A recent Acute Medicine digest,
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Study Type: Target trial emulation (observational cohort study using linked EHR/claims data)

Key Question: Do GLP-1 receptor agonists or SGLT-2 inhibitors reduce renal deterioration risk compared with DPP-4 inhibitors in type 2 diabetes, and does this benefit differ by albuminuria status?

Key Findings:

• In people with albuminuria, 5-year risk of renal deterioration (creatinine doubling or eGFR <15) was lower with GLP-1RA/SGLT-2i vs DPP-4i (3.2% vs 5.4%; risk ratio 0.60, 95% CI 0.42–0.82).
• In people without albuminuria, no protective effect was seen (2.4% vs 2.1%; risk ratio 1.10, 95% CI 0.90–1.38).
• Cohort of 75,455 patients, median follow-up 32 months; 82% had no albuminuria at baseline.

Clinical Relevance: Supports prioritising SGLT-2 inhibitors or GLP-1 receptor agonists as second-line agents specifically in diabetic patients with albuminuria to prevent renal deterioration, informing NHS prescribing pathways and NICE-aligned risk stratification.

Limitations: Observational design with residual confounding despite target trial emulation methodology, and relatively short follow-up limits assessment of long-term renal outcomes in the non-albuminuric group.

Study Type: Nationwide nested case-control study (Danish registry data, 2003–2021)

Key Question: Does current use of menopausal hormone therapy (oral vs transdermal) increase risk of venous thromboembolism (VTE), ischaemic stroke, or myocardial infarction (MI) in women aged 50–69?

Key Findings:

• Oral oestrogen therapy (alone or combined) was associated with increased risk of VTE (HR 1.6, 95% CI 1.5–1.8), ischaemic stroke (HR 1.3, 1.2–1.4), and MI (HR 1.2, 1.1–1.3); numbers needed to harm for one year of use were 1055, 1642, and 3846 respectively.
• High-dose oral oestradiol (>1mg/day) for >5 years carried further elevated stroke (HR 1.8) and MI (HR 1.8) risk.
• Transdermal therapy showed no increased thrombotic risk overall, except transdermal combined cyclic therapy and MI (HR 2.1, 1.1–4.1).

Clinical Relevance: Supports UK/NHS prescribing practice favouring transdermal over oral HRT formulations to minimise thrombotic risk, particularly relevant for acute physicians assessing VTE, stroke, or MI in women on hormone therapy.

Limitations: Observational design with potential residual confounding (e.g., indication bias, unmeasured lifestyle/cardiovascular risk factors) despite matching and exclusion criteria.

Study Type: Individual participant data (IPD) network meta-regression combined with aggregate pairwise meta-analysis of double-blind RCTs.

Key Question: Do specific antidepressants differ in their effect on QTc interval and early cardiovascular risk during the first eight weeks of treatment for major depressive disorder?

Key Findings:

• Escitalopram (+8.7ms, 95% CrI 1.6–15.8) and amitriptyline (+5.3ms, 0.8–9.8) significantly prolonged QTc versus placebo; when risk factors were incorporated, amitriptyline and escitalopram showed the greatest prolongation, venlafaxine and vortioxetine the least.
• Considerable individual variability in QTc response, particularly with escitalopram, fluoxetine, and mirtazapine.
• No association between antidepressant use and early MACE or non-suicidal sudden death (risk difference 0.01%, 95% CrI −0.01% to 0.02%; 139 trials, 52,398 participants).

Clinical Relevance: For NHS clinicians initiating antidepressants in acute/general medical settings, drug choice should account for baseline QTc and modifiable risk factors (electrolytes, renal function, BMI), though absolute cardiovascular event risk in early treatment appears low.

Limitations: Only 27% of eligible trials contributed individual-level QTc data, limiting precision and generalisability of risk-factor-adjusted estimates.

Study Type: Historical/biographical commentary (medical history essay)

Key Question: What was the nature and origin of the professional rivalry between Erasmus Darwin and William Withering, two 18th-century Edinburgh-trained physicians central to the early history of digitalis therapy?

Key Findings:

• A 1780 case in Staffordshire, where Withering's digitalis apparently succeeded after Darwin's treatment failed, was published by Darwin anonymously without crediting Withering, seemingly fuelling lasting animosity.
• Withering countered by criticising Darwin in his seminal 1785 monograph *An Account of the Foxglove*.
• A separate 1788 dispute over a patient's care (via Darwin's son Robert) reignited hostilities, possibly instigated or encouraged by Erasmus.

Clinical Relevance: Illustrates the historical and interpersonal origins of foundational cardiovascular pharmacology (digitalis/foxglove), of ongoing relevance to clinicians using cardiac glycosides today.

Limitations: Relies on historical correspondence and secondary interpretation rather than verifiable primary clinical data.

Study Type: Retrospective, single-centre, uncontrolled observational cohort study

Key Question: Is hypertonic saline plus high-dose IV furosemide feasible and effective for decongestion in very elderly, comorbid patients hospitalised with acute heart failure?

Key Findings:

• Among 191 treatment episodes (140 patients, median age 84, 75% preserved ejection fraction, 41% advanced CKD), diuretic response was good in 41%, intermediate in 45%, poor in 13%; renal function remained stable and NT-proBNP fell.
• Poor diuretic response strongly predicted early clinical failure (penalised OR 7.90, 95% CI 1.09–102) and markedly shorter survival (restricted mean survival 4.4 vs 27.3 days).
• Overall 30-day mortality was high (35.7%), reflecting the frailty of this population; most episodes ended due to clinical improvement (71.2%).

Clinical Relevance: Supports feasibility and safety of aggressive combined diuretic strategies for elderly, multimorbid AHF patients typical of UK acute medicine/internal medicine wards, while highlighting poor diuretic response as an early prognostic red flag warranting escalation or goals-of-care discussion.

Limitations: Uncontrolled, single-centre design without a comparator arm limits causal inference regarding efficacy versus natural disease course.

Study Type: Cohort study (nationwide Italian multicentre registry, COPE)

Key Question: Does central embolic localization on CTPA independently predict adverse outcomes in acute symptomatic PE, beyond established risk stratification?

Key Findings:

• Central PE (61.5% of 4,415 patients) was not associated with all-cause 30-day death, but independently predicted PE-related death (1.7% vs 0.6%, HR 2.11, 95% CI 1.08–4.11) and death/clinical deterioration (HR 1.37, 95% CI 1.05–1.79).
• Among ESC intermediate-risk patients, central localization identified a subgroup with markedly higher PE-related mortality (1.6% vs 0.4%, HR 4.69, 95% CI 1.67–13.22).
• Central emboli were present in >83% of high and intermediate-high risk patients, reflecting correlation with haemodynamic burden.

Clinical Relevance: For UK acute medicine clinicians, CTPA-defined central clot burden could refine risk stratification within intermediate-risk PE—a group where escalation decisions (monitoring vs advanced therapy) are often uncertain.

Limitations: Observational design limits causal inference and radiological clot localization assessment was not centrally adjudicated for reproducibility.

Study Type: Cross-sectional survey

Key Question: How do European clinicians currently screen and monitor MCTD patients for ILD and pulmonary hypertension, given the absence of disease-specific guidelines?

Key Findings:

• Baseline screening was widely performed: PFTs (91.1%), TTE (85.9%), HRCT (74.1%), NFC (71.9%) among 135 clinicians across 21 countries.
• Follow-up practice was highly inconsistent: 61.5% used clinical judgement alone (rather than protocolised intervals) to guide repeat HRCT in ILD-negative patients, and 35.6% did not repeat NFC after a baseline scleroderma-like pattern.
• PH referral pathways were variable, with 34.8% requiring DETECT algorithm validation before right heart catheterisation, despite DETECT lacking validation in MCTD.

Clinical Relevance: Acute medicine clinicians managing MCTD patients presenting with respiratory or cardiac symptoms should be aware that monitoring practices are unstandardised across Europe, increasing the risk of delayed detection of ILD/PH—leading causes of mortality—until MCTD-specific guidelines are developed.

Limitations: Survey-based design relying on self-reported practice introduces response and selection bias, and does not capture actual patient outcomes.

Study Type: Exploratory prospective observational cohort study (matched case-control design)

Key Question: Can circulating angiogenic/inflammatory biomarkers help monitor bevacizumab response and quantify disease severity in hereditary hemorrhagic telangiectasia (HHT)?

Key Findings:

• VEGF-A rose markedly during bevacizumab therapy, making it unsuitable as a monitoring marker; PDGF and TSP1 rose significantly more in treatment responders vs non-responders.
• At baseline, HHT patients (n=9) showed lower BMP9, sENG, sVEGFR1, sVEGFR2, VEGFc, TSP1, TSP2, and PDGF, but higher IL-6, compared to controls.
• VEGFc, sVEGFR1, and TSP1 correlated positively with haemoglobin, suggesting utility as anaemia severity markers.

Clinical Relevance: These biomarkers may eventually help UK HHT centres objectively monitor bevacizumab response and disease burden, supporting individualised treatment decisions in this NHS-commissioned specialist service.

Limitations: Very small sample size (n=9 treated patients) limits statistical power and generalisability; findings require external validation.