Evidence for Primary Care: the latest evidence from the Trip Database

Clinical Correlations

How Does Diabetes Contribute to Immunocompromise in Patients?

Clinical Bottom Line: Individuals with diabetes exhibit an increased susceptibility to infections due to multiple factors associated with the disease. Chronic hyperglycemia impairs immune cell function, leading to diminished responses to pathogens. Additionally, diabetes-related complications such as neuropathy and vascular insufficiency can compromise physical barriers to infection and impede wound healing. Maintaining optimal glycemic control is essential to mitigate these risks and enhance the body’s ability to combat infections.​

Summary: Patients with diabetes are more prone to infections, including respiratory illnesses like pneumonia and COVID-19, as well as skin and soft tissue infections. This heightened vulnerability is primarily due to the adverse effects of elevated blood sugar levels on the immune system. Hyperglycemia can alter lung dendritic cell function, increasing susceptibility to respiratory pathogens. Furthermore, chronic inflammation and microangiopathy associated with diabetes can lead to restrictive lung disease, further complicating respiratory infections. Effective management of blood glucose levels is crucial in reducing the incidence and severity of infections in diabetic patients. ​

Agency for Care Effectiveness

Are Triple Therapy Inhalers Effective and Cost-Effective for Treating Asthma and COPD?

Clinical Bottom Line: Trelegy Ellipta, a single-inhaler triple therapy (ICS/LAMA/LABA), is recommended for inclusion on the Standard Drug List in Singapore for the treatment of both asthma and COPD. Evidence supports its clinical efficacy, safety, and cost-effectiveness compared to dual therapies and other triple therapy options. It simplifies treatment regimens and may improve adherence and quality of life for patients inadequately controlled on dual therapy.

Summary: The Ministry of Health Drug Advisory Committee reviewed the evidence on triple therapy inhalers for asthma and COPD, focusing on Trelegy Ellipta. Clinical trials demonstrated improvements in lung function (FEV₁) and reductions in exacerbations, although not all asthma trials reached statistical significance for exacerbation rates. For COPD, triple therapy showed significant benefits in reducing exacerbations and improving lung function compared to dual therapy.

NIHR HTA

Are Paramedics in General Practice Clinically and Cost-Effective?

Clinical Bottom Line: Integrating paramedics into general practice teams can enhance patient care by leveraging their clinical skills to manage urgent and unscheduled care needs. This collaboration may improve access to timely care and reduce the burden on general practitioners. However, the overall clinical and cost-effectiveness of this model depends on factors such as training, role definition, and practice context. Further research is needed to establish standardized guidelines and evaluate long-term outcomes.​

Summary: A mixed-methods realist evaluation explored the integration of paramedics into general practice settings. The study included a rapid realist review and an evaluation of paramedics working in general practice. Findings suggest that paramedics can effectively manage a range of patient presentations, particularly those requiring urgent attention, thereby enhancing practice capacity and patient access to care. The success of this integration is influenced by clear role definitions, appropriate training, and the specific needs of the practice population. While there is potential for cost savings and improved patient outcomes, further research is necessary to fully understand the long-term impacts and to develop best practice models for incorporating paramedics into general practice teams.​

Tools for Practice

Is a Single Dose Enough to Treat Yeast Infections Effectively?

Clinical Bottom Line: For uncomplicated vulvovaginal candidiasis in non-pregnant women, a single dose of antifungal treatment—either oral fluconazole (150 mg) or intravaginal clotrimazole (500 mg)—is equally effective. Route and duration do not significantly affect outcomes. Treatment choice should be guided by patient preference, considering slight differences in side effects.

Summary: Evidence from multiple RCTs and a meta-analysis suggests that single-dose antifungal therapy is sufficient for treating uncomplicated yeast infections. Clinical cure rates were around 80–85% across both oral and intravaginal routes, with no significant difference in effectiveness. Oral treatment was associated with more systemic side effects (e.g., headache, GI symptoms), while intravaginal treatment had more local reactions (e.g., irritation, burning).

There is no added benefit from longer-duration intravaginal treatments, and there is insufficient evidence to support adding lactic acid. An external antifungal cream may provide additional symptom relief for vulvar symptoms.

Patients should be informed that symptom resolution may take a few days, but no further doses are needed unless symptoms persist. In such cases, a repeat swab is advised to confirm the diagnosis before retreatment.

Age Ageing

Can a Mobile Self-Assessment Effectively Screen for Cognitive Impairment Due to Alzheimer's Disease?

Clinical Bottom Line: The CogSAS mobile cognitive self-assessment tool demonstrates strong reliability, validity, and diagnostic accuracy for detecting mild cognitive impairment (MCI) and dementia due to Alzheimer’s disease (AD)—even in individuals with low educational levels. With high sensitivity and moderate-to-good specificity, it is a promising tool for community-based screening and early identification of AD-related cognitive decline.

Summary: This study introduced and validated CogSAS, a mobile, self-administered cognitive assessment designed to screen for mild cognitive impairment (MCI) and dementia due to Alzheimer’s disease (AD). The tool focuses on memory and executive function and is tailored for use by older adults with low educational levels. CogSAS is a practical and scalable tool for early detection of cognitive impairment, particularly suitable for community screening, including populations with limited formal education.

SBU

What does the evidence say about the use of combination therapy (levothyroxine + liothyronine) versus levothyroxine monotherapy in adults with hypothyroidism?

Clinical Bottom Line: Combination therapy with levothyroxine (LT4) and liothyronine (LT3) does not improve clinical outcomes compared to LT4 monotherapy in adults with hypothyroidism. Although a minority of patients express preference for combination therapy, these preferences are not statistically significant, and there is no consistent evidence of benefit in symptom relief, quality of life, or psychological outcomes. Routine use is not supported, but individualized trials may be considered in patients with persistent symptoms.

Summary: A 2025 SBU review examined two moderate-quality systematic reviews comparing LT4 monotherapy to LT4+LT3 combination therapy for hypothyroidism.

• Clinical outcomes (fatigue, mood, QoL, depression) showed no significant difference between the two approaches.
• Patient preference leaned slightly toward combination therapy (~43–46%), but this was not statistically different from chance.
• Adverse event profiles were similar between groups.

Overall, while combination therapy may appeal to some patients, evidence does not justify routine use, and current best practice remains LT4 monotherapy.

Arch Dis Child.

What Are the Effects of Gender-Affirming Hormone Therapy in Individuals Under 26 with Gender Dysphoria?

Clinical Bottom Line: There is very low to low certainty evidence regarding the effects of gender-affirming hormone therapy (GAHT) in individuals under 26 with gender dysphoria. While some data suggest a potential reduction in depression, the evidence overall remains inconclusive, and both benefits and harms cannot be excluded. High-quality prospective studies are needed to guide practice with greater confidence.

Summary: This systematic review and meta-analysis assessed 24 studies evaluating the effects of GAHT in individuals younger than 26 years with gender dysphoria. Most of the included studies were either comparative observational studies or before-and-after designs, both contributing primarily very low certainty evidence. One comparative study reported a possible reduction in depression among those receiving GAHT compared to those who did not, but the certainty of this finding was low. Additionally, the review identified a single case series offering high certainty evidence that the incidence of cardiovascular events following GAHT was low, at around 4% over a 7–109 month follow-up period. However, the majority of outcomes, including psychological wellbeing, global functioning, and bone health, remain supported by uncertain evidence. The authors concluded that, given the current limitations in the literature, there is considerable uncertainty about the true effects of GAHT in this population, underscoring the need for rigorous future research.

AHRQ

How Is Digestible Carbohydrate Intake Associated With Cardiovascular Disease, Type 2 Diabetes, and Body Composition?

Clinical Bottom Line: Higher or lower intake of digestible carbohydrates—outside moderate ranges—is associated with increased risk of cardiovascular disease (CVD) and type 2 diabetes (T2D) in adults. The relationship appears nonlinear and U-shaped, with lowest risk observed around 45–55% of energy intake or 250–300g/day of carbohydrates. Evidence for an association with body weight or composition is insufficient, and the overall strength of evidence across outcomes is low due to high risk of bias and confounding in many studies.

Summary: This article reports two systematic reviews examining the relationship between digestible carbohydrate intake and chronic health outcomes in individuals over the age of 2. The cardiovascular-focused review included 21 cohort studies (1.28 million participants), while the diabetes/body composition review included 17 studies (nearly 500,000 participants). Most studies suffered from serious risk of bias and inadequate control for confounding.

Findings suggest a U-shaped relationship between carbohydrate intake and both CVD and T2D. For CVD, risk increased when intake exceeded 65% of total energy or 300g/day, while the lowest risk was observed at 50% of energy or 250g/day. A similar pattern was seen for T2D, with risk decreasing up to 45% of energy intake, plateauing between 45–55%, and increasing again beyond that. No clear relationship was found between carbohydrate intake and weight or body composition.

Lancet Diabetes Endocrinol.

Does Vitamin D Supplementation Prevent Acute Respiratory Infections?

Clinical Bottom Line: Updated evidence from a large meta-analysis suggests that vitamin D supplementation does not significantly reduce the risk of acute respiratory infections (ARIs). Although previous analyses showed a modest benefit, the current analysis—with a larger dataset—found the effect size was no longer statistically significant. Subgroup analyses did not identify any populations (e.g. by age, vitamin D status, dose) that clearly benefited, and no safety concerns were identified. Routine vitamin D supplementation should not be recommended solely for ARI prevention.

Summary: This updated systematic review and meta-analysis incorporated data from 46 randomized controlled trials, including over 61,000 participants, to evaluate whether vitamin D supplementation reduces the risk of acute respiratory infections. The main finding was that vitamin D did not significantly reduce ARI risk compared with placebo (OR 0.94, 95% CI 0.88–1.00; p = 0.057). This result contrasts with a previous meta-analysis in 2021, which had shown a statistically significant protective effect. Importantly, subgroup analyses showed no variation in effect by age, baseline vitamin D level, dosing frequency, or dose amount. The intervention was found to be safe, with no increase in serious adverse events.

Although the point estimate still suggests a slight possible benefit, the inclusion of the null value (1.00) in the confidence interval means the result is not statistically significant, and any effect is likely clinically negligible. These findings do not support vitamin D supplementation as an effective strategy for preventing ARIs in the general population.

Diabetes Obes Metab.

Can Probiotics Improve Glycaemic Control and Inflammation in People With Impaired Glucose Tolerance or Type 2 Diabetes?

Clinical Bottom Line: Probiotic supplementation may modestly improve glycaemic control and reduce inflammation in patients with impaired glucose tolerance or type 2 diabetes. Some trials have demonstrated improvements in HbA1c and reductions in inflammatory markers, including C-reactive protein, IL-6, and increases in anti-inflammatory cytokines such as IL-10. However, evidence is not yet conclusive, and the mechanistic link between inflammation reduction and glycaemic improvements remains unclear. Probiotics appear well tolerated and may be a helpful adjunct, but they should not replace established diabetes treatments.

Summary: This review examined randomized controlled trials investigating the effects of probiotics in individuals with impaired glucose tolerance or type 2 diabetes, focusing on glycaemic outcomes and inflammation-related markers. The rationale stems from the role of intestinal dysfunction and inflammation in promoting insulin resistance and chronic disease. Several trials showed that probiotic use led to improvements in glycaemic measures, such as HbA1c, and reductions in markers of systemic inflammation, including C-reactive protein and IL-6. Some studies suggested these effects might be mediated by increased levels of IL-10, an anti-inflammatory cytokine. Conversely, the discontinuation of probiotics was linked to worsened glycaemic control and reduced anti-inflammatory cytokine levels in one study. Other evidence indicated potential benefits such as reduced endotoxins and improved gut barrier function.

Tools for Practice

How Effective Is Topical Minoxidil for Treating Androgenetic Alopecia?

Clinical Bottom Line: Topical minoxidil improves hair density in both men and women with androgenetic alopecia, adding approximately 12–21 hairs/cm² over placebo after 16–48 weeks. Oral and topical minoxidil appear similarly effective, but differ in side effect profiles. In men, finasteride is likely more effective than topical minoxidil. While topical minoxidil is generally safe, side effects such as scalp irritation or shedding are not uncommon.

Summary: Topical minoxidil improves hair growth in both men and women, though the clinical impact is modest. Oral minoxidil offers similar benefits but more side effects. Finasteride is likely more effective in men, but not without risks. Minoxidil remains a safe, accessible first-line option.

UK Health Security Agency

Does RSV Vaccination During Pregnancy Protect Infants From Severe Respiratory Illness?

Clinical Bottom Line: RSV vaccination with Abrysvo from 28 weeks of pregnancy is recommended to protect infants from severe RSV infection during their most vulnerable early months. Clinical trials show it is around 70% effective at preventing severe RSV-related illness in infants for at least six months. The vaccine is safe, well tolerated, and has been approved for use in multiple countries. It should be offered in each pregnancy, ideally at 28 weeks, to maximize passive antibody transfer across the placenta.

Summary: RSV causes significant illness in infants, especially in the first six months. The UK now offers routine RSV vaccination during pregnancy using Abrysvo®, a non-live bivalent vaccine. When given from 28 weeks, it helps transfer protective antibodies to the fetus, reducing the risk of severe RSV.

Trial data show the vaccine is 70% effective with no major safety concerns, and side effects are typically mild. Vaccination is safe for breastfeeding mothers and those under 18, and can be given with other routine vaccines. It complements but does not replace monoclonal antibody immunisation for high-risk infants.

UK Health Security Agency

Should Older Adults Receive RSV Vaccination to Reduce Illness and Hospitalisation?

Clinical Bottom Line: From 1 September 2024, the RSV vaccine Abrysvo is recommended as a single dose for adults aged 75–79 in the UK. The vaccine is safe and effective, reducing RSV-related lower respiratory illness by up to 89% in older adults. It should ideally be administered before the winter season to maximise protection.

Summary: Respiratory syncytial virus (RSV) causes substantial illness and hospitalisations in adults aged 75 and over, particularly during the winter. The UK now recommends RSV vaccination with Abrysvo®, a non-live recombinant vaccine, for adults aged 75–79 as part of a routine and catch-up programme. Clinical trials showed 65–89% efficacy against RSV-related respiratory illness, with a good safety profile.

Although rare cases of Guillain-Barré syndrome have been reported post-vaccination, the overall benefit-risk profile remains favourable. Co-administration with flu or COVID-19 vaccines is possible but may slightly reduce immune response, so spacing doses is preferred when feasible. Vaccination is not currently recommended for revaccination or individuals under 75 years.

Diabetes Obes Metab.

Is High-Intensity Interval Training (HIIT) Effective for Improving Glycaemic and Cardiometabolic Outcomes in People With Type 2 Diabetes?

Clinical Bottom Line: HIIT is an effective exercise strategy for people with type 2 diabetes mellitus (T2DM), showing greater improvements in HbA1c and cardiorespiratory fitness compared with both moderate-intensity continuous training (MICT) and no exercise. It also positively affects fasting glucose, insulin sensitivity, body composition, lipid levels, and blood pressure. While evidence quality is mixed, HIIT can be considered a safe and efficient option to support glycaemic and cardiometabolic health in T2DM management.

Summary: This umbrella review analysed 10 systematic reviews with meta-analyses (76 studies, 2954 participants) comparing HIIT with MICT or no exercise in people with type 2 diabetes. HIIT led to significant reductions in HbA1c (up to –0.83%) and greater improvements in VO₂ max, outperforming both MICT and control. Additional benefits included improved fasting glucose, insulin levels, HOMA-IR, lipid profiles, and blood pressure. Although the methodological quality of included reviews was moderate to low, the overall evidence supports HIIT as an effective, time-efficient approach to improving key health outcomes in T2DM.

JAMA Psychiatry

Can Once-Weekly Semaglutide Reduce Alcohol Consumption and Craving in Adults With Alcohol Use Disorder?

Clinical Bottom Line: Low-dose, once-weekly semaglutide showed moderate reductions in alcohol consumption, craving, and heavy drinking episodes in adults with alcohol use disorder (AUD), despite not reducing overall drinking days or average drinks per day. These promising early findings support further investigation of GLP-1 receptor agonists as a novel treatment approach for AUD.

Summary: In this phase 2 double-blind randomized trial involving 48 adults with AUD, semaglutide significantly reduced alcohol intake in a lab setting, drinks per drinking day, and alcohol craving compared to placebo. The trial also found a reduction in heavy drinking and cigarette use among smokers. While average drinking frequency did not change, semaglutide’s effect on specific consumption metrics suggests a potential therapeutic role in managing AUD, warranting larger-scale trials to confirm efficacy and safety.