Guidelines Committee Research Articles

The Dutch Working Party on Antibiotic Policy (SWAB) guideline for the approach to suspected antibiotic allergy

ObjectivesPrudent handling of reported antibiotic allergies is an important aspect of antibiotic stewardship. The Dutch Working Party on Antibiotic Policy (SWAB) constituted a multidisciplinary expert committee to provide evidence-based recommendations for bedside decision-making in antibiotic therapy in patients that report an antibiotic allergy. MethodsThe guideline committee generated 12 key questions, most of which were population, intervention, comparison, and outcome questions relevant to both children and adults with suspected antibiotic allergies. For each question, a systematic literature search was performed and reviewed for the best available evidence according to the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system. The quality of evidence was graded from very low to high, and recommendations were formulated in structured discussions as strong or weak. ResultsSixty recommendations were provided for suspected allergy to β-lactam antibiotics (BLAs) and non–β-lactam antibiotics. Owing to the absence of randomized controlled trials in this field, the underlying evidence was predominantly graded as low or very low. Available data support that a detailed allergy history should always be performed and critically appraised. When cross-allergy between BLA groups is not to be expected due to the absence of molecular similarity of the side chains, the patient can be safely exposed to the alternative BLA. An exception to this rule is severe delayed-type reactions in which re-exposure to a BLA should only be considered after consultation with a multidisciplinary team. ConclusionsAccumulated scientific data now support a more liberal approach that better balances the benefits of treatment with first choice and usually smaller spectrum antibiotics with appropriate avoidance of antibiotics in case of a truly high risk of a (severe) allergic reaction. In The Netherlands, a formal guideline was developed that provides recommendations for the approach toward suspected allergy to BLA and frequently used non–β-lactam antibiotics, thereby strongly supporting antimicrobial stewardship.

ESTRO-EANO guideline on target delineation and radiotherapy details for glioblastoma

Background and PurposeTarget delineation in glioblastoma is still a matter of extensive research and debate. This guideline aims to update the existing joint European consensus on delineation of the clinical target volume (CTV) in adult glioblastoma patients. Material and MethodsThe ESTRO Guidelines Committee identified 14 European experts in close interaction with the ESTRO clinical committee and EANO who discussed and analysed the body of evidence concerning contemporary glioblastoma target delineation, then took part in a two-step modified Delphi process to address open questions. ResultsSeveral key issues were identified and are discussed including i) pre-treatment steps and immobilisation, ii) target delineation and the use of standard and novel imaging techniques, and iii) technical aspects of treatment including planning techniques and fractionation. Based on the EORTC recommendation focusing on the resection cavity and residual enhancing regions on T1-sequences with the addition of a reduced 15 mm margin, special situations are presented with corresponding potential adaptations depending on the specific clinical situation. ConclusionsThe EORTC consensus recommends a single clinical target volume definition based on postoperative contrast-enhanced T1 abnormalities, using isotropic margins without the need to cone down. A PTV margin based on the individual mask system and IGRT procedures available is advised; this should usually be no greater than 3 mm when using IGRT.

Successful Treatment of Refractory Neuropathic Pain Following Axillary Dissection and Lipoma Resection Using Cervical and Thoracic Dorsal Root Ganglion Stimulation

BACKGROUND: Neuropathy is a pain condition that is caused by an insult to the somatosensory system. Providing adequate management of neuropathic pain (NP) conditions can be challenging as the dis-ease may become progressively nonresponsive to conventional therapies. If conventional treatment options prove ineffective, cervical dorsal root ganglion (DRG) stimulation is a relatively effective, off-label-use therapy for NP, which requires expert cervical placement to be completed safely and effectively. The Neuromodulation Appropriateness Consensus Committee guidelines highlight safety features and general indications for DRG stimulation, which includes current on-label usage up to T10. Although this committee’s expert opinions stated that DRG is safe up to the C5 level, there is limited published efficacy and safety data at levels higher than T10. CASE REPORT: A 36-year-old woman with a significant medical history of anxiety developed intractable right upper extremity NP following an axillary dissection for a lipoma excision. De-spite conservative management, she presented with debilitating NP and severe right upper ex-tremity functional restrictions following the procedure. The patient underwent a C8-T1 DRG stimulation trial, which decreased her pain levels over 50%, and significantly increased her functional abilities. Right-sided C8-T1 permanent DRG leads were placed, which resulted in improved sleep, increased ability to use her right upper extremity, a 95% to 97% reduction in pain, and elimination of regularly scheduled analgesic medications. CONCLUSIONS: Cervical and high thoracic DRG was safe and successful in the treatment of right upper extremity NP in the upper dermatomal levels secondary to axillary dissection and lipoma resection. KEY WORDS: Cervical and high thoracic DRG, neuropathic pain, axillary dissection, lipoma re-section, neuromodulation, case report

Practice harmonization workshops of EBMT: an expert-based approach to generate practical and contemporary guidelines within the arena of hematopoietic cell transplantation and cellular therapy

For hematopoietic cell transplantation (HCT) and cellular therapy (CT), clinical patient care is localized, and practices may differ between countries and from center to center even within the same country. Historically, international guidelines were not always adapted to the changing daily clinical practice and practical topics there were not always addressed. In the absence of well-established guidelines, centers tended to develop local procedures/policies, frequently with limited communication with other centers. To try to harmonize localized clinical practices for malignant and non-malignant hematological disorders within EBMT scope, the practice harmonization and guidelines (PH&G) committee of the EBMT will co-ordinate workshops with topic-specific experts from interested centers. Each workshop will discuss a specific issue and write guidelines/recommendations that practically addresses the topic under review. To provide clear, practical and user-friendly guidelines when international consensus is lacking, the EBMT PH&G committee plans to develop European guidelines by HCT and CT physicians for peers’ use. Here, we define how workshops will be conducted and guidelines/recommendations produced, approved and published. Ultimately, there is an aspiration for some topics, where there is sufficient evidence base to be considered for systematic reviews, which are a more robust and future-proofed basis for guidelines/recommendations than consensus opinion.

HbA1c-based rather than fasting plasma glucose-based definitions of prediabetes identifies high-risk patients with angiographic coronary intermediate lesions: a prospective cohort study

BackgroundPrediabetes is common and associated with poor prognosis in patients with acute coronary syndrome and those undergoing revascularization. However, the impact of prediabetes on prognosis in patients with coronary intermediate lesions remains unclear. The objective of the current study is to explore the impact of prediabetes and compare the prognostic value of the different definitions of prediabetes in patients with coronary intermediate lesions.MethodsA total of 1532 patients attending Fuwai hospital (Beijing, China), with intermediate angiographic coronary lesions, not undergoing revascularization, were followed-up from 2013 to 2021. Patients were classified as normal glucose tolerance (NGT), prediabetes and diabetes according to various definitions based on HbA1c or admission fasting plasma glucose (FPG). The primary endpoint was defined as major adverse cardiovascular events (MACE), the composite endpoint of all-cause death, non-fatal myocardial infarction and repeated revascularization therapy. Multivariate cox regression model was used to explore the association between categories of abnormal glucose category and MACE risk.ResultsThe proportion of patients defined as prediabetes ranged from 3.92% to 47.06% depending on the definition used. A total of 197 MACE occurred during a median follow-up time of 6.1 years. Multivariate cox analysis showed that prediabetes according to the International Expert Committee (IEC) guideline (6.0 ≤ HbA1c < 6.5%) was associated with increased risk of MACE compared with NGT (hazard ratio [HR]: 1.705, 95% confidence interval [CI] 1.143–2.543) and after confounding adjustment (HR: 1.513, 95%CI 1.005–2.277). Consistently, the best cut-off point of glycated haemoglobin (HbA1c) identified based on the Youden’s index was also 6%. Restricted cubic spline analysis delineated a linear positive relationship between baseline HbA1c and MACE risk. Globally, FPG or FPG-based definition of prediabetes was not associated with patients’ outcome.ConclusionsIn this cohort of patients with intermediate coronary lesions not undergoing revascularization therapy, prediabetes based on the IEC-HbA1c definition was associated with increased MACE risk compared with NGT, and may assist in identifying high-risk patients who can benefit from early lifestyle intervention.

Prophylactic Inferior Vena Cava Filters for Venous Thromboembolism in Adults With Trauma: An Updated Systematic Review and Meta-Analysis.

Background: Trauma is an independent risk factor for venous thromboembolism (VTE). Due to contraindications or delay in starting pharmacological prophylaxis among trauma patients with a high risk of bleeding, the inferior vena cava (IVC) filter has been utilized as alternative prevention for pulmonary embolism (PE). Albeit, its clinical efficacy has remained uncertain. Therefore, we performed an updated systematic review and meta-analysis on the effectiveness and safety of prophylactic IVC filters in severely injured patients. Methods: Three databases (MEDLINE, EMBASE, and Cochrane) were searched from August 1, 2012, to October 27, 2021. Independent reviewers performed data extraction and quality assessment. Relative risk (RR) at 95% confidence interval (CI) pooled in a randomized meta-analysis. A parallel clinical practice guideline committee assessed the certainty of evidence using the GRADE approach. The outcomes of interest included VTE, PE, deep venous thrombosis, mortality, and IVC filter complications. Results: We included 10 controlled studies (47 140 patients), of which 3 studies (310 patients) were randomized controlled trials (RCTs) and 7 were observational studies (46 830 patients). IVC filters demonstrated no significant reduction in PE and fatal PE (RR, 0.27; 95% CI, 0.06-1.28 and RR, 0.32; 95% CI, 0.01-7.84, respectively) by pooling RCTs with low certainty. However, it demonstrated a significant reduction in the risk of PE and fatal PE (RR, 0.25; 95% CI, 0.12-0.55 and RR, 0.09; 95% CI, 0.011-0.81, respectively) by pooling observational studies with very low certainty. IVC filter did not improve mortality in both RCTs and observational studies (RR, 1.44; 95% CI, 0.86-2.43 and RR, 0.63; 95% CI, 0.3-1.31, respectively). Conclusion: In trauma patients, moderate risk reduction of PE and fatal PE was demonstrated among observational data but not RCTs. The desirable effect is not robust to outweigh the undesirable effects associated with IVC filter complications. Current evidence suggests against routinely using prophylactic IVC filters.

Surviving Sepsis Campaign.

Surviving Sepsis Campaign.

Financial Disclosures Reported by Industry Among Authors of the American Academy of Ophthalmology Clinical Practice Guidelines

Recommendations of clinical guidelines affect physicians' care delivery. Potential bias and undeclared conflicts of interests (COIs) among guideline authors can impact clinical practice decisions. To assess financial disclosures reported by physician authors of the American Academy of Ophthalmology (AAO) Practice Pattern Guidelines compared with those reported by industry to evaluate the disclosures' accuracy. In this cross-sectional study, all clinical guidelines in the AAO Preferred Practice Patterns (PPP) since 2013 (first year with publicly available industry payment reports) were reviewed on May 1, 2022. Guideline physician authors' name and their reported COI disclosure were extracted from the guideline publication. Payments to physician authors reported by industry were retrieved from the US Centers for Medicare & Medicaid Open Payments database. Physician authors serving on the AAO guideline committee were included. The primary outcome measure was the accuracy of authors' COIs disclosure. Secondary outcome measures were payments to physician authors reported by industry, the types of payments, and authors' gender. A total of 24 AAO guidelines released between 2016 and 2020 were included. Per guideline, there was a mean (SD) of 7.83 (2.24) physician authors. After removing 14 nonphysician authors, 188 physician author names remained, including 83 names assigned as women (44.1%) and 105 names assigned as men (55.9%). Authors could be counted multiple times in these 188 names. According to the Open Payments database, industry reported that 112 of 188 physician authors (59.6%) had at least received 1 payment while serving on the guideline committee, with a payment mean (SD) of $29 849.35 ($54 131.56). According to AAO guidelines, 149 authors (79.3%) had no financial disclosures while serving on the guideline committee. Among these 149 authors, most authors (81 [54.4%]) had payments reported by industry on the Open Payments database not disclosed within the guideline reports. Women physicians were paid significantly more than men for total payments (median [IQR] payments, $15 265 [$598.47-$41 104.67] vs $301.48 [$218.85-$14 615.09]; difference, $14 963.52; P = .003). Industry reported physician guideline authors to have received significant industry payments, some of which were not disclosed within information of the guidelines. To strengthen author transparency regarding these reported disclosures, the authors may want to review and resolve such potential discrepancies during the review and subsequent publication of guidelines.

Sickening: who is protecting pharma consumers?

In 2022, John Abramson published Sickening: How Big Pharma Broke American Healthcare and How We Can Repair It. The book illustrates how large pharmaceutical companies have become misinformation machines that have corrupted peer-reviewed journals, systematic review authors, and guideline committees. Industry influence includes selective reporting of clinical trial results and selection of control groups likely to enhance benefits and disguise side effects. Other documented forms of influence include clear conflicts of interest for members of guideline committees and even direct intimidation. The book concludes with a series of implementable reforms, such as ensuring the accuracy and completeness of evidence, developing an independent National Health Board, designing clinical research to optimize health outcomes, requiring the posting of research data so that independent scholars can replicate analyses, and ensuring the accuracy of direct consumer advertising. Abramson's book is a must read for students of medicine, public health, and public policy.

Remdesivir saves lives. Were 3 years needed to learn that?

Remdesivir saves lives. Were 3 years needed to learn that?

Brain imaging in lung cancer staging: A real-world, multi-centre study of prevalence of brain metastases, impact on treatment and re-modelling of the NICE health economic analysis

IntroductionIn 2019, the National Institute for Health and Care Excellence (NICE) updated their recommendations with respect to brain imaging in the staging of non-small cell lung cancer (NSCLC) based on an analytic cost-effectiveness model using published data and modelling assumptions from committee experts. In this study, we aimed to re-run this model using real-world multi-centre UK data. Materials and MethodsRetrospective data was collected on consecutive patients with radically treatable clinical stage II and III lung cancer from eleven acute NHS Trusts during the calendar year 01/01/2018 to 31/12/2018. Following a written application to the NICE lung cancer guideline committee, we were granted access to the NG122 brain imaging economic model for the purpose of updating the input parameters in line with the real-world findings from this study. ResultsA total of 444 patients had data for analysis. The combined prevalence of occult brain metastases was 6.2% (10/165) in stage II and 6% (17/283) in stage III, compared to 9.5% and 9.3% used in the NICE economic model. 30% of patients with clinical stage III NSCLC and occult BMs on pre-treatment imaging went onto complete the planned curative intent treatment of extracranial disease, 60% completed SRS to the brain and 30% completed WBRT. This compares to 0%, 10% and 0% in the NICE assumptions. The health economic analysis concluded that brain imaging was no longer cost-effective in stage II disease (ICERs £50,023-£115,785) whilst brain imaging remained cost-effective for stage III patients (ICERs 17,000-£22,173), with MRI being the most cost-effective strategy. ConclusionThis re-running of the NICE health economic model with real-world data strongly supports the NICE guideline recommendation for brain imaging prior to curative-intent treatment in stage III lung cancer but questions the cost-effectiveness of CT brain imaging prior to curative-intent treatment in stage II lung cancer.

Minimizing the Risks of Simethicone in Endoscope Reprocessing.

This statement was written under the auspices of the World Gastroenterology Organization's Guidelines Committee. The authors are members of the Review Team of the WGO Endoscope Disinfection Guideline and have experience in endoscopy, endoscope reprocessing, and microbiology, including biofilms. During the preparation of the WGO Update on Endoscope Disinfection Guidelines, concerns about simethicone on endoscope channel surfaces compromising cleaning and disinfection were raised. Publications on simethicone, including modes of delivery, effectiveness, and risks, have been reviewed. The paper was written as a companion to the new guidelines with a focus on minimizing the risks of simethicone in endoscope reprocessing.

P845 Increased incidence of herpes zoster in patients with Inflammatory Bowel Diseases in Europe

Abstract Background Immunocompromised (IC) patients, including those with autoimmune Inflammatory Bowel Diseases (IBD), are at increased risk for herpes zoster (HZ). HZ affects one in three adults aged ≥50 years, with complications of post-herpetic neuralgia (PHN) in around one in ten affected adults. PHN impacts patients’ health-related quality of life and is difficult to treat. Both HZ and PHN place a financial burden on healthcare systems. The objective was to systematically review the incidence of HZ in IC populations. Methods A systematic literature review was performed to identify observational studies reporting on the HZ incidence in a broad range of IC populations in the European Union/European Economic Area, Switzerland and United Kingdom (2002-2022). The results for IBD patients are reported here. Results Overall, 26 studies reported HZ incidence rates, with three reporting on IBD patients. In Valencia, Spain, using hospital and primary care data in adult patients (≥18 years), HZ incidence rates were higher in IBD patients versus non-IC patients, and increased with age (Table 1). In this study, IBD versus non-IC patients had significantly higher rates of HZ complications (7.67 [3.51-14.57] vs. 2.64 [2.42-2.86] per 100,000 person-years [PY]) and of HZ recurrence (2.48 [2.06-2.96] vs. 1.56 [1.53-1.59] per 100 PY), driven by high rates in patients ≥60 years.1 In England, data from the Clinical Practice Research Datalink matched IBD patients (≥18 years) to non-IC patients. HZ incidence was higher in IBD versus non-IC patients and increased with age (Table 1).2 From German claims data (2012) in over ten million adults (≥18 years), HZ incidence in patients with ulcerative colitis and Crohn’s disease were higher than in the non-IC population (Table 1).3 Table 1. HZ incidence rate (per 1,000 person-years) in IBD versus non-IC patients Conclusion Three large real-world studies confirmed significantly higher HZ incidence rates in IBD versus non-IC patients, with higher rates in older age groups. These findings support healthcare providers and guideline committees in reinforcing HZ prevention strategies for IBD patients. An adjuvanted recombinant HZ vaccine is the first approved for use in IC populations, and may help reduce the healthcare system and patient burden.

Nonpharmacologic and Pharmacologic Treatments of Adults in the Acute Phase of Major Depressive Disorder: A Living Clinical Guideline From the American College of Physicians.

The purpose of this guideline from the American College of Physicians (ACP) is to present updated clinical recommendations on nonpharmacologic and pharmacologic interventions as initial and second-line treatments during the acute phase of a major depressive disorder (MDD) episode, based on the best available evidence on the comparative benefits and harms, consideration of patient values and preferences, and cost. The ACP Clinical Guidelines Committee based these recommendations on an updated systematic review of the evidence. The audience for this guideline includes clinicians caring for adult patients in the acute phase of MDD in ambulatory care. The patient population includes adults in the acute phase of MDD. ACP recommends monotherapy with either cognitive behavioral therapy or a second-generation antidepressant as initial treatment in patients in the acute phase of moderate to severe major depressive disorder (strong recommendation; moderate-certainty evidence). ACP suggests combination therapy with cognitive behavioral therapy and a second-generation antidepressant as initial treatment in patients in the acute phase of moderate to severe major depressive disorder (conditional recommendation; low-certainty evidence). The informed decision on the options of monotherapy with cognitive behavioral therapy versus second-generation antidepressants or combination therapy should be personalized and based on discussion of potential treatment benefits, harms, adverse effect profiles, cost, feasibility, patients' specific symptoms (such as insomnia, hypersomnia, or fluctuation in appetite), comorbidities, concomitant medication use, and patient preferences. ACP suggests monotherapy with cognitive behavioral therapy as initial treatment in patients in the acute phase of mild major depressive disorder (conditional recommendation; low-certainty evidence). ACP suggests one of the following options for patients in the acute phase of moderate to severe major depressive disorder who did not respond to initial treatment with an adequate dose of a second-generation antidepressant: • Switching to or augmenting with cognitive behavioral therapy (conditional recommendation; low-certainty evidence) • Switching to a different second-generation antidepressant or augmenting with a second pharmacologic treatment (see Clinical Considerations) (conditional recommendation; low-certainty evidence) The informed decision on the options should be personalized and based on discussion of potential treatment benefits, harms, adverse effect profiles, cost, feasibility, patients' specific symptoms (such as insomnia, hypersomnia, or fluctuation in appetite), comorbidities, concomitant medication use, and patient preferences.

Effectiveness of the Spot Vision Screener using updated 2021 AAPOS guidelines

To evaluate the Spot Vision Screener according to updated 2021 AAPOS Vision Screening Committee guidelines for instrument-based pediatric vision screen validation. As part of an IRB-approved ongoing prospective study, children were screened with the Spot prior to a complete examination. Spot screening was successful in 1,036 of 1,090 children (95%). Forty-eight percent of participants were referred for further screening using the Spot manufacturer guidelines, and 40% of all children were found to have a 2021 amblyopia risk factor or visually significant refractive error by gold standard examination. The Spot recommendation compared reasonably well to the 2021 criteria, with an overall sensitivity of 0.88 and a specificity of 0.78. Applying updated guidelines to the Spot for hyperopia, anisometropia, and astigmatism yielded moderate-to-poor sensitivity (0.27-0.77) but excellent specificity (>0.9). The area under the curve of the receiver operating characteristic analysis demonstrates overall good prediction performance for the Spot for each diagnosis-myopia, hyperopia, astigmatism, anisometropia (range, 0.87-0.97). Results of our study suggest increasing the instrument referral criterion for astigmatism from 1.5 D (manufacturer thresholds of the screener used in this study) to 2 D in older children. Decreasing the anisometropia cut-off from 1 D to 0.75 D would improve sensitivity from 0.59 to >0.8. In our study population, the overall predictive ability of the Spot is good, with a sensitivity of 0.88 and a specificity of 0.78. We recommend specific device refractive referral criteria to maximize screening effectiveness using the updated AAPOS guidelines.

Selecting appropriate compression for lymphedema patients: American Vein and Lymphatic Society position statement.

Lymphedema is a significant and disabling disorder affecting millions of people worldwide. Compression therapy is an important component of lifelong treatment but the specifics of appropriate compression garment selection and prescribing is not always well understood by practitioners and payers. An expert panel of the American Vein and Lymphatic Society was convened to write a Position Statement with explanations and recommendations for the appropriate compression therapy to be used in the treatment of lymphedema patients. A Position Statement was produced by the expert panel with recommendations for documentation and compression therapy treatment. Their recommendations were reviewed, edited, and approved by the Guidelines Committee of the society. This societal Position Statement provides a useful document for reference for medical care providers for the appropriate compression therapy selection and treatment of patients with lymphedema.

Pharmacologic Treatment of Primary Osteoporosis or Low Bone Mass to Prevent Fractures in Adults: A Living Clinical Guideline From the American College of Physicians.

This guideline updates the 2017 American College of Physicians (ACP) recommendations on pharmacologic treatment of primary osteoporosis or low bone mass to prevent fractures in adults. The ACP Clinical Guidelines Committee based these recommendations on an updated systematic review of evidence and graded them using the GRADE (Grading of Recommendations Assessment, Development and Evaluation) system. The audience for this guideline includes all clinicians. The patient population includes adults with primary osteoporosis or low bone mass. ACP recommends that clinicians use bisphosphonates for initial pharmacologic treatment to reduce the risk of fractures in postmenopausal females diagnosed with primary osteoporosis (strong recommendation; high-certainty evidence). ACP suggests that clinicians use bisphosphonates for initial pharmacologic treatment to reduce the risk of fractures in males diagnosed with primary osteoporosis (conditional recommendation; low-certainty evidence). ACP suggests that clinicians use the RANK ligand inhibitor (denosumab) as a second-line pharmacologic treatment to reduce the risk of fractures in postmenopausal females diagnosed with primary osteoporosis who have contraindications to or experience adverse effects of bisphosphonates (conditional recommendation; moderate-certainty evidence). ACP suggests that clinicians use the RANK ligand inhibitor (denosumab) as a second-line pharmacologic treatment to reduce the risk of fractures in males diagnosed with primary osteoporosis who have contraindications to or experience adverse effects of bisphosphonates (conditional recommendation; low-certainty evidence). ACP suggests that clinicians use the sclerostin inhibitor (romosozumab, moderate-certainty evidence) or recombinant PTH (teriparatide, low-certainty evidence), followed by a bisphosphonate, to reduce the risk of fractures only in females with primary osteoporosis with very high risk of fracture (conditional recommendation). ACP suggests that clinicians take an individualized approach regarding whether to start pharmacologic treatment with a bisphosphonate in females over the age of 65 with low bone mass (osteopenia) to reduce the risk of fractures (conditional recommendation; low-certainty evidence).

ASRA Pain Medicine consensus guidelines on the management of the perioperative patient on cannabis and cannabinoids

BackgroundThe past two decades have seen an increase in cannabis use due to both regulatory changes and an interest in potential therapeutic effects of the substance, yet many aspects of...

DB-2-2: STARTING ANTIHYPERTENSIVE TREATMENT WITH COMBINATION THERAPY: CON SIDE OF THE ARGUMENT

The 2018 ESC/ESH and the 2020 ISH guidelines for the management of hypertension proposed that initial combination therapy with two antihypertensive agents in a single-pill combination (SPC) is preferred in most patients in need of blood-pressure (BP) lowering treatment and should replace the long-standing concept of starting treatment with a single agent, rotating through antihypertensive drug classes, and next moving towards combining drug classes. The 2019 Japanese guidelines took a more balanced approach in formulating their recommendation for the use of SPCs. The Japanese document states that when a systolic/diastolic BP decrease of 20/10 mmHg is targeted, combination therapy is an option to be considered in starting treatment. However, the Japanese guideline also recommended that if a drug shows only a weak depressor effect or is poorly tolerated, it must be replaced by another agent with a different mechanism of action, implying that starting with SPCs is not mandatory. By moving SPCs forward as the initial BP lowering strategy, the ESC/ESH and ISH guideline committees overlooked several vested principles in hypertension management: (i) understanding the pathophysiology of hypertension; (ii) prioritizing evidence from randomized clinical trials above observational studies and expert opinion; and (iii) giving consideration to the cost-effectiveness of antihypertensive drug treatment and the sustainability of health care. This article addresses these points. Sources of information included: (i) guidelines issued by European, American, International, British and Japanese Expert Committees, published between 1999 and 2020; (ii) a PubMed search with as terms in the abstract or title hypertension combined with fixed combination OR hypertension combined with single and costs; (iii) the placebo-controlled trials of antihypertensive drug treatment; (iv) three randomized controlled trials of usual versus intensive BP control; and (v) the retail costs of antihypertensive drugs. We propose that starting antihypertensive therapy in treatment-naive hypertensive patients might be based on a few simple principles. First, use antihypertensive drugs with different modes of action. Second, use antihypertensive agents with a long duration of action based on their molecular structure, so-called forgiving drugs, rather than extended-release dosage formulations. Third, titrate each drug to the highest dose that does not produce adverse effects. Fourth, include a thiazide in the drug combination. Finally, once the right combination has been found by rotating through and combining drug classes as well as the timing of dosing, stimulate adherence by reducing the pill load by prescribing of SPCs including 2 or 3 antihypertensive agents in adjustable doses.

Identification and Prioritization of Canadian Society of Nephrology Clinical Practice Guideline Topics With Multidisciplinary Stakeholders and People Living With Kidney Disease: A Clinical Research Protocol.

Despite efforts to provide evidence-based care for people living with kidney disease, health care provider goals and priorities are often misaligned with those of individuals with lived experience of disease. Coupled with competing interests of time, resources, and an abundance of suitable guideline topics, identifying and prioritizing areas of focus for the Canadian nephrology community with a patient-oriented perspective is necessary and important. Similar priority-setting exercises have been undertaken to establish research priorities for kidney disease and to standardize outcomes for kidney disease research and clinical care; however, research priorities are distinct from priorities for guideline development. Inclusion of people living with health conditions in the selection and prioritization of guideline topics is suggested by patient engagement frameworks, though the process to operationalizing this is variable. We propose that the Canadian Society of Nephrology Clinical Practice Guideline Committee (CSN CPGC) takes the opportunity at this juncture to incorporate evidence-based prioritization exercises with involvement of people living with kidney disease and their caregivers to inform future guideline activities. In this protocol, we describe our planned research methods to address this. To establish consensus-based guideline topic priorities for the CSN CPGC using a modified Delphi survey with involvement of multidisciplinary stakeholders, including people living with kidney disease and their caregivers. Protocol for a Modified Delphi Survey. Pilot-tested surveys will be distributed via email and conducted using the online platform SurveyMonkey, in both French and English. We will establish a group of multidisciplinary clinical and research stakeholders (both within and outside CSN membership) from Canada, in addition to people living with kidney disease and/or their caregivers. A comprehensive literature search will be conducted to generate an initial list of guideline topics, which will be organized into three main categories: (1) International nephrology-focused guidelines that may require Canadian commentary, (2) Non-nephrology specific guidelines from Canada that may require CSN commentary, and (3) Novel topics for guideline development. Participants will engage in a multi-round Modified Delphi Survey to prioritize a set of "important guideline topics." Consensus will be reached for an item based on both median score on the Likert-type scale (≥ 7) and the percentage agreement (≥ 75%); the Delphi process will be complete when consensus is reached on each item. Guideline topics will then be given a priority score calculated from the total Likert ratings across participants, adjusted for the number of participants. Potential limitations include participant response rates and compliance to survey completion. We propose to incorporate evidence-based prioritization exercises with the engagement of people living with kidney disease and their caregivers to establish consensus-based guideline topics and inform future guidelines activities of the CSN CPGC.