Key clinical point: Dermatological symptoms are substantially associated with the quality of life (QoL) in patients with active psoriatic arthritis (PsA) and improvements in dermatology measures could translate to clinically meaningful improvements in their QoL.

Major finding: Itch severity item (ISI) scores of 7-10, Physician’s Global Assessment of Psoriasis (PGA-PsO) scores of 4, and Patient’s Global Joint and Skin Assessment-Visual Analog Scale (PGJS-VAS) scores of 90-100 mm corresponded with Dermatology Life Quality Index (DLQI) scores categorized as having a very large effect on a patient’s life. An improvement of ≥3 points in ISI, ≥2 points in PGA-PsO, and ≥40 mm in PGJS-VAS translated to a clinically meaningful improvement in DLQI scores.

Study details: This post hoc analysis of two phase 3 studies, OPAL Broaden and OPAL Beyond, included 816 patients with active PsA and an inadequate response to previous therapies who received tofacitinib, adalimumab, or placebo.

Disclosures: This study was funded by Pfizer. Four authors reported being employees or stockholders of Pfizer. The other authors reported ties with several sources, including Pfizer.

Source: Taylor PC et al. Relationships of dermatologic symptoms and quality of life in patients with psoriatic arthritis: analysis of two tofacitinib phase III studies. J Dermatol Treat. 2022 (Apr 11). Doi: 10.1080/09546634.2022.2060924

Key clinical point: Dermatological symptoms are substantially associated with the quality of life (QoL) in patients with active psoriatic arthritis (PsA) and improvements in dermatology measures could translate to clinically meaningful improvements in their QoL.

Major finding: Itch severity item (ISI) scores of 7-10, Physician’s Global Assessment of Psoriasis (PGA-PsO) scores of 4, and Patient’s Global Joint and Skin Assessment-Visual Analog Scale (PGJS-VAS) scores of 90-100 mm corresponded with Dermatology Life Quality Index (DLQI) scores categorized as having a very large effect on a patient’s life. An improvement of ≥3 points in ISI, ≥2 points in PGA-PsO, and ≥40 mm in PGJS-VAS translated to a clinically meaningful improvement in DLQI scores.

Study details: This post hoc analysis of two phase 3 studies, OPAL Broaden and OPAL Beyond, included 816 patients with active PsA and an inadequate response to previous therapies who received tofacitinib, adalimumab, or placebo.

Disclosures: This study was funded by Pfizer. Four authors reported being employees or stockholders of Pfizer. The other authors reported ties with several sources, including Pfizer.

Source: Taylor PC et al. Relationships of dermatologic symptoms and quality of life in patients with psoriatic arthritis: analysis of two tofacitinib phase III studies. J Dermatol Treat. 2022 (Apr 11). Doi: 10.1080/09546634.2022.2060924

Key clinical point: Dermatological symptoms are substantially associated with the quality of life (QoL) in patients with active psoriatic arthritis (PsA) and improvements in dermatology measures could translate to clinically meaningful improvements in their QoL.

Major finding: Itch severity item (ISI) scores of 7-10, Physician’s Global Assessment of Psoriasis (PGA-PsO) scores of 4, and Patient’s Global Joint and Skin Assessment-Visual Analog Scale (PGJS-VAS) scores of 90-100 mm corresponded with Dermatology Life Quality Index (DLQI) scores categorized as having a very large effect on a patient’s life. An improvement of ≥3 points in ISI, ≥2 points in PGA-PsO, and ≥40 mm in PGJS-VAS translated to a clinically meaningful improvement in DLQI scores.

Study details: This post hoc analysis of two phase 3 studies, OPAL Broaden and OPAL Beyond, included 816 patients with active PsA and an inadequate response to previous therapies who received tofacitinib, adalimumab, or placebo.

Disclosures: This study was funded by Pfizer. Four authors reported being employees or stockholders of Pfizer. The other authors reported ties with several sources, including Pfizer.

Source: Taylor PC et al. Relationships of dermatologic symptoms and quality of life in patients with psoriatic arthritis: analysis of two tofacitinib phase III studies. J Dermatol Treat. 2022 (Apr 11). Doi: 10.1080/09546634.2022.2060924

Key clinical point: Upadacitinib led to early, clinically meaningful, and sustained improvements in pain in patients with psoriatic arthritis (PsA) and an inadequate response to prior biological or nonbiological disease-modifying antirheumatic drugs (b/nbDMARD).

Major finding: A significantly higher proportion of patients receiving 15 mg upadacitinib vs. placebo achieved ≥30%, ≥50%, and ≥70% reductions in pain as early as at 2 weeks (P < .05), with improvements sustained till week 56.

Study details: Findings are from an analysis of 2 phase 3 trials, SELECT-PsA 1 and SELECT-PsA 2 , including 1113 patients with active PsA and an inadequate response to ≥1 nb/bDMARD who were randomly assigned to receive 15 mg upadacitinib once daily, placebo, or adalimumab (only in the SELECT-PsA 1 study).

Disclosures: This study was sponsored by AbbVie. Eight authors declared serving as employees or owning stock/stock options in AbbVie and other authors reported ties with several sources, including AbbVie.

Source: McInnes IB et al. Effect of upadacitinib on reducing pain in patients with active psoriatic arthritis or ankylosing spondylitis: Post hoc analysis of three randomised clinical trials. RMD Open. 2022;8:e002049 (Mar 24). Doi: 10.1136/rmdopen-2021-002049

Key clinical point: Upadacitinib led to early, clinically meaningful, and sustained improvements in pain in patients with psoriatic arthritis (PsA) and an inadequate response to prior biological or nonbiological disease-modifying antirheumatic drugs (b/nbDMARD).

Major finding: A significantly higher proportion of patients receiving 15 mg upadacitinib vs. placebo achieved ≥30%, ≥50%, and ≥70% reductions in pain as early as at 2 weeks (P < .05), with improvements sustained till week 56.

Study details: Findings are from an analysis of 2 phase 3 trials, SELECT-PsA 1 and SELECT-PsA 2 , including 1113 patients with active PsA and an inadequate response to ≥1 nb/bDMARD who were randomly assigned to receive 15 mg upadacitinib once daily, placebo, or adalimumab (only in the SELECT-PsA 1 study).

Disclosures: This study was sponsored by AbbVie. Eight authors declared serving as employees or owning stock/stock options in AbbVie and other authors reported ties with several sources, including AbbVie.

Source: McInnes IB et al. Effect of upadacitinib on reducing pain in patients with active psoriatic arthritis or ankylosing spondylitis: Post hoc analysis of three randomised clinical trials. RMD Open. 2022;8:e002049 (Mar 24). Doi: 10.1136/rmdopen-2021-002049

Key clinical point: Upadacitinib led to early, clinically meaningful, and sustained improvements in pain in patients with psoriatic arthritis (PsA) and an inadequate response to prior biological or nonbiological disease-modifying antirheumatic drugs (b/nbDMARD).

Major finding: A significantly higher proportion of patients receiving 15 mg upadacitinib vs. placebo achieved ≥30%, ≥50%, and ≥70% reductions in pain as early as at 2 weeks (P < .05), with improvements sustained till week 56.

Study details: Findings are from an analysis of 2 phase 3 trials, SELECT-PsA 1 and SELECT-PsA 2 , including 1113 patients with active PsA and an inadequate response to ≥1 nb/bDMARD who were randomly assigned to receive 15 mg upadacitinib once daily, placebo, or adalimumab (only in the SELECT-PsA 1 study).

Disclosures: This study was sponsored by AbbVie. Eight authors declared serving as employees or owning stock/stock options in AbbVie and other authors reported ties with several sources, including AbbVie.

Source: McInnes IB et al. Effect of upadacitinib on reducing pain in patients with active psoriatic arthritis or ankylosing spondylitis: Post hoc analysis of three randomised clinical trials. RMD Open. 2022;8:e002049 (Mar 24). Doi: 10.1136/rmdopen-2021-002049

Key clinical point: A dose of 100 mg guselkumab every 4 weeks (Q4W) or 8 weeks (Q8W) effectively improved the signs and symptoms of psoriatic arthritis (PsA) at week 24, with effects sustained till week 52, in subgroups of patients with diverse baseline characteristics.

Major finding: At week 24, a higher proportion of patients receiving guselkumab Q4W/Q8W (62%/60%) vs. placebo (29%) achieved ≥20% improvement in the American College of Rheumatology (ACR20) criteria, with guselkumab demonstrating superior efficacy over placebo regardless of baseline patient demographics, disease characteristics, or medication use, with effects sustained till week 52.

Study details: This post hoc analysis of two phase 3 trials, DISCOVER-1, and DISCOVER-2, and included 1120 patients with active PsA with an inadequate response to standard therapies who were randomly assigned to receive subcutaneous 100 mg guselkumab Q4W, 100 mg guselkumab Q8W, or placebo.

Disclosures: This study was funded by Janssen Research & Development, LLC. Six authors declared being employees of Janssen and owned stocks in Johnson & Johnson, the parent of Janssen. The other authors reported ties with several sources, including Janssen.

Source: Ritchlin CT et al. Sustained and improved guselkumab response in patients with active psoriatic arthritis regardless of baseline demographic and disease characteristics: Pooled results through week 52 of two phase III, randomised, placebo-controlled studies.  RMD Open. 2022;8:e002195 (Mar 16). Doi: 10.1136/rmdopen-2022-002195

Key clinical point: A dose of 100 mg guselkumab every 4 weeks (Q4W) or 8 weeks (Q8W) effectively improved the signs and symptoms of psoriatic arthritis (PsA) at week 24, with effects sustained till week 52, in subgroups of patients with diverse baseline characteristics.

Major finding: At week 24, a higher proportion of patients receiving guselkumab Q4W/Q8W (62%/60%) vs. placebo (29%) achieved ≥20% improvement in the American College of Rheumatology (ACR20) criteria, with guselkumab demonstrating superior efficacy over placebo regardless of baseline patient demographics, disease characteristics, or medication use, with effects sustained till week 52.

Study details: This post hoc analysis of two phase 3 trials, DISCOVER-1, and DISCOVER-2, and included 1120 patients with active PsA with an inadequate response to standard therapies who were randomly assigned to receive subcutaneous 100 mg guselkumab Q4W, 100 mg guselkumab Q8W, or placebo.

Disclosures: This study was funded by Janssen Research & Development, LLC. Six authors declared being employees of Janssen and owned stocks in Johnson & Johnson, the parent of Janssen. The other authors reported ties with several sources, including Janssen.

Source: Ritchlin CT et al. Sustained and improved guselkumab response in patients with active psoriatic arthritis regardless of baseline demographic and disease characteristics: Pooled results through week 52 of two phase III, randomised, placebo-controlled studies.  RMD Open. 2022;8:e002195 (Mar 16). Doi: 10.1136/rmdopen-2022-002195

Key clinical point: A dose of 100 mg guselkumab every 4 weeks (Q4W) or 8 weeks (Q8W) effectively improved the signs and symptoms of psoriatic arthritis (PsA) at week 24, with effects sustained till week 52, in subgroups of patients with diverse baseline characteristics.

Major finding: At week 24, a higher proportion of patients receiving guselkumab Q4W/Q8W (62%/60%) vs. placebo (29%) achieved ≥20% improvement in the American College of Rheumatology (ACR20) criteria, with guselkumab demonstrating superior efficacy over placebo regardless of baseline patient demographics, disease characteristics, or medication use, with effects sustained till week 52.

Study details: This post hoc analysis of two phase 3 trials, DISCOVER-1, and DISCOVER-2, and included 1120 patients with active PsA with an inadequate response to standard therapies who were randomly assigned to receive subcutaneous 100 mg guselkumab Q4W, 100 mg guselkumab Q8W, or placebo.

Disclosures: This study was funded by Janssen Research & Development, LLC. Six authors declared being employees of Janssen and owned stocks in Johnson & Johnson, the parent of Janssen. The other authors reported ties with several sources, including Janssen.

Source: Ritchlin CT et al. Sustained and improved guselkumab response in patients with active psoriatic arthritis regardless of baseline demographic and disease characteristics: Pooled results through week 52 of two phase III, randomised, placebo-controlled studies.  RMD Open. 2022;8:e002195 (Mar 16). Doi: 10.1136/rmdopen-2022-002195

Key clinical point: Interleukin-17 (IL-17) inhibitors were associated with higher treatment persistence than tumor necrosis factor (TNF) inhibitors or IL-12/23 inhibitors in patients with psoriatic arthritis (PsA) who initiated treatment with biologics.

Major finding: Treatment persistence was higher with IL-17 inhibitors than TNF inhibitors (weighted hazard ratio [HR] 0.70; P < .001) or IL-12/23 inhibitor (weighted HR 0.69; P < .001); however, IL-12/23 and TNF inhibitors showed similar persistence (P = .70).

Study details: This nationwide cohort study included 16,892 adults with psoriasis and 6531 adults with PsA who initiated first-line treatment with TNF, IL-12/23, or IL-17 inhibitors.

Disclosures: The study did not report any source of funding. P Claudepierre reported receiving consulting fees and serving as an investigator for several pharmaceutical companies.

Source: Vegas LP et al. Long-term persistence of first-line biologics for patients with psoriasis and psoriatic arthritis in the french health insurance database. JAMA Dermatol. 2022 (Mar 23). Doi: 10.1001/jamadermatol.2022.0364

Key clinical point: Interleukin-17 (IL-17) inhibitors were associated with higher treatment persistence than tumor necrosis factor (TNF) inhibitors or IL-12/23 inhibitors in patients with psoriatic arthritis (PsA) who initiated treatment with biologics.

Major finding: Treatment persistence was higher with IL-17 inhibitors than TNF inhibitors (weighted hazard ratio [HR] 0.70; P < .001) or IL-12/23 inhibitor (weighted HR 0.69; P < .001); however, IL-12/23 and TNF inhibitors showed similar persistence (P = .70).

Study details: This nationwide cohort study included 16,892 adults with psoriasis and 6531 adults with PsA who initiated first-line treatment with TNF, IL-12/23, or IL-17 inhibitors.

Disclosures: The study did not report any source of funding. P Claudepierre reported receiving consulting fees and serving as an investigator for several pharmaceutical companies.

Source: Vegas LP et al. Long-term persistence of first-line biologics for patients with psoriasis and psoriatic arthritis in the french health insurance database. JAMA Dermatol. 2022 (Mar 23). Doi: 10.1001/jamadermatol.2022.0364

Key clinical point: Interleukin-17 (IL-17) inhibitors were associated with higher treatment persistence than tumor necrosis factor (TNF) inhibitors or IL-12/23 inhibitors in patients with psoriatic arthritis (PsA) who initiated treatment with biologics.

Major finding: Treatment persistence was higher with IL-17 inhibitors than TNF inhibitors (weighted hazard ratio [HR] 0.70; P < .001) or IL-12/23 inhibitor (weighted HR 0.69; P < .001); however, IL-12/23 and TNF inhibitors showed similar persistence (P = .70).

Study details: This nationwide cohort study included 16,892 adults with psoriasis and 6531 adults with PsA who initiated first-line treatment with TNF, IL-12/23, or IL-17 inhibitors.

Disclosures: The study did not report any source of funding. P Claudepierre reported receiving consulting fees and serving as an investigator for several pharmaceutical companies.

Source: Vegas LP et al. Long-term persistence of first-line biologics for patients with psoriasis and psoriatic arthritis in the french health insurance database. JAMA Dermatol. 2022 (Mar 23). Doi: 10.1001/jamadermatol.2022.0364

Heart failure with preserved ejection fraction (HFpEF) is common in elderly adults with type 2 diabetes (T2D), and these individuals are at high risk for frailty and cognitive impairment. Empagliflozin has been shown to reduce cardiovascular death or hospitalization for heart failure in individuals with HFpEF with or without diabetes, but little is known about the impact of empagliflozin on cognition in patients with diabetes and HFpEF. In a prospective observation study of 162 frail older adults with T2D and HFpEF, Mone and colleagues reported that after receiving empagliflozin for 1 month, there was a significant improvement in the Montreal Cognitive Assessment score, but no improvement was seen with metformin or insulin. Although the study was limited by its observational design, small sample size, and short follow-up, it indicates that improved cognition may be another unexpected benefit of empagliflozin in patients with HFpEF.

The Action to Control Cardiovascular Risk in Diabetes (ACCORD) study continues to provide valuable information for the management of T2D. ACCORD Lipid had previously shown that fenofibrate vs. placebo added to simvastatin did not reduce major atherosclerotic cardiovascular events in about 5500 patients with T2D who were at high risk for cardiovascular disease. Ferreira and colleagues have now reported that fenofibrate in ACCORD Lipid reduced hospitalization for heart failure or cardiovascular death by 18%, with the benefit predominantly in those treated with standard glucose-lowering therapy. This analysis was done post hoc and is hypothesis-generating for fenofibrate reducing HF-related events. The soon to be completed PROMINENT study of pemafibrate includes a secondary composite cardiovascular outcome with hospitalization for heart failure as a component, so more information regarding the impact of fibrates on heart failure will be available soon.

Diabetes is associated with a threefold greater risk for stroke and microvascular disease. In another analysis of ACCORD, Kaze and colleagues reported that a higher urine albumin‐to‐creatinine ratio and a lower estimated glomerular filtration rate were each independently associated with an increased risk for stroke. Although further adequately powered studies are required, this analysis suggests that prevention of kidney disease and its progression may help mitigate the risk for stroke in people with T2D.

People with severe mental illness (SMI), such as schizophrenia, bipolar disorder, or depression, are at increased risk for T2D, but it is unknown whether they are more likely to develop the complications of diabetes. Scheuer and colleagues published data from a large nationwide registry in Denmark. They found that, compared with people without SMI, people with SMI were more likely to develop nephropathy or cardiovascular disease, have an amputation, and that the nephropathy and cardiovascular disease occurred at younger ages in those with SMI. Although there are limitations with registry data, this study supports diabetes guidelines that recommend cardiorenal protection with sodium-glucose cotransporter 2 (SGLT2) inhibitors and glucagon-like peptide 1 (GLP-1) receptor agonists in patients with T2D who are at high risk for nephropathy progression and cardiovascular disease. Because this study suggests that SMI along with T2D confers greater risk for nephropathy and cardiovascular disease at younger ages, perhaps we should consider these cardiorenal protective agents early on in persons with T2D and SMI.

Heart failure with preserved ejection fraction (HFpEF) is common in elderly adults with type 2 diabetes (T2D), and these individuals are at high risk for frailty and cognitive impairment. Empagliflozin has been shown to reduce cardiovascular death or hospitalization for heart failure in individuals with HFpEF with or without diabetes, but little is known about the impact of empagliflozin on cognition in patients with diabetes and HFpEF. In a prospective observation study of 162 frail older adults with T2D and HFpEF, Mone and colleagues reported that after receiving empagliflozin for 1 month, there was a significant improvement in the Montreal Cognitive Assessment score, but no improvement was seen with metformin or insulin. Although the study was limited by its observational design, small sample size, and short follow-up, it indicates that improved cognition may be another unexpected benefit of empagliflozin in patients with HFpEF.

The Action to Control Cardiovascular Risk in Diabetes (ACCORD) study continues to provide valuable information for the management of T2D. ACCORD Lipid had previously shown that fenofibrate vs. placebo added to simvastatin did not reduce major atherosclerotic cardiovascular events in about 5500 patients with T2D who were at high risk for cardiovascular disease. Ferreira and colleagues have now reported that fenofibrate in ACCORD Lipid reduced hospitalization for heart failure or cardiovascular death by 18%, with the benefit predominantly in those treated with standard glucose-lowering therapy. This analysis was done post hoc and is hypothesis-generating for fenofibrate reducing HF-related events. The soon to be completed PROMINENT study of pemafibrate includes a secondary composite cardiovascular outcome with hospitalization for heart failure as a component, so more information regarding the impact of fibrates on heart failure will be available soon.

Diabetes is associated with a threefold greater risk for stroke and microvascular disease. In another analysis of ACCORD, Kaze and colleagues reported that a higher urine albumin‐to‐creatinine ratio and a lower estimated glomerular filtration rate were each independently associated with an increased risk for stroke. Although further adequately powered studies are required, this analysis suggests that prevention of kidney disease and its progression may help mitigate the risk for stroke in people with T2D.

People with severe mental illness (SMI), such as schizophrenia, bipolar disorder, or depression, are at increased risk for T2D, but it is unknown whether they are more likely to develop the complications of diabetes. Scheuer and colleagues published data from a large nationwide registry in Denmark. They found that, compared with people without SMI, people with SMI were more likely to develop nephropathy or cardiovascular disease, have an amputation, and that the nephropathy and cardiovascular disease occurred at younger ages in those with SMI. Although there are limitations with registry data, this study supports diabetes guidelines that recommend cardiorenal protection with sodium-glucose cotransporter 2 (SGLT2) inhibitors and glucagon-like peptide 1 (GLP-1) receptor agonists in patients with T2D who are at high risk for nephropathy progression and cardiovascular disease. Because this study suggests that SMI along with T2D confers greater risk for nephropathy and cardiovascular disease at younger ages, perhaps we should consider these cardiorenal protective agents early on in persons with T2D and SMI.

Heart failure with preserved ejection fraction (HFpEF) is common in elderly adults with type 2 diabetes (T2D), and these individuals are at high risk for frailty and cognitive impairment. Empagliflozin has been shown to reduce cardiovascular death or hospitalization for heart failure in individuals with HFpEF with or without diabetes, but little is known about the impact of empagliflozin on cognition in patients with diabetes and HFpEF. In a prospective observation study of 162 frail older adults with T2D and HFpEF, Mone and colleagues reported that after receiving empagliflozin for 1 month, there was a significant improvement in the Montreal Cognitive Assessment score, but no improvement was seen with metformin or insulin. Although the study was limited by its observational design, small sample size, and short follow-up, it indicates that improved cognition may be another unexpected benefit of empagliflozin in patients with HFpEF.

The Action to Control Cardiovascular Risk in Diabetes (ACCORD) study continues to provide valuable information for the management of T2D. ACCORD Lipid had previously shown that fenofibrate vs. placebo added to simvastatin did not reduce major atherosclerotic cardiovascular events in about 5500 patients with T2D who were at high risk for cardiovascular disease. Ferreira and colleagues have now reported that fenofibrate in ACCORD Lipid reduced hospitalization for heart failure or cardiovascular death by 18%, with the benefit predominantly in those treated with standard glucose-lowering therapy. This analysis was done post hoc and is hypothesis-generating for fenofibrate reducing HF-related events. The soon to be completed PROMINENT study of pemafibrate includes a secondary composite cardiovascular outcome with hospitalization for heart failure as a component, so more information regarding the impact of fibrates on heart failure will be available soon.

Diabetes is associated with a threefold greater risk for stroke and microvascular disease. In another analysis of ACCORD, Kaze and colleagues reported that a higher urine albumin‐to‐creatinine ratio and a lower estimated glomerular filtration rate were each independently associated with an increased risk for stroke. Although further adequately powered studies are required, this analysis suggests that prevention of kidney disease and its progression may help mitigate the risk for stroke in people with T2D.

People with severe mental illness (SMI), such as schizophrenia, bipolar disorder, or depression, are at increased risk for T2D, but it is unknown whether they are more likely to develop the complications of diabetes. Scheuer and colleagues published data from a large nationwide registry in Denmark. They found that, compared with people without SMI, people with SMI were more likely to develop nephropathy or cardiovascular disease, have an amputation, and that the nephropathy and cardiovascular disease occurred at younger ages in those with SMI. Although there are limitations with registry data, this study supports diabetes guidelines that recommend cardiorenal protection with sodium-glucose cotransporter 2 (SGLT2) inhibitors and glucagon-like peptide 1 (GLP-1) receptor agonists in patients with T2D who are at high risk for nephropathy progression and cardiovascular disease. Because this study suggests that SMI along with T2D confers greater risk for nephropathy and cardiovascular disease at younger ages, perhaps we should consider these cardiorenal protective agents early on in persons with T2D and SMI.

Introduction

Patients presenting with the symptoms of gastroparesis (Gp) are commonly seen in gastroenterology practice. This article reviews the presentation, pathophysiology, diagnosis, and treatment of gastroparesis syndromes with an emphasis on newer approaches evolving in clinical practice.

Presentation

Patients with foregut symptoms of Gp have characteristic presentations, with nausea, vomiting/retching, and abdominal pain often associated with bloating and distension, early satiety, anorexia, and heartburn. Mid- and hindgut gastrointestinal and/or urinary symptoms may be seen in patients with Gp as well.

The precise epidemiology of gastroparesis syndromes (GpS) is unknown. Classic gastroparesis, defined as delayed gastric emptying without known mechanical obstruction, has a prevalence of about 10 per 100,000 population in men and 30 per 100,000 in women with women being affected 3 to 4 times more than men.^1,2 Some risk factors for GpS, such as diabetes mellitus (DM) in up to 5% of patients with Type 1 DM, are known.³ Caucasians have the highest prevalence of GpS, followed by African Americans.^4,5

Pathophysiology

Specific types of gastroparesis syndromes have variable pathophysiology (Figure 1). In some cases, like GpS associated with DM, pathophysiology is partially related to diabetic autonomic dysfunction. GpS are multifactorial, however, and rather than focusing on subtypes, this discussion focuses on shared pathophysiology. Understanding pathophysiology is key to determining treatment options and potential future targets for therapy.

Intragastric mechanical dysfunction, both proximal (fundic relaxation and accommodation and/or lack of fundic contractility) and distal stomach (antral hypomotility) may be involved. Additionally, intragastric electrical disturbances in frequency, amplitude, and propagation of gastric electrical waves can be seen with low/high resolution gastric mapping.

Both gastroesophageal and gastropyloric sphincter dysfunction may be seen. Esophageal dysfunction is frequently seen but is not always categorized in GpS. Pyloric dysfunction is increasingly a focus of both diagnosis and therapy. GI anatomic abnormalities can be identified with gastric biopsies of full thickness muscle and mucosa. CD117/interstitial cells of Cajal, neural fibers, inflammatory and other cells can be evaluated by light microscopy, electron microscopy, and special staining techniques.

Diagnosis of GpS

Diagnosis of GpS is often delayed and can be challenging; various tools have been developed, but not all are used. A diagnostic approach for patients with symptoms of Gp is listed below, and Figure 2 details a diagnostic approach and treatment options for symptomatic patients.

Symptom Assessment: Initially Gp symptoms can be assessed using Food and Drug Administration–approved patient-reported outcomes, including frequency and severity of nausea, vomiting, anorexia/early satiety, bloating/distention, and abdominal pain on a 0-4, 0-5 or 0-10 scale. The Gastrointestinal Cardinal Symptom Index or visual analog scales can also be used. It is also important to evaluate midgut and hindgut symptoms.^9-11

Mechanical obstruction assessment: Mechanical obstruction can be ruled out using upper endoscopy or barium studies.

Physiologic testing: The most common is radionuclide gastric emptying testing (GET). Compliance with guidelines, standardization, and consistency of GETs is vital to help with an accurate diagnosis. Currently, two consensus recommendations for the standardized performance of GETs exist.^12,13 Breath testing is FDA approved in the United States and can be used as an alternative. Wireless motility capsule testing can be complimentary.

Gastric dysrhythmias assessment: Assessment of gastric dysrhythmias can be performed in outpatient settings using cutaneous electrogastrogram, currently available in many referral centers. Most patients with GpS have an underlying gastric electrical abnormality.^14,15

Sphincter dysfunction assessment: Both proximal and distal sphincter abnormalities have been described for many years and are of particular interest recently. Use of the functional luminal imaging probe (FLIP) shows patients with GpS may have decreased sphincter distensibility when examining the comparisons of the cross-sectional area relative to pressure Using this information, sphincter therapies can be offered.^16-18

Other testing: Neurologic and autonomic testing, along with psychosocial, genetic and frailty assessments, are helpful to explore.¹⁹ Nutritional evaluation can be done using standardized scales, such as subjective global assessment and serologic testing for micronutrient deficiency or electrical impedance.²⁰

Treatment of GpS

Therapies for GpS can be viewed as the five D’s: Diet, Drug, Disruption, Devices, and Details.

Diet and nutrition: The mainstay treatment of GpS remains dietary modification. The most common recommendation is to limit meal size, often with increased meal frequency, as well as nutrient composition, in areas that may retard gastric emptying. In addition, some patients with GpS report intolerances of specific foods, such as specific carbohydrates. Nutritional consultation can assist patients with meals tailored for their current nutritional needs. Nutritional supplementation is widely used for patients with GpS.²⁰

Pharmacological treatment: The next tier of treatment for GpS is drugs. Review of a patient’s medications is important to minimize drugs that may retard gastric emptying such as opiates and GLP-1 agonists. A full discussion of medications is beyond the scope of this article, but classes of drugs available include: prokinetics, antiemetics, neuromodulators, and investigational agents.

Bioelectric therapy: Another approach for patients with symptomatic drug refractory GpS is bioelectric device therapies, which can be delivered several ways, including directly to the stomach or to the spinal cord or the vagus nerve in the neck or ear, as well as by electro-acupuncture. High-frequency, low-energy gastric electrical stimulation (GES) is the best studied. First done in 1992 as an experimental therapy, GES was investigational from 1995 to 2000, when it became FDA approved as a humanitarian-use device. GES has been used in over 10,000 patients worldwide; only a small number (greater than 700 study patients) have been in controlled trials. Nine controlled trials of GES have been primarily positive, and durability for over 10 years has been shown. Temporary GES can also be performed endoscopically, although that is an off-label procedure. It has been shown to predict long-term therapy outcome.^23-26 

Nutritional support: Nutritional abnormalities in some cases of GpS lead to consideration of enteral tubes, starting with a trial of feeding with an N-J tube placed endoscopically. An N-J trial is most often performed in patients who have macro-malnutrition and weight loss but can be considered for other highly symptomatic patients. Other endoscopic tubes can be PEG or PEG-J or direct PEJ tubes. Some patients may require surgical placement of enteral tubes, presenting an opportunity for a small bowel or gastric full-thickness biopsy. Enteral tubes are sometimes used for decompression in highly symptomatic patients.²⁷

For patients presenting with neurological symptoms, findings and serologic abnormalities have led to interest in immunotherapies. One is intravenous immunoglobulin, given parenterally. Several open-label studies have been published, the most recent one with 47 patients showing better response if glutamic acid decarboxylase–65 antibodies were present and with longer therapeutic dosing.²⁸ Drawbacks to immunotherapies like intravenous immunoglobulin are cost and requiring parenteral access.

Other evaluation/treatments for drug refractory patients can be detailed as follows: First, an overall quality of life assessment can be helpful, especially one that includes impact of GpS on the patients and family. Nutritional considerations, which may not have been fully assessed, can be examined in more detail. Frailty assessments may show the need for physical therapy. Assessment for home care needs may indicate, in severe patients, needs for IV fluids at home, either enteral or parenteral, if nutrition is not adequate. Psychosocial and/or psychiatric assessments may lead to the need for medications, psychotherapy, and/or support groups. Lastly, an assessment of overall health status may lead to approaches for minimizing visits to emergency rooms and hospitalizations.^29,30

Conclusion

Patients with Gp symptoms are becoming increasingly recognized and referred to gastroenterologists. Better understandings of the pathophysiology of the spectrum of gastroparesis syndromes, assisted by innovations in diagnosis, have led to expansion of existing and new therapeutic approaches. Fortunately, most patients can benefit from a standardized diagnostic approach and directed noninvasive therapies. Patients with refractory gastroparesis symptoms, often with complex issues referred to gastroenterologists, remain a challenge, and novel approaches may improve their quality of life.
 

Dr. Mathur is a GI motility research fellow at the University of Louisville, Ky. He reports no conflicts of interest. Dr. Abell is the Arthur M. Schoen, MD, Chair in Gastroenterology at the University of Louisville. His main funding is NIH GpCRC and NIH Definitive Evaluation of Gastric Dysrhythmia. He is an investigator for Cindome, Vanda, Allergan, and Neurogastrx; a consultant for Censa, Nuvaira, and Takeda; a speaker for Takeda and Medtronic; and a reviewer for UpToDate. He is also the founder of ADEPT-GI, which holds IP related to mucosal stimulation and autonomic and enteric profiling.

References

1. Jung HK et al. Gastroenterology. 2009;136(4):1225-33.

2. Ye Y et al. Gut. 2021;70(4):644-53.

3. Oshima T et al. J Neurogastroenterol Motil. 2021;27(1):46-54.

4. Soykan I et al. Dig Dis Sci. 1998;43(11):2398-404.

5. Syed AR et al. J Clin Gastroenterol. 2020;54(1):50-4.

6.Pasricha PJ et al. Clin Gastroenterol Hepatol. 2011;9(7):567-76.e1-4.

7. Pasricha PJ et al. Gastroenterology. 2021;160(6):2006-17.

8. Almario CV et al. Am J Gastroenterol. 2018;113(11):1701-10.

9. Abell TL et al. Dig Dis Sci. 2021 Apr;66(4):1127-41.

10. Abell TL et al. Neurogastroenterol Motil. 2019;31(3):e13534.

11. Elmasry M et al. Neurogastroenterol Motil. 2021 Oct 26;e14274.

12. Maurer AH et al. J Nucl Med. 2020;61(3):11N-7N.

13. Abell TL et al. J Nucl Med Technol. 2008 Mar;36(1):44-54.

14. Shine A et al. Neuromodulation. 2022 Feb 16;S1094-7159(21)06986-5.

15. O’Grady G et al. Am J Physiol Gastrointest Liver Physiol. 2021;321(5):G527-g42.

16. Saadi M et al. Rev Gastroenterol Mex (Engl Ed). Oct-Dec 2018;83(4):375-84.

17. Kamal F et al. Aliment Pharmacol Ther. 2022;55(2):168-77.

18. Harberson J et al. Dig Dis Sci. 2010;55(2):359-70.

19. Winston J. Gastrointestinal Disorders. 2021;3(2):78-83.

20. Parkman HP et al. Gastroenterology. 2011;141(2):486-98, 98.e1-7.

21. Heckroth M et al. J Clin Gastroenterol. 2021;55(4):279-99.

22. Camilleri M. Clin Gastroenterol Hepatol. 2022;20(1):19-24.

23. Payne SC et al. Nat Rev Gastroenterol Hepatol. 2019;16(2):89-105.

24. Ducrotte P et al. Gastroenterology. 2020;158(3):506-14.e2.

25. Burlen J et al. Gastroenterology Res. 2018;11(5):349-54.

26. Hedjoudje A et al. Neurogastroenterol Motil. 2020;32(11):e13949.

27. Petrov RV et al. Gastroenterol Clin North Am. 2020;49(3):539-56.

28. Gala K et al. J Clin Gastroenterol. 2021 Dec 31. doi: 10.1097/MCG.0000000000001655.

29. Abell TL et al. Neurogastroenterol Motil. 2006;18(4):263-83.

30. Camilleri M et al. Am J Gastroenterol. 2013;108(1):18-37.


 

Introduction

Patients presenting with the symptoms of gastroparesis (Gp) are commonly seen in gastroenterology practice. This article reviews the presentation, pathophysiology, diagnosis, and treatment of gastroparesis syndromes with an emphasis on newer approaches evolving in clinical practice.

Presentation

Patients with foregut symptoms of Gp have characteristic presentations, with nausea, vomiting/retching, and abdominal pain often associated with bloating and distension, early satiety, anorexia, and heartburn. Mid- and hindgut gastrointestinal and/or urinary symptoms may be seen in patients with Gp as well.

The precise epidemiology of gastroparesis syndromes (GpS) is unknown. Classic gastroparesis, defined as delayed gastric emptying without known mechanical obstruction, has a prevalence of about 10 per 100,000 population in men and 30 per 100,000 in women with women being affected 3 to 4 times more than men.^1,2 Some risk factors for GpS, such as diabetes mellitus (DM) in up to 5% of patients with Type 1 DM, are known.³ Caucasians have the highest prevalence of GpS, followed by African Americans.^4,5

Pathophysiology

Specific types of gastroparesis syndromes have variable pathophysiology (Figure 1). In some cases, like GpS associated with DM, pathophysiology is partially related to diabetic autonomic dysfunction. GpS are multifactorial, however, and rather than focusing on subtypes, this discussion focuses on shared pathophysiology. Understanding pathophysiology is key to determining treatment options and potential future targets for therapy.

Intragastric mechanical dysfunction, both proximal (fundic relaxation and accommodation and/or lack of fundic contractility) and distal stomach (antral hypomotility) may be involved. Additionally, intragastric electrical disturbances in frequency, amplitude, and propagation of gastric electrical waves can be seen with low/high resolution gastric mapping.

Both gastroesophageal and gastropyloric sphincter dysfunction may be seen. Esophageal dysfunction is frequently seen but is not always categorized in GpS. Pyloric dysfunction is increasingly a focus of both diagnosis and therapy. GI anatomic abnormalities can be identified with gastric biopsies of full thickness muscle and mucosa. CD117/interstitial cells of Cajal, neural fibers, inflammatory and other cells can be evaluated by light microscopy, electron microscopy, and special staining techniques.

Diagnosis of GpS

Diagnosis of GpS is often delayed and can be challenging; various tools have been developed, but not all are used. A diagnostic approach for patients with symptoms of Gp is listed below, and Figure 2 details a diagnostic approach and treatment options for symptomatic patients.

Symptom Assessment: Initially Gp symptoms can be assessed using Food and Drug Administration–approved patient-reported outcomes, including frequency and severity of nausea, vomiting, anorexia/early satiety, bloating/distention, and abdominal pain on a 0-4, 0-5 or 0-10 scale. The Gastrointestinal Cardinal Symptom Index or visual analog scales can also be used. It is also important to evaluate midgut and hindgut symptoms.^9-11

Mechanical obstruction assessment: Mechanical obstruction can be ruled out using upper endoscopy or barium studies.

Physiologic testing: The most common is radionuclide gastric emptying testing (GET). Compliance with guidelines, standardization, and consistency of GETs is vital to help with an accurate diagnosis. Currently, two consensus recommendations for the standardized performance of GETs exist.^12,13 Breath testing is FDA approved in the United States and can be used as an alternative. Wireless motility capsule testing can be complimentary.

Gastric dysrhythmias assessment: Assessment of gastric dysrhythmias can be performed in outpatient settings using cutaneous electrogastrogram, currently available in many referral centers. Most patients with GpS have an underlying gastric electrical abnormality.^14,15

Sphincter dysfunction assessment: Both proximal and distal sphincter abnormalities have been described for many years and are of particular interest recently. Use of the functional luminal imaging probe (FLIP) shows patients with GpS may have decreased sphincter distensibility when examining the comparisons of the cross-sectional area relative to pressure Using this information, sphincter therapies can be offered.^16-18

Other testing: Neurologic and autonomic testing, along with psychosocial, genetic and frailty assessments, are helpful to explore.¹⁹ Nutritional evaluation can be done using standardized scales, such as subjective global assessment and serologic testing for micronutrient deficiency or electrical impedance.²⁰

Treatment of GpS

Therapies for GpS can be viewed as the five D’s: Diet, Drug, Disruption, Devices, and Details.

Diet and nutrition: The mainstay treatment of GpS remains dietary modification. The most common recommendation is to limit meal size, often with increased meal frequency, as well as nutrient composition, in areas that may retard gastric emptying. In addition, some patients with GpS report intolerances of specific foods, such as specific carbohydrates. Nutritional consultation can assist patients with meals tailored for their current nutritional needs. Nutritional supplementation is widely used for patients with GpS.²⁰

Pharmacological treatment: The next tier of treatment for GpS is drugs. Review of a patient’s medications is important to minimize drugs that may retard gastric emptying such as opiates and GLP-1 agonists. A full discussion of medications is beyond the scope of this article, but classes of drugs available include: prokinetics, antiemetics, neuromodulators, and investigational agents.

Bioelectric therapy: Another approach for patients with symptomatic drug refractory GpS is bioelectric device therapies, which can be delivered several ways, including directly to the stomach or to the spinal cord or the vagus nerve in the neck or ear, as well as by electro-acupuncture. High-frequency, low-energy gastric electrical stimulation (GES) is the best studied. First done in 1992 as an experimental therapy, GES was investigational from 1995 to 2000, when it became FDA approved as a humanitarian-use device. GES has been used in over 10,000 patients worldwide; only a small number (greater than 700 study patients) have been in controlled trials. Nine controlled trials of GES have been primarily positive, and durability for over 10 years has been shown. Temporary GES can also be performed endoscopically, although that is an off-label procedure. It has been shown to predict long-term therapy outcome.^23-26 

Nutritional support: Nutritional abnormalities in some cases of GpS lead to consideration of enteral tubes, starting with a trial of feeding with an N-J tube placed endoscopically. An N-J trial is most often performed in patients who have macro-malnutrition and weight loss but can be considered for other highly symptomatic patients. Other endoscopic tubes can be PEG or PEG-J or direct PEJ tubes. Some patients may require surgical placement of enteral tubes, presenting an opportunity for a small bowel or gastric full-thickness biopsy. Enteral tubes are sometimes used for decompression in highly symptomatic patients.²⁷

For patients presenting with neurological symptoms, findings and serologic abnormalities have led to interest in immunotherapies. One is intravenous immunoglobulin, given parenterally. Several open-label studies have been published, the most recent one with 47 patients showing better response if glutamic acid decarboxylase–65 antibodies were present and with longer therapeutic dosing.²⁸ Drawbacks to immunotherapies like intravenous immunoglobulin are cost and requiring parenteral access.

Other evaluation/treatments for drug refractory patients can be detailed as follows: First, an overall quality of life assessment can be helpful, especially one that includes impact of GpS on the patients and family. Nutritional considerations, which may not have been fully assessed, can be examined in more detail. Frailty assessments may show the need for physical therapy. Assessment for home care needs may indicate, in severe patients, needs for IV fluids at home, either enteral or parenteral, if nutrition is not adequate. Psychosocial and/or psychiatric assessments may lead to the need for medications, psychotherapy, and/or support groups. Lastly, an assessment of overall health status may lead to approaches for minimizing visits to emergency rooms and hospitalizations.^29,30

Conclusion

Patients with Gp symptoms are becoming increasingly recognized and referred to gastroenterologists. Better understandings of the pathophysiology of the spectrum of gastroparesis syndromes, assisted by innovations in diagnosis, have led to expansion of existing and new therapeutic approaches. Fortunately, most patients can benefit from a standardized diagnostic approach and directed noninvasive therapies. Patients with refractory gastroparesis symptoms, often with complex issues referred to gastroenterologists, remain a challenge, and novel approaches may improve their quality of life.
 

Dr. Mathur is a GI motility research fellow at the University of Louisville, Ky. He reports no conflicts of interest. Dr. Abell is the Arthur M. Schoen, MD, Chair in Gastroenterology at the University of Louisville. His main funding is NIH GpCRC and NIH Definitive Evaluation of Gastric Dysrhythmia. He is an investigator for Cindome, Vanda, Allergan, and Neurogastrx; a consultant for Censa, Nuvaira, and Takeda; a speaker for Takeda and Medtronic; and a reviewer for UpToDate. He is also the founder of ADEPT-GI, which holds IP related to mucosal stimulation and autonomic and enteric profiling.

References

1. Jung HK et al. Gastroenterology. 2009;136(4):1225-33.

2. Ye Y et al. Gut. 2021;70(4):644-53.

3. Oshima T et al. J Neurogastroenterol Motil. 2021;27(1):46-54.

4. Soykan I et al. Dig Dis Sci. 1998;43(11):2398-404.

5. Syed AR et al. J Clin Gastroenterol. 2020;54(1):50-4.

6.Pasricha PJ et al. Clin Gastroenterol Hepatol. 2011;9(7):567-76.e1-4.

7. Pasricha PJ et al. Gastroenterology. 2021;160(6):2006-17.

8. Almario CV et al. Am J Gastroenterol. 2018;113(11):1701-10.

9. Abell TL et al. Dig Dis Sci. 2021 Apr;66(4):1127-41.

10. Abell TL et al. Neurogastroenterol Motil. 2019;31(3):e13534.

11. Elmasry M et al. Neurogastroenterol Motil. 2021 Oct 26;e14274.

12. Maurer AH et al. J Nucl Med. 2020;61(3):11N-7N.

13. Abell TL et al. J Nucl Med Technol. 2008 Mar;36(1):44-54.

14. Shine A et al. Neuromodulation. 2022 Feb 16;S1094-7159(21)06986-5.

15. O’Grady G et al. Am J Physiol Gastrointest Liver Physiol. 2021;321(5):G527-g42.

16. Saadi M et al. Rev Gastroenterol Mex (Engl Ed). Oct-Dec 2018;83(4):375-84.

17. Kamal F et al. Aliment Pharmacol Ther. 2022;55(2):168-77.

18. Harberson J et al. Dig Dis Sci. 2010;55(2):359-70.

19. Winston J. Gastrointestinal Disorders. 2021;3(2):78-83.

20. Parkman HP et al. Gastroenterology. 2011;141(2):486-98, 98.e1-7.

21. Heckroth M et al. J Clin Gastroenterol. 2021;55(4):279-99.

22. Camilleri M. Clin Gastroenterol Hepatol. 2022;20(1):19-24.

23. Payne SC et al. Nat Rev Gastroenterol Hepatol. 2019;16(2):89-105.

24. Ducrotte P et al. Gastroenterology. 2020;158(3):506-14.e2.

25. Burlen J et al. Gastroenterology Res. 2018;11(5):349-54.

26. Hedjoudje A et al. Neurogastroenterol Motil. 2020;32(11):e13949.

27. Petrov RV et al. Gastroenterol Clin North Am. 2020;49(3):539-56.

28. Gala K et al. J Clin Gastroenterol. 2021 Dec 31. doi: 10.1097/MCG.0000000000001655.

29. Abell TL et al. Neurogastroenterol Motil. 2006;18(4):263-83.

30. Camilleri M et al. Am J Gastroenterol. 2013;108(1):18-37.


 

Introduction

Patients presenting with the symptoms of gastroparesis (Gp) are commonly seen in gastroenterology practice. This article reviews the presentation, pathophysiology, diagnosis, and treatment of gastroparesis syndromes with an emphasis on newer approaches evolving in clinical practice.

Presentation

Patients with foregut symptoms of Gp have characteristic presentations, with nausea, vomiting/retching, and abdominal pain often associated with bloating and distension, early satiety, anorexia, and heartburn. Mid- and hindgut gastrointestinal and/or urinary symptoms may be seen in patients with Gp as well.

The precise epidemiology of gastroparesis syndromes (GpS) is unknown. Classic gastroparesis, defined as delayed gastric emptying without known mechanical obstruction, has a prevalence of about 10 per 100,000 population in men and 30 per 100,000 in women with women being affected 3 to 4 times more than men.^1,2 Some risk factors for GpS, such as diabetes mellitus (DM) in up to 5% of patients with Type 1 DM, are known.³ Caucasians have the highest prevalence of GpS, followed by African Americans.^4,5

Pathophysiology

Specific types of gastroparesis syndromes have variable pathophysiology (Figure 1). In some cases, like GpS associated with DM, pathophysiology is partially related to diabetic autonomic dysfunction. GpS are multifactorial, however, and rather than focusing on subtypes, this discussion focuses on shared pathophysiology. Understanding pathophysiology is key to determining treatment options and potential future targets for therapy.

Intragastric mechanical dysfunction, both proximal (fundic relaxation and accommodation and/or lack of fundic contractility) and distal stomach (antral hypomotility) may be involved. Additionally, intragastric electrical disturbances in frequency, amplitude, and propagation of gastric electrical waves can be seen with low/high resolution gastric mapping.

Both gastroesophageal and gastropyloric sphincter dysfunction may be seen. Esophageal dysfunction is frequently seen but is not always categorized in GpS. Pyloric dysfunction is increasingly a focus of both diagnosis and therapy. GI anatomic abnormalities can be identified with gastric biopsies of full thickness muscle and mucosa. CD117/interstitial cells of Cajal, neural fibers, inflammatory and other cells can be evaluated by light microscopy, electron microscopy, and special staining techniques.

Diagnosis of GpS

Diagnosis of GpS is often delayed and can be challenging; various tools have been developed, but not all are used. A diagnostic approach for patients with symptoms of Gp is listed below, and Figure 2 details a diagnostic approach and treatment options for symptomatic patients.

Symptom Assessment: Initially Gp symptoms can be assessed using Food and Drug Administration–approved patient-reported outcomes, including frequency and severity of nausea, vomiting, anorexia/early satiety, bloating/distention, and abdominal pain on a 0-4, 0-5 or 0-10 scale. The Gastrointestinal Cardinal Symptom Index or visual analog scales can also be used. It is also important to evaluate midgut and hindgut symptoms.^9-11

Mechanical obstruction assessment: Mechanical obstruction can be ruled out using upper endoscopy or barium studies.

Physiologic testing: The most common is radionuclide gastric emptying testing (GET). Compliance with guidelines, standardization, and consistency of GETs is vital to help with an accurate diagnosis. Currently, two consensus recommendations for the standardized performance of GETs exist.^12,13 Breath testing is FDA approved in the United States and can be used as an alternative. Wireless motility capsule testing can be complimentary.

Gastric dysrhythmias assessment: Assessment of gastric dysrhythmias can be performed in outpatient settings using cutaneous electrogastrogram, currently available in many referral centers. Most patients with GpS have an underlying gastric electrical abnormality.^14,15

Sphincter dysfunction assessment: Both proximal and distal sphincter abnormalities have been described for many years and are of particular interest recently. Use of the functional luminal imaging probe (FLIP) shows patients with GpS may have decreased sphincter distensibility when examining the comparisons of the cross-sectional area relative to pressure Using this information, sphincter therapies can be offered.^16-18

Other testing: Neurologic and autonomic testing, along with psychosocial, genetic and frailty assessments, are helpful to explore.¹⁹ Nutritional evaluation can be done using standardized scales, such as subjective global assessment and serologic testing for micronutrient deficiency or electrical impedance.²⁰

Treatment of GpS

Therapies for GpS can be viewed as the five D’s: Diet, Drug, Disruption, Devices, and Details.

Diet and nutrition: The mainstay treatment of GpS remains dietary modification. The most common recommendation is to limit meal size, often with increased meal frequency, as well as nutrient composition, in areas that may retard gastric emptying. In addition, some patients with GpS report intolerances of specific foods, such as specific carbohydrates. Nutritional consultation can assist patients with meals tailored for their current nutritional needs. Nutritional supplementation is widely used for patients with GpS.²⁰

Pharmacological treatment: The next tier of treatment for GpS is drugs. Review of a patient’s medications is important to minimize drugs that may retard gastric emptying such as opiates and GLP-1 agonists. A full discussion of medications is beyond the scope of this article, but classes of drugs available include: prokinetics, antiemetics, neuromodulators, and investigational agents.

Bioelectric therapy: Another approach for patients with symptomatic drug refractory GpS is bioelectric device therapies, which can be delivered several ways, including directly to the stomach or to the spinal cord or the vagus nerve in the neck or ear, as well as by electro-acupuncture. High-frequency, low-energy gastric electrical stimulation (GES) is the best studied. First done in 1992 as an experimental therapy, GES was investigational from 1995 to 2000, when it became FDA approved as a humanitarian-use device. GES has been used in over 10,000 patients worldwide; only a small number (greater than 700 study patients) have been in controlled trials. Nine controlled trials of GES have been primarily positive, and durability for over 10 years has been shown. Temporary GES can also be performed endoscopically, although that is an off-label procedure. It has been shown to predict long-term therapy outcome.^23-26 

Nutritional support: Nutritional abnormalities in some cases of GpS lead to consideration of enteral tubes, starting with a trial of feeding with an N-J tube placed endoscopically. An N-J trial is most often performed in patients who have macro-malnutrition and weight loss but can be considered for other highly symptomatic patients. Other endoscopic tubes can be PEG or PEG-J or direct PEJ tubes. Some patients may require surgical placement of enteral tubes, presenting an opportunity for a small bowel or gastric full-thickness biopsy. Enteral tubes are sometimes used for decompression in highly symptomatic patients.²⁷

For patients presenting with neurological symptoms, findings and serologic abnormalities have led to interest in immunotherapies. One is intravenous immunoglobulin, given parenterally. Several open-label studies have been published, the most recent one with 47 patients showing better response if glutamic acid decarboxylase–65 antibodies were present and with longer therapeutic dosing.²⁸ Drawbacks to immunotherapies like intravenous immunoglobulin are cost and requiring parenteral access.

Other evaluation/treatments for drug refractory patients can be detailed as follows: First, an overall quality of life assessment can be helpful, especially one that includes impact of GpS on the patients and family. Nutritional considerations, which may not have been fully assessed, can be examined in more detail. Frailty assessments may show the need for physical therapy. Assessment for home care needs may indicate, in severe patients, needs for IV fluids at home, either enteral or parenteral, if nutrition is not adequate. Psychosocial and/or psychiatric assessments may lead to the need for medications, psychotherapy, and/or support groups. Lastly, an assessment of overall health status may lead to approaches for minimizing visits to emergency rooms and hospitalizations.^29,30

Conclusion

Patients with Gp symptoms are becoming increasingly recognized and referred to gastroenterologists. Better understandings of the pathophysiology of the spectrum of gastroparesis syndromes, assisted by innovations in diagnosis, have led to expansion of existing and new therapeutic approaches. Fortunately, most patients can benefit from a standardized diagnostic approach and directed noninvasive therapies. Patients with refractory gastroparesis symptoms, often with complex issues referred to gastroenterologists, remain a challenge, and novel approaches may improve their quality of life.
 

Dr. Mathur is a GI motility research fellow at the University of Louisville, Ky. He reports no conflicts of interest. Dr. Abell is the Arthur M. Schoen, MD, Chair in Gastroenterology at the University of Louisville. His main funding is NIH GpCRC and NIH Definitive Evaluation of Gastric Dysrhythmia. He is an investigator for Cindome, Vanda, Allergan, and Neurogastrx; a consultant for Censa, Nuvaira, and Takeda; a speaker for Takeda and Medtronic; and a reviewer for UpToDate. He is also the founder of ADEPT-GI, which holds IP related to mucosal stimulation and autonomic and enteric profiling.

References

1. Jung HK et al. Gastroenterology. 2009;136(4):1225-33.

2. Ye Y et al. Gut. 2021;70(4):644-53.

3. Oshima T et al. J Neurogastroenterol Motil. 2021;27(1):46-54.

4. Soykan I et al. Dig Dis Sci. 1998;43(11):2398-404.

5. Syed AR et al. J Clin Gastroenterol. 2020;54(1):50-4.

6.Pasricha PJ et al. Clin Gastroenterol Hepatol. 2011;9(7):567-76.e1-4.

7. Pasricha PJ et al. Gastroenterology. 2021;160(6):2006-17.

8. Almario CV et al. Am J Gastroenterol. 2018;113(11):1701-10.

9. Abell TL et al. Dig Dis Sci. 2021 Apr;66(4):1127-41.

10. Abell TL et al. Neurogastroenterol Motil. 2019;31(3):e13534.

11. Elmasry M et al. Neurogastroenterol Motil. 2021 Oct 26;e14274.

12. Maurer AH et al. J Nucl Med. 2020;61(3):11N-7N.

13. Abell TL et al. J Nucl Med Technol. 2008 Mar;36(1):44-54.

14. Shine A et al. Neuromodulation. 2022 Feb 16;S1094-7159(21)06986-5.

15. O’Grady G et al. Am J Physiol Gastrointest Liver Physiol. 2021;321(5):G527-g42.

16. Saadi M et al. Rev Gastroenterol Mex (Engl Ed). Oct-Dec 2018;83(4):375-84.

17. Kamal F et al. Aliment Pharmacol Ther. 2022;55(2):168-77.

18. Harberson J et al. Dig Dis Sci. 2010;55(2):359-70.

19. Winston J. Gastrointestinal Disorders. 2021;3(2):78-83.

20. Parkman HP et al. Gastroenterology. 2011;141(2):486-98, 98.e1-7.

21. Heckroth M et al. J Clin Gastroenterol. 2021;55(4):279-99.

22. Camilleri M. Clin Gastroenterol Hepatol. 2022;20(1):19-24.

23. Payne SC et al. Nat Rev Gastroenterol Hepatol. 2019;16(2):89-105.

24. Ducrotte P et al. Gastroenterology. 2020;158(3):506-14.e2.

25. Burlen J et al. Gastroenterology Res. 2018;11(5):349-54.

26. Hedjoudje A et al. Neurogastroenterol Motil. 2020;32(11):e13949.

27. Petrov RV et al. Gastroenterol Clin North Am. 2020;49(3):539-56.

28. Gala K et al. J Clin Gastroenterol. 2021 Dec 31. doi: 10.1097/MCG.0000000000001655.

29. Abell TL et al. Neurogastroenterol Motil. 2006;18(4):263-83.

30. Camilleri M et al. Am J Gastroenterol. 2013;108(1):18-37.


 

Although lipoprotein(a) is causally related to coronary artery disease and aortic valve stenosis – two known risk factors for atrial fibrillation (AFib) – evidence linking Lp(a) to a causal role in the development of AFib has been lukewarm at best.

A recent Mendelian randomization study showed only a nominally significant effect of Lp(a) on AFib, whereas an ARIC substudy showed high levels of Lp(a) to be associated with elevated ischemic stroke risk but not incident AFib.

A new study that adds the heft of Mendelian randomization to large observational and genetic analyses, however, implicates Lp(a) as a potential causal mediator of AFib, independent of its known effects on atherosclerotic cardiovascular disease (ASCVD).

“Why this is exciting is because it shows that Lp(a) has effects beyond the arteries and beyond the aortic valve, and that provides two things,” senior author Guillaume Paré, MD, MSc, Population Health Research Institute, Hamilton, Ontario, told this news organization.

“First, it provides a potential means to decrease the risk, because there are all these Lp(a) inhibitors in development,” he said. “But I think the other thing is that it just points to a new pathway that leads to atrial fibrillation development that could potentially be targeted with other drugs when it’s better understood. We don’t pretend that we understand the biology there, but it opens this possibility.”

The results were published in the Journal of the American College of Cardiology.

Using data from 435,579 participants in the UK Biobank, the researchers identified 20,432 cases of incident AFib over a median of 11 years of follow-up. They also constructed a genetic risk score for Lp(a) using genetic variants within 500 kb of the LPA gene.

After common AFib risk factors were controlled for, results showed a 3% increased risk for incident AFib per 50 nmol/L increase in Lp(a) at enrollment (hazard ratio, 1.03; 95% confidence interval, 1.02-1.05).

A Mendelian randomization analysis showed a similar association between genetically predicted Lp(a) and AFib (odds ratio, 1.03; 95% CI, 1.02-1.05).

To replicate the results, the investigators performed separate Mendelian randomization analyses using publicly available genome-wide association study (GWAS) statistics from the largest GWAS of AFib involving more than 1 million participants and from the FinnGen cohort involving more than 114,000 Finnish residents.

The analyses showed a 3% increase in risk for AFib in the genome-wide study (OR, 1.03; 95% CI, 1.02-1.05) and an 8% increase in risk in the Finnish study (OR, 1.08; 95% CI, 1.04-1.12) per 50 nmol/L increase in Lp(a).

There was no evidence that the effect of observed or genetically predicted Lp(a) was modified by prevalent ischemic heart disease or aortic stenosis.

Further, MR analyses revealed no risk effect of low-density-lipoprotein cholesterol or triglycerides on AFib.

Notably, only 39% of Lp(a) was mediated through ASCVD, suggesting that Lp(a) partly influences AFib independent of its known effect on ASCVD.

“To me, the eureka moment is when we repeated the same analysis for LDL cholesterol and it had absolutely no association with AFib,” Dr. Paré said. “Because up to that point, there was always this lingering doubt that, well, it’s because of coronary artery disease, and that’s logical. But the signal is completely flat with LDL, and we see this strong signal with Lp(a).”

Another ‘red flag’

Erin D. Michos, MD, MHS, senior author of the ARIC substudy and associate director of preventive cardiology at Johns Hopkins School of Medicine, Baltimore, said the findings are “another red flag that lipoprotein(a) is a marker we need to pay attention to and potentially needs treatment.”

“The fact that it was Mendelian randomization does suggest that there’s a causal role,” she said. “I think the relationship is relatively modest compared to its known risk for stroke, ASCVD, coronary disease, and aortic stenosis, ... which may be why we didn’t see it in the ARIC cohort with 12,000 participants. You needed to have a million participants and 60,000 cases to see an effect here.”

Dr. Michos said she hopes the findings encourage increased testing, particularly with multiple potential treatments currently in the pipeline. She pointed out that the researchers estimated that the experimental antisense agent pelacarsen, which lowers Lp(a) by about 80%, would translate into about an 8% reduction in AFib risk, or “the same effect as 2 kg of weight loss or a 5 mm Hg reduction in blood pressure, which we do think are meaningful.”

Adding to this point in an accompanying editorial, Daniel Seung Kim, MD, PhD, and Abha Khandelwal, MD, MS, Stanford University School of Medicine, California, say that “moreover, reduction of Lp(a) levels would have multifactorial effects on CAD, cerebrovascular/peripheral artery disease, and AS risk.

“Therefore, approaches to reduce Lp(a) should be prioritized to further reduce the morbidity and mortality of a rapidly aging population,” they write.

The editorialists also join the researchers in calling for inclusion of AFib as a secondary outcome in ongoing Lp(a) trials, in addition to cerebrovascular disease and peripheral vascular disease.
 

Unanswered questions

As to what’s driving the risk effect of Lp(a), first author Pedrum Mohammadi-Shemirani, PhD, also from the Population Health Research Institute, explained that in aortic stenosis, “mechanical stress increases endothelial permeability, allowing Lp(a) to infiltrate valvular tissue and induce gene expression that results in microcalcifications and cell death.”

“So, in theory, a similar sort of mechanism could be at play in atrial tissue that may lead to damage and the electrical remodeling that causes atrial fibrillation,” he told this news organization.

Dr. Mohammadi-Shemirani also noted that Lp(a) has proinflammatory properties, but added that any potential mechanisms are “speculative and require further research to disentangle.”

Dr. Paré and colleagues say follow-up studies are also warranted, noting that generalizability of the results may be limited because AFib cases were found using electronic health records in the population-scale cohorts and because few UK Biobank participants were of non-European ancestry and Lp(a) levels vary among ethnic groups.

Another limitation is that the number of kringle IV type 2 domain repeats within the LPA gene, the largest contributor to genetic variation in Lp(a), could not be directly measured. Still, 71.4% of the variation in Lp(a) was explained using the genetic risk score alone, they say.

Dr. Paré holds the Canada Research Chair in Genetic and Molecular Epidemiology and Cisco Systems Professorship in Integrated Health Biosystems. Dr. Mohammadi-Shemirani is supported by the Frederick Banting and Charles Best Canada Graduate Scholarship from the Canadian Institute of Health Research. Dr. Michos reports consulting for Novartis and serving on advisory boards for Novartis, AstraZeneca, Bayer, and Boehringer Ingelheim. Dr. Kim reports grant support from the National Institutes of Health and the American Heart Association. Dr. Khandelwal serves on the advisory board of Amgen and has received funding from Novartis CTQJ and Akcea.

A version of this article first appeared on Medscape.com.

Although lipoprotein(a) is causally related to coronary artery disease and aortic valve stenosis – two known risk factors for atrial fibrillation (AFib) – evidence linking Lp(a) to a causal role in the development of AFib has been lukewarm at best.

A recent Mendelian randomization study showed only a nominally significant effect of Lp(a) on AFib, whereas an ARIC substudy showed high levels of Lp(a) to be associated with elevated ischemic stroke risk but not incident AFib.

A new study that adds the heft of Mendelian randomization to large observational and genetic analyses, however, implicates Lp(a) as a potential causal mediator of AFib, independent of its known effects on atherosclerotic cardiovascular disease (ASCVD).

“Why this is exciting is because it shows that Lp(a) has effects beyond the arteries and beyond the aortic valve, and that provides two things,” senior author Guillaume Paré, MD, MSc, Population Health Research Institute, Hamilton, Ontario, told this news organization.

“First, it provides a potential means to decrease the risk, because there are all these Lp(a) inhibitors in development,” he said. “But I think the other thing is that it just points to a new pathway that leads to atrial fibrillation development that could potentially be targeted with other drugs when it’s better understood. We don’t pretend that we understand the biology there, but it opens this possibility.”

The results were published in the Journal of the American College of Cardiology.

Using data from 435,579 participants in the UK Biobank, the researchers identified 20,432 cases of incident AFib over a median of 11 years of follow-up. They also constructed a genetic risk score for Lp(a) using genetic variants within 500 kb of the LPA gene.

After common AFib risk factors were controlled for, results showed a 3% increased risk for incident AFib per 50 nmol/L increase in Lp(a) at enrollment (hazard ratio, 1.03; 95% confidence interval, 1.02-1.05).

A Mendelian randomization analysis showed a similar association between genetically predicted Lp(a) and AFib (odds ratio, 1.03; 95% CI, 1.02-1.05).

To replicate the results, the investigators performed separate Mendelian randomization analyses using publicly available genome-wide association study (GWAS) statistics from the largest GWAS of AFib involving more than 1 million participants and from the FinnGen cohort involving more than 114,000 Finnish residents.

The analyses showed a 3% increase in risk for AFib in the genome-wide study (OR, 1.03; 95% CI, 1.02-1.05) and an 8% increase in risk in the Finnish study (OR, 1.08; 95% CI, 1.04-1.12) per 50 nmol/L increase in Lp(a).

There was no evidence that the effect of observed or genetically predicted Lp(a) was modified by prevalent ischemic heart disease or aortic stenosis.

Further, MR analyses revealed no risk effect of low-density-lipoprotein cholesterol or triglycerides on AFib.

Notably, only 39% of Lp(a) was mediated through ASCVD, suggesting that Lp(a) partly influences AFib independent of its known effect on ASCVD.

“To me, the eureka moment is when we repeated the same analysis for LDL cholesterol and it had absolutely no association with AFib,” Dr. Paré said. “Because up to that point, there was always this lingering doubt that, well, it’s because of coronary artery disease, and that’s logical. But the signal is completely flat with LDL, and we see this strong signal with Lp(a).”

Another ‘red flag’

Erin D. Michos, MD, MHS, senior author of the ARIC substudy and associate director of preventive cardiology at Johns Hopkins School of Medicine, Baltimore, said the findings are “another red flag that lipoprotein(a) is a marker we need to pay attention to and potentially needs treatment.”

“The fact that it was Mendelian randomization does suggest that there’s a causal role,” she said. “I think the relationship is relatively modest compared to its known risk for stroke, ASCVD, coronary disease, and aortic stenosis, ... which may be why we didn’t see it in the ARIC cohort with 12,000 participants. You needed to have a million participants and 60,000 cases to see an effect here.”

Dr. Michos said she hopes the findings encourage increased testing, particularly with multiple potential treatments currently in the pipeline. She pointed out that the researchers estimated that the experimental antisense agent pelacarsen, which lowers Lp(a) by about 80%, would translate into about an 8% reduction in AFib risk, or “the same effect as 2 kg of weight loss or a 5 mm Hg reduction in blood pressure, which we do think are meaningful.”

Adding to this point in an accompanying editorial, Daniel Seung Kim, MD, PhD, and Abha Khandelwal, MD, MS, Stanford University School of Medicine, California, say that “moreover, reduction of Lp(a) levels would have multifactorial effects on CAD, cerebrovascular/peripheral artery disease, and AS risk.

“Therefore, approaches to reduce Lp(a) should be prioritized to further reduce the morbidity and mortality of a rapidly aging population,” they write.

The editorialists also join the researchers in calling for inclusion of AFib as a secondary outcome in ongoing Lp(a) trials, in addition to cerebrovascular disease and peripheral vascular disease.
 

Unanswered questions

As to what’s driving the risk effect of Lp(a), first author Pedrum Mohammadi-Shemirani, PhD, also from the Population Health Research Institute, explained that in aortic stenosis, “mechanical stress increases endothelial permeability, allowing Lp(a) to infiltrate valvular tissue and induce gene expression that results in microcalcifications and cell death.”

“So, in theory, a similar sort of mechanism could be at play in atrial tissue that may lead to damage and the electrical remodeling that causes atrial fibrillation,” he told this news organization.

Dr. Mohammadi-Shemirani also noted that Lp(a) has proinflammatory properties, but added that any potential mechanisms are “speculative and require further research to disentangle.”

Dr. Paré and colleagues say follow-up studies are also warranted, noting that generalizability of the results may be limited because AFib cases were found using electronic health records in the population-scale cohorts and because few UK Biobank participants were of non-European ancestry and Lp(a) levels vary among ethnic groups.

Another limitation is that the number of kringle IV type 2 domain repeats within the LPA gene, the largest contributor to genetic variation in Lp(a), could not be directly measured. Still, 71.4% of the variation in Lp(a) was explained using the genetic risk score alone, they say.

Dr. Paré holds the Canada Research Chair in Genetic and Molecular Epidemiology and Cisco Systems Professorship in Integrated Health Biosystems. Dr. Mohammadi-Shemirani is supported by the Frederick Banting and Charles Best Canada Graduate Scholarship from the Canadian Institute of Health Research. Dr. Michos reports consulting for Novartis and serving on advisory boards for Novartis, AstraZeneca, Bayer, and Boehringer Ingelheim. Dr. Kim reports grant support from the National Institutes of Health and the American Heart Association. Dr. Khandelwal serves on the advisory board of Amgen and has received funding from Novartis CTQJ and Akcea.

A version of this article first appeared on Medscape.com.

Although lipoprotein(a) is causally related to coronary artery disease and aortic valve stenosis – two known risk factors for atrial fibrillation (AFib) – evidence linking Lp(a) to a causal role in the development of AFib has been lukewarm at best.

A recent Mendelian randomization study showed only a nominally significant effect of Lp(a) on AFib, whereas an ARIC substudy showed high levels of Lp(a) to be associated with elevated ischemic stroke risk but not incident AFib.

A new study that adds the heft of Mendelian randomization to large observational and genetic analyses, however, implicates Lp(a) as a potential causal mediator of AFib, independent of its known effects on atherosclerotic cardiovascular disease (ASCVD).

“Why this is exciting is because it shows that Lp(a) has effects beyond the arteries and beyond the aortic valve, and that provides two things,” senior author Guillaume Paré, MD, MSc, Population Health Research Institute, Hamilton, Ontario, told this news organization.

“First, it provides a potential means to decrease the risk, because there are all these Lp(a) inhibitors in development,” he said. “But I think the other thing is that it just points to a new pathway that leads to atrial fibrillation development that could potentially be targeted with other drugs when it’s better understood. We don’t pretend that we understand the biology there, but it opens this possibility.”

The results were published in the Journal of the American College of Cardiology.

Using data from 435,579 participants in the UK Biobank, the researchers identified 20,432 cases of incident AFib over a median of 11 years of follow-up. They also constructed a genetic risk score for Lp(a) using genetic variants within 500 kb of the LPA gene.

After common AFib risk factors were controlled for, results showed a 3% increased risk for incident AFib per 50 nmol/L increase in Lp(a) at enrollment (hazard ratio, 1.03; 95% confidence interval, 1.02-1.05).

A Mendelian randomization analysis showed a similar association between genetically predicted Lp(a) and AFib (odds ratio, 1.03; 95% CI, 1.02-1.05).

To replicate the results, the investigators performed separate Mendelian randomization analyses using publicly available genome-wide association study (GWAS) statistics from the largest GWAS of AFib involving more than 1 million participants and from the FinnGen cohort involving more than 114,000 Finnish residents.

The analyses showed a 3% increase in risk for AFib in the genome-wide study (OR, 1.03; 95% CI, 1.02-1.05) and an 8% increase in risk in the Finnish study (OR, 1.08; 95% CI, 1.04-1.12) per 50 nmol/L increase in Lp(a).

There was no evidence that the effect of observed or genetically predicted Lp(a) was modified by prevalent ischemic heart disease or aortic stenosis.

Further, MR analyses revealed no risk effect of low-density-lipoprotein cholesterol or triglycerides on AFib.

Notably, only 39% of Lp(a) was mediated through ASCVD, suggesting that Lp(a) partly influences AFib independent of its known effect on ASCVD.

“To me, the eureka moment is when we repeated the same analysis for LDL cholesterol and it had absolutely no association with AFib,” Dr. Paré said. “Because up to that point, there was always this lingering doubt that, well, it’s because of coronary artery disease, and that’s logical. But the signal is completely flat with LDL, and we see this strong signal with Lp(a).”

Another ‘red flag’

Erin D. Michos, MD, MHS, senior author of the ARIC substudy and associate director of preventive cardiology at Johns Hopkins School of Medicine, Baltimore, said the findings are “another red flag that lipoprotein(a) is a marker we need to pay attention to and potentially needs treatment.”

“The fact that it was Mendelian randomization does suggest that there’s a causal role,” she said. “I think the relationship is relatively modest compared to its known risk for stroke, ASCVD, coronary disease, and aortic stenosis, ... which may be why we didn’t see it in the ARIC cohort with 12,000 participants. You needed to have a million participants and 60,000 cases to see an effect here.”

Dr. Michos said she hopes the findings encourage increased testing, particularly with multiple potential treatments currently in the pipeline. She pointed out that the researchers estimated that the experimental antisense agent pelacarsen, which lowers Lp(a) by about 80%, would translate into about an 8% reduction in AFib risk, or “the same effect as 2 kg of weight loss or a 5 mm Hg reduction in blood pressure, which we do think are meaningful.”

Adding to this point in an accompanying editorial, Daniel Seung Kim, MD, PhD, and Abha Khandelwal, MD, MS, Stanford University School of Medicine, California, say that “moreover, reduction of Lp(a) levels would have multifactorial effects on CAD, cerebrovascular/peripheral artery disease, and AS risk.

“Therefore, approaches to reduce Lp(a) should be prioritized to further reduce the morbidity and mortality of a rapidly aging population,” they write.

The editorialists also join the researchers in calling for inclusion of AFib as a secondary outcome in ongoing Lp(a) trials, in addition to cerebrovascular disease and peripheral vascular disease.
 

Unanswered questions

As to what’s driving the risk effect of Lp(a), first author Pedrum Mohammadi-Shemirani, PhD, also from the Population Health Research Institute, explained that in aortic stenosis, “mechanical stress increases endothelial permeability, allowing Lp(a) to infiltrate valvular tissue and induce gene expression that results in microcalcifications and cell death.”

“So, in theory, a similar sort of mechanism could be at play in atrial tissue that may lead to damage and the electrical remodeling that causes atrial fibrillation,” he told this news organization.

Dr. Mohammadi-Shemirani also noted that Lp(a) has proinflammatory properties, but added that any potential mechanisms are “speculative and require further research to disentangle.”

Dr. Paré and colleagues say follow-up studies are also warranted, noting that generalizability of the results may be limited because AFib cases were found using electronic health records in the population-scale cohorts and because few UK Biobank participants were of non-European ancestry and Lp(a) levels vary among ethnic groups.

Another limitation is that the number of kringle IV type 2 domain repeats within the LPA gene, the largest contributor to genetic variation in Lp(a), could not be directly measured. Still, 71.4% of the variation in Lp(a) was explained using the genetic risk score alone, they say.

Dr. Paré holds the Canada Research Chair in Genetic and Molecular Epidemiology and Cisco Systems Professorship in Integrated Health Biosystems. Dr. Mohammadi-Shemirani is supported by the Frederick Banting and Charles Best Canada Graduate Scholarship from the Canadian Institute of Health Research. Dr. Michos reports consulting for Novartis and serving on advisory boards for Novartis, AstraZeneca, Bayer, and Boehringer Ingelheim. Dr. Kim reports grant support from the National Institutes of Health and the American Heart Association. Dr. Khandelwal serves on the advisory board of Amgen and has received funding from Novartis CTQJ and Akcea.

A version of this article first appeared on Medscape.com.

Pregnant women who had a higher adherence to a Mediterranean-style diet had a lower risk of preeclampsia, according to the results of a new study.

“As an observational study, it obviously has limitations that need to be considered, but these results build on other evidence that Mediterranean diet reduces cardiovascular risk and extends those findings to pregnancy as preeclampsia is a cardiovascular outcome,” senior author Noel T. Mueller, PhD, associate professor at Johns Hopkins Bloomberg School of Public Health, Baltimore, said in an interview.

The study was published online April 20 in the Journal of the American Heart Association.

The authors noted that preeclampsia, characterized by a range of symptoms including hypertension, proteinuria, and end-organ dysfunction, is a disorder that occurs in up to 5%-10% of all pregnant women worldwide, and is more common in Black women. It is a major cause of maternal and fetal morbidity and raises the risk for long-term cardiovascular disease (CVD), including chronic hypertension, coronary artery disease, ischemic stroke, and heart failure.

Children born to mothers with preeclampsia are at an elevated risk of having higher blood pressure and other abnormal cardiometabolic parameters.

The authors noted that multiple studies have demonstrated the benefit of the Mediterranean diet – characterized primarily by high intake of vegetables, fruits, and unsaturated fats – in reducing cardiovascular risk in the nonpregnant population. The current study was conducted to investigate whether benefits could also be seen in pregnant women in the form of a reduced risk of preeclampsia.

For the study, which used data from the Boston Birth Cohort, maternal sociodemographic and dietary data were obtained from 8,507 women via interview and food frequency questionnaire within 24-72 hours of giving birth. A Mediterranean-style diet score was calculated from the food frequency questionnaire. Additional clinical information, including physician diagnoses of preexisting conditions and preeclampsia, were extracted from medical records.

Of the women in the sample, 848 developed preeclampsia, of whom 47% were Black, and 28% were Hispanic.

After multivariable adjustment, the greatest adherence to a Mediterranean-style diet was associated with lower odds of developing preeclampsia (adjusted odds ratio comparing tertile 3 to tertile 1, 0.78; 95% confidence interval [CI], 0.64-0.96).

A subgroup analysis of Black women demonstrated a similar benefit with an adjusted odds ratio comparing tertile 3 to tertile 1 of 0.74 (95% CI, 0.76-0.96).

“In this racially and ethnically diverse cohort, women who had greater adherence to a Mediterranean-style diet during pregnancy had a greater than 20% lower odds of developing preeclampsia, after [adjustment] for potential confounders. In addition, the evidence for the protective effect of a Mediterranean-style diet against the odds of developing preeclampsia remained present in a subgroup analysis of Black women,” the researchers concluded.

Asked whether this would be enough evidence to recommend a Mediterranean diet to pregnant women, Dr. Mueller said that the organizations that issue dietary guidelines would probably require replication of these results and also possibly a randomized trial in a diverse population group before advocating such a diet.

“That is something we would like to do but this will take time and money,” he added.

Lead study author Anum Minhas, MD, Johns Hopkins University, Baltimore, said that in the meantime she would be recommending a Mediterranean diet to her pregnant patients. 

“The Mediterranean diet is a very healthy way of eating. I can’t see any downside of following such a diet in pregnancy, especially for high-risk women – those with obesity, hypertension or gestational diabetes, and there are likely other potential benefits such as reduced weight gain and reduced gestational diabetes,” she said.  

Dr. Mueller said he appreciated this pragmatic approach. “Sometimes there can be hesitation on making recommendations from observational studies, but the alternative to recommending this diet is either no recommendations on diet or recommending an alternative diet,” he said. “The Mediterranean diet or the DASH diet, which is quite similar, have shown by far the most evidence of cardioprotection of any diets. They have been shown to reduce blood pressure and lipids and improve cardiovascular risk, and I think we can now assume that that likely extends to pregnancy. I feel comfortable for this diet to be recommended to pregnant women.”

But he added: “Having said that, there is still a need for a randomized trial in pregnancy. We think it works but until we have a randomized trial we won’t know for sure, and we won’t know how much of a benefit we can get.”

Commenting on the study, JoAnn Manson, MD, chief of the division of preventive medicine at Brigham and Women’s Hospital, Boston, pointed out that this type of observational study is important for hypothesis generation but cannot prove cause and effect relationships.

“The evidence is promising enough,” said Dr. Manson, who was not involved with this study. But she added that to move forward, a randomized trial in women at elevated risk of preeclampsia would be needed, beginning in early pregnancy, if not earlier.

“In the meantime,” she noted, “several large-scale cohorts could be leveraged to look at diet assessed before or during pregnancy to see if this dietary pattern is prospectively related to lower risk of preeclampsia.

“With additional supportive data, and in view of the diet’s safety and general cardiovascular benefits, it could become a major tool for preventing adverse pregnancy outcomes.”

The Boston Birth Cohort study was supported in part by grants from the March of Dimes, the National Institutes of Health, and the Health Resources and Services Administration of the U.S. Department of Health and Human Services. The authors have disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Pregnant women who had a higher adherence to a Mediterranean-style diet had a lower risk of preeclampsia, according to the results of a new study.

“As an observational study, it obviously has limitations that need to be considered, but these results build on other evidence that Mediterranean diet reduces cardiovascular risk and extends those findings to pregnancy as preeclampsia is a cardiovascular outcome,” senior author Noel T. Mueller, PhD, associate professor at Johns Hopkins Bloomberg School of Public Health, Baltimore, said in an interview.

The study was published online April 20 in the Journal of the American Heart Association.

The authors noted that preeclampsia, characterized by a range of symptoms including hypertension, proteinuria, and end-organ dysfunction, is a disorder that occurs in up to 5%-10% of all pregnant women worldwide, and is more common in Black women. It is a major cause of maternal and fetal morbidity and raises the risk for long-term cardiovascular disease (CVD), including chronic hypertension, coronary artery disease, ischemic stroke, and heart failure.

Children born to mothers with preeclampsia are at an elevated risk of having higher blood pressure and other abnormal cardiometabolic parameters.

The authors noted that multiple studies have demonstrated the benefit of the Mediterranean diet – characterized primarily by high intake of vegetables, fruits, and unsaturated fats – in reducing cardiovascular risk in the nonpregnant population. The current study was conducted to investigate whether benefits could also be seen in pregnant women in the form of a reduced risk of preeclampsia.

For the study, which used data from the Boston Birth Cohort, maternal sociodemographic and dietary data were obtained from 8,507 women via interview and food frequency questionnaire within 24-72 hours of giving birth. A Mediterranean-style diet score was calculated from the food frequency questionnaire. Additional clinical information, including physician diagnoses of preexisting conditions and preeclampsia, were extracted from medical records.

Of the women in the sample, 848 developed preeclampsia, of whom 47% were Black, and 28% were Hispanic.

After multivariable adjustment, the greatest adherence to a Mediterranean-style diet was associated with lower odds of developing preeclampsia (adjusted odds ratio comparing tertile 3 to tertile 1, 0.78; 95% confidence interval [CI], 0.64-0.96).

A subgroup analysis of Black women demonstrated a similar benefit with an adjusted odds ratio comparing tertile 3 to tertile 1 of 0.74 (95% CI, 0.76-0.96).

“In this racially and ethnically diverse cohort, women who had greater adherence to a Mediterranean-style diet during pregnancy had a greater than 20% lower odds of developing preeclampsia, after [adjustment] for potential confounders. In addition, the evidence for the protective effect of a Mediterranean-style diet against the odds of developing preeclampsia remained present in a subgroup analysis of Black women,” the researchers concluded.

Asked whether this would be enough evidence to recommend a Mediterranean diet to pregnant women, Dr. Mueller said that the organizations that issue dietary guidelines would probably require replication of these results and also possibly a randomized trial in a diverse population group before advocating such a diet.

“That is something we would like to do but this will take time and money,” he added.

Lead study author Anum Minhas, MD, Johns Hopkins University, Baltimore, said that in the meantime she would be recommending a Mediterranean diet to her pregnant patients. 

“The Mediterranean diet is a very healthy way of eating. I can’t see any downside of following such a diet in pregnancy, especially for high-risk women – those with obesity, hypertension or gestational diabetes, and there are likely other potential benefits such as reduced weight gain and reduced gestational diabetes,” she said.  

Dr. Mueller said he appreciated this pragmatic approach. “Sometimes there can be hesitation on making recommendations from observational studies, but the alternative to recommending this diet is either no recommendations on diet or recommending an alternative diet,” he said. “The Mediterranean diet or the DASH diet, which is quite similar, have shown by far the most evidence of cardioprotection of any diets. They have been shown to reduce blood pressure and lipids and improve cardiovascular risk, and I think we can now assume that that likely extends to pregnancy. I feel comfortable for this diet to be recommended to pregnant women.”

But he added: “Having said that, there is still a need for a randomized trial in pregnancy. We think it works but until we have a randomized trial we won’t know for sure, and we won’t know how much of a benefit we can get.”

Commenting on the study, JoAnn Manson, MD, chief of the division of preventive medicine at Brigham and Women’s Hospital, Boston, pointed out that this type of observational study is important for hypothesis generation but cannot prove cause and effect relationships.

“The evidence is promising enough,” said Dr. Manson, who was not involved with this study. But she added that to move forward, a randomized trial in women at elevated risk of preeclampsia would be needed, beginning in early pregnancy, if not earlier.

“In the meantime,” she noted, “several large-scale cohorts could be leveraged to look at diet assessed before or during pregnancy to see if this dietary pattern is prospectively related to lower risk of preeclampsia.

“With additional supportive data, and in view of the diet’s safety and general cardiovascular benefits, it could become a major tool for preventing adverse pregnancy outcomes.”

The Boston Birth Cohort study was supported in part by grants from the March of Dimes, the National Institutes of Health, and the Health Resources and Services Administration of the U.S. Department of Health and Human Services. The authors have disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Pregnant women who had a higher adherence to a Mediterranean-style diet had a lower risk of preeclampsia, according to the results of a new study.

“As an observational study, it obviously has limitations that need to be considered, but these results build on other evidence that Mediterranean diet reduces cardiovascular risk and extends those findings to pregnancy as preeclampsia is a cardiovascular outcome,” senior author Noel T. Mueller, PhD, associate professor at Johns Hopkins Bloomberg School of Public Health, Baltimore, said in an interview.

The study was published online April 20 in the Journal of the American Heart Association.

The authors noted that preeclampsia, characterized by a range of symptoms including hypertension, proteinuria, and end-organ dysfunction, is a disorder that occurs in up to 5%-10% of all pregnant women worldwide, and is more common in Black women. It is a major cause of maternal and fetal morbidity and raises the risk for long-term cardiovascular disease (CVD), including chronic hypertension, coronary artery disease, ischemic stroke, and heart failure.

Children born to mothers with preeclampsia are at an elevated risk of having higher blood pressure and other abnormal cardiometabolic parameters.

The authors noted that multiple studies have demonstrated the benefit of the Mediterranean diet – characterized primarily by high intake of vegetables, fruits, and unsaturated fats – in reducing cardiovascular risk in the nonpregnant population. The current study was conducted to investigate whether benefits could also be seen in pregnant women in the form of a reduced risk of preeclampsia.

For the study, which used data from the Boston Birth Cohort, maternal sociodemographic and dietary data were obtained from 8,507 women via interview and food frequency questionnaire within 24-72 hours of giving birth. A Mediterranean-style diet score was calculated from the food frequency questionnaire. Additional clinical information, including physician diagnoses of preexisting conditions and preeclampsia, were extracted from medical records.

Of the women in the sample, 848 developed preeclampsia, of whom 47% were Black, and 28% were Hispanic.

After multivariable adjustment, the greatest adherence to a Mediterranean-style diet was associated with lower odds of developing preeclampsia (adjusted odds ratio comparing tertile 3 to tertile 1, 0.78; 95% confidence interval [CI], 0.64-0.96).

A subgroup analysis of Black women demonstrated a similar benefit with an adjusted odds ratio comparing tertile 3 to tertile 1 of 0.74 (95% CI, 0.76-0.96).

“In this racially and ethnically diverse cohort, women who had greater adherence to a Mediterranean-style diet during pregnancy had a greater than 20% lower odds of developing preeclampsia, after [adjustment] for potential confounders. In addition, the evidence for the protective effect of a Mediterranean-style diet against the odds of developing preeclampsia remained present in a subgroup analysis of Black women,” the researchers concluded.

Asked whether this would be enough evidence to recommend a Mediterranean diet to pregnant women, Dr. Mueller said that the organizations that issue dietary guidelines would probably require replication of these results and also possibly a randomized trial in a diverse population group before advocating such a diet.

“That is something we would like to do but this will take time and money,” he added.

Lead study author Anum Minhas, MD, Johns Hopkins University, Baltimore, said that in the meantime she would be recommending a Mediterranean diet to her pregnant patients. 

“The Mediterranean diet is a very healthy way of eating. I can’t see any downside of following such a diet in pregnancy, especially for high-risk women – those with obesity, hypertension or gestational diabetes, and there are likely other potential benefits such as reduced weight gain and reduced gestational diabetes,” she said.  

Dr. Mueller said he appreciated this pragmatic approach. “Sometimes there can be hesitation on making recommendations from observational studies, but the alternative to recommending this diet is either no recommendations on diet or recommending an alternative diet,” he said. “The Mediterranean diet or the DASH diet, which is quite similar, have shown by far the most evidence of cardioprotection of any diets. They have been shown to reduce blood pressure and lipids and improve cardiovascular risk, and I think we can now assume that that likely extends to pregnancy. I feel comfortable for this diet to be recommended to pregnant women.”

But he added: “Having said that, there is still a need for a randomized trial in pregnancy. We think it works but until we have a randomized trial we won’t know for sure, and we won’t know how much of a benefit we can get.”

Commenting on the study, JoAnn Manson, MD, chief of the division of preventive medicine at Brigham and Women’s Hospital, Boston, pointed out that this type of observational study is important for hypothesis generation but cannot prove cause and effect relationships.

“The evidence is promising enough,” said Dr. Manson, who was not involved with this study. But she added that to move forward, a randomized trial in women at elevated risk of preeclampsia would be needed, beginning in early pregnancy, if not earlier.

“In the meantime,” she noted, “several large-scale cohorts could be leveraged to look at diet assessed before or during pregnancy to see if this dietary pattern is prospectively related to lower risk of preeclampsia.

“With additional supportive data, and in view of the diet’s safety and general cardiovascular benefits, it could become a major tool for preventing adverse pregnancy outcomes.”

The Boston Birth Cohort study was supported in part by grants from the March of Dimes, the National Institutes of Health, and the Health Resources and Services Administration of the U.S. Department of Health and Human Services. The authors have disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Approximately two-thirds of pediatric acute care concerns managed in telemedicine visits required no additional visits or follow-up, based on data from more than 600 visits.

The increase in use of telemedicine during the first year of the COVID-19 pandemic enabled access to care and connection to doctors for many pediatric patients, said Kristina Kissiova, MD, of Children’s National Health System, Washington, and colleagues. Some advantages of telemedicine include enhanced medical homes, reduced health care costs, and less crowding and wait time for patients in offices and emergency departments; however, the optimal use of telemedicine for acute primary care has not been examined, they said.

In a study presented at the annual meeting of the Pediatric Academic Societies, the researchers conducted a retrospective chart review of 638 acute care telemedicine visits conducted by 21 health care providers at a single practice in Washington in October 2020 and November 2020. Approximately half of the patients were male, 65% were white, and 89% had commercial insurance. The most common age group was 6-12 years (23%), followed by 2-3 years (16%), 3-6 years (15%), and 12-18 years (14%).

The primary outcome was the number and nature of visits completed via telemedicine without the need for referral or a subsequent in-person visit. Telemedicine visits for well-child checks and follow-up visits were excluded.

Overall, 60% of the visits (384 of 638) were completed over telemedicine with no need for additional visits or referrals. The most common acute complaints were upper respiratory infections, dermatologic issues, gastrointestinal issues, COVID-19 related issues, and fever (18.7%, 16.3%, 12.9%, 11.9%, and 10.3%, respectively).

Of these, dermatologic and GI concerns were most often completed via telemedicine (93.3% and 81.7%, respectively), while upper respiratory tract infections and fever issues were the least likely to be completed via telemedicine (22.7% and 13.6%), mainly because of the need to report for in-person COVID-19 testing, the researchers said.

Among other less common chief complaints, 100% of breathing concerns, behavior/mental health concerns, and head trauma or falls were addressed via telemedicine without additional referrals or follow-up visits. In addition, 90.9% of urgent care or emergency department follow-ups, 88.9% of ear concerns, and 87.5% of eye concerns were completely resolved via telemedicine visits.

Overall, 3% of patients who were not referred after a telemedicine visit presented in person for worsening symptoms. Of these who were referred after a telemedicine visit, 90% were seen in person within 48 hours.

The study findings were limited by the inclusion of data from only a single center. However, “These early findings provide insight into the utility of telehealth in the primary care setting for a broad array of urgent concerns,” the researchers concluded.
 

Pandemic propelled telemedicine to improve patient care

The widespread adoption of telemedicine in primary care has been a beneficial side effect of the COVID-19 pandemic, said Tim Joos, MD, a Seattle-based clinician with a combination internal medicine/pediatrics practice, in an interview.

“Toward the end of World War II and in the push to form the United Nations, Winston Churchill was credited with the saying, ‘Never let a good crisis go to waste,’” said Dr. Joos, who was not connected with the study.

“As awful as this pandemic has been, it has propelled health care delivery at an unprecedented pace into the digital age,” he noted.

The current study is important because it highlights the number of complaints that can be successfully resolved through telemedicine, offering patients and families quicker access and more options for care, Dr. Joos said.

“I feel that giving patients and families an open choice for either telemedicine or in-person visits improves the likelihood that the issue will be resolved efficiently and satisfactorily with fewer visits,” he added.

Approximately two-thirds of pediatric acute care concerns managed in telemedicine visits required no additional visits or follow-up, based on data from more than 600 visits.

The increase in use of telemedicine during the first year of the COVID-19 pandemic enabled access to care and connection to doctors for many pediatric patients, said Kristina Kissiova, MD, of Children’s National Health System, Washington, and colleagues. Some advantages of telemedicine include enhanced medical homes, reduced health care costs, and less crowding and wait time for patients in offices and emergency departments; however, the optimal use of telemedicine for acute primary care has not been examined, they said.

In a study presented at the annual meeting of the Pediatric Academic Societies, the researchers conducted a retrospective chart review of 638 acute care telemedicine visits conducted by 21 health care providers at a single practice in Washington in October 2020 and November 2020. Approximately half of the patients were male, 65% were white, and 89% had commercial insurance. The most common age group was 6-12 years (23%), followed by 2-3 years (16%), 3-6 years (15%), and 12-18 years (14%).

The primary outcome was the number and nature of visits completed via telemedicine without the need for referral or a subsequent in-person visit. Telemedicine visits for well-child checks and follow-up visits were excluded.

Overall, 60% of the visits (384 of 638) were completed over telemedicine with no need for additional visits or referrals. The most common acute complaints were upper respiratory infections, dermatologic issues, gastrointestinal issues, COVID-19 related issues, and fever (18.7%, 16.3%, 12.9%, 11.9%, and 10.3%, respectively).

Of these, dermatologic and GI concerns were most often completed via telemedicine (93.3% and 81.7%, respectively), while upper respiratory tract infections and fever issues were the least likely to be completed via telemedicine (22.7% and 13.6%), mainly because of the need to report for in-person COVID-19 testing, the researchers said.

Among other less common chief complaints, 100% of breathing concerns, behavior/mental health concerns, and head trauma or falls were addressed via telemedicine without additional referrals or follow-up visits. In addition, 90.9% of urgent care or emergency department follow-ups, 88.9% of ear concerns, and 87.5% of eye concerns were completely resolved via telemedicine visits.

Overall, 3% of patients who were not referred after a telemedicine visit presented in person for worsening symptoms. Of these who were referred after a telemedicine visit, 90% were seen in person within 48 hours.

The study findings were limited by the inclusion of data from only a single center. However, “These early findings provide insight into the utility of telehealth in the primary care setting for a broad array of urgent concerns,” the researchers concluded.
 

Pandemic propelled telemedicine to improve patient care

The widespread adoption of telemedicine in primary care has been a beneficial side effect of the COVID-19 pandemic, said Tim Joos, MD, a Seattle-based clinician with a combination internal medicine/pediatrics practice, in an interview.

“Toward the end of World War II and in the push to form the United Nations, Winston Churchill was credited with the saying, ‘Never let a good crisis go to waste,’” said Dr. Joos, who was not connected with the study.

“As awful as this pandemic has been, it has propelled health care delivery at an unprecedented pace into the digital age,” he noted.

The current study is important because it highlights the number of complaints that can be successfully resolved through telemedicine, offering patients and families quicker access and more options for care, Dr. Joos said.

“I feel that giving patients and families an open choice for either telemedicine or in-person visits improves the likelihood that the issue will be resolved efficiently and satisfactorily with fewer visits,” he added.

Approximately two-thirds of pediatric acute care concerns managed in telemedicine visits required no additional visits or follow-up, based on data from more than 600 visits.

The increase in use of telemedicine during the first year of the COVID-19 pandemic enabled access to care and connection to doctors for many pediatric patients, said Kristina Kissiova, MD, of Children’s National Health System, Washington, and colleagues. Some advantages of telemedicine include enhanced medical homes, reduced health care costs, and less crowding and wait time for patients in offices and emergency departments; however, the optimal use of telemedicine for acute primary care has not been examined, they said.

In a study presented at the annual meeting of the Pediatric Academic Societies, the researchers conducted a retrospective chart review of 638 acute care telemedicine visits conducted by 21 health care providers at a single practice in Washington in October 2020 and November 2020. Approximately half of the patients were male, 65% were white, and 89% had commercial insurance. The most common age group was 6-12 years (23%), followed by 2-3 years (16%), 3-6 years (15%), and 12-18 years (14%).

The primary outcome was the number and nature of visits completed via telemedicine without the need for referral or a subsequent in-person visit. Telemedicine visits for well-child checks and follow-up visits were excluded.

Overall, 60% of the visits (384 of 638) were completed over telemedicine with no need for additional visits or referrals. The most common acute complaints were upper respiratory infections, dermatologic issues, gastrointestinal issues, COVID-19 related issues, and fever (18.7%, 16.3%, 12.9%, 11.9%, and 10.3%, respectively).

Of these, dermatologic and GI concerns were most often completed via telemedicine (93.3% and 81.7%, respectively), while upper respiratory tract infections and fever issues were the least likely to be completed via telemedicine (22.7% and 13.6%), mainly because of the need to report for in-person COVID-19 testing, the researchers said.

Among other less common chief complaints, 100% of breathing concerns, behavior/mental health concerns, and head trauma or falls were addressed via telemedicine without additional referrals or follow-up visits. In addition, 90.9% of urgent care or emergency department follow-ups, 88.9% of ear concerns, and 87.5% of eye concerns were completely resolved via telemedicine visits.

Overall, 3% of patients who were not referred after a telemedicine visit presented in person for worsening symptoms. Of these who were referred after a telemedicine visit, 90% were seen in person within 48 hours.

The study findings were limited by the inclusion of data from only a single center. However, “These early findings provide insight into the utility of telehealth in the primary care setting for a broad array of urgent concerns,” the researchers concluded.
 

Pandemic propelled telemedicine to improve patient care

The widespread adoption of telemedicine in primary care has been a beneficial side effect of the COVID-19 pandemic, said Tim Joos, MD, a Seattle-based clinician with a combination internal medicine/pediatrics practice, in an interview.

“Toward the end of World War II and in the push to form the United Nations, Winston Churchill was credited with the saying, ‘Never let a good crisis go to waste,’” said Dr. Joos, who was not connected with the study.

“As awful as this pandemic has been, it has propelled health care delivery at an unprecedented pace into the digital age,” he noted.

The current study is important because it highlights the number of complaints that can be successfully resolved through telemedicine, offering patients and families quicker access and more options for care, Dr. Joos said.

“I feel that giving patients and families an open choice for either telemedicine or in-person visits improves the likelihood that the issue will be resolved efficiently and satisfactorily with fewer visits,” he added.

One of the largest studies to date on myocarditis after COVID-19 vaccination confirms an increased risk with both the Pfizer and Moderna vaccines in young men and shows that the risk is higher with the Moderna than with the Pfizer vaccine.

The study also suggests for the first time that in young men 16 to 24 years of age, the risk for myocarditis after vaccination with either the Pfizer or Moderna vaccine is higher than the risk for myocarditis after COVID-19 infection.

The population-based study involved data on 23.1 million residents across four Scandinavian countries – Denmark, Finland, Norway, and Sweden – 74% of whom had received two vaccine doses and 7% of whom had received one dose.

By linking data from high-quality nationwide health registers on COVID-19 vaccination, infection rates, and myocarditis diagnoses, the researchers were able to evaluate the risk for myocarditis by vaccine product, vaccination dose number, sex, and age.

The study was published online in JAMA Cardiology.

The results confirm that the risk for myocarditis after COVID-19 mRNA vaccines is highest in young men 16 to 24 years of age after the second dose.

For men in this age group who received two doses of the same vaccine, data were compatible, with between four and seven excess myocarditis events in 28 days per 100,000 individuals after the second dose of the Pfizer vaccine, and between nine and 28 per 100,000 individuals after the second dose of the Moderna vaccine.

“This is one of the largest studies on this topic to date. The first population studies were in Israel, with 5 million individuals, and looked at just the Pfizer vaccine. We have data on 23 million people from Scandinavia that include both the Pfizer and Moderna vaccines,” senior author Rickard Ljung, MD, Swedish Medical Products Agency, told this news organization.

“We show a clearly higher risk of myocarditis after the Moderna vaccine than after the Pfizer vaccine. This has been suggested before, but our data confirm definitively that the Moderna vaccine has a higher risk of myocarditis than the Pfizer vaccine,” he added.

“In the group at highest risk of myocarditis after COVID vaccination – young men aged 16 to 24 – the Pfizer vaccine shows a five times higher risk of myocarditis versus the unvaccinated cohort, while the Moderna vaccine shows a 15 times higher risk,” Dr. Ljung noted.

After seeing these data, the Swedish regulatory authority is no longer recommending use of the Moderna vaccine for people younger than 30 years, Dr. Ljung said. Similar recommendations have been made in Norway and Finland.

The researchers report that their finding of a higher risk for myocarditis after the Moderna vaccine than after the Pfizer vaccine in young men is in line with data from the Canada, France, the United Kingdom, and the United States. But they point out that, compared with previous studies, the current study had the advantage of data analyzed according to a common protocol from four different countries and that showed similar directions of associations, despite considerable differences in previous COVID-19 infection levels and lockdown policies.

Risk higher with vaccination than infection?

For what is believed to be the first time, the Scandinavian data also suggest a higher risk for myocarditis after COVID-19 vaccination with both the Pfizer and Moderna vaccines than after COVID-19 infection in young men 16 to 24 years.

Although previous studies have shown that males in this age group have the highest risk for myocarditis after vaccination, it has always been suggested that the risk after vaccination is lower than the risk after infection. The Scandinavian data suggest otherwise for this age group.

Dr. Ljung explained that the myocarditis risk after COVID infection is very hard to study.

“It is highly dependent on the testing strategy,” he said. “For example, in the first half of 2020, the only people being tested were those admitted to hospital, so studies would have included the sickest patients and would therefore likely have found a higher rate of myocarditis. But this current Scandinavian dataset only included individuals with a positive COVID test after August 2020, reflecting a broader range of people.”

The researchers found an excess rate of myocarditis of 3.26 per 100,000 individuals within 28 days of a positive COVID-19 test among all males, and 1.37 per 100,000 individuals among males 16 to 24 years of age.

“We show that the risk of myocarditis after COVID infection is lower in younger people and higher in older people, but the opposite is true after COVID vaccination, where the risk of myocarditis is higher in younger people and lower in older people,” Dr. Ljung said.

The study was not able to look at severity of myocarditis but did record length of hospital stay, which was similar in patients who developed myocarditis after vaccination and those in the unvaccinated cohort (4 to 5 days). Deaths were rare, with no deaths in people younger than 40 years.

“I think we can say that in people aged over 40, the risk of myocarditis is greater with infection than with vaccination, but in those under 40, it is not so clear. And our data suggest that for young men aged 16 to 24 years, the risk of myocarditis after COVID vaccination with either the Pfizer or Moderna vaccine is higher than after COVID infection,” Dr. Ljung commented.

Although the Swedish regulatory agency has already stopped recommending use of Moderna vaccine in those younger than 30 years on the basis of these data, Dr. Ljung was reluctant to make any recommendations regarding the use of the Pfizer vaccine in young males, saying it was up to individual public-health agencies to makes these decisions. 

But he pointed out that the current study only looked at myocarditis, and COVID infection can result in many other complications that can lead to hospitalization and death, which needs to be taken into account when assessing the risk and benefit of vaccination.

Dr. Ljung noted that the current data only applied to the first two doses of the vaccines; data after booster injections have not been included, although the researchers are looking at that now.

What to advise patients?

In an accompanying Editor’s Note, Ann Marie Navar, MD, University of Texas Southwestern Medical Center, Dallas, who is editor of JAMA Cardiology, and Robert Bonow, MD, Northwestern University Feinberg School of Medicine, Chicago, who is deputy editor of JAMA Cardiology, try to explain how these data can inform the way health care professionals communicate with their patients about vaccination.

They point out the “good news,” that older adults who are at highest risk for COVID-19 complications appear to be at extremely low risk for vaccine-associated myocarditis.

They note that for both men and women older than 40 years, the excess number of cases of myocarditis after vaccination was fewer than two in 100,000 vaccinees across all vaccines studied, and the death toll from COVID-19 in the United States as of March was more than 200 per 100,000 population.

“Given the high rates of morbidity and mortality from COVID-19 infection in older adults and the efficacy of the vaccine in preventing severe infection and death, the benefits of immunization in those older than 40 years clearly outweigh the risks,” the editors say.

But given these data in young men, they suggest that health care professionals consider recommending the Pfizer vaccine over the Moderna vaccine for certain populations, including young men and other individuals for whom concerns about myocarditis present a barrier to immunization.

The editors also point out that although the risk for myocarditis after COVID-19 immunization is real, this low risk must be considered in the context of the overall benefit of the vaccine.

“At the individual level, immunization prevents not only COVID-19-related myocarditis but also severe disease, hospitalization, long-term complications after COVID-19 infection, and death. At the population level, immunization helps to decrease community spread, decrease the chances of new variants emerging, protect people who are immunocompromised, and ensure our health care system can continue to provide for our communities,” they conclude.

Dr. Ljung reports grants from Sanofi Aventis paid to his institution outside the submitted work and personal fees from Pfizer outside the submitted work. Dr. Navar reports personal fees from Pfizer and AstraZeneca, outside the scope of this work.

A version of this article first appeared on Medscape.com.

One of the largest studies to date on myocarditis after COVID-19 vaccination confirms an increased risk with both the Pfizer and Moderna vaccines in young men and shows that the risk is higher with the Moderna than with the Pfizer vaccine.

The study also suggests for the first time that in young men 16 to 24 years of age, the risk for myocarditis after vaccination with either the Pfizer or Moderna vaccine is higher than the risk for myocarditis after COVID-19 infection.

The population-based study involved data on 23.1 million residents across four Scandinavian countries – Denmark, Finland, Norway, and Sweden – 74% of whom had received two vaccine doses and 7% of whom had received one dose.

By linking data from high-quality nationwide health registers on COVID-19 vaccination, infection rates, and myocarditis diagnoses, the researchers were able to evaluate the risk for myocarditis by vaccine product, vaccination dose number, sex, and age.

The study was published online in JAMA Cardiology.

The results confirm that the risk for myocarditis after COVID-19 mRNA vaccines is highest in young men 16 to 24 years of age after the second dose.

For men in this age group who received two doses of the same vaccine, data were compatible, with between four and seven excess myocarditis events in 28 days per 100,000 individuals after the second dose of the Pfizer vaccine, and between nine and 28 per 100,000 individuals after the second dose of the Moderna vaccine.

“This is one of the largest studies on this topic to date. The first population studies were in Israel, with 5 million individuals, and looked at just the Pfizer vaccine. We have data on 23 million people from Scandinavia that include both the Pfizer and Moderna vaccines,” senior author Rickard Ljung, MD, Swedish Medical Products Agency, told this news organization.

“We show a clearly higher risk of myocarditis after the Moderna vaccine than after the Pfizer vaccine. This has been suggested before, but our data confirm definitively that the Moderna vaccine has a higher risk of myocarditis than the Pfizer vaccine,” he added.

“In the group at highest risk of myocarditis after COVID vaccination – young men aged 16 to 24 – the Pfizer vaccine shows a five times higher risk of myocarditis versus the unvaccinated cohort, while the Moderna vaccine shows a 15 times higher risk,” Dr. Ljung noted.

After seeing these data, the Swedish regulatory authority is no longer recommending use of the Moderna vaccine for people younger than 30 years, Dr. Ljung said. Similar recommendations have been made in Norway and Finland.

The researchers report that their finding of a higher risk for myocarditis after the Moderna vaccine than after the Pfizer vaccine in young men is in line with data from the Canada, France, the United Kingdom, and the United States. But they point out that, compared with previous studies, the current study had the advantage of data analyzed according to a common protocol from four different countries and that showed similar directions of associations, despite considerable differences in previous COVID-19 infection levels and lockdown policies.

Risk higher with vaccination than infection?

For what is believed to be the first time, the Scandinavian data also suggest a higher risk for myocarditis after COVID-19 vaccination with both the Pfizer and Moderna vaccines than after COVID-19 infection in young men 16 to 24 years.

Although previous studies have shown that males in this age group have the highest risk for myocarditis after vaccination, it has always been suggested that the risk after vaccination is lower than the risk after infection. The Scandinavian data suggest otherwise for this age group.

Dr. Ljung explained that the myocarditis risk after COVID infection is very hard to study.

“It is highly dependent on the testing strategy,” he said. “For example, in the first half of 2020, the only people being tested were those admitted to hospital, so studies would have included the sickest patients and would therefore likely have found a higher rate of myocarditis. But this current Scandinavian dataset only included individuals with a positive COVID test after August 2020, reflecting a broader range of people.”

The researchers found an excess rate of myocarditis of 3.26 per 100,000 individuals within 28 days of a positive COVID-19 test among all males, and 1.37 per 100,000 individuals among males 16 to 24 years of age.

“We show that the risk of myocarditis after COVID infection is lower in younger people and higher in older people, but the opposite is true after COVID vaccination, where the risk of myocarditis is higher in younger people and lower in older people,” Dr. Ljung said.

The study was not able to look at severity of myocarditis but did record length of hospital stay, which was similar in patients who developed myocarditis after vaccination and those in the unvaccinated cohort (4 to 5 days). Deaths were rare, with no deaths in people younger than 40 years.

“I think we can say that in people aged over 40, the risk of myocarditis is greater with infection than with vaccination, but in those under 40, it is not so clear. And our data suggest that for young men aged 16 to 24 years, the risk of myocarditis after COVID vaccination with either the Pfizer or Moderna vaccine is higher than after COVID infection,” Dr. Ljung commented.

Although the Swedish regulatory agency has already stopped recommending use of Moderna vaccine in those younger than 30 years on the basis of these data, Dr. Ljung was reluctant to make any recommendations regarding the use of the Pfizer vaccine in young males, saying it was up to individual public-health agencies to makes these decisions. 

But he pointed out that the current study only looked at myocarditis, and COVID infection can result in many other complications that can lead to hospitalization and death, which needs to be taken into account when assessing the risk and benefit of vaccination.

Dr. Ljung noted that the current data only applied to the first two doses of the vaccines; data after booster injections have not been included, although the researchers are looking at that now.

What to advise patients?

In an accompanying Editor’s Note, Ann Marie Navar, MD, University of Texas Southwestern Medical Center, Dallas, who is editor of JAMA Cardiology, and Robert Bonow, MD, Northwestern University Feinberg School of Medicine, Chicago, who is deputy editor of JAMA Cardiology, try to explain how these data can inform the way health care professionals communicate with their patients about vaccination.

They point out the “good news,” that older adults who are at highest risk for COVID-19 complications appear to be at extremely low risk for vaccine-associated myocarditis.

They note that for both men and women older than 40 years, the excess number of cases of myocarditis after vaccination was fewer than two in 100,000 vaccinees across all vaccines studied, and the death toll from COVID-19 in the United States as of March was more than 200 per 100,000 population.

“Given the high rates of morbidity and mortality from COVID-19 infection in older adults and the efficacy of the vaccine in preventing severe infection and death, the benefits of immunization in those older than 40 years clearly outweigh the risks,” the editors say.

But given these data in young men, they suggest that health care professionals consider recommending the Pfizer vaccine over the Moderna vaccine for certain populations, including young men and other individuals for whom concerns about myocarditis present a barrier to immunization.

The editors also point out that although the risk for myocarditis after COVID-19 immunization is real, this low risk must be considered in the context of the overall benefit of the vaccine.

“At the individual level, immunization prevents not only COVID-19-related myocarditis but also severe disease, hospitalization, long-term complications after COVID-19 infection, and death. At the population level, immunization helps to decrease community spread, decrease the chances of new variants emerging, protect people who are immunocompromised, and ensure our health care system can continue to provide for our communities,” they conclude.

Dr. Ljung reports grants from Sanofi Aventis paid to his institution outside the submitted work and personal fees from Pfizer outside the submitted work. Dr. Navar reports personal fees from Pfizer and AstraZeneca, outside the scope of this work.

A version of this article first appeared on Medscape.com.

One of the largest studies to date on myocarditis after COVID-19 vaccination confirms an increased risk with both the Pfizer and Moderna vaccines in young men and shows that the risk is higher with the Moderna than with the Pfizer vaccine.

The study also suggests for the first time that in young men 16 to 24 years of age, the risk for myocarditis after vaccination with either the Pfizer or Moderna vaccine is higher than the risk for myocarditis after COVID-19 infection.

The population-based study involved data on 23.1 million residents across four Scandinavian countries – Denmark, Finland, Norway, and Sweden – 74% of whom had received two vaccine doses and 7% of whom had received one dose.

By linking data from high-quality nationwide health registers on COVID-19 vaccination, infection rates, and myocarditis diagnoses, the researchers were able to evaluate the risk for myocarditis by vaccine product, vaccination dose number, sex, and age.

The study was published online in JAMA Cardiology.

The results confirm that the risk for myocarditis after COVID-19 mRNA vaccines is highest in young men 16 to 24 years of age after the second dose.

For men in this age group who received two doses of the same vaccine, data were compatible, with between four and seven excess myocarditis events in 28 days per 100,000 individuals after the second dose of the Pfizer vaccine, and between nine and 28 per 100,000 individuals after the second dose of the Moderna vaccine.

“This is one of the largest studies on this topic to date. The first population studies were in Israel, with 5 million individuals, and looked at just the Pfizer vaccine. We have data on 23 million people from Scandinavia that include both the Pfizer and Moderna vaccines,” senior author Rickard Ljung, MD, Swedish Medical Products Agency, told this news organization.

“We show a clearly higher risk of myocarditis after the Moderna vaccine than after the Pfizer vaccine. This has been suggested before, but our data confirm definitively that the Moderna vaccine has a higher risk of myocarditis than the Pfizer vaccine,” he added.

“In the group at highest risk of myocarditis after COVID vaccination – young men aged 16 to 24 – the Pfizer vaccine shows a five times higher risk of myocarditis versus the unvaccinated cohort, while the Moderna vaccine shows a 15 times higher risk,” Dr. Ljung noted.

After seeing these data, the Swedish regulatory authority is no longer recommending use of the Moderna vaccine for people younger than 30 years, Dr. Ljung said. Similar recommendations have been made in Norway and Finland.

The researchers report that their finding of a higher risk for myocarditis after the Moderna vaccine than after the Pfizer vaccine in young men is in line with data from the Canada, France, the United Kingdom, and the United States. But they point out that, compared with previous studies, the current study had the advantage of data analyzed according to a common protocol from four different countries and that showed similar directions of associations, despite considerable differences in previous COVID-19 infection levels and lockdown policies.

Risk higher with vaccination than infection?

For what is believed to be the first time, the Scandinavian data also suggest a higher risk for myocarditis after COVID-19 vaccination with both the Pfizer and Moderna vaccines than after COVID-19 infection in young men 16 to 24 years.

Although previous studies have shown that males in this age group have the highest risk for myocarditis after vaccination, it has always been suggested that the risk after vaccination is lower than the risk after infection. The Scandinavian data suggest otherwise for this age group.

Dr. Ljung explained that the myocarditis risk after COVID infection is very hard to study.

“It is highly dependent on the testing strategy,” he said. “For example, in the first half of 2020, the only people being tested were those admitted to hospital, so studies would have included the sickest patients and would therefore likely have found a higher rate of myocarditis. But this current Scandinavian dataset only included individuals with a positive COVID test after August 2020, reflecting a broader range of people.”

The researchers found an excess rate of myocarditis of 3.26 per 100,000 individuals within 28 days of a positive COVID-19 test among all males, and 1.37 per 100,000 individuals among males 16 to 24 years of age.

“We show that the risk of myocarditis after COVID infection is lower in younger people and higher in older people, but the opposite is true after COVID vaccination, where the risk of myocarditis is higher in younger people and lower in older people,” Dr. Ljung said.

The study was not able to look at severity of myocarditis but did record length of hospital stay, which was similar in patients who developed myocarditis after vaccination and those in the unvaccinated cohort (4 to 5 days). Deaths were rare, with no deaths in people younger than 40 years.

“I think we can say that in people aged over 40, the risk of myocarditis is greater with infection than with vaccination, but in those under 40, it is not so clear. And our data suggest that for young men aged 16 to 24 years, the risk of myocarditis after COVID vaccination with either the Pfizer or Moderna vaccine is higher than after COVID infection,” Dr. Ljung commented.

Although the Swedish regulatory agency has already stopped recommending use of Moderna vaccine in those younger than 30 years on the basis of these data, Dr. Ljung was reluctant to make any recommendations regarding the use of the Pfizer vaccine in young males, saying it was up to individual public-health agencies to makes these decisions. 

But he pointed out that the current study only looked at myocarditis, and COVID infection can result in many other complications that can lead to hospitalization and death, which needs to be taken into account when assessing the risk and benefit of vaccination.

Dr. Ljung noted that the current data only applied to the first two doses of the vaccines; data after booster injections have not been included, although the researchers are looking at that now.

What to advise patients?

In an accompanying Editor’s Note, Ann Marie Navar, MD, University of Texas Southwestern Medical Center, Dallas, who is editor of JAMA Cardiology, and Robert Bonow, MD, Northwestern University Feinberg School of Medicine, Chicago, who is deputy editor of JAMA Cardiology, try to explain how these data can inform the way health care professionals communicate with their patients about vaccination.

They point out the “good news,” that older adults who are at highest risk for COVID-19 complications appear to be at extremely low risk for vaccine-associated myocarditis.

They note that for both men and women older than 40 years, the excess number of cases of myocarditis after vaccination was fewer than two in 100,000 vaccinees across all vaccines studied, and the death toll from COVID-19 in the United States as of March was more than 200 per 100,000 population.

“Given the high rates of morbidity and mortality from COVID-19 infection in older adults and the efficacy of the vaccine in preventing severe infection and death, the benefits of immunization in those older than 40 years clearly outweigh the risks,” the editors say.

But given these data in young men, they suggest that health care professionals consider recommending the Pfizer vaccine over the Moderna vaccine for certain populations, including young men and other individuals for whom concerns about myocarditis present a barrier to immunization.

The editors also point out that although the risk for myocarditis after COVID-19 immunization is real, this low risk must be considered in the context of the overall benefit of the vaccine.

“At the individual level, immunization prevents not only COVID-19-related myocarditis but also severe disease, hospitalization, long-term complications after COVID-19 infection, and death. At the population level, immunization helps to decrease community spread, decrease the chances of new variants emerging, protect people who are immunocompromised, and ensure our health care system can continue to provide for our communities,” they conclude.

Dr. Ljung reports grants from Sanofi Aventis paid to his institution outside the submitted work and personal fees from Pfizer outside the submitted work. Dr. Navar reports personal fees from Pfizer and AstraZeneca, outside the scope of this work.

A version of this article first appeared on Medscape.com.