Vol 14 - Oct 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
Of Paracetamol, Peptides, and Hot Flushes: This Month in Medicine
If medicine had a mood this month, it would be one of cautious reassurance — a collective sigh of relief that some long-debated questions are finally calming down.
First up, acetaminophen in pregnancy gets a welcome thumbs-up. The American College of Obstetricians and Gynecologists confirms it’s still the safest choice for mums-to-be when used sensibly. No link to autism or ADHD has been found — and untreated fever remains the greater danger. So clinicians can keep calm and carry on prescribing.
Over in GLP-1 land, the much-hyped drugs transforming diabetes and waistlines show a small uptick in reflux and gallstones but no major gastrointestinal harm. A few extra burps aside, the benefits for glucose control and weight still win the day.
And speaking of hormones — not the peptide kind — menopausal hormone therapy (HT) proves once again that timing is everything. Starting HT near menopause (ages 50–59) is safe and symptom-soothing, but in older women, cardiovascular risk climbs sharply.
Beyond these top stories, this issue touches on eczema in children, chronic kidney disease, colorectal cancer triage, acupuncture for sciatica, and even continuous glucose monitoring in pregnancy. The through-line? Thoughtful, evidence-based balance — whether in managing pain, hormones, or peptides.
If only prescribing that balance were as easy as writing for an SGLT2 inhibitor.
In This Edition
- Does acetaminophen use during pregnancy increase the risk of neurodevelopmental disorders such as autism or ADHD in children?
- Do glucagon-like peptide-1 receptor agonists (GLP-1RAs) increase the risk of gastrointestinal adverse events?
- What is the cardiovascular risk of menopausal hormone therapy in women with vasomotor symptoms across different age groups?
- How should atopic eczema be diagnosed and managed in children under 12 years?
- What is the role of inflammation in cardiovascular disease, and how should it be assessed and managed in clinical practice?
- Do GLP-1 receptor agonists differ in cardiovascular and renal efficacy between men and women?
- Can quantitative faecal immunochemical tests (FIT) improve colorectal cancer referral decisions in primary care?
- Are GLP-1 receptor agonists effective and safe for children and adolescents with obesity or type 2 diabetes?
- Is candesartan effective and safe for preventing episodic migraine?
- How should chronic kidney disease be diagnosed and managed in adults?
- Is acupuncture an effective and safe treatment for sciatica?
- Does continuous glucose monitoring improve glucose control and perinatal outcomes compared with self-monitoring in diabetes during pregnancy?
American College of Obstetricians and Gynecologists
Does acetaminophen use during pregnancy increase the risk of neurodevelopmental disorders such as autism or ADHD in children?
Clinical Bottom Line: Current evidence does not support a causal relationship between prenatal acetaminophen use and neurodevelopmental disorders (e.g., autism, ADHD, or intellectual disability).
Acetaminophen remains the analgesic and antipyretic of choice during pregnancy, when used judiciously—at the lowest effective dose for the shortest necessary duration. No change in clinical practice is warranted.
Summary: Current evidence does not support a causal link between prenatal acetaminophen use and neurodevelopmental disorders such as autism or ADHD. The American College of Obstetricians and Gynecologists (ACOG) reaffirms that acetaminophen remains the safest first-line treatment for pain and fever in pregnancy when used at the lowest effective dose for the shortest duration. Recent studies addressing genetic and familial confounders show no significant association, and untreated maternal fever or pain poses greater risks to both mother and fetus. Clinicians should reassure patients and continue evidence-based use of acetaminophen in pregnancy.
View ArticleGastroenterology
Do glucagon-like peptide-1 receptor agonists (GLP-1RAs) increase the risk of gastrointestinal adverse events?
Clinical Bottom Line: GLP-1 receptor agonists are associated with a modest increase in risk of cholelithiasis and gastroesophageal reflux disease (GERD) but show no significant increase in other gastrointestinal or biliary adverse events such as pancreatitis, ulcers, or intestinal obstruction. These risks appear higher with weight-loss–inducing or higher-dose formulations, though subgroup differences were not statistically significant.
Summary: A systematic review and meta-analysis of 55 randomized controlled trials including over 106,000 participants found that GLP-1 receptor agonists modestly raise the risk of cholelithiasis (RR 1.46; ~2 extra cases per 1000) and GERD (RR 2.19; ~4 extra cases per 1000) compared with placebo. No clear association was seen with other gastrointestinal or biliary events such as pancreatitis, gastritis, or bowel obstruction.
The elevated risk was more evident in trials involving obesity or fatty liver disease populations and high-dose or potent weight-loss agents, though subgroup findings were not conclusive. Overall, GLP-1RAs remain safe and effective, with gastrointestinal risks generally low and manageable relative to their metabolic benefits.
JAMA Intern Med.
What is the cardiovascular risk of menopausal hormone therapy in women with vasomotor symptoms across different age groups?
Clinical Bottom Line: In women with vasomotor symptoms, menopausal hormone therapy (HT)—either conjugated equine estrogen (CEE) alone or CEE plus medroxyprogesterone acetate (MPA)—is safe for healthy women aged 50–59 years, showing no significant increase in atherosclerotic cardiovascular disease (ASCVD) risk and effective symptom relief. However, cardiovascular risk increases with age, particularly in women 70 years and older, where HT significantly raises ASCVD events. Hormone therapy should therefore be initiated near menopause, avoided in older women, and used for symptom control at the lowest effective dose and duration.
Summary: This secondary analysis of the Women’s Health Initiative trials included 27,347 postmenopausal women who received conjugated equine estrogen (CEE) alone or with medroxyprogesterone acetate (MPA) versus placebo, followed for about seven years. Hormone therapy effectively reduced vasomotor symptoms, particularly with CEE, but cardiovascular effects varied by age. Women aged 50–59 showed no increased risk of atherosclerotic cardiovascular disease, while risk rose modestly in those 60–69 and markedly in women 70 and older. Hormone therapy remains appropriate for healthy women near menopause but should be avoided in older age due to elevated cardiovascular risk.
View ArticleNICE
How should atopic eczema be diagnosed and managed in children under 12 years?
Clinical Bottom Line: Diagnose eczema based on itch plus typical features (flexural or age-specific rash, dry skin, early onset, atopy). Use a holistic assessment of severity and quality of life. Emollients are first-line; add topical corticosteroids according to severity and site, and calcineurin inhibitors if corticosteroids are unsuitable. Avoid bath additives, use antihistamines only when indicated, and refer if severe, uncontrolled, or causing psychosocial problems.
Summary: NICE recommends a stepwise approach to managing atopic eczema in children under 12. Daily emollient use forms the foundation of care, with short courses of appropriate-strength corticosteroids for flares. Identify and avoid triggers such as irritants or allergens, and ensure families understand treatment plans. Specialist referral is needed for severe, resistant, or psychologically distressing cases.
View ArticleAmerican College of Cardiology
What is the role of inflammation in cardiovascular disease, and how should it be assessed and managed in clinical practice?
Clinical Bottom Line: Chronic inflammation is a key, modifiable cause of cardiovascular disease (CVD). Measuring hsCRP helps identify patients at higher risk even with normal cholesterol. Lifestyle changes, statins, and in selected patients low-dose colchicine or IL-1 inhibitors can reduce recurrent events.
Summary: The 2025 ACC statement confirms inflammation as central to CVD pathogenesis. Routine hsCRP testing is recommended for risk assessment and treatment guidance. Managing inflammation through diet, exercise, smoking cessation, and targeted therapies should now be a core part of CVD prevention and care.
View ArticleDiabetes Obes Metab.
Do GLP-1 receptor agonists differ in cardiovascular and renal efficacy between men and women?
Clinical Bottom Line: GLP-1 receptor agonists (GLP-1RAs) provide similar cardiovascular, renal, and cerebrovascular benefits in both men and women with type 2 diabetes. While women showed numerically greater relative risk reductions for some outcomes (e.g., kidney events and stroke), these differences were not statistically significant. Current evidence supports equal use of GLP-1RAs across sexes for cardiorenal protection.
Summary: This systematic review and meta-analysis of 11 randomized controlled trials involving over 85,000 participants found that GLP-1 receptor agonists provided similar cardiovascular and renal benefits in men and women with type 2 diabetes. Risk reductions for major outcomes, including kidney disease, stroke, and major adverse cardiovascular events, were consistent across sexes with no significant interactions. Overall, GLP-1RAs offer comparable protection for both men and women, though future studies should improve female representation and further explore potential sex-based differences in response.
View ArticleNIHR HTA
Can quantitative faecal immunochemical tests (FIT) improve colorectal cancer referral decisions in primary care?
Clinical Bottom Line: Quantitative faecal immunochemical tests (FIT) are more effective and cost-efficient than symptom-based referral alone for identifying patients in primary care who need urgent investigation for colorectal cancer. Across multiple FIT brands and thresholds, all tested strategies offered a positive cost-benefit compared with current practice, reducing unnecessary colonoscopies without missing significant disease. The optimal test brand or threshold remains uncertain, but FIT-guided triage should be adopted as standard practice in symptomatic patients.
Summary: This systematic review, meta-analysis, and cost-effectiveness study assessed the use of quantitative FIT in symptomatic primary care patients. Across multiple test brands, FIT showed strong diagnostic accuracy and consistently generated a positive incremental net monetary benefit of £200–350 per patient compared with current care. FIT-guided triage improves efficiency by reducing unwarranted colonoscopies and enabling earlier detection of colorectal cancer.
View ArticleJAMA Pediatr.
Are GLP-1 receptor agonists effective and safe for children and adolescents with obesity or type 2 diabetes?
Clinical Bottom Line: GLP-1 receptor agonists significantly improve glycemic control, body weight, and BMI in children and adolescents with obesity or type 2 diabetes. Gastrointestinal side effects are more common, but serious adverse events, including suicidal ideation or behaviors, were not increased over short-term follow-up.
Summary: This systematic review and meta-analysis of 18 randomized controlled trials involving 1,402 participants found that GLP-1 receptor agonists reduced HbA1c by 0.44%, fasting glucose by 9.9 mg/dL, body weight by 3.0 kg, and BMI by 1.45 points compared with placebo. Systolic blood pressure also fell modestly. Gastrointestinal side effects were more frequent, but no significant increase was seen in psychiatric or other serious adverse events. GLP-1 RAs appear effective and generally safe for metabolic management in youth with obesity or type 2 diabetes, though long-term safety remains to be confirmed.
View ArticleLancet Neurol.
Is candesartan effective and safe for preventing episodic migraine?
Clinical Bottom Line: Candesartan 16 mg daily significantly reduces migraine frequency and is generally well tolerated, making it a viable preventive option for episodic migraine. Dizziness is the most common side effect, but serious adverse events are rare.
Summary: In this randomized, triple-blind, placebo-controlled phase 2 trial involving 457 adults with episodic migraine, candesartan 16 mg reduced migraine days by 2.04 per month versus 0.82 with placebo—a difference of 1.22 days (p<0.0001). Adverse effects were mostly mild, with dizziness occurring in 30% of the candesartan group compared to 13% with placebo. Serious adverse events were uncommon and occurred at similar rates between groups. Candesartan demonstrates meaningful efficacy and good tolerability as a preventive therapy for episodic migraine.
View ArticleBritish Columbia Clinical Guidelines
How should chronic kidney disease be diagnosed and managed in adults?
Clinical Bottom Line: The 2025 BC guideline emphasizes early detection, accurate diagnosis, and evidence-based management of chronic kidney disease (CKD) to slow progression and reduce cardiovascular risk. Screening of high-risk groups using eGFR and urine ACR is essential, with confirmation of abnormal results. All CKD patients should receive an ACE inhibitor or ARB, and those with albuminuria, diabetes, or heart failure should also be treated with an SGLT2 inhibitor. In diabetic CKD, adding a nonsteroidal MRA and GLP-1 RA further improves renal and cardiovascular outcomes.
Summary: This updated BC guideline (2025) provides a comprehensive framework for evaluating, classifying, and managing CKD in adults. It recommends routine screening for high-risk individuals (e.g., with diabetes, hypertension, or cardiovascular disease) and confirmation of persistent eGFR <60 mL/min/1.73 m² or elevated ACR over ≥3 months for diagnosis. Management focuses on disease-modifying therapies (ACE-I/ARB, SGLT2i, ns-MRA, GLP-1 RA), blood pressure and lipid control, and lifestyle measures such as dietary sodium restriction and regular physical activity. Referral to nephrology is guided by declining eGFR, heavy proteinuria, or uncertain etiology. The guideline aligns with KDIGO 2024 recommendations and supports individualized, multidisciplinary care to prevent kidney failure and associated complications.
View ArticleJ Pain Res.
Is acupuncture an effective and safe treatment for sciatica?
Clinical Bottom Line: Acupuncture appears to reduce pain and improve overall treatment response in patients with sciatica, with few reported safety concerns. However, existing evidence is limited by poor methodological quality, publication bias, and inconsistent reporting, so results should be interpreted cautiously until more rigorous trials are conducted.
Summary: This overview analyzed seven systematic reviews and meta-analyses evaluating acupuncture for sciatica. Despite significant methodological limitations and moderate study overlap, pooled data from a secondary meta-analysis showed that acupuncture improved treatment effectiveness (RR = 1.23) and reduced pain intensity compared with control treatments. While findings suggest potential clinical benefits and good safety, the overall evidence base is weakened by bias and poor reporting standards, highlighting the need for better-designed randomized controlled trials.
View ArticleAm J Obstet Gynecol.
Does continuous glucose monitoring improve glucose control and perinatal outcomes compared with self-monitoring in diabetes during pregnancy?
Clinical Bottom Line: Continuous glucose monitoring (CGM) provides better glycemic control and may improve perinatal outcomes compared with self-monitoring of blood glucose in pregnant women with diabetes. Benefits are strongest for type 1 diabetes and gestational diabetes, with reductions in HbA1c and large-for-gestational-age births. Evidence for type 2 diabetes remains limited.
Summary: This systematic review and meta-analysis of randomized and quasi-experimental studies found that CGM use during pregnancy reduced HbA1c by 0.22% compared with self-monitoring and was linked to lower rates of large-for-gestational-age infants. The strongest evidence came from type 1 diabetes (HbA1c reduction of 0.18%, OR for large-for-gestational-age 0.51) and gestational diabetes (HbA1c reduction of 0.18%, OR 0.46). Improvements in glucose time-in-range and mean sensor glucose were associated with better perinatal outcomes. CGM appears to optimize glycemic control and may reduce neonatal complications, particularly in type 1 and gestational diabetes.
View Article
