Early Metformin in Gestational Diabetes: A Randomized Clinical Trial.

Importance: Gestational diabetes is a common complication of pregnancy and the optimal management is uncertain. Objective: To test whether early initiation of metformin reduces insulin initiation or improves fasting hyperglycemia at gestation weeks 32 or 38. Design, Setting, and Participants: Double-blind, placebo-controlled trial conducted in 2 centers in Ireland (one tertiary hospital and one smaller regional hospital). Participants were enrolled from June 2017 through September 2022 and followed up until 12 weeks' postpartum. Participants comprised 510 individuals (535 pregnancies) diagnosed with gestational diabetes based on World Health Organization 2013 criteria. Interventions: Randomized 1:1 to either placebo or metformin (maximum dose, 2500 mg) in addition to usual care. Main Outcomes And Measures: The primary outcome was a composite of insulin initiation or a fasting glucose level of 5.1 mmol/L or greater at gestation weeks 32 or 38. Results: Among 510 participants (mean age, 34.3 years), 535 pregnancies were randomized. The primary composite outcome was not significantly different between groups and occurred in 150 pregnancies (56.8%) in the metformin group and 167 pregnancies (63.7%) in the placebo group (between-group difference, -6.9% [95% CI, -15.1% to 1.4%]; relative risk, 0.89 [95% CI, 0.78-1.02]; P = .13). Of 6 prespecified secondary maternal outcomes, 3 favored the metformin group, including time to insulin initiation, self-reported capillary glycemic control, and gestational weight gain. Secondary neonatal outcomes differed by group, with smaller neonates (lower mean birth weights, a lower proportion weighing >4 kg, a lower proportion in the >90% percentile, and smaller crown-heel length) in the metformin group without differences in neonatal intensive care needs, respiratory distress requiring respiratory support, jaundice requiring phototherapy, major congenital anomalies, neonatal hypoglycemia, or proportion with 5-minute Apgar scores less than 7. Conclusion and relevance: Early treatment with metformin was not superior to placebo for the composite primary outcome. Prespecified secondary outcome data support further investigation of metformin in larger clinical trials. Trial Registration: ClinicalTrials.gov Identifier: NCT02980276; EudraCT: 2016-001644-19.

The Impact of and Interaction between Diabetes and Frailty on Psychosocial Wellbeing and Mortality in Ireland.

Frailty in middle-aged and older adults is associated with diabetes-related complications. The impact of and interaction between diabetes and frailty on psychosocial wellbeing and mortality in Ireland for adults aged ≥50 years were assessed using data from the Survey of Health, Ageing and Retirement in Europe. Measures included diabetes status (self-reported), frailty phenotype (≥3/5 criteria), low self-rated health ("fair" or "poor"), depression screening (EURO-D index score ≥4), and low quality of life (QoL) (CASP-12 index score < 35). Among the 970 participants, those with diabetes (n = 87) were more likely to be frail (23% vs. 8%; p < 0.001), have low self-rated health (46% vs. 19%; p < 0.001), depression (25% vs. 17%; p = 0.070), and low QoL (25% vs. 18%, p = 0.085). Adjusting for diabetes, age and sex, frailty independently predicted low self-rated health (OR: 9.79 (5.85-16.36)), depression (9.82 (5.93-16.25)), and low QoL (8.52 (5.19-13.97)). Adjusting for frailty, age and sex, diabetes independently predicted low self-rated health (2.70 (1.63-4.47)). The age-sex adjusted mortality hazard ratio was highest for frailty with diabetes (4.67 (1.08-20.15)), followed by frailty without diabetes (2.86 (1.17-6.99)) and being non-frail with diabetes (1.76 (0.59-5.22)). Frailty independently predicts lower self-reported wellbeing and is associated with reduced survival, underpinning its role as an integral part of holistic diabetes care.

Defining the characteristics of intermediate care models including transitional care: an international Delphi study.

BACKGROUND: Although there is growing utilisation of intermediate care to improve the health and well-being of older adults with complex care needs, there is no international agreement on how it is defined, limiting comparability between studies and reducing the ability to scale effective interventions. AIM: To identify and define the characteristics of intermediate care models. METHODS: A scoping review, a modified two-round electronic Delphi study involving 27 multi-professional experts from 13 countries, and a virtual consensus meeting were conducted. RESULTS: Sixty-six records were included in the scoping review, which identified four main themes: transitions, components, benefits and interchangeability. These formed the basis of the first round of the Delphi survey. After Round 2, 16 statements were agreed, refined and collapsed further. Consensus was established for 10 statements addressing the definitions, purpose, target populations, approach to care and organisation of intermediate care models. DISCUSSION: There was agreement that intermediate care represents time-limited services which ensure continuity and quality of care, promote recovery, restore independence and confidence at the interface between home and acute services, with transitional care representing a subset of intermediate care. Models are best delivered by an interdisciplinary team within an integrated health and social care system where a single contact point optimises service access, communication and coordination. CONCLUSIONS: This study identified key defining features of intermediate care to improve understanding and to support comparisons between models and studies evaluating them. More research is required to develop operational definitions for use in different healthcare systems.

The Efficacy of Prophylactic Negative Pressure Wound Therapy for Closed Incisions in Breast Surgery: A Systematic Review and Meta-Analysis.

BACKGROUND: Negative pressure wound therapy (NPWT) is a promising advance in the management of closed surgical incisions. NPWT application induces several effects locally within the wound including reduced lateral tension and improving lymphatic drainage. As a result, NPWT may improve wound healing and reduce surgical site complications. We aim to evaluate the efficacy of prophylactic application of NPWT in preventing surgical site complications for closed incisions in breast surgery. METHODS: This systematic review was reported according to PRISMA guidelines. The protocol was published in PROSPERO (CRD42018114625). Medline, Embase, CINAHL and Cochrane Library databases were searched for studies which compare the efficacy of NPWT versus non-NPWT dressings for closed incisions in breast surgery. Specific outcomes of interest were total wound complications, surgical site infection (SSI), seroma, haematoma, wound dehiscence and necrosis. RESULTS: Seven studies (1500 breast incisions in 904 patients) met the inclusion criteria. NPWT was associated with a significantly lower rate of total wound complications [odds ratio (OR) 0.36; 95% CI 0.19-069; P = 0.002], SSI (OR 0.45; 95% CI 0.24-0.86; P = 0.015), seroma (OR 0.28; 95% CI 0.13-0.59; P = 0.001), wound dehiscence (OR 0.49; 95% CI 0.32-0.72; P < 0.001) and wound necrosis (OR 0.38; 95% CI 0.19-0.78; P = 0.008). There was no significant difference in haematoma rate (OR 0.8; 95% CI 0.19-3.2; P = 0.75). Statistically significant heterogeneity existed for total wound complications, but no other outcomes. CONCLUSION: Compared with conventional non-NPWT dressings, prophylactic application of NPWT is associated with significantly fewer surgical site complications including SSI, seroma, wound dehiscence and wound necrosis for closed breast incisions.

Non-pharmacological treatments for sleep disturbance in mild cognitive impairment and dementia: A systematic review and meta-analysis.

No disease-modifying treatments for dementia are available. Sleep disturbance is strongly associated with cognitive impairment. Non-pharmacological treatments targeting sleep may offer an alternative therapeutic approach. We searched PubMed, CINAHL, EMBASE and the Cochrane library for non-pharmacological treatments for sleep disturbance in mild cognitive impairment (MCI) and dementia, published in English from October 1965 to 2018, including all designs, excluding studies of drug therapies. In all, 53 papers representing 48 studies were included. Participant age ranged from 67.3 to 89.4 years. Most studies (79%) had small samples (<50 participants, range 1-173) and were conducted in long-term/residential care (62%). The majority (85%) recruited participants with moderate-severe dementia; mean MMSE scores ranged from 0 to 28.3/30. Four studies examined MCI. Light therapy delivered over 1-10 weeks was the most studied stand-alone intervention (n = 27), and the majority (81.5%) of these studies found improvements on objective or subjective sleep measures, though the evidence was inconclusive with significant clinical and methodological heterogeneity. Seven multi-modal intervention studies were identified, all incorporating light exposure, and six of these reported improved sleep. Other interventions included electrotherapy stimulation (n = 4), physical exercises/activities (n = 4), acupressure/acupuncture (n = 3) and mindfulness/cognitive behavioural therapy (n = 3). Those examining MCI utilised different mono-modal approaches. A meta-analysis of data from randomised controlled trials showed a statistically significant (mean difference = 3.44, 95% CI: 0.89-5.99, I2=0%; p = 0.008) improvement in sleep efficiency between interventions and controls, favouring the pooled interventions (bright light, multi-domain and other therapies). No other significant differences in sleep or non-sleep outcomes were found. While evidence is available for non-pharmacological sleep interventions, particularly multi-domain approaches, studies were diverse and had small samples. More research examining multi-modal interventions, community-dwellers and those with MCI is required.

Approach to the new oral anticoagulants in family practice: part 1: comparing the options.

OBJECTIVE: To compare key features of the new oral anticoagulants (NOACs)-dabigatran, rivaroxaban, and apixaban-and to address questions that arise when comparing the NOACs. SOURCES OF INFORMATION: PubMed was searched for recent (January 2008 to week 32 of 2013) clinical studies relating to NOAC use for stroke prevention in atrial fibrillation (AF) and for the treatment of acute venous thromboembolism (VTE). MAIN MESSAGE: All NOACs are at least as effective as warfarin for stroke prevention in patients with nonvalvular AF, and are at least as safe in terms of bleeding risk according to 3 large trials. Meta-analyses of these trials have shown that, compared with warfarin therapy, NOACs reduced total mortality, cardiovascular mortality, and intracranial bleeding, and there was a trend toward less overall bleeding. Practical advantages of NOACs over warfarin include fixed once- or twice-daily oral dosing without the need for coagulation monitoring, and few known or defined drug or food interactions. Potential drawbacks of NOACs include a risk of bleeding that might be increased in patients older than 75 years, increased major gastrointestinal bleeding with high-dose dabigatran, increased dyspepsia with dabigatran, the lack of a routine laboratory test to reliably measure anticoagulant effect, and the lack of an antidote for reversal. No direct comparisons of NOACs have been made in randomized controlled trials, and the choice of NOAC is influenced by individual patient characteristics, including risk of stroke or VTE, risk of bleeding, and comorbidity (eg, renal dysfunction). CONCLUSION: The NOACs represent important alternatives in the management of patients with AF and VTE, especially for patients who have difficulty accessing regular coagulation monitoring. The companion to this article addresses common "what if" questions that arise in the long-term clinical follow-up and management of patients receiving NOACs.

Approach to the new oral anticoagulants in family practice: part 2: addressing frequently asked questions.

OBJECTIVE: To address common "what if" questions that arise relating to the long-term clinical follow-up and management of patients receiving the new oral anticoagulants (NOACs). SOURCES OF INFORMATION: For this narrative review, we searched the PubMed database for recent (January 2008 to week 32 of 2013) clinical studies relating to NOAC use for stroke prevention in atrial fibrillation and for the treatment of acute venous thromboembolism. We used this evidence base to address prespecified questions relating to NOAC use in primary care settings. MAIN MESSAGE: Dabigatran and rivaroxaban should be taken with meals to decrease dyspepsia and increase absorption, respectively. There are no dietary restrictions with any of the NOACs, beyond moderating alcohol intake, and rivaroxaban and apixaban can be crushed if required. The use of acid suppressive therapies does not appear to affect the efficacy of the NOACs. As with warfarin, patients taking NOACs should avoid long-term use of nonsteroidal anti-inflammatory and antiplatelet drugs. For patients requiring surgery, generally NOACs should be stopped 2 to 5 days before the procedure, depending on bleeding risk, and the NOAC should usually be resumed at least 24 hours after surgery. Preoperative coagulation testing is generally unnecessary. In patients who develop bleeding, minor bleeding typically does not require laboratory testing or discontinuation of NOACs; with major bleeding, the focus should be on local measures to control the bleeding and supportive care, and coagulation testing should be performed. There are currently no antidotes to reverse NOACs. The NOACs should not be used in patients with valvular heart disease, prosthetic heart valves, cancer-associated deep vein thrombosis, or superficial thrombophlebitis. CONCLUSION: Management of "what if" scenarios for patients taking NOACs have been proposed, but additional study is needed to address these issues, especially periprocedural management and bleeding.

Perioperative management of patients who are receiving a novel oral anticoagulant.

The use of novel oral anticoagulants (NOACs) is increasing since these drugs are at least as efficacious and safe as vitamin K antagonists (VKAs) for the management of patients with non-valvular atrial fibrillation and venous thromboembolism. Compared with VKAs, NOACs have a faster onset and offset of action, a predictable and consistent pharmacokinetic profile, fewer drug interactions, and ease of use since anticoagulant monitoring is not required. Current perioperative management will be affected by these characteristics, with the potential to obviate the need for heparin bridging. This review aims to summarize the current evidence of perioperative thromboembolic and bleeding risk during anticoagulant interruption, which is derived predominantly from patients receiving VKA therapy, and early studies involving NOACs which mainly focus on patients who are receiving dabigatran. The role of heparin bridging is discussed. We also provide a practical approach for the perioperative management of patients who are receiving NOAC therapy.

Therapeutic potential for mesenchymal stem cell transplantation in critical limb ischemia.

The therapeutic potential of mesenchymal stem cell (MSC) transplantation for the treatment of ischemic conditions such as coronary artery disease, peripheral arterial disease, and stroke has been explored in animal models and early-phase clinical trials. A substantial database documents the safety profile of MSC administration to humans in a large number of disease states. The mechanism of the therapeutic effect of MSC transplantation in ischemic disease has been postulated to be due to paracrine, immunomodulatory, and differentiation effects. This review provides an overview of the potential role of MSC-based therapy for critical limb ischemia (CLI), the comparison of MSC cellular therapy with angiogenesis gene therapy in CLI, and the proposed mechanism of action of MSC therapy. Preclinical efficacy data in animal models of hindlimb ischemia, current early-phase human trial data, and considerations for future MSC-based therapy in CLI will also be discussed.