Open research questions in Clinical practice guidelines implementation
67 unresolved questions extracted from the limitations and future-work sections of 293 Clinical practice guidelines implementation papers in our library. Each links back to the study that raised it.
What the literature leaves open
Abstract Purpose The Patient Reported Outcomes Measurement Information System ( PROMIS®) is a family of patient-reported outcome measures used in research and clinical practice, but little is known about its use in clinical care.
Denmark Dansk Idrætmedicinsk Selskab No guidelines available. (VSG) Norway Sweden Norsk Idrettsmedisinsk Forening No guidelines available. Svensk Förening För Fysisk Aktivitet No guidelines available. och Idrottsmedicin Switzerland Sports and Exercise Medicine No guidelines available. United States American Orthopaedic Society for No guidelines available.
Clinical practice guidelines in sport and exercise medicine: time for capacity building · 2026 · DOIFor hypertensive patients with comorbid depression or anxiety, a combination of antihypertensive medication and antidepressants/anxiolytics is recommended (2C).
Evidence and rationale Hypertensive patients with onset age ≤35 years, abnormal blood potassium, a low plasma renin level, and common secondary hypertension excluded are recommended for genetic testing to screen for monogenic hypertension (2D).
CPAP during sleep is suggested for hypertensive patients with moderate to severe OSA (2C). Mineral corticoid receptor antagonists are suggested for patients with moderate to severe OSA complicated with resistant hypertension (2C).
Medical therapy is primarily recommended in patients with ARAS (1B). In ARAS patients with resistant hypertension, renal dysfunction, flash pulmonary edema, or refractory HF, interventional therapy may be considered (2D). In patients with ARAS ≥70% and stenosis-related hyper- tension or renal function deterioration, interventional therapy should be considered (GPS).
RASI is recommended for the treatment of hypertension associated with unilateral RAS, under close monitoring 2934 www.cmj.org Chinese Medical Journal 2024;137(24) of urine output, serum electrolytes, and serum creatinine (1C). RASI should be considered in RAS patients after success- ful revascularization (2C). RASI may be cautiously initiated at a low dose under close monitoring of renal function in patients with bilateral RAS, solitary kidney, or single functioning kidney when other indications for RASI are present (2D). Dosage reduction or discontinuation is recommended if oligu- ria occurs, or serum creatinine rises >0.5 mg/dL (44 µmol/L) or >30% from the baseline during RASI therapy (GPS).
For patients with eGFR ≥30 mL·min–1·1.73 m–2, renal artery computed tomography angiography (CTA) is recommended as the first choice. Gadolinium-enhanced magnetic resonance angiography (MRA) and ultrasonography are alternative modalities (1B). For patients with eGFR <30 mL·min–1·1.73 m–2, ultrasonography is recommended as the first choice, and non-enhanced magnetic resonance angiography (MRA) is recommended as an alternative. CTA or contrast-enhanced MRA should be avoided (GPS). Digital subtraction angiography (DSA) remains the gold standard for the diagnosis of RAS. DSA may be considered when RAS is highly suspected and the results of non-invasive examinations are inconclusive, or when a revascularization is planned. Captopril renal scintigraphy may be considered in those without obvious (eGFR ≥60 mL·min–1·1.73 m–2) (2C).
RAS screening should be considered if hypertensive patients meet one of the following conditions: (1) a history of atherosclerotic CVD (2C); (2) early onset hypertension (<40 years old) (2D); (3) continuous BP ≥160/100 mmHg, or a negative change from good previous BP control, inde- pendent of any changes to antihypertensive drugs or any other causes (GPS); (4) normal LVEF in conjunction with transient pulmonary edema (2D); (5) refractory hyper- tension (2C); (6) periumbilical vascular murmur (GPS) detected on physical examination; (7) significant increase of serum creatinine or significant decrease of BP after the use of antihypertensive drugs (especially ACEI/ARB) (2D); (8) unilateral renal atrophy (GPS); (9) hypokalemia (GPS).
We recommend computed tomography (CT) as the first choice of imaging modality to locate PPGL (1B). We recommend magnetic resonance imaging (MRI) to detect skull base and neck paragangliomas (1C) in patients with metastatic PPGL. We suggest the use of metaiodobenzylguanidine (MIBG) scintigraphy (1C), 68Ga-Dotatate PET/CT scanning (2B), and somatostatin receptor imaging (2C) as functional imaging modalities in patients with metastatic PPGL.
We recommend plasma-free or urinary fractionated meta- nephrine (MN) and normetanephrine (NMN) as the first choice for biochemical testing of PPGL (1B).
The following patients should be considered for PPGL screening: (1) Patients with paroxysmal hypertension and triad symptoms (headaches, palpitations, and sweating) (1C). (2) Patients with symptoms of PPGL triggered by adrenergic drugs, changes in abdominal pressure, anes- thesia, or surgery (1C). (3) Patients with an incidentally discovered adrenal mass (1C). (4) Patients with a pre- disposition to hereditary causes (1C). (5) Patients with myocardial damage of unknown causes and stress-in- duced cardiomyopathy (2D).
For initial screening, we recommend one of the following tests for patients clinically suspected of Cushing’s syn- drome: (1) 1-mg overnight dexamethasone suppression test (2D). (2) 24-h urinary free cortisol (2C). (3) Late- night salivary cortisol (2C).
We recommend screening for Cushing’s syndrome among adult hypertensive patients with the following characteristics (2C): (1) features that best discriminate Cushing’s syn- drome: easy bruising, facial plethora, proximal muscle weakness, and purple striae. (2) Other common clinical features: menstrual abnormalities, acne, weight gain, and central obesity. (3) Refractory hypertension. (4) Unusual osteoporosis for age. (5) Adrenal incidentaloma. (6) Type 2 diabetic patients who need insulin treatment or are on two or more anti-hypertensive drugs.
We recommend screening for PA without stopping inter- fering medications, though PA screening results should be carefully interpreted if these medications cannot be discontinued (2D).
For PA screening, we recommend the plasma aldos- terone-to-renin ratio (ARR) after patients remain in a non-recumbent position for at least 2 h (1B) as the cutoff. We recommend an ARR of 2.0 ng·dL–1/mU·L–1 as the cutoff if ARR is calculated by plasma aldosterone con- centration (PAC)/plasma renin concentration (PRC), and 30 ng·dL–1/ng·mL–1·h–1 as the cutoff if ARR is calculated by PAC/plasma renin activity (PRA) (2C).
The following patients are recommended to be screened for common secondary hypertension (2C): (1) newly diagnosed hypertensive patients; (2) patients with hyper- tension onset at <40 years; (3) patients with resistant hypertension; (4) hypertensive patients with clinical clues of secondary hypertension or extensive hypertension-me- diated target organ damage.
Recommendations RDN can be used as a BP-lowering strategy in hyperten- sive patients with resistant hypertension, intolerance to antihypertensive therapy, and clinical features consistent with sympathetic hyperactivity (2B).
A low dose of spironolactone (20–40 mg/day) is recommended as the fourth-line medication for patients with resistant hypertension whose serum potassium is <4.5 mmol/L and eGFR is ≥45 mL·min–1·1.73 m–2 (1B).
We recommend following up hypertensive patients within 2–4 weeks after the initiation or adjustment of antihyper- tensive medication until the BP target is reached (GPS). We recommend following up hypertensive patients at three-month intervals after reaching the BP target (GPS).
For hypertensive patients with CHD, ischemic stroke, or peripheral vascular disease, it is recommended to take 75–100 mg/day of aspirin for long-term secondary pre- vention (1A). For those aged 40–65 years with hypertension and cardiovas- cular risk, if the risk of bleeding is not high, low-dose aspirin (75–100 mg/day) can be considered for primary prevention (2B). For high-risk groups for bleeding (e.g., history of gastroin- testinal bleeding, recent cerebral hemorrhage, use of drugs that increase bleeding risk, uncontrolled hypertension), aspirin for primary prevention is not recommended (2C).
We recommend that a RASI be used in CKD patients with microalbuminuria and proteinuria (1B). We suggest that a RASI may be used in CKD patients without microalbuminuria and proteinuria (2B).
For hypertensive patients with a history of stroke or TIA, ACEI (1A), diuretic (1A), or ACEI plus diuretic (1A) are 2923 www.cmj.org Chinese Medical Journal 2024;137(24) recommended. CCB (2C) or ARB (2C) may be considered if these agents are inappropriate or ineffective. For hypertensive patients with a history of stroke or TIA, β-blockers are not recommended as first-line antihyper- tensive agents (1A).
Individualized medication should be based on patient complications, drug tolerance, and contraindications. For example, beta-blockers should be discontinued in patients with severe bradycardia, high atrioventricular block, or asthma. Non-dihydropyridine CCB should be avoided in patients with HF, severe bradycardia, and atrioventricular block, because they inhibit cardiac conduction. ARBs can be used as an alternative in patients who cannot tolerate ACEIs.
In hypertensive patients with CHD who manifest angina pectoris, β-blocker and CCB are recommended (1C). In hypertensive patients with CHD and prior myocardial infarction, β-blocker and ACEI/ARB are recommended (1C).
Most-cited papers in Clinical practice guidelines implementation
- Why Don't Physicians Follow Clinical Practice Guidelines? · JAMA · 1999 · 5,138 citations
- Guidelines 2.0: systematic development of a comprehensive checklist for a successful guideline enterprise · Canadian Medical Association Journal · 2013 · 555 citations
- Clinical practice guidelines: The good, the bad, and the ugly · Injury · 2022 · 185 citations
- Acceptance of guideline recommendations and perceived implementation of coronary heart disease prevention among primary care physicians in five European countries: the Reassessing European Attitudes about Cardiovascular Treatment (REACT) survey · Family Practice · 2002 · 176 citations
- Too many digits: the presentation of numerical data · Archives of Disease in Childhood · 2015 · 113 citations
- Implementation strategies used to implement nursing guidelines in daily practice: A systematic review · International Journal of Nursing Studies · 2020 · 74 citations
- Patient involvement in guidelines is poor five years after institute of medicine standards: review of guideline methodologies · Research Involvement and Engagement · 2017 · 73 citations
- Influencing Diagnostic and Preventive Performance in Ambulatory Care by Feedback and Reminders. A Review · Family Practice · 1993 · 71 citations
- Large Language Models for More Efficient Reporting of Hospital Quality Measures · NEJM AI · 2024 · 50 citations
- Inappropriate use of clinical practices in Canada: a systematic review · Canadian Medical Association Journal · 2022 · 47 citations
Most recent work
- Shared Decision Making: Aids and Promotion in Clinical Practice Guidelines for Type 2 Diabetes Treatment · Journal of Evaluation in Clinical Practice · 2026
- Development, implementation, and evaluation of clinical practice guidelines, protocols, and pathways used in rural and remote Australia, Canada, and Aotearoa New Zealand: a scoping review · JBI Evidence Synthesis · 2026
- Clinical practice guidelines in sport and exercise medicine: time for capacity building · 2026
- Ensuring Clinical Practice Guidelines Meet the Needs of the End-User: a Prioritization Survey for Guideline Topics for Behavioural and Psychological Symptoms of Dementia. · Canadian Geriatrics Journal · 2026
- Development and prioritization of ERIC-informed implementation strategies for Traditional Chinese Medicine guidelines: a two-phase mixed methods study · Critical Public Health · 2026
- Effectiveness of Guideline-Based Clinical Decision Support Systems: Protocol for a Systematic Review · JMIR Research Protocols · 2026
- Voices in clinical guideline development: a qualitative study of Irish guideline developers’ perspectives on developing recommendations · Evidence & Policy · 2026
- Introduction to the Special Issue on Advanced Gestalt Practice · The Journal of Humanistic Counseling · 2026
- American Heart Association updated 2025 practice guidelines · Nursing · 2026
- Clinical Resource/Quick Reference · NASN School Nurse · 2026
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