radiotherapy (MRgRT) on patient reported outcomes (PROs) in patients with prostate... (Review)
Review
PURPOSE
This systematic review provides an overview of literature on the impact of MR-guided radiotherapy (MRgRT) on patient reported outcomes (PROs) in patients with prostate cancer (PC).
METHODS
A systematic search was performed in October 2023 in PubMed, EMBASE and Cochrane Library. The PICOS framework (i.e., patient, intervention, comparison, outcome, study design) was used to determine eligibility criteria. Included were studies assessing PROs following MRgRT for PC with sample size >10. Methodological quality was assessed using the ROBINS-I and RoB 2. Relevant mean differences (MD) compared to pre-RT were interpreted using minimal important differences (MID). Meta-analyses were performed using random-effects models. Between-study heterogeneity was assessed using the I-statistic.
RESULTS
Eleven observational studies and one randomized controlled trial (n=897) were included. Nine studies included patients with primary PC with MRgRT as first-line treatment (n=813) and three with MRgRT as second-line treatment (n=84). Substantial risk of bias was found in five studies. EORTC QLQ-C30 and EORTC QLQ-PR25 scores were pooled from three studies, and EPIC-26 scores from four studies. Relevant MDs for the urinary domain were found with the EPIC-26 (MD-10.0 [95%CI -12.0 - -8.1]; I0%) and the EORTC QLQ-PR25 (MD8.6 [95%CI -4.7-22.0]; I97%), both at end-RT to one month follow-up. Relevant MDs for the bowel domain were found with the EPIC-26 (MD-4.7 [95%CI -9.2 - -0.2]; I82%), at end-RT or one month follow-up, but not with the EORTC QLQ-PR25. For both domains, no relevant MDs were found after three months of follow-up. No relevant MDs were found in the general QoL domains of the EORTC QLQ-C30.
CONCLUSION
MRgRT for PC results in a temporarily worsening of patient-reported urinary and bowel symptoms during the first month after treatment compared to pre-RT, resolving at 3 months. No clinically relevant changes were found for general QoL domains. These results provide important information for patient counseling and can serve as a benchmark for future studies.
PubMed: 38838994
DOI: 10.1016/j.ijrobp.2024.05.028 -
The Cochrane Database of Systematic... Jun 2024Practitioners in the field of assisted reproductive technology (ART) continually seek alternative or adjunct treatments to improve ART outcomes. This Cochrane review... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Practitioners in the field of assisted reproductive technology (ART) continually seek alternative or adjunct treatments to improve ART outcomes. This Cochrane review investigates the adjunct use of synthetic versions of two naturally produced hormones, dehydroepiandrosterone (DHEA) and testosterone (T), in assisted reproduction. Steroid hormones are proposed to increase conception rates by positively affecting follicular response to gonadotrophin stimulation. This may lead to a greater oocyte yield and, subsequently, an increased chance of pregnancy.
OBJECTIVES
To assess the effectiveness and safety of DHEA and T as pre- or co-treatments in infertile women undergoing assisted reproduction.
SEARCH METHODS
We searched the following electronic databases up to 8 January 2024: the Gynaecology and Fertility Group (CGF) Specialised Register, CENTRAL, MEDLINE, Embase, PsycINFO, and trial registries for ongoing trials. We also searched citation indexes, Web of Science, PubMed, and OpenGrey. We searched the reference lists of relevant studies and contacted experts in the field for any additional trials. There were no language restrictions.
SELECTION CRITERIA
Randomised controlled trials (RCTs) comparing DHEA or T as an adjunct treatment to any other active intervention, placebo, or no treatment in women undergoing assisted reproduction.
DATA COLLECTION AND ANALYSIS
Two review authors independently selected studies, extracted relevant data, and assessed risk of bias. We pooled data from studies using fixed-effect models. We calculated odds ratios (ORs) for each dichotomous outcome. Analyses were stratified by type of treatment. We assessed the certainty of evidence for the main findings using GRADE methods.
MAIN RESULTS
We included 29 RCTs. There were 1599 women in the intervention group and 1469 in the control group. Apart from three trials, the trial participants were women identified as 'poor responders' to standard in vitro fertilisation (IVF) protocols. The included trials compared either T or DHEA treatment with placebo or no treatment. Pre-treatment with DHEA versus placebo/no treatment: DHEA likely results in little to no difference in live birth/ongoing pregnancy rates (OR 1.30, 95% confidence interval (CI) 0.95 to 1.76; I² = 16%, 9 RCTs, N = 1433, moderate certainty evidence). This suggests that in women with a 12% chance of live birth/ongoing pregnancy with placebo or no treatment, the live birth/ongoing pregnancy rate in women using DHEA will be between 12% and 20%. DHEA likely does not decrease miscarriage rates (OR 0.85, 95% CI 0.53 to 1.37; I² = 0%, 10 RCTs, N =1601, moderate certainty evidence). DHEA likely results in little to no difference in clinical pregnancy rates (OR 1.18, 95% CI 0.93 to 1.49; I² = 0%, 13 RCTs, N = 1886, moderate certainty evidence). This suggests that in women with a 17% chance of clinical pregnancy with placebo or no treatment, the clinical pregnancy rate in women using DHEA will be between 16% and 24%. We are very uncertain about the effect of DHEA on multiple pregnancy (OR 3.05, 95% CI 0.47 to 19.66; 7 RCTs, N = 463, very low certainty evidence). Pre-treatment with T versus placebo/no treatment: T likely improves live birth rates (OR 2.53, 95% CI 1.61 to 3.99; I² = 0%, 8 RCTs, N = 716, moderate certainty evidence). This suggests that in women with a 10% chance of live birth with placebo or no treatment, the live birth rate in women using T will be between 15% and 30%. T likely does not decrease miscarriage rates (OR 1.63, 95% CI 0.76 to 3.51; I² = 0%, 9 RCTs, N = 755, moderate certainty evidence). T likely increases clinical pregnancy rates (OR 2.17, 95% CI 1.54 to 3.06; I² = 0%, 13 RCTs, N = 1152, moderate certainty evidence). This suggests that in women with a 12% chance of clinical pregnancy with placebo or no treatment, the clinical pregnancy rate in women using T will be between 17% and 29%. We are very uncertain about the effect of T on multiple pregnancy (OR 2.56, 95% CI 0.59 to 11.20; 5 RCTs, N = 449, very low certainty evidence). We are uncertain about the effect of T versus oestradiol or T versus oestradiol + oral contraceptive pills. The certainty of the evidence was moderate to very low, the main limitations being lack of blinding in the included trials, inadequate reporting of study methods, and low event and sample sizes in the trials. Data on adverse events were sparse; any reported events were minor.
AUTHORS' CONCLUSIONS
Pre-treatment with T likely improves, and pre-treatment with DHEA likely results in little to no difference, in live birth and clinical pregnancy rates in women undergoing IVF who have been identified as poor responders. DHEA and T probably do not decrease miscarriage rates in women under IVF treatment. The effects of DHEA and T on multiple pregnancy are uncertain. Data regarding adverse events were very limited; any reported events were minor. Research is needed to identify the optimal duration of treatment with T. Future studies should include data collection on adverse events and multiple pregnancy.
Topics: Humans; Female; Dehydroepiandrosterone; Randomized Controlled Trials as Topic; Pregnancy; Testosterone; Reproductive Techniques, Assisted; Pregnancy Rate; Live Birth; Infertility, Female; Androgens; Bias; Abortion, Spontaneous; Ovulation Induction
PubMed: 38837771
DOI: 10.1002/14651858.CD009749.pub3 -
European Journal of Cancer (Oxford,... May 2024Cancer patients with autoimmune disease have been excluded from randomized trials of immune checkpoint blockers (ICBs). We conducted a systematic review of observational... (Review)
Review
A systematic review and meta-analysis of observational studies and uncontrolled trials reporting on the use of checkpoint blockers in patients with cancer and pre-existing autoimmune disease.
BACKGROUND
Cancer patients with autoimmune disease have been excluded from randomized trials of immune checkpoint blockers (ICBs). We conducted a systematic review of observational studies and uncontrolled trials including cancer patients with pre-existing autoimmune disease who received ICBs.
METHODS
We searched 5 electronic databases through November 2023. Study selection, data collection, and quality assessment were performed independently by 2 investigators. We performed a meta-analysis to pool incidence of immune-related adverse events (irAEs), including de novo events and flares of existing autoimmune disease, hospitalizations due to irAEs, as well as deaths.
RESULTS
A total of 95 studies were included (23,897 patients with cancer and preexisting autoimmune disease). The most common cancer evaluated was lung cancer (30.7 %) followed by skin cancer (15.7 %). Patients with autoimmune disease were more likely to report irAEs compared to patients without autoimmune disease (relative risk 1.3, 95 % CI 1.0 to 1.6). The pooled occurrence rate of any irAEs (flares or de novo) was 61 % (95 % CI 54 % to 68 %); that of flares was 36 % (95 % CI 30 % to 43 %), and that of de novo irAEs was 23 % (95 % CI 16 % to 30 %). Flares were mild (grade <3) in half of cases and more commonly reported in patients with psoriasis/psoriatic arthritis (39 %), inflammatory bowel disease (37 %), and rheumatoid arthritis (36 %). 32 % of the patients with irAEs required hospitalization and treatment of irAEs included corticosteroids in 72 % of the cases. The irAEs mortality rate was 0.07 %. There were no statistically significant differences in cancer response to ICBs between patients with and without autoimmune disease.
CONCLUSIONS
Although more patients with pre-existing autoimmune disease had irAEs, these were mild and managed with corticosteroids in most cases, with no impact on cancer response. These results suggest that ICBs can be used in these patients, but careful monitoring is required, as over a third of the patients will experience a flare of their autoimmune disease and/or require hospitalization. These findings provide a crucial foundation for oncologists to refine their monitoring and management strategies, ensuring that the benefits of ICB therapy are maximized while minimizing its risks.
PubMed: 38834015
DOI: 10.1016/j.ejca.2024.114148 -
Anaesthesia Jun 2024Noradrenaline is a standard treatment for hypotension in acute care. The precise effects of noradrenaline on cerebral blood flow in health and disease remain unclear. (Review)
Review
BACKGROUND
Noradrenaline is a standard treatment for hypotension in acute care. The precise effects of noradrenaline on cerebral blood flow in health and disease remain unclear.
METHODS
We systematically reviewed and synthesised data from studies examining changes in cerebral blood flow in healthy participants and patients with traumatic brain injury and critical illness.
RESULTS
Twenty-eight eligible studies were included. In healthy subjects and patients without critical illness or traumatic brain injury, noradrenaline did not significantly change cerebral blood flow velocity (-1.7%, 95%CI -4.7-1.3%) despite a 24.1% (95%CI 19.4-28.7%) increase in mean arterial pressure. In patients with traumatic brain injury, noradrenaline significantly increased cerebral blood flow velocity (21.5%, 95%CI 11.0-32.0%), along with a 33.8% (95%CI 14.7-52.9%) increase in mean arterial pressure. In patients who were critically ill, noradrenaline significantly increased cerebral blood flow velocity (20.0%, 95%CI 9.7-30.3%), along with a 32.4% (95%CI 25.0-39.9%) increase in mean arterial pressure. Our analyses suggest intact cerebral autoregulation in healthy subjects and patients without critical illness or traumatic brain injury., and impaired cerebral autoregulation in patients with traumatic brain injury and who were critically ill. The extent of mean arterial pressure changes and the pre-treatment blood pressure levels may affect the magnitude of cerebral blood flow changes. Studies assessing cerebral blood flow using non-transcranial Doppler methods were inadequate and heterogeneous in enabling meaningful meta-analysis.
CONCLUSIONS
Noradrenaline significantly increases cerebral blood flow in humans with impaired, not intact, cerebral autoregulation, with the extent of changes related to the severity of functional impairment, the extent of mean arterial pressure changes and pre-treatment blood pressure levels.
PubMed: 38831595
DOI: 10.1111/anae.16313 -
Musculoskeletal Care Jun 2024Medical guidelines recommend structured prehabilitation protocols consisting of lifestyle modifications and exercise to enhance post-operative outcomes for patients...
BACKGROUND
Medical guidelines recommend structured prehabilitation protocols consisting of lifestyle modifications and exercise to enhance post-operative outcomes for patients undergoing a total knee replacement (TKR). However, current research showing effectiveness is limited and has primarily focused on outcomes of exercise-based prehabilitation.
OBJECTIVES
To investigate whether a structured prehabilitation protocol consisting of exercise and lifestyle modifications improves physical function and patient-reported outcomes following TKR surgery compared with usual care.
DESIGN
Systematic review.
METHODS
Five databases were searched to identify randomised controlled trials comparing structured prehabilitation programs consisting of lifestyle modifications and exercise, with usual care, for those undergoing a TKR. Methodological quality of included studies was assessed via the RoB 2.0 tool and results synthesis via a Grading of Recommendation Assessment, Development and Evaluation approach was performed to determine the certainty evidence for each outcome.
RESULTS/FINDINGS
Four studies were included in this review. Despite a positive trend supporting the inclusion of a structured prehabilitation protocol, additional improvements in post-operative pain, physical function and self-reported function were only seen in one study. Reductions in hospital length of stay were also seen in one study. No additional improvements in post-operative quality of life following prehabilitation were reported.
CONCLUSION
Limited evidence supporting prehabilitation reported in our review is likely attributed to the intervention type, intensity, and delivery model of included studies. However, there remains to be strong evidence supporting the use of a structured prehabilitation protocol consisting of lifestyle modifications and exercise to improve post-operative outcome.
Topics: Humans; Arthroplasty, Replacement, Knee; Preoperative Exercise; Exercise Therapy; Life Style; Treatment Outcome; Preoperative Care
PubMed: 38831384
DOI: 10.1002/msc.1899 -
Prostate Cancer and Prostatic Diseases Jun 2024Prostate cancer (PCa) (early) detection poses significant challenges, including unnecessary testing and the risk of potential overdiagnosis. The European Association of...
BACKGROUND
Prostate cancer (PCa) (early) detection poses significant challenges, including unnecessary testing and the risk of potential overdiagnosis. The European Association of Urology therefore suggests an individual risk-adapted approach, incorporating risk calculators (RCs) into the PCa detection pathway. In the context of 'The PRostate Cancer Awareness and Initiative for Screening in the European Union' (PRAISE-U) project ( https://uroweb.org/praise-u ), we aim to provide an overview of the currently available clinical RCs applicable in an early PCa detection algorithm.
METHODS
We performed a systematic review to identify RCs predicting detection of clinically significant PCa at biopsy. A search was performed in the databases Medline ALL, Embase, Web of Science Core Collection, Cochrane Central Register of Controlled Trials and Google Scholar for publications between January 2010 and July 2023. We retrieved relevant literature by using the terms "prostate cancer", "screening/diagnosis" and "predictive model". Inclusion criteria included systematic reviews, meta-analyses, and clinical trials. Exclusion criteria applied to studies involving pre-targeted high-risk populations, diagnosed PCa patients, or a sample sizes under 50 men.
RESULTS
We identified 6474 articles, of which 140 were included after screening abstracts and full texts. In total, we identified 96 unique RCs. Among these, 45 underwent external validation, with 28 validated in multiple cohorts. Of the externally validated RCs, 17 are based on clinical factors, 19 incorporate clinical factors along with MRI details, 4 were based on blood biomarkers alone or in combination with clinical factors, and 5 included urinary biomarkers. The median AUC of externally validated RCs ranged from 0.63 to 0.93.
CONCLUSIONS
This systematic review offers an extensive analysis of currently available RCs, their variable utilization, and performance within validation cohorts. RCs have consistently demonstrated their capacity to mitigate the limitations associated with early detection and have been integrated into modern practice and screening trials. Nevertheless, the lack of external validation data raises concerns about numerous RCs, and it is crucial to factor in this omission when evaluating whether a specific RC is applicable to one's target population.
PubMed: 38830997
DOI: 10.1038/s41391-024-00852-w -
Diabetic Medicine : a Journal of the... Jun 2024To identify barriers and enablers that influence engagement in and acceptability of diabetes prevention programmes for people with pre-diabetes. The results will provide... (Review)
Review
AIMS
To identify barriers and enablers that influence engagement in and acceptability of diabetes prevention programmes for people with pre-diabetes. The results will provide insights for developing strategies and recommendations to improve design and delivery of diabetes prevention programmes with enhanced engagement and acceptability for people with pre-diabetes.
METHODS
This review used a critical realist approach to examine context and mechanisms of diabetes prevention programmes. Medline, Embase, PsycInfo, Cinahl, Web of Science, Scopus and Pre-Medline were searched for English language studies published between 2000 and 2023. A quality assessment was conducted using Joanna Briggs Institute critical appraisal tools.
RESULTS
A total of 90 papers met inclusion criteria. The included studies used a variety of quantitative and qualitative methodologies. Data extracted focused on barriers and enablers to engagement in and acceptability of diabetes prevention programmes, with seven key mechanisms identified. These included financial, environmental, personal, healthcare, social and cultural, demographic and programme mechanisms. Findings highlighted diverse factors that influenced engagement in preventive programmes and the importance of considering these factors when planning, developing and implementing future diabetes prevention programmes.
CONCLUSIONS
Mechanisms identified in this review can inform design and development of diabetes prevention programmes for people with pre-diabetes and provide guidance for healthcare professionals and policymakers. This will facilitate increased participation and engagement in preventive programmes, potentially reducing progression and/or incidence of pre-diabetes to type 2 diabetes and improving health outcomes.
PubMed: 38829966
DOI: 10.1111/dme.15323