Vol 16 - Dec 2025 Evidence for Primary Care
Evidence for Primary Care: the latest evidence from the Trip Database
A summary of some of the most important new documents for primary care that have recently been added to the Trip Database
Three Flavours of Sepsis, Plus AI, Exercise, and a Few Surprises Along the Way
This edition opens with a clear message: think sepsis, and think it early. We lead with three linked articles on recognising and managing suspected sepsis in children, adults, and pregnant or recently pregnant people. Different groups, different nuances — but the same core lesson. Structured assessment, sensible risk stratification, and timely escalation still make the biggest difference, and atypical presentations (especially in children and pregnancy) are where vigilance matters most.
Beyond sepsis, the pace eases but the insights keep coming. We look at whether continuing metformin in early pregnancy for PCOS improves outcomes (it probably does), what happens when GLP-1 receptor agonists are stopped (benefits tend to fade), and how SGLT2 inhibitors seem to work across the full albuminuria spectrum. There’s also a grounded look at AI in general practice — already useful for admin, still a work in progress for decision-making.
Rounding things out are practical reminders about chronic pain management, exercise dosing for fibromyalgia, diabetic foot care after healing, lifestyle habits that stick, and a few well-chosen challenges to current assumptions. Start with sepsis — because seconds matter — and dip into the rest as time allows.
In This Edition
- How should suspected sepsis be recognised, risk-stratified, and managed early in children and young people under 16 years?
- How should suspected sepsis be recognised, risk-stratified, and managed early in people aged 16 or over?
- How should suspected sepsis be recognised, risk-stratified, and managed early in pregnant or recently pregnant people?
- Does continuing metformin from preconception through the first trimester improve pregnancy outcomes in women with polycystic ovary syndrome?
- How are UK general practitioners currently using AI in clinical practice, and what are the benefits, risks, and barriers to wider adoption?
- How should chronic non-malignant pain be managed in adults in non-specialist settings?
- Do the metabolic and weight-loss benefits of GLP-1 receptor agonists persist after treatment withdrawal?
- How does chronic inflammation contribute to cardiovascular disease, and how should it be assessed and targeted in clinical practice?
- How should adults with diabetes be managed after diabetic foot ulcer closure to reduce reulceration and improve mobility and fitness?
- How accurately does the UKPDS Outcomes Model predict cardiovascular events and mortality in people with type 2 diabetes?
- When should healthcare professionals suspect child maltreatment in children and young people under 18 years?
- Does treating male sexual partners reduce recurrence of bacterial vaginosis in women?
- What dose of aerobic exercise best reduces pain and improves health status in people with fibromyalgia?
- Can a habit-based lifestyle intervention achieve sustained remission of metabolic syndrome?
- Do SGLT2 inhibitors improve cardiovascular and kidney outcomes across all levels of albuminuria?
NICE
How should suspected sepsis be recognised, risk-stratified, and managed early in children and young people under 16 years?
Clinical Bottom Line: Early recognition of suspected sepsis in under-16s requires a high index of suspicion, structured physiological assessment, and age-specific risk stratification. Children meeting high-risk criteria should receive urgent senior review, broad-spectrum antibiotics within 1 hour, appropriate intravenous fluids, and escalation of care, while lower-risk children require close monitoring, safety-netting, and clear discharge advice.
Summary: This NICE guideline sets out how to recognise and manage suspected sepsis in children under 16 using early clinical suspicion, structured observations, and age-specific risk stratification. High-risk children require urgent antibiotics, fluids, and escalation of care, while lower-risk cases need close monitoring and clear safety-netting.
View ArticleNICE
How should suspected sepsis be recognised, risk-stratified, and managed early in people aged 16 or over?
Clinical Bottom Line: In adults with suspected infection, early recognition of sepsis relies on structured assessment and NEWS2-based risk stratification. People at high risk should receive prompt broad-spectrum antibiotics (within 1 hour), intravenous fluids, and senior escalation, while lower-risk patients require close monitoring, diagnostic clarification, and careful antibiotic stewardship.
Summary: This NICE guideline provides a structured approach to recognising and managing suspected sepsis in people aged 16 or over, emphasising early clinical suspicion, use of NEWS2 to assess risk, and timely escalation of care. Management is tailored to risk level, balancing rapid treatment for high-risk patients with close observation and judicious antibiotic use in those at lower risk.
View ArticleNICE
How should suspected sepsis be recognised, risk-stratified, and managed early in pregnant or recently pregnant people?
Clinical Bottom Line: Pregnant and recently pregnant people are at higher risk of sepsis and may present without typical signs such as fever. Early recognition requires structured assessment and pregnancy-specific risk stratification, with prompt antibiotics (within 1 hour), intravenous fluids, senior obstetric review, and early escalation for those at high risk.
Summary: This NICE guideline outlines the recognition and early management of suspected sepsis in pregnant or recently pregnant people, emphasising early clinical suspicion, structured physiological assessment, pregnancy-specific risk stratification, and rapid escalation of care for high-risk cases, while supporting close monitoring and safety-netting for lower-risk presentations.
View ArticleAm J Obstet Gynecol.
Does continuing metformin from preconception through the first trimester improve pregnancy outcomes in women with polycystic ovary syndrome?
Clinical Bottom Line: In women with PCOS, starting metformin before conception and continuing it through the first trimester increases clinical pregnancy rates and may reduce miscarriage and increase live birth rates compared with placebo or no treatment, with continuation appearing more beneficial than stopping metformin after a positive pregnancy test.
Summary: This systematic review and meta-analysis of 12 randomized trials (1708 women) found that preconception metformin use in women with PCOS improved clinical pregnancy rates. Continuing metformin into the first trimester showed trends toward reduced miscarriage and increased live birth compared with placebo or no treatment, whereas stopping metformin after conception was associated with a possible increase in miscarriage. Overall evidence was low to moderate quality, and further high-quality trials are needed.
View ArticleNuffield Trust
How are UK general practitioners currently using AI in clinical practice, and what are the benefits, risks, and barriers to wider adoption?
Clinical Bottom Line: Around one in four UK GPs are already using AI—mainly for documentation and administrative tasks—but adoption is uneven and constrained by concerns about regulation, liability, safety, and equity. Without clear national guidance, training, and governance, AI is more likely to reduce GP burnout than rapidly increase patient access.
Summary: This large mixed-methods study, based on a national survey of 2,108 UK GPs and follow-up focus groups, found that 28% currently use AI tools in practice, primarily for clinical documentation, administration, and professional development rather than direct clinical decision-making. Adoption varies by gender, age, geography, and deprivation, with lower uptake in more deprived areas. While GPs value AI for saving time and reducing workload, major concerns remain about regulation, medico-legal liability, data security, and clinical safety, highlighting the need for clear national standards, training, and safeguards before wider rollout.
View ArticleSIGN
How should chronic non-malignant pain be managed in adults in non-specialist settings?
Clinical Bottom Line: Chronic pain should be managed using a person-centred, biopsychosocial approach that prioritises supported self-management, psychological and multidisciplinary interventions, and careful prescribing. Opioids should not be used routinely and, if considered at all, should be short term, carefully selected, and regularly reviewed due to limited benefit and substantial risk of harm.
Summary: This national SIGN guideline provides evidence-based recommendations for managing chronic non-malignant pain in adults, mainly in primary and community care. It emphasises realistic goals focused on function and quality of life rather than pain elimination, recommends multimodal and multidisciplinary care, and highlights limited effectiveness and significant harms of many pharmacological treatments—particularly long-term opioids—while supporting pain management programmes, psychological interventions, and self-management strategies.
View ArticleJ Gen Intern Med.
Do the metabolic and weight-loss benefits of GLP-1 receptor agonists persist after treatment withdrawal?
Clinical Bottom Line: After stopping GLP-1 receptor agonists, patients experience substantial rebound in weight, glycaemic control, and cardiometabolic markers, with only modest residual benefit. Sustained weight and metabolic improvements generally require ongoing treatment rather than short-term use.
Summary: This systematic review and meta-analysis of five randomized controlled trials (719 participants) examined outcomes at least six months after GLP-1 receptor agonist discontinuation. Although some reductions in weight, BMI, waist circumference, HbA1c, and systolic blood pressure persisted compared with controls, significant rebound in weight, adiposity, and glycaemia occurred after stopping treatment. Overall, the findings suggest that the durability of GLP-1RA benefits is limited, supporting the need for continued therapy to maintain clinically meaningful effects.
View ArticleAmerican College of Cardiology
How does chronic inflammation contribute to cardiovascular disease, and how should it be assessed and targeted in clinical practice?
Clinical Bottom Line: Chronic low-grade inflammation is a key, independent driver of cardiovascular risk, with elevated hsCRP identifying patients at higher risk even when LDL-cholesterol is controlled. Measuring residual inflammatory risk can help refine cardiovascular risk assessment, and selected anti-inflammatory strategies—alongside statins and lifestyle interventions—can reduce cardiovascular events, although evidence does not yet support routine use of most anti-inflammatory drugs.
Summary: This 2025 American College of Cardiology scientific statement synthesises current evidence linking inflammation to cardiovascular disease across conditions including atherosclerosis, myocardial infarction, heart failure, and pericarditis. It highlights hsCRP as a clinically useful biomarker for residual inflammatory risk, summarises evidence for lifestyle, pharmacological, and emerging anti-inflammatory interventions, and provides consensus recommendations for risk assessment and prevention. While inflammation is now recognised as a clinically actionable target, the statement emphasises the need for stronger trial evidence before widespread adoption of additional anti-inflammatory therapies.
View ArticlePhys Ther.
How should adults with diabetes be managed after diabetic foot ulcer closure to reduce reulceration and improve mobility and fitness?
Clinical Bottom Line: After diabetic foot ulcer closure, care should extend beyond wound healing to include structured assessment of mobility and physical fitness, personalised exercise prescription, and cautious, staged reloading of the foot with maximal offloading in the first three months to reduce ulcer recurrence and improve long-term outcomes.
Summary: This clinical practice guideline synthesises evidence from 38 studies to address gaps in post–diabetic foot ulcer care. It provides recommendations on assessing and improving mobility and physical fitness, incorporating exercise into care plans, and safely reloading the foot after ulcer closure using a graded footwear schedule. The guideline emphasises individualised exercise prescription, prolonged offloading after healing, and the potential for improved quality of life and reduced healthcare costs, while highlighting the need for further research on optimal reloading and exercise during wound healing.
View ArticleDiabetes Obes Metab.
How accurately does the UKPDS Outcomes Model predict cardiovascular events and mortality in people with type 2 diabetes?
Clinical Bottom Line: The UKPDS Outcomes Model version 2 reliably estimates relative cardiovascular risk between treatment groups in type 2 diabetes but may underestimate absolute event rates in some populations, highlighting the need for caution when using it for absolute risk prediction in contemporary clinical trials.
Summary: This validation study compared cardiovascular and mortality outcomes predicted by the UKPDS-OM2 with observed events from the TECOS and EXSCEL cardiovascular outcome trials. While the model accurately reproduced relative risks between randomized treatment groups in both trials and closely matched observed event rates in TECOS, it substantially underestimated absolute event rates in EXSCEL. These findings support UKPDS-OM2 for comparative risk modelling but indicate limitations when estimating absolute cardiovascular risk across different trial populations.
View ArticleNICE
When should healthcare professionals suspect child maltreatment in children and young people under 18 years?
Clinical Bottom Line: Healthcare professionals should maintain a high index of suspicion for child maltreatment when injuries, clinical presentations, behaviours, or parent–child interactions are inconsistent with the child’s developmental stage or the explanation provided. Prompt recognition, careful documentation, and referral to safeguarding services are essential to prevent further harm.
Summary: This NICE guideline outlines alerting clinical features that may indicate physical, sexual, or emotional abuse, neglect, or fabricated or induced illness in children and young people under 18 years. It supports non-specialist healthcare professionals to recognise concerning patterns in physical findings, behaviour, development, and family interactions, and provides a structured approach to observing, recording, and escalating concerns without aiming to diagnose maltreatment.
View ArticleTools for Practice
Does treating male sexual partners reduce recurrence of bacterial vaginosis in women?
Clinical Bottom Line: Treating male partners with oral metronidazole alone does not reduce bacterial vaginosis recurrence. However, combining oral metronidazole with topical clindamycin applied to the penis may meaningfully reduce recurrence at 12 weeks, based on one randomized controlled trial, and may be reasonable given limited harms—though this approach is not yet guideline-recommended.
Summary: Evidence from randomized trials shows that partner treatment with oral antibiotics alone does not reduce bacterial vaginosis recurrence. One open-label RCT found that treating male partners with combined oral metronidazole and topical clindamycin reduced recurrence compared with no partner treatment, but the trial was stopped early and may overestimate benefit. Current guidelines do not recommend routine partner treatment, and further high-quality trials are needed before widespread adoption.
View ArticlePhys Ther.
What dose of aerobic exercise best reduces pain and improves health status in people with fibromyalgia?
Clinical Bottom Line: In fibromyalgia, aerobic exercise produces clinically meaningful improvements in pain and health status, with benefits starting at around 50–65 minutes per week and maximal effects seen at 90–150 minutes per week, supporting a graduated, dose-based approach to exercise prescription.
Summary: This dose–response meta-analysis of 23 randomized controlled trials found that aerobic exercise significantly reduces pain intensity and improves functional health status in people with fibromyalgia. Meaningful pain reduction was observed with as little as 50 minutes of exercise per week, while greater weekly volumes and longer total program duration produced progressively larger benefits. The findings help define minimum and optimal exercise doses to guide individualized exercise programs for fibromyalgia.
View ArticleJAMA Intern Med.
Can a habit-based lifestyle intervention achieve sustained remission of metabolic syndrome?
Clinical Bottom Line: A 6-month, habit-based lifestyle program added to education and activity monitoring modestly but significantly increases sustained remission of metabolic syndrome at 24 months compared with education alone, supporting simple, repeatable behaviour changes as a viable long-term management strategy.
Summary: This randomized clinical trial of 618 adults with metabolic syndrome found that a habit-focused lifestyle intervention—emphasising vegetables at meals, daily brisk walking, sensory awareness, and emotion regulation—produced higher rates of metabolic syndrome remission at both 6 and 24 months than education and activity monitoring alone. Benefits were supported by sustained improvements in fasting glucose, physical activity, and dietary habits, suggesting that behaviour-based programs targeting everyday habits can achieve durable cardiometabolic gains.
View ArticleDiabetes Obes Metab.
Do SGLT2 inhibitors improve cardiovascular and kidney outcomes across all levels of albuminuria?
Clinical Bottom Line: SGLT2 inhibitors reduce cardiovascular events, kidney disease progression, heart failure hospitalisations, and mortality across the entire spectrum of albuminuria—including patients with normal or low albuminuria—supporting their use beyond traditionally albuminuric chronic kidney disease.
Summary: This pooled individual-patient analysis of randomized trials including 26,750 participants showed that higher albuminuria was linearly associated with increased cardiovascular and kidney risk. SGLT2 inhibitors significantly reduced kidney events, heart failure hospitalisations, atherothrombotic events, and mortality compared with placebo, with consistent benefits across all urinary albumin-to-creatinine ratio categories. Albuminuria levels were modestly reduced, indicating that the clinical benefits of SGLT2 inhibitors extend even to patients without albuminuria.
View Article
