Internal Medicine News

For gout, xanthine oxidase (XO) inhibitors are the choice for first-line urate-lowering therapy (ULT) according to the 2020 American College of Rheumatology Guideline for the Management of Gout, which endorsed allopurinol, but should that be the approach for all patients, or should first-line therapy be tailored to the mechanism of each patient’s hyperuricemia? Two gout experts, Lisa Stamp, MBChB, PhD, a rheumatologist and professor of medicine at the University of Otago in Christchurch, New Zealand, and Fernando Pérez-Ruiz, MD, PhD, consultant in the Rheumatology Division of Cruces University Hospital, Barakaldo, head of the Investigation Group for Arthritis at Biocruces Health Research Institute, Barakaldo, and associate professor in the Department of Medicine at the Faculty of Medicine and Nursing at the University of the Basque Country in Leioa, Spain, debated this question recently at the annual research symposium of the Gout, Hyperuricemia and Crystal-Associated Disease Network.

Before the debate began, audience members voted on the question and 56% favored using XO inhibitors as a first-line therapy for all rather than tailoring first-line therapy to disease mechanism.

Up first, Stamp argued that XO inhibitors should be first-line therapy for all patients with gout. She said that XO inhibitors have been demonstrated to work regardless of the cause of hyperuricemia and degree of kidney function, and they are cheap, readily available, and easy to administer. She showed results from a study published by her debate opponent, Pérez-Ruiz, which demonstrated efficacy of XO inhibitors in both under-excreters and over-excreters of uric acid. That study compared the efficacy of the XO inhibitor allopurinol to the uricosuric agent benzbromarone and found the latter to be more effective, but Stamp argued that the allopurinol dose used in the study — 300 mg/d — “may not be enough for many patients who have gout. Dose-restricting allopurinol is one way to demonstrate that an alternative agent is superior,” she said.

A more recent study showed low-dose benzbromarone was better than low-dose febuxostat, another XO inhibitor. “I think we do need to have clinical trials that reflect real-world practice. I accept that this may have reflected [accepted practice where the studies] were undertaken, but these [XO inhibitor] doses don’t represent what many of us would do in other parts of the world,” Stamp said.

One concern is the utility of a ULT in patients with impaired renal function. Stamp cited her own post hoc analysis of a randomized, controlled trial showing that allopurinol is effective irrespective of renal function, as long as the dose is escalated to achieve target urate level, and a meta-analysis of observational studies suggesting that febuxostat is effective irrespective of renal function.

On the other hand, she showed data from a 1994 study of benzbromarone in renal transplant recipients, which showed that the drug’s effect on decreasing plasma uric acid dropped off significantly with lower creatinine clearance. “It does work, but the efficacy really drops off as renal function decreases. Benzbromarone is probably the most effective uricosuric in patients with renal impairment, but this agent is not readily available,” Stamp said.

The uricosuric agent probenecid, which is generally available across the world, led to only about 30% success in achieving target levels of uric acid among patients with an estimated glomerular filtration rate < 50 mL/min/1.73 m². “I think we can all agree that getting 30% of our patients to target uric acid is not an acceptable outcome,” she said.

Stamp emphasized the importance of drug availability and noted that allopurinol is also the only medication for gout that is on the World Health Organization list of essential medications. “I think we should be recommending medications that are readily available, irrespective of where you live,” she said, noting that this is true of allopurinol, febuxostat, and probenecid.

Stamp also addressed the mechanism of action of ULTs. “Does the cause of hyperuricemia affect treatment response? I don’t think it does. Most people respond to allopurinol whether they’re a normal excreter or an under-excreter. Everyone who is lacking uricase will respond to allopurinol. Not everyone will respond to a uricosuric [agent], particularly in the setting of comorbidities such as renal impairment, which many of our patients with gout have,” she said.

 

Counterargument: Combine Therapies With Different Mechanisms of Action

In his counterargument, Pérez-Ruiz contended that gout is not in fact a metabolic disease and suggested that combining therapies with different mechanisms of action could be the best approach for difficult-to-treat gout. “The problem we face in clinical practice is how to treat difficult-to-treat patients,” he said. He referenced his own PhD thesis, which showed both high urinary uric acid output and underexcretion among patients with gout.

Pérez-Ruiz agreed that XO inhibitors should be used as first-line therapy but noted that the effect of allopurinol tapers off at higher doses. “If you use very high doses of allopurinol, you cannot expect to get much more effect,” he said. This is also true of febuxostat, he said.

He showed another study that illustrated difficulties in achieving target serum urate level with intensive therapy. “Even using a high dose of allopurinol, if you would like to get lower than 3 mg/dL for intensive therapy, close to 50% of patients will fail,” he said.

Pérez-Ruiz described a strategy of combining XO inhibitors with a uricosuric therapy, creating what he called a “uricase-like effect” on serum uric acid levels. Ruiz-Perez uses high-dose febuxostat in patients with chronic kidney disease who cannot be given uricosuric agents. “You can go to very low [serum urate levels] by raising up the doses,” he said.

He does not believe that allopurinol is the best agent for combination therapy in the treatment of tophaceous deposits. Instead, he favors combinations with febuxostat. He presented his own experience with 12 patients with very severe tophaceous gout who he treated with a combination of febuxostat and benzbromarone, which reduced serum urate to just over 2 mg/dL. “So this is a pegloticase-like effect [that is] very useful for tophaceous gout,” he said.

In her response, Stamp noted that most of the studies presented by Pérez-Ruiz showed XO inhibitors as first-line therapies, with other medications added on. “I think I heard Fernando agree with me. In just about all of those slides, he showed that a xanthine oxidase inhibitor was the first-line therapy, and subsequently a uricosuric was added,” she said.

Still, Stamp took issue with the idea that serum urate needs to get as low as Pérez-Ruiz advocated for. “What’s the risk associated with getting a serum urate to that level? I’m not sure that a sustained serum urate of around 1 [mg/dL] is necessarily good in the long term,” she said.

Stamp also pointed out the potential risks of polypharmacy, along with adherence issues. “If we can give our patients one therapy, one drug that’s going to get them to a target that we know is going to have beneficial long-term effects, that’s going to help improve our adherence. Maybe we are coming to a new era of [treatment, with] remission induction driving the serum urate very low, and then a maintenance therapy where we can back off. But irrespective, if you use that strategy, Fernando nicely showed that every time you’re going to start with a xanthine oxidase inhibitor,” she said.

After the debate, audience members voted again, and this time the result was 66% in favor of XO inhibitors as a first-line treatment.

Pérez-Ruiz is an adviser for Arthrosi, LG, Novartis, Protalix, and SOBI. He is a speaker for Menarini Central America and the Spanish Foundation for Rheumatology and has received funding from Cruces Rheumatology Association. Stamp did not disclose any financial relationships.

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

For gout, xanthine oxidase (XO) inhibitors are the choice for first-line urate-lowering therapy (ULT) according to the 2020 American College of Rheumatology Guideline for the Management of Gout, which endorsed allopurinol, but should that be the approach for all patients, or should first-line therapy be tailored to the mechanism of each patient’s hyperuricemia? Two gout experts, Lisa Stamp, MBChB, PhD, a rheumatologist and professor of medicine at the University of Otago in Christchurch, New Zealand, and Fernando Pérez-Ruiz, MD, PhD, consultant in the Rheumatology Division of Cruces University Hospital, Barakaldo, head of the Investigation Group for Arthritis at Biocruces Health Research Institute, Barakaldo, and associate professor in the Department of Medicine at the Faculty of Medicine and Nursing at the University of the Basque Country in Leioa, Spain, debated this question recently at the annual research symposium of the Gout, Hyperuricemia and Crystal-Associated Disease Network.

Before the debate began, audience members voted on the question and 56% favored using XO inhibitors as a first-line therapy for all rather than tailoring first-line therapy to disease mechanism.

Up first, Stamp argued that XO inhibitors should be first-line therapy for all patients with gout. She said that XO inhibitors have been demonstrated to work regardless of the cause of hyperuricemia and degree of kidney function, and they are cheap, readily available, and easy to administer. She showed results from a study published by her debate opponent, Pérez-Ruiz, which demonstrated efficacy of XO inhibitors in both under-excreters and over-excreters of uric acid. That study compared the efficacy of the XO inhibitor allopurinol to the uricosuric agent benzbromarone and found the latter to be more effective, but Stamp argued that the allopurinol dose used in the study — 300 mg/d — “may not be enough for many patients who have gout. Dose-restricting allopurinol is one way to demonstrate that an alternative agent is superior,” she said.

A more recent study showed low-dose benzbromarone was better than low-dose febuxostat, another XO inhibitor. “I think we do need to have clinical trials that reflect real-world practice. I accept that this may have reflected [accepted practice where the studies] were undertaken, but these [XO inhibitor] doses don’t represent what many of us would do in other parts of the world,” Stamp said.

One concern is the utility of a ULT in patients with impaired renal function. Stamp cited her own post hoc analysis of a randomized, controlled trial showing that allopurinol is effective irrespective of renal function, as long as the dose is escalated to achieve target urate level, and a meta-analysis of observational studies suggesting that febuxostat is effective irrespective of renal function.

On the other hand, she showed data from a 1994 study of benzbromarone in renal transplant recipients, which showed that the drug’s effect on decreasing plasma uric acid dropped off significantly with lower creatinine clearance. “It does work, but the efficacy really drops off as renal function decreases. Benzbromarone is probably the most effective uricosuric in patients with renal impairment, but this agent is not readily available,” Stamp said.

The uricosuric agent probenecid, which is generally available across the world, led to only about 30% success in achieving target levels of uric acid among patients with an estimated glomerular filtration rate < 50 mL/min/1.73 m². “I think we can all agree that getting 30% of our patients to target uric acid is not an acceptable outcome,” she said.

Stamp emphasized the importance of drug availability and noted that allopurinol is also the only medication for gout that is on the World Health Organization list of essential medications. “I think we should be recommending medications that are readily available, irrespective of where you live,” she said, noting that this is true of allopurinol, febuxostat, and probenecid.

Stamp also addressed the mechanism of action of ULTs. “Does the cause of hyperuricemia affect treatment response? I don’t think it does. Most people respond to allopurinol whether they’re a normal excreter or an under-excreter. Everyone who is lacking uricase will respond to allopurinol. Not everyone will respond to a uricosuric [agent], particularly in the setting of comorbidities such as renal impairment, which many of our patients with gout have,” she said.

 

Counterargument: Combine Therapies With Different Mechanisms of Action

In his counterargument, Pérez-Ruiz contended that gout is not in fact a metabolic disease and suggested that combining therapies with different mechanisms of action could be the best approach for difficult-to-treat gout. “The problem we face in clinical practice is how to treat difficult-to-treat patients,” he said. He referenced his own PhD thesis, which showed both high urinary uric acid output and underexcretion among patients with gout.

Pérez-Ruiz agreed that XO inhibitors should be used as first-line therapy but noted that the effect of allopurinol tapers off at higher doses. “If you use very high doses of allopurinol, you cannot expect to get much more effect,” he said. This is also true of febuxostat, he said.

He showed another study that illustrated difficulties in achieving target serum urate level with intensive therapy. “Even using a high dose of allopurinol, if you would like to get lower than 3 mg/dL for intensive therapy, close to 50% of patients will fail,” he said.

Pérez-Ruiz described a strategy of combining XO inhibitors with a uricosuric therapy, creating what he called a “uricase-like effect” on serum uric acid levels. Ruiz-Perez uses high-dose febuxostat in patients with chronic kidney disease who cannot be given uricosuric agents. “You can go to very low [serum urate levels] by raising up the doses,” he said.

He does not believe that allopurinol is the best agent for combination therapy in the treatment of tophaceous deposits. Instead, he favors combinations with febuxostat. He presented his own experience with 12 patients with very severe tophaceous gout who he treated with a combination of febuxostat and benzbromarone, which reduced serum urate to just over 2 mg/dL. “So this is a pegloticase-like effect [that is] very useful for tophaceous gout,” he said.

In her response, Stamp noted that most of the studies presented by Pérez-Ruiz showed XO inhibitors as first-line therapies, with other medications added on. “I think I heard Fernando agree with me. In just about all of those slides, he showed that a xanthine oxidase inhibitor was the first-line therapy, and subsequently a uricosuric was added,” she said.

Still, Stamp took issue with the idea that serum urate needs to get as low as Pérez-Ruiz advocated for. “What’s the risk associated with getting a serum urate to that level? I’m not sure that a sustained serum urate of around 1 [mg/dL] is necessarily good in the long term,” she said.

Stamp also pointed out the potential risks of polypharmacy, along with adherence issues. “If we can give our patients one therapy, one drug that’s going to get them to a target that we know is going to have beneficial long-term effects, that’s going to help improve our adherence. Maybe we are coming to a new era of [treatment, with] remission induction driving the serum urate very low, and then a maintenance therapy where we can back off. But irrespective, if you use that strategy, Fernando nicely showed that every time you’re going to start with a xanthine oxidase inhibitor,” she said.

After the debate, audience members voted again, and this time the result was 66% in favor of XO inhibitors as a first-line treatment.

Pérez-Ruiz is an adviser for Arthrosi, LG, Novartis, Protalix, and SOBI. He is a speaker for Menarini Central America and the Spanish Foundation for Rheumatology and has received funding from Cruces Rheumatology Association. Stamp did not disclose any financial relationships.

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

For gout, xanthine oxidase (XO) inhibitors are the choice for first-line urate-lowering therapy (ULT) according to the 2020 American College of Rheumatology Guideline for the Management of Gout, which endorsed allopurinol, but should that be the approach for all patients, or should first-line therapy be tailored to the mechanism of each patient’s hyperuricemia? Two gout experts, Lisa Stamp, MBChB, PhD, a rheumatologist and professor of medicine at the University of Otago in Christchurch, New Zealand, and Fernando Pérez-Ruiz, MD, PhD, consultant in the Rheumatology Division of Cruces University Hospital, Barakaldo, head of the Investigation Group for Arthritis at Biocruces Health Research Institute, Barakaldo, and associate professor in the Department of Medicine at the Faculty of Medicine and Nursing at the University of the Basque Country in Leioa, Spain, debated this question recently at the annual research symposium of the Gout, Hyperuricemia and Crystal-Associated Disease Network.

Before the debate began, audience members voted on the question and 56% favored using XO inhibitors as a first-line therapy for all rather than tailoring first-line therapy to disease mechanism.

Up first, Stamp argued that XO inhibitors should be first-line therapy for all patients with gout. She said that XO inhibitors have been demonstrated to work regardless of the cause of hyperuricemia and degree of kidney function, and they are cheap, readily available, and easy to administer. She showed results from a study published by her debate opponent, Pérez-Ruiz, which demonstrated efficacy of XO inhibitors in both under-excreters and over-excreters of uric acid. That study compared the efficacy of the XO inhibitor allopurinol to the uricosuric agent benzbromarone and found the latter to be more effective, but Stamp argued that the allopurinol dose used in the study — 300 mg/d — “may not be enough for many patients who have gout. Dose-restricting allopurinol is one way to demonstrate that an alternative agent is superior,” she said.

A more recent study showed low-dose benzbromarone was better than low-dose febuxostat, another XO inhibitor. “I think we do need to have clinical trials that reflect real-world practice. I accept that this may have reflected [accepted practice where the studies] were undertaken, but these [XO inhibitor] doses don’t represent what many of us would do in other parts of the world,” Stamp said.

One concern is the utility of a ULT in patients with impaired renal function. Stamp cited her own post hoc analysis of a randomized, controlled trial showing that allopurinol is effective irrespective of renal function, as long as the dose is escalated to achieve target urate level, and a meta-analysis of observational studies suggesting that febuxostat is effective irrespective of renal function.

On the other hand, she showed data from a 1994 study of benzbromarone in renal transplant recipients, which showed that the drug’s effect on decreasing plasma uric acid dropped off significantly with lower creatinine clearance. “It does work, but the efficacy really drops off as renal function decreases. Benzbromarone is probably the most effective uricosuric in patients with renal impairment, but this agent is not readily available,” Stamp said.

The uricosuric agent probenecid, which is generally available across the world, led to only about 30% success in achieving target levels of uric acid among patients with an estimated glomerular filtration rate < 50 mL/min/1.73 m². “I think we can all agree that getting 30% of our patients to target uric acid is not an acceptable outcome,” she said.

Stamp emphasized the importance of drug availability and noted that allopurinol is also the only medication for gout that is on the World Health Organization list of essential medications. “I think we should be recommending medications that are readily available, irrespective of where you live,” she said, noting that this is true of allopurinol, febuxostat, and probenecid.

Stamp also addressed the mechanism of action of ULTs. “Does the cause of hyperuricemia affect treatment response? I don’t think it does. Most people respond to allopurinol whether they’re a normal excreter or an under-excreter. Everyone who is lacking uricase will respond to allopurinol. Not everyone will respond to a uricosuric [agent], particularly in the setting of comorbidities such as renal impairment, which many of our patients with gout have,” she said.

 

Counterargument: Combine Therapies With Different Mechanisms of Action

In his counterargument, Pérez-Ruiz contended that gout is not in fact a metabolic disease and suggested that combining therapies with different mechanisms of action could be the best approach for difficult-to-treat gout. “The problem we face in clinical practice is how to treat difficult-to-treat patients,” he said. He referenced his own PhD thesis, which showed both high urinary uric acid output and underexcretion among patients with gout.

Pérez-Ruiz agreed that XO inhibitors should be used as first-line therapy but noted that the effect of allopurinol tapers off at higher doses. “If you use very high doses of allopurinol, you cannot expect to get much more effect,” he said. This is also true of febuxostat, he said.

He showed another study that illustrated difficulties in achieving target serum urate level with intensive therapy. “Even using a high dose of allopurinol, if you would like to get lower than 3 mg/dL for intensive therapy, close to 50% of patients will fail,” he said.

Pérez-Ruiz described a strategy of combining XO inhibitors with a uricosuric therapy, creating what he called a “uricase-like effect” on serum uric acid levels. Ruiz-Perez uses high-dose febuxostat in patients with chronic kidney disease who cannot be given uricosuric agents. “You can go to very low [serum urate levels] by raising up the doses,” he said.

He does not believe that allopurinol is the best agent for combination therapy in the treatment of tophaceous deposits. Instead, he favors combinations with febuxostat. He presented his own experience with 12 patients with very severe tophaceous gout who he treated with a combination of febuxostat and benzbromarone, which reduced serum urate to just over 2 mg/dL. “So this is a pegloticase-like effect [that is] very useful for tophaceous gout,” he said.

In her response, Stamp noted that most of the studies presented by Pérez-Ruiz showed XO inhibitors as first-line therapies, with other medications added on. “I think I heard Fernando agree with me. In just about all of those slides, he showed that a xanthine oxidase inhibitor was the first-line therapy, and subsequently a uricosuric was added,” she said.

Still, Stamp took issue with the idea that serum urate needs to get as low as Pérez-Ruiz advocated for. “What’s the risk associated with getting a serum urate to that level? I’m not sure that a sustained serum urate of around 1 [mg/dL] is necessarily good in the long term,” she said.

Stamp also pointed out the potential risks of polypharmacy, along with adherence issues. “If we can give our patients one therapy, one drug that’s going to get them to a target that we know is going to have beneficial long-term effects, that’s going to help improve our adherence. Maybe we are coming to a new era of [treatment, with] remission induction driving the serum urate very low, and then a maintenance therapy where we can back off. But irrespective, if you use that strategy, Fernando nicely showed that every time you’re going to start with a xanthine oxidase inhibitor,” she said.

After the debate, audience members voted again, and this time the result was 66% in favor of XO inhibitors as a first-line treatment.

Pérez-Ruiz is an adviser for Arthrosi, LG, Novartis, Protalix, and SOBI. He is a speaker for Menarini Central America and the Spanish Foundation for Rheumatology and has received funding from Cruces Rheumatology Association. Stamp did not disclose any financial relationships.

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

The Food and Drug Administration (FDA) has approved tapinarof cream, 1% for the treatment of atopic dermatitis (AD) in adults and pediatric patients 2 years of age and older.

An aryl hydrocarbon receptor agonist, tapinarof cream, 1% was first approved in May 2022 for the topical treatment of plaque psoriasis in adults.

According to a press release from the manufacturer, Organon — which markets tapinarof cream, 1%, under the brand name VTAMA — the new indication for AD is based on results from the ADORING pivotal studies. In ADORING 1, the proportion of patients in the tapinarof cream, 1% treatment group who achieved a score of clear (0) or almost clear (1) and a minimum 2-grade improvement from baseline at week 8 on the Validated Investigator Global Assessment for AD was 45.4%, compared with 13.9% of patients who received vehicle alone. ADORING 2 yielded similar results (46.4% vs 18.0%, respectively; P < .0001 for both associations).

Secondary endpoints measured at week 8 also significantly favored the treatment group over the vehicle group, including the Eczema Area and Severity Index score improvement of at least 75% from baseline and achievement of a ≥ 4-point improvement in the patient-reported Peak Pruritus Numerical Rating Scale from baseline.

The most common adverse reactions (incidence ≥ 1%) were upper respiratory tract infection (12%), folliculitis (9%), lower respiratory tract infection (5%), headache (4%), asthma (2%), vomiting (2%), ear infection (2%), pain in extremity (2%), and abdominal pain (1%), according to the release.

Among 728 patients in the ADORING studies who enrolled in an open-label 48-week extension trial (ADORING 3), 378 entered with or achieved complete disease clearance and discontinued treatment. In this subset of patients, the mean duration of the first treatment-free interval was approximately 80 consecutive days, according to the release.

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

The Food and Drug Administration (FDA) has approved tapinarof cream, 1% for the treatment of atopic dermatitis (AD) in adults and pediatric patients 2 years of age and older.

An aryl hydrocarbon receptor agonist, tapinarof cream, 1% was first approved in May 2022 for the topical treatment of plaque psoriasis in adults.

According to a press release from the manufacturer, Organon — which markets tapinarof cream, 1%, under the brand name VTAMA — the new indication for AD is based on results from the ADORING pivotal studies. In ADORING 1, the proportion of patients in the tapinarof cream, 1% treatment group who achieved a score of clear (0) or almost clear (1) and a minimum 2-grade improvement from baseline at week 8 on the Validated Investigator Global Assessment for AD was 45.4%, compared with 13.9% of patients who received vehicle alone. ADORING 2 yielded similar results (46.4% vs 18.0%, respectively; P < .0001 for both associations).

Secondary endpoints measured at week 8 also significantly favored the treatment group over the vehicle group, including the Eczema Area and Severity Index score improvement of at least 75% from baseline and achievement of a ≥ 4-point improvement in the patient-reported Peak Pruritus Numerical Rating Scale from baseline.

The most common adverse reactions (incidence ≥ 1%) were upper respiratory tract infection (12%), folliculitis (9%), lower respiratory tract infection (5%), headache (4%), asthma (2%), vomiting (2%), ear infection (2%), pain in extremity (2%), and abdominal pain (1%), according to the release.

Among 728 patients in the ADORING studies who enrolled in an open-label 48-week extension trial (ADORING 3), 378 entered with or achieved complete disease clearance and discontinued treatment. In this subset of patients, the mean duration of the first treatment-free interval was approximately 80 consecutive days, according to the release.

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

The Food and Drug Administration (FDA) has approved tapinarof cream, 1% for the treatment of atopic dermatitis (AD) in adults and pediatric patients 2 years of age and older.

An aryl hydrocarbon receptor agonist, tapinarof cream, 1% was first approved in May 2022 for the topical treatment of plaque psoriasis in adults.

According to a press release from the manufacturer, Organon — which markets tapinarof cream, 1%, under the brand name VTAMA — the new indication for AD is based on results from the ADORING pivotal studies. In ADORING 1, the proportion of patients in the tapinarof cream, 1% treatment group who achieved a score of clear (0) or almost clear (1) and a minimum 2-grade improvement from baseline at week 8 on the Validated Investigator Global Assessment for AD was 45.4%, compared with 13.9% of patients who received vehicle alone. ADORING 2 yielded similar results (46.4% vs 18.0%, respectively; P < .0001 for both associations).

Secondary endpoints measured at week 8 also significantly favored the treatment group over the vehicle group, including the Eczema Area and Severity Index score improvement of at least 75% from baseline and achievement of a ≥ 4-point improvement in the patient-reported Peak Pruritus Numerical Rating Scale from baseline.

The most common adverse reactions (incidence ≥ 1%) were upper respiratory tract infection (12%), folliculitis (9%), lower respiratory tract infection (5%), headache (4%), asthma (2%), vomiting (2%), ear infection (2%), pain in extremity (2%), and abdominal pain (1%), according to the release.

Among 728 patients in the ADORING studies who enrolled in an open-label 48-week extension trial (ADORING 3), 378 entered with or achieved complete disease clearance and discontinued treatment. In this subset of patients, the mean duration of the first treatment-free interval was approximately 80 consecutive days, according to the release.

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

Long COVID can have an enormous impact on people’s ability to work, particularly if they do not have workplace accommodations and support. Although some patients experience symptoms so severe that they cannot work under any conditions, medical providers and employers can help ensure many patients with long COVID can stay in the workforce.

Long COVID is an infection-associated chronic condition that occurs after SARS-CoV-2 infection and is present for at least 3 months as a continuous, relapsing and remitting, or progressive disease state that affects one or more organ systems. By the end of 2023, at least 400 million people worldwide were estimated to have long COVID.

As members of the Patient-Led Research Collaborative, an international group of more than 60 researchers and health advocates living with long COVID and other infection-associated chronic conditions, we have published one of the first research studies of people with long COVID and their desire to work, the specific needs they have, and what doctors and employers can do to create a path for returning to the workforce. 

In our recent paper, we document the barriers and facilitators that individuals living with long COVID experience when attempting to return to work. Our recommendations are based on these findings and include recommendations for both medical providers and employers. 

If you are a medical provider:

• Ensure you adequately document your patients’ COVID cases, any long COVID diagnoses, and the functional impairment that long COVID causes. Remember that you can diagnose a patient with long COVID on the basis of their symptoms, and clinical guidelines do not require a record of a positive COVID-19 test, which many patients lack owing to testing barriers.
• Keep up to date on research on long COVID and related infection-associated chronic conditions — for example, through the Project ECHO Long COVID and Fatiguing Illness Recovery Program — and learn about pacing and other treatment options.

If you are an employer: 

• Utilize a return-to-work model in which any worker with suspected or confirmed COVID discusses support they may need with their employer when they return to work, with additional check-in dates scheduled to reevaluate supports as needed. Planning for this collaborative and iterative evaluation of return-to-work supports for all workers with COVID-19 is important because it may not be immediately clear to a worker whether they have developed long COVID or are generally recuperating from the illness.
• Do not require medical documentation of a SARS-CoV-2 infection or a Long COVID diagnosis to access accommodations — this is owing to disparities in accessing documentation.
• Tailor job responsibilities, provide remote options, allow flexible hours, and provide longer-range deadlines to account for symptoms for people with long COVID and other infection-associated chronic conditions.
• Provide accommodations to any caregivers of people with long COVID in your workplace.
• If requiring in-person work, make the workplace as safe as possible through ventilation and masking requirements, which will help ensure fewer of your workers develop long COVID, and those already with infection-associated chronic conditions will not get worse.

Our findings and recommendations are specific to long COVID, but they can and should apply to other disabilities. Given that our study’s sample was predominately White and working in jobs that did not require substantial physical labor, additional recommendations may be needed for other populations and workers who have labor-intensive jobs.

 

510 Study Participants

Long COVID is characterized as a relapsing-remitting illness, often described as episodic, in which an individual’s symptoms may fluctuate. Symptoms can become more or less severe depending on tasks, exertion, and social support in addition to physiologic processes and medical intervention. In our paper, we illustrate how the long COVID return-to-work experience and individuals’ symptoms can be shaped by workplace, home, and medical environments. 

We randomly selected 510 participants from a global survey of people living with long COVID and systematically analyzed their open-ended responses using established qualitative analysis methods. In this study, we specifically analyzed what patients wrote about their return-to-work experiences, considering how work experiences and relapsing and remitting long COVID symptoms intersected with personal lives and medical care. 

Most of the study participants identified as White, were 30-60 years old (ie, in their key earning years), and had at least a baccalaureate degree. Participants lived in the United States (38%), United Kingdom (25%), continental Europe (8%), Canada (4%), or other countries (25%). Most participants worked in professions that did not require substantial physical labor, and individuals in those fields may experience even greater return-to-work barriers than are reported in this study.

 

Key Findings

Through our qualitative analysis, we identified four primary return-to-work themes: 

1. People living with long COVID have a strong desire and financial need to return to work. 

The participants in our study described how they had experienced financial hardship because they could not successfully return to work and may have incurred new expenses with long COVID. They also often wrote how they wanted to return to work because their jobs provided meaning and structure for their lives. Some people in this study shared how they had tried to return to their jobs but relapsed. As a result, they considered leaving the workforce.

2. Workers’ long COVID symptoms intersect with organization of work and home life.

Most of the people in our study were employed in positions that did not require substantial physical labor. Even so, workers described how their long COVID symptoms were exacerbated by some job tasks. Computer screen time; reading dense material or writing (including emails); and conversations and meetings, regardless of whether they were in-person or via phone or video conferencing, could trigger or make symptoms worse. Workers who needed to stand for long periods of time, such as teachers and healthcare workers, and workers who needed to do lifting as part of their jobs described how these requirements were too taxing and could lead to relapses.

Because of the relapsing and remitting nature of many long COVID symptoms, people reported how it could be difficult to predict how job tasks, long hours, or pressing deadlines may exacerbate symptoms, which would require them to take time off work. For these participants, “pushing through” symptoms only made the symptoms worse. However, people in the study who were allowed to work from home reported how pacing, elevating their legs, and conserving energy (especially by not commuting) was key to doing their jobs well.

Some people in the study described how they were only able to return to work because they had substantial support from family or partners at home. These individuals shared how the people they lived with did most of the cooking, cleaning, and other household tasks so that the person living with long COVID could conserve their energy for work. This reorganization of home life notably shifted household tasks and caregiving to other people in the household, but without this shift, the individual’s long COVID symptoms may be too severe to work.

3. People with long COVID experience disbelief and stigma at work and healthcare settings.

Some people in our study described how their colleagues, supervisors, and human resource managers insinuated that they were fabricating or exaggerating their symptoms. This made it hard for workers to communicate what support they needed and could limit access to necessary work accommodations.

Many people in our study also described how medical providers did not believe that they had long COVID despite experiencing debilitating symptoms, often because they did not have a positive COVID-19 test to prove they had had an acute infection. Many people with long COVID may not have a positive COVID-19 test because:

• They could not access a test because testing access was limited at the start of the COVID-19 pandemic, there are transportation and cost barriers to tests, many health insurance providers no longer cover tests; and there are fewer public testing sites since the World Health Organization declared an end to the public health emergency;
• There is a high probability of false-negative results for viral and antibody tests (especially during the first wave of the pandemic and for individuals with limited immune response); and
• People can develop long COVID after asymptomatic acute infection.

Although healthcare providers can provide a long COVID diagnosis without a positive COVID-19 test on the basis of a patient’s presentation of symptoms and clinical history, many people in our study said that their providers would not provide this diagnosis, which restricted access to worker’s compensation, paid time off, and job accommodations.

Many people in the study also reported that their medical providers misdiagnosed them with a mental health disorder, such as anxiety, instead of long COVID. Although some people with long COVID may experience poor mental health as a natural consequence of dealing with a debilitating medical condition or may have neuropsychiatric symptoms as part of their long COVID, long COVID is not caused by an underlying psychiatric illness.

4. Support of medical providers is key to successful return to work for people living with long COVID.

Some people in our study described how they were able to get workplace accommodations or access workers’ compensation or sick leave because their medical providers recognized they had long COVID and provided them with this documentation. Some of these participants did not have a positive COVID-19 test, but their medical providers were able to diagnose them with long COVID on the basis of symptom presentation and clinical history. This documentation was critical for helping workers remain financially stable and able to return to work.

 

Conclusion

While we continue to search for treatment and cures for long COVID and work to provide a robust social safety net, it is crucial to address the stigma, inaccessibility, and lack of support often experienced by patients in their workplaces. Disabled people have long faced these issues; long COVID may be an opportunity to revolutionize the workplace to ensure an inclusive and accessible environment that can improve the lives of all workers.

For more on how to best be inclusive of employees with long COVID, read Harvard Business Review’s “Long Covid at Work: A Manager’s Guide” and visit the Job Accommodation Network webpage dedicated to long COVID.

Additional discussion about our study and applying the findings to improve work and medical care can be found by listening to the Healthy Work podcast episode titled “Supporting Long COVID at Work.” 

 

Elisabeth Stelson, Gina Assaf, and Lisa McCorkell are members of the Patient-Led Research Collaborative, an international group of more than 60 researchers. Dr Stelson, Postdoctoral Research Fellow, Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, has disclosed no relevant financial relationships. Gina Assaf is Research Lead, Patient-Led Research Collaborative, Washington, DC. Lisa McCorkell is a long COVID patient; Cofounder, Team Lead, Researcher, Patient-Led Research Collaborative, Washington, DC.

A version of this article appeared on Medscape.com.

Long COVID can have an enormous impact on people’s ability to work, particularly if they do not have workplace accommodations and support. Although some patients experience symptoms so severe that they cannot work under any conditions, medical providers and employers can help ensure many patients with long COVID can stay in the workforce.

Long COVID is an infection-associated chronic condition that occurs after SARS-CoV-2 infection and is present for at least 3 months as a continuous, relapsing and remitting, or progressive disease state that affects one or more organ systems. By the end of 2023, at least 400 million people worldwide were estimated to have long COVID.

As members of the Patient-Led Research Collaborative, an international group of more than 60 researchers and health advocates living with long COVID and other infection-associated chronic conditions, we have published one of the first research studies of people with long COVID and their desire to work, the specific needs they have, and what doctors and employers can do to create a path for returning to the workforce. 

In our recent paper, we document the barriers and facilitators that individuals living with long COVID experience when attempting to return to work. Our recommendations are based on these findings and include recommendations for both medical providers and employers. 

If you are a medical provider:

• Ensure you adequately document your patients’ COVID cases, any long COVID diagnoses, and the functional impairment that long COVID causes. Remember that you can diagnose a patient with long COVID on the basis of their symptoms, and clinical guidelines do not require a record of a positive COVID-19 test, which many patients lack owing to testing barriers.
• Keep up to date on research on long COVID and related infection-associated chronic conditions — for example, through the Project ECHO Long COVID and Fatiguing Illness Recovery Program — and learn about pacing and other treatment options.

If you are an employer: 

• Utilize a return-to-work model in which any worker with suspected or confirmed COVID discusses support they may need with their employer when they return to work, with additional check-in dates scheduled to reevaluate supports as needed. Planning for this collaborative and iterative evaluation of return-to-work supports for all workers with COVID-19 is important because it may not be immediately clear to a worker whether they have developed long COVID or are generally recuperating from the illness.
• Do not require medical documentation of a SARS-CoV-2 infection or a Long COVID diagnosis to access accommodations — this is owing to disparities in accessing documentation.
• Tailor job responsibilities, provide remote options, allow flexible hours, and provide longer-range deadlines to account for symptoms for people with long COVID and other infection-associated chronic conditions.
• Provide accommodations to any caregivers of people with long COVID in your workplace.
• If requiring in-person work, make the workplace as safe as possible through ventilation and masking requirements, which will help ensure fewer of your workers develop long COVID, and those already with infection-associated chronic conditions will not get worse.

Our findings and recommendations are specific to long COVID, but they can and should apply to other disabilities. Given that our study’s sample was predominately White and working in jobs that did not require substantial physical labor, additional recommendations may be needed for other populations and workers who have labor-intensive jobs.

 

510 Study Participants

Long COVID is characterized as a relapsing-remitting illness, often described as episodic, in which an individual’s symptoms may fluctuate. Symptoms can become more or less severe depending on tasks, exertion, and social support in addition to physiologic processes and medical intervention. In our paper, we illustrate how the long COVID return-to-work experience and individuals’ symptoms can be shaped by workplace, home, and medical environments. 

We randomly selected 510 participants from a global survey of people living with long COVID and systematically analyzed their open-ended responses using established qualitative analysis methods. In this study, we specifically analyzed what patients wrote about their return-to-work experiences, considering how work experiences and relapsing and remitting long COVID symptoms intersected with personal lives and medical care. 

Most of the study participants identified as White, were 30-60 years old (ie, in their key earning years), and had at least a baccalaureate degree. Participants lived in the United States (38%), United Kingdom (25%), continental Europe (8%), Canada (4%), or other countries (25%). Most participants worked in professions that did not require substantial physical labor, and individuals in those fields may experience even greater return-to-work barriers than are reported in this study.

 

Key Findings

Through our qualitative analysis, we identified four primary return-to-work themes: 

1. People living with long COVID have a strong desire and financial need to return to work. 

The participants in our study described how they had experienced financial hardship because they could not successfully return to work and may have incurred new expenses with long COVID. They also often wrote how they wanted to return to work because their jobs provided meaning and structure for their lives. Some people in this study shared how they had tried to return to their jobs but relapsed. As a result, they considered leaving the workforce.

2. Workers’ long COVID symptoms intersect with organization of work and home life.

Most of the people in our study were employed in positions that did not require substantial physical labor. Even so, workers described how their long COVID symptoms were exacerbated by some job tasks. Computer screen time; reading dense material or writing (including emails); and conversations and meetings, regardless of whether they were in-person or via phone or video conferencing, could trigger or make symptoms worse. Workers who needed to stand for long periods of time, such as teachers and healthcare workers, and workers who needed to do lifting as part of their jobs described how these requirements were too taxing and could lead to relapses.

Because of the relapsing and remitting nature of many long COVID symptoms, people reported how it could be difficult to predict how job tasks, long hours, or pressing deadlines may exacerbate symptoms, which would require them to take time off work. For these participants, “pushing through” symptoms only made the symptoms worse. However, people in the study who were allowed to work from home reported how pacing, elevating their legs, and conserving energy (especially by not commuting) was key to doing their jobs well.

Some people in the study described how they were only able to return to work because they had substantial support from family or partners at home. These individuals shared how the people they lived with did most of the cooking, cleaning, and other household tasks so that the person living with long COVID could conserve their energy for work. This reorganization of home life notably shifted household tasks and caregiving to other people in the household, but without this shift, the individual’s long COVID symptoms may be too severe to work.

3. People with long COVID experience disbelief and stigma at work and healthcare settings.

Some people in our study described how their colleagues, supervisors, and human resource managers insinuated that they were fabricating or exaggerating their symptoms. This made it hard for workers to communicate what support they needed and could limit access to necessary work accommodations.

Many people in our study also described how medical providers did not believe that they had long COVID despite experiencing debilitating symptoms, often because they did not have a positive COVID-19 test to prove they had had an acute infection. Many people with long COVID may not have a positive COVID-19 test because:

• They could not access a test because testing access was limited at the start of the COVID-19 pandemic, there are transportation and cost barriers to tests, many health insurance providers no longer cover tests; and there are fewer public testing sites since the World Health Organization declared an end to the public health emergency;
• There is a high probability of false-negative results for viral and antibody tests (especially during the first wave of the pandemic and for individuals with limited immune response); and
• People can develop long COVID after asymptomatic acute infection.

Although healthcare providers can provide a long COVID diagnosis without a positive COVID-19 test on the basis of a patient’s presentation of symptoms and clinical history, many people in our study said that their providers would not provide this diagnosis, which restricted access to worker’s compensation, paid time off, and job accommodations.

Many people in the study also reported that their medical providers misdiagnosed them with a mental health disorder, such as anxiety, instead of long COVID. Although some people with long COVID may experience poor mental health as a natural consequence of dealing with a debilitating medical condition or may have neuropsychiatric symptoms as part of their long COVID, long COVID is not caused by an underlying psychiatric illness.

4. Support of medical providers is key to successful return to work for people living with long COVID.

Some people in our study described how they were able to get workplace accommodations or access workers’ compensation or sick leave because their medical providers recognized they had long COVID and provided them with this documentation. Some of these participants did not have a positive COVID-19 test, but their medical providers were able to diagnose them with long COVID on the basis of symptom presentation and clinical history. This documentation was critical for helping workers remain financially stable and able to return to work.

 

Conclusion

While we continue to search for treatment and cures for long COVID and work to provide a robust social safety net, it is crucial to address the stigma, inaccessibility, and lack of support often experienced by patients in their workplaces. Disabled people have long faced these issues; long COVID may be an opportunity to revolutionize the workplace to ensure an inclusive and accessible environment that can improve the lives of all workers.

For more on how to best be inclusive of employees with long COVID, read Harvard Business Review’s “Long Covid at Work: A Manager’s Guide” and visit the Job Accommodation Network webpage dedicated to long COVID.

Additional discussion about our study and applying the findings to improve work and medical care can be found by listening to the Healthy Work podcast episode titled “Supporting Long COVID at Work.” 

 

Elisabeth Stelson, Gina Assaf, and Lisa McCorkell are members of the Patient-Led Research Collaborative, an international group of more than 60 researchers. Dr Stelson, Postdoctoral Research Fellow, Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, has disclosed no relevant financial relationships. Gina Assaf is Research Lead, Patient-Led Research Collaborative, Washington, DC. Lisa McCorkell is a long COVID patient; Cofounder, Team Lead, Researcher, Patient-Led Research Collaborative, Washington, DC.

A version of this article appeared on Medscape.com.

Long COVID can have an enormous impact on people’s ability to work, particularly if they do not have workplace accommodations and support. Although some patients experience symptoms so severe that they cannot work under any conditions, medical providers and employers can help ensure many patients with long COVID can stay in the workforce.

Long COVID is an infection-associated chronic condition that occurs after SARS-CoV-2 infection and is present for at least 3 months as a continuous, relapsing and remitting, or progressive disease state that affects one or more organ systems. By the end of 2023, at least 400 million people worldwide were estimated to have long COVID.

As members of the Patient-Led Research Collaborative, an international group of more than 60 researchers and health advocates living with long COVID and other infection-associated chronic conditions, we have published one of the first research studies of people with long COVID and their desire to work, the specific needs they have, and what doctors and employers can do to create a path for returning to the workforce. 

In our recent paper, we document the barriers and facilitators that individuals living with long COVID experience when attempting to return to work. Our recommendations are based on these findings and include recommendations for both medical providers and employers. 

If you are a medical provider:

• Ensure you adequately document your patients’ COVID cases, any long COVID diagnoses, and the functional impairment that long COVID causes. Remember that you can diagnose a patient with long COVID on the basis of their symptoms, and clinical guidelines do not require a record of a positive COVID-19 test, which many patients lack owing to testing barriers.
• Keep up to date on research on long COVID and related infection-associated chronic conditions — for example, through the Project ECHO Long COVID and Fatiguing Illness Recovery Program — and learn about pacing and other treatment options.

If you are an employer: 

• Utilize a return-to-work model in which any worker with suspected or confirmed COVID discusses support they may need with their employer when they return to work, with additional check-in dates scheduled to reevaluate supports as needed. Planning for this collaborative and iterative evaluation of return-to-work supports for all workers with COVID-19 is important because it may not be immediately clear to a worker whether they have developed long COVID or are generally recuperating from the illness.
• Do not require medical documentation of a SARS-CoV-2 infection or a Long COVID diagnosis to access accommodations — this is owing to disparities in accessing documentation.
• Tailor job responsibilities, provide remote options, allow flexible hours, and provide longer-range deadlines to account for symptoms for people with long COVID and other infection-associated chronic conditions.
• Provide accommodations to any caregivers of people with long COVID in your workplace.
• If requiring in-person work, make the workplace as safe as possible through ventilation and masking requirements, which will help ensure fewer of your workers develop long COVID, and those already with infection-associated chronic conditions will not get worse.

Our findings and recommendations are specific to long COVID, but they can and should apply to other disabilities. Given that our study’s sample was predominately White and working in jobs that did not require substantial physical labor, additional recommendations may be needed for other populations and workers who have labor-intensive jobs.

 

510 Study Participants

Long COVID is characterized as a relapsing-remitting illness, often described as episodic, in which an individual’s symptoms may fluctuate. Symptoms can become more or less severe depending on tasks, exertion, and social support in addition to physiologic processes and medical intervention. In our paper, we illustrate how the long COVID return-to-work experience and individuals’ symptoms can be shaped by workplace, home, and medical environments. 

We randomly selected 510 participants from a global survey of people living with long COVID and systematically analyzed their open-ended responses using established qualitative analysis methods. In this study, we specifically analyzed what patients wrote about their return-to-work experiences, considering how work experiences and relapsing and remitting long COVID symptoms intersected with personal lives and medical care. 

Most of the study participants identified as White, were 30-60 years old (ie, in their key earning years), and had at least a baccalaureate degree. Participants lived in the United States (38%), United Kingdom (25%), continental Europe (8%), Canada (4%), or other countries (25%). Most participants worked in professions that did not require substantial physical labor, and individuals in those fields may experience even greater return-to-work barriers than are reported in this study.

 

Key Findings

Through our qualitative analysis, we identified four primary return-to-work themes: 

1. People living with long COVID have a strong desire and financial need to return to work. 

The participants in our study described how they had experienced financial hardship because they could not successfully return to work and may have incurred new expenses with long COVID. They also often wrote how they wanted to return to work because their jobs provided meaning and structure for their lives. Some people in this study shared how they had tried to return to their jobs but relapsed. As a result, they considered leaving the workforce.

2. Workers’ long COVID symptoms intersect with organization of work and home life.

Most of the people in our study were employed in positions that did not require substantial physical labor. Even so, workers described how their long COVID symptoms were exacerbated by some job tasks. Computer screen time; reading dense material or writing (including emails); and conversations and meetings, regardless of whether they were in-person or via phone or video conferencing, could trigger or make symptoms worse. Workers who needed to stand for long periods of time, such as teachers and healthcare workers, and workers who needed to do lifting as part of their jobs described how these requirements were too taxing and could lead to relapses.

Because of the relapsing and remitting nature of many long COVID symptoms, people reported how it could be difficult to predict how job tasks, long hours, or pressing deadlines may exacerbate symptoms, which would require them to take time off work. For these participants, “pushing through” symptoms only made the symptoms worse. However, people in the study who were allowed to work from home reported how pacing, elevating their legs, and conserving energy (especially by not commuting) was key to doing their jobs well.

Some people in the study described how they were only able to return to work because they had substantial support from family or partners at home. These individuals shared how the people they lived with did most of the cooking, cleaning, and other household tasks so that the person living with long COVID could conserve their energy for work. This reorganization of home life notably shifted household tasks and caregiving to other people in the household, but without this shift, the individual’s long COVID symptoms may be too severe to work.

3. People with long COVID experience disbelief and stigma at work and healthcare settings.

Some people in our study described how their colleagues, supervisors, and human resource managers insinuated that they were fabricating or exaggerating their symptoms. This made it hard for workers to communicate what support they needed and could limit access to necessary work accommodations.

Many people in our study also described how medical providers did not believe that they had long COVID despite experiencing debilitating symptoms, often because they did not have a positive COVID-19 test to prove they had had an acute infection. Many people with long COVID may not have a positive COVID-19 test because:

• They could not access a test because testing access was limited at the start of the COVID-19 pandemic, there are transportation and cost barriers to tests, many health insurance providers no longer cover tests; and there are fewer public testing sites since the World Health Organization declared an end to the public health emergency;
• There is a high probability of false-negative results for viral and antibody tests (especially during the first wave of the pandemic and for individuals with limited immune response); and
• People can develop long COVID after asymptomatic acute infection.

Although healthcare providers can provide a long COVID diagnosis without a positive COVID-19 test on the basis of a patient’s presentation of symptoms and clinical history, many people in our study said that their providers would not provide this diagnosis, which restricted access to worker’s compensation, paid time off, and job accommodations.

Many people in the study also reported that their medical providers misdiagnosed them with a mental health disorder, such as anxiety, instead of long COVID. Although some people with long COVID may experience poor mental health as a natural consequence of dealing with a debilitating medical condition or may have neuropsychiatric symptoms as part of their long COVID, long COVID is not caused by an underlying psychiatric illness.

4. Support of medical providers is key to successful return to work for people living with long COVID.

Some people in our study described how they were able to get workplace accommodations or access workers’ compensation or sick leave because their medical providers recognized they had long COVID and provided them with this documentation. Some of these participants did not have a positive COVID-19 test, but their medical providers were able to diagnose them with long COVID on the basis of symptom presentation and clinical history. This documentation was critical for helping workers remain financially stable and able to return to work.

 

Conclusion

While we continue to search for treatment and cures for long COVID and work to provide a robust social safety net, it is crucial to address the stigma, inaccessibility, and lack of support often experienced by patients in their workplaces. Disabled people have long faced these issues; long COVID may be an opportunity to revolutionize the workplace to ensure an inclusive and accessible environment that can improve the lives of all workers.

For more on how to best be inclusive of employees with long COVID, read Harvard Business Review’s “Long Covid at Work: A Manager’s Guide” and visit the Job Accommodation Network webpage dedicated to long COVID.

Additional discussion about our study and applying the findings to improve work and medical care can be found by listening to the Healthy Work podcast episode titled “Supporting Long COVID at Work.” 

 

Elisabeth Stelson, Gina Assaf, and Lisa McCorkell are members of the Patient-Led Research Collaborative, an international group of more than 60 researchers. Dr Stelson, Postdoctoral Research Fellow, Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, has disclosed no relevant financial relationships. Gina Assaf is Research Lead, Patient-Led Research Collaborative, Washington, DC. Lisa McCorkell is a long COVID patient; Cofounder, Team Lead, Researcher, Patient-Led Research Collaborative, Washington, DC.

A version of this article appeared on Medscape.com.

TOPLINE:

Virtual visits for urinary tract infections (UTIs) increased by more than 600% from 2015 to 2022, with overall UTI encounters growing by 325.9%. The rate of antibiotic dispensation climbed by 227.3% per 1000 patients, outpacing the 159.8% increase in positive urine cultures.

METHODOLOGY:

• Researchers conducted a retrospective cohort study analyzing 1,220,698 UTI encounters among 428,855 nonpregnant women aged ≥ 18 years at Kaiser Permanente Southern California from 2015 to 2022.
• Analysis included outpatient UTI encounters in ambulatory and urgent care settings, excluding emergency and inpatient visits.
• Data collection encompassed demographic information, urine tests, antibiotic dispensation, and UTI diagnoses using International Classification of Diseases, 9th and 10th Revision codes.
• Encounters conducted by physicians, physician assistants, nurse practitioners, and registered nurses through in-person, phone, video, and health portal platforms were evaluated.

TAKEAWAY:

• Virtual encounters grew by 603.2% compared with a 122.8% increase for in-person visits, with virtual visits accounting for 60% (733,263) of all UTI encounters.
• The rate of UTI encounters per 1000 adult female patients increased by 241.6%, while membership in the health system grew by only 24.4%.
• Antibiotics were prescribed without urine testing in 42.5% (519,135) of encounters, and among encounters with both antibiotic dispensation and urine testing, 57.1% (278,903) had a positive culture.
• According to the authors, the increasing rate of antibiotic dispensation surpassed the growth in positive urine culture rates, suggesting increased use of empiric antibiotics.

IN PRACTICE:

“Our findings underscore the importance of balancing telemedicine’s accessibility with maintaining antibiotic stewardship and highlight the need for updated guidelines,” wrote the authors of the study. An accompanying editorial said, “Unfortunately, our misguided conceptual model has led to several decades of UTI research focusing on bad bugs rather than investigating the natural host defenses, how we might boost these, what perturbs the ecosystem, and how microbial defense occurs within the bladder.”

SOURCE:

The study was led by Ghanshyam Yadav, MD, Kaiser Permanente Southern California in San Diego. It was published online in Obstetrics & Gynecology. The editorial, written by Nazema Y. Siddiqui, MD, MHSc, from the Department of Obstetrics and Gynecology, Duke University Medical Center, Durham, North Carolina, was also published in Obstetrics & Gynecology.

LIMITATIONS:

The retrospective design and analysis at the encounter level did not allow for control of patient and clinician clustering. The study was limited to a single health maintenance organization, which may affect the generalizability of the findings.

DISCLOSURES:

This research received support through a grant from the Regional Research Committee of Kaiser Permanente Southern California (RRC grant number: KP-RRC-20221002). Heidi Brown and Jasmine Tan-Kim disclosed receiving royalties from UpToDate. Additional disclosures are noted in the original article.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

TOPLINE:

Virtual visits for urinary tract infections (UTIs) increased by more than 600% from 2015 to 2022, with overall UTI encounters growing by 325.9%. The rate of antibiotic dispensation climbed by 227.3% per 1000 patients, outpacing the 159.8% increase in positive urine cultures.

METHODOLOGY:

• Researchers conducted a retrospective cohort study analyzing 1,220,698 UTI encounters among 428,855 nonpregnant women aged ≥ 18 years at Kaiser Permanente Southern California from 2015 to 2022.
• Analysis included outpatient UTI encounters in ambulatory and urgent care settings, excluding emergency and inpatient visits.
• Data collection encompassed demographic information, urine tests, antibiotic dispensation, and UTI diagnoses using International Classification of Diseases, 9th and 10th Revision codes.
• Encounters conducted by physicians, physician assistants, nurse practitioners, and registered nurses through in-person, phone, video, and health portal platforms were evaluated.

TAKEAWAY:

• Virtual encounters grew by 603.2% compared with a 122.8% increase for in-person visits, with virtual visits accounting for 60% (733,263) of all UTI encounters.
• The rate of UTI encounters per 1000 adult female patients increased by 241.6%, while membership in the health system grew by only 24.4%.
• Antibiotics were prescribed without urine testing in 42.5% (519,135) of encounters, and among encounters with both antibiotic dispensation and urine testing, 57.1% (278,903) had a positive culture.
• According to the authors, the increasing rate of antibiotic dispensation surpassed the growth in positive urine culture rates, suggesting increased use of empiric antibiotics.

IN PRACTICE:

“Our findings underscore the importance of balancing telemedicine’s accessibility with maintaining antibiotic stewardship and highlight the need for updated guidelines,” wrote the authors of the study. An accompanying editorial said, “Unfortunately, our misguided conceptual model has led to several decades of UTI research focusing on bad bugs rather than investigating the natural host defenses, how we might boost these, what perturbs the ecosystem, and how microbial defense occurs within the bladder.”

SOURCE:

The study was led by Ghanshyam Yadav, MD, Kaiser Permanente Southern California in San Diego. It was published online in Obstetrics & Gynecology. The editorial, written by Nazema Y. Siddiqui, MD, MHSc, from the Department of Obstetrics and Gynecology, Duke University Medical Center, Durham, North Carolina, was also published in Obstetrics & Gynecology.

LIMITATIONS:

The retrospective design and analysis at the encounter level did not allow for control of patient and clinician clustering. The study was limited to a single health maintenance organization, which may affect the generalizability of the findings.

DISCLOSURES:

This research received support through a grant from the Regional Research Committee of Kaiser Permanente Southern California (RRC grant number: KP-RRC-20221002). Heidi Brown and Jasmine Tan-Kim disclosed receiving royalties from UpToDate. Additional disclosures are noted in the original article.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

TOPLINE:

Virtual visits for urinary tract infections (UTIs) increased by more than 600% from 2015 to 2022, with overall UTI encounters growing by 325.9%. The rate of antibiotic dispensation climbed by 227.3% per 1000 patients, outpacing the 159.8% increase in positive urine cultures.

METHODOLOGY:

• Researchers conducted a retrospective cohort study analyzing 1,220,698 UTI encounters among 428,855 nonpregnant women aged ≥ 18 years at Kaiser Permanente Southern California from 2015 to 2022.
• Analysis included outpatient UTI encounters in ambulatory and urgent care settings, excluding emergency and inpatient visits.
• Data collection encompassed demographic information, urine tests, antibiotic dispensation, and UTI diagnoses using International Classification of Diseases, 9th and 10th Revision codes.
• Encounters conducted by physicians, physician assistants, nurse practitioners, and registered nurses through in-person, phone, video, and health portal platforms were evaluated.

TAKEAWAY:

• Virtual encounters grew by 603.2% compared with a 122.8% increase for in-person visits, with virtual visits accounting for 60% (733,263) of all UTI encounters.
• The rate of UTI encounters per 1000 adult female patients increased by 241.6%, while membership in the health system grew by only 24.4%.
• Antibiotics were prescribed without urine testing in 42.5% (519,135) of encounters, and among encounters with both antibiotic dispensation and urine testing, 57.1% (278,903) had a positive culture.
• According to the authors, the increasing rate of antibiotic dispensation surpassed the growth in positive urine culture rates, suggesting increased use of empiric antibiotics.

IN PRACTICE:

“Our findings underscore the importance of balancing telemedicine’s accessibility with maintaining antibiotic stewardship and highlight the need for updated guidelines,” wrote the authors of the study. An accompanying editorial said, “Unfortunately, our misguided conceptual model has led to several decades of UTI research focusing on bad bugs rather than investigating the natural host defenses, how we might boost these, what perturbs the ecosystem, and how microbial defense occurs within the bladder.”

SOURCE:

The study was led by Ghanshyam Yadav, MD, Kaiser Permanente Southern California in San Diego. It was published online in Obstetrics & Gynecology. The editorial, written by Nazema Y. Siddiqui, MD, MHSc, from the Department of Obstetrics and Gynecology, Duke University Medical Center, Durham, North Carolina, was also published in Obstetrics & Gynecology.

LIMITATIONS:

The retrospective design and analysis at the encounter level did not allow for control of patient and clinician clustering. The study was limited to a single health maintenance organization, which may affect the generalizability of the findings.

DISCLOSURES:

This research received support through a grant from the Regional Research Committee of Kaiser Permanente Southern California (RRC grant number: KP-RRC-20221002). Heidi Brown and Jasmine Tan-Kim disclosed receiving royalties from UpToDate. Additional disclosures are noted in the original article.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

This transcript has been edited for clarity. 

We often see urinary tract infections in primary care, so these guidelines for the prevention, diagnosis and management of urinary tract infection (UTI) are very helpful to reaffirm our knowledge in the areas where know what we’re doing and update our knowledge in areas of uncertainty. These guidelines are from a new group called the WikiGuidelines group. Ordinarily, I wouldn’t have considered reviewing one of these guidelines, but this one was published in JAMA Network Open. It is evidence based and covers the topic really well. 

Diagnosis. Order a urinalysis or a urine culture only if the patient is having symptoms of a UTI. This may seem obvious, but particularly among older individuals, in whom asymptomatic bacteriuria is very common and should not be treated, nonspecific symptoms such as just not feeling well for a day do not warrant obtaining a urinalysis and culture. With no clear way to distinguish between asymptomatic bacteriuria and a true UTI, the first step in making the diagnosis of a UTI accurately is ordering urine studies only in people who have a reasonable chance of having an infection.

The guideline suggests that the diagnosis of UTI should be primarily based on clinical symptoms. A urinalysis can provide further information, but the authors caution us against relying solely on the urinalysis. This is an incredibly important evidence-based recommendation. If you think about it, this supports the common practice of treating UTIs over the phone without having to see the patient or check a urinalysis. 

The rationale for this recommendation is that urinalysis is neither a sensitive nor specific test for UTI. The sensitivity of leukocyte esterase is only about 80%, and the specificity is even lower. For positive nitrite on urinalysis, the sensitivity is below 50%, meaning the test would be negative more than half the time when someone actually has a UTI. The specificity of urine nitrate is very high (more than 90%), so if the patient is nitrite positive, they clearly have a UTI. This means that a patient’s report of classic UTI symptoms — urinary burning, frequency, and urgency — is about as good if not a better indicator of a UTI than a urinalysis. 

The guidelines also say that in simple uncomplicated cystitis in healthy nonpregnant patients, routine urine cultures are not necessary. A fascinating meta-analysis in JAMA showed that, for women presenting to outpatient clinics with at least two symptoms of UTI and absence of vaginal discharge, there was a greater than 90% likelihood of having acute cystitis. A reminder here, however: If a woman is sexually active and at risk for sexually transmitted infections, then consider testing for STIs as well, because the symptoms of an STI can mimic those of a UTI.

Treatment. Treatment for UTI is usually empiric, with treatment initiated before the culture results are known and with cultures being done only for people with complicated infections, such as pyelonephritis, or with recurrent infections. Decisions about what to use for treatment can be influenced by local patterns of resistance and an individual’s risk factors for antimicrobial resistance. As a general rule, for uncomplicated cystitis, nitrofurantoin for 5 days is a reasonable first-line agent. Evidence of efficacy is good, and the risk for antimicrobial resistance is lower vs using antibiotics for other systemic infections. 

Other reasonable first-line agents for uncomplicated cystitis include trimethoprim-sulfamethoxazole (TMP-SMX) for 3 days; fosfomycin (oral) single dose; or a beta-lactam (most commonly a first generation cephalosporin), although evidence for duration is unclear. Also mentioned are two unfamiliar antibiotics: pivmecillinam (a beta-lactam agent recently approved by the Food and Drug Administration [FDA], given for 3 days) and gepotidacin (from a new class of antibiotic that is currently under FDA review). Fluoroquinolones should not usually be first-line agents unless other treatment options are not appropriate. 

It’s important to distinguish between uncomplicated cystitis and pyelonephritis. For pyelonephritis (infection of the upper urinary tract), the first decision has to do with setting for care, depending on how sick someone is, and the likelihood of gram-negative bacteremia — all of which help whether the patient needs to be hospitalized for intravenous antibiotics, or can be treated as an outpatient. Determine if they need to be admitted for intravenous antibiotics or whether they can be treated as an outpatient. For outpatient treatment of pyelonephritis, the guideline suggests that TMP-SMX or a first-generation cephalosporin are both reasonable first-line agents, with fluoroquinolones being a reasonable choice as well. Ceftriaxone is recommended for first-line therapy for patients who require intravenous treatment. 

People often forget that we can do a lot to prevent UTIs, particularly among women with recurrent UTIs. The prevention of UTIs has both nonpharmacologic and pharmacologic approaches.

Nonpharmacologic prevention. One nonpharmacologic strategy is increasing water intake. A randomized controlled trial in women with recurrent cystitis who drank less than 1.5 L of fluid a day showed that the women randomized to consume an additional 1.5 L of water daily had significantly reduced cystitis frequency — approximately 50%. Because this was the only randomized trial to show this effect, this is not a strong recommendation, but there is very little downside in healthy women, so increasing water intake is a reasonable recommendation.

Another commonly discussed intervention is the use of cranberry products. As it turns out, most prospective studies have shown that cranberry products can reduce the risk for symptomatic UTIs in women with recurrent UTI. 

Pharmacologic prevention. For postmenopausal women with recurrent UTI, topical vaginal estrogen has a strong base of evidence — more than 30 randomized trials — supporting its effectiveness in UTI: a 50%-90% reduction in the incidence of recurrent UTIs. Topical estrogen has minimal systemic absorption, and there are no concerning safety signals with respect to either thromboembolic disease or cancer (endometrial or breast). 

Methenamine hippurate is also recommended and is FDA-approved for prevention of UTIs. It works by releasing formaldehyde in the urine, leading to bacteriostasis, which is how it leads to a decrease in UTIs. Finally, postcoital or daily administration of TMP-SMX, nitrofurantoin, norfloxacin, and ciprofloxacin all have comparable efficacy for prophylaxis, with a meta-analysis showing a decrease in recurrence rate of approximately 85%. The guideline states that there is insufficient evidence to support the use of either probiotics or D-mannose to prevent UTIs. 

This is a wonderful update on a common problem. We all have a lot of clinical experience here.

Dr Skolnik, Department of Family Medicine, Sidney Kimmel Medical College of Thomas Jefferson University, Philadelphia; Associate Director, Department of Family Medicine, Abington Jefferson Health, Abington, Pennsylvania, disclosed ties with AstraZeneca, Teva, Eli Lilly, Boehringer Ingelheim, Sanofi, Sanofi Pasteur, GlaxoSmithKline, Merck, and Bayer. 

A version of this article appeared on Medscape.com.

This transcript has been edited for clarity. 

We often see urinary tract infections in primary care, so these guidelines for the prevention, diagnosis and management of urinary tract infection (UTI) are very helpful to reaffirm our knowledge in the areas where know what we’re doing and update our knowledge in areas of uncertainty. These guidelines are from a new group called the WikiGuidelines group. Ordinarily, I wouldn’t have considered reviewing one of these guidelines, but this one was published in JAMA Network Open. It is evidence based and covers the topic really well. 

Diagnosis. Order a urinalysis or a urine culture only if the patient is having symptoms of a UTI. This may seem obvious, but particularly among older individuals, in whom asymptomatic bacteriuria is very common and should not be treated, nonspecific symptoms such as just not feeling well for a day do not warrant obtaining a urinalysis and culture. With no clear way to distinguish between asymptomatic bacteriuria and a true UTI, the first step in making the diagnosis of a UTI accurately is ordering urine studies only in people who have a reasonable chance of having an infection.

The guideline suggests that the diagnosis of UTI should be primarily based on clinical symptoms. A urinalysis can provide further information, but the authors caution us against relying solely on the urinalysis. This is an incredibly important evidence-based recommendation. If you think about it, this supports the common practice of treating UTIs over the phone without having to see the patient or check a urinalysis. 

The rationale for this recommendation is that urinalysis is neither a sensitive nor specific test for UTI. The sensitivity of leukocyte esterase is only about 80%, and the specificity is even lower. For positive nitrite on urinalysis, the sensitivity is below 50%, meaning the test would be negative more than half the time when someone actually has a UTI. The specificity of urine nitrate is very high (more than 90%), so if the patient is nitrite positive, they clearly have a UTI. This means that a patient’s report of classic UTI symptoms — urinary burning, frequency, and urgency — is about as good if not a better indicator of a UTI than a urinalysis. 

The guidelines also say that in simple uncomplicated cystitis in healthy nonpregnant patients, routine urine cultures are not necessary. A fascinating meta-analysis in JAMA showed that, for women presenting to outpatient clinics with at least two symptoms of UTI and absence of vaginal discharge, there was a greater than 90% likelihood of having acute cystitis. A reminder here, however: If a woman is sexually active and at risk for sexually transmitted infections, then consider testing for STIs as well, because the symptoms of an STI can mimic those of a UTI.

Treatment. Treatment for UTI is usually empiric, with treatment initiated before the culture results are known and with cultures being done only for people with complicated infections, such as pyelonephritis, or with recurrent infections. Decisions about what to use for treatment can be influenced by local patterns of resistance and an individual’s risk factors for antimicrobial resistance. As a general rule, for uncomplicated cystitis, nitrofurantoin for 5 days is a reasonable first-line agent. Evidence of efficacy is good, and the risk for antimicrobial resistance is lower vs using antibiotics for other systemic infections. 

Other reasonable first-line agents for uncomplicated cystitis include trimethoprim-sulfamethoxazole (TMP-SMX) for 3 days; fosfomycin (oral) single dose; or a beta-lactam (most commonly a first generation cephalosporin), although evidence for duration is unclear. Also mentioned are two unfamiliar antibiotics: pivmecillinam (a beta-lactam agent recently approved by the Food and Drug Administration [FDA], given for 3 days) and gepotidacin (from a new class of antibiotic that is currently under FDA review). Fluoroquinolones should not usually be first-line agents unless other treatment options are not appropriate. 

It’s important to distinguish between uncomplicated cystitis and pyelonephritis. For pyelonephritis (infection of the upper urinary tract), the first decision has to do with setting for care, depending on how sick someone is, and the likelihood of gram-negative bacteremia — all of which help whether the patient needs to be hospitalized for intravenous antibiotics, or can be treated as an outpatient. Determine if they need to be admitted for intravenous antibiotics or whether they can be treated as an outpatient. For outpatient treatment of pyelonephritis, the guideline suggests that TMP-SMX or a first-generation cephalosporin are both reasonable first-line agents, with fluoroquinolones being a reasonable choice as well. Ceftriaxone is recommended for first-line therapy for patients who require intravenous treatment. 

People often forget that we can do a lot to prevent UTIs, particularly among women with recurrent UTIs. The prevention of UTIs has both nonpharmacologic and pharmacologic approaches.

Nonpharmacologic prevention. One nonpharmacologic strategy is increasing water intake. A randomized controlled trial in women with recurrent cystitis who drank less than 1.5 L of fluid a day showed that the women randomized to consume an additional 1.5 L of water daily had significantly reduced cystitis frequency — approximately 50%. Because this was the only randomized trial to show this effect, this is not a strong recommendation, but there is very little downside in healthy women, so increasing water intake is a reasonable recommendation.

Another commonly discussed intervention is the use of cranberry products. As it turns out, most prospective studies have shown that cranberry products can reduce the risk for symptomatic UTIs in women with recurrent UTI. 

Pharmacologic prevention. For postmenopausal women with recurrent UTI, topical vaginal estrogen has a strong base of evidence — more than 30 randomized trials — supporting its effectiveness in UTI: a 50%-90% reduction in the incidence of recurrent UTIs. Topical estrogen has minimal systemic absorption, and there are no concerning safety signals with respect to either thromboembolic disease or cancer (endometrial or breast). 

Methenamine hippurate is also recommended and is FDA-approved for prevention of UTIs. It works by releasing formaldehyde in the urine, leading to bacteriostasis, which is how it leads to a decrease in UTIs. Finally, postcoital or daily administration of TMP-SMX, nitrofurantoin, norfloxacin, and ciprofloxacin all have comparable efficacy for prophylaxis, with a meta-analysis showing a decrease in recurrence rate of approximately 85%. The guideline states that there is insufficient evidence to support the use of either probiotics or D-mannose to prevent UTIs. 

This is a wonderful update on a common problem. We all have a lot of clinical experience here.

Dr Skolnik, Department of Family Medicine, Sidney Kimmel Medical College of Thomas Jefferson University, Philadelphia; Associate Director, Department of Family Medicine, Abington Jefferson Health, Abington, Pennsylvania, disclosed ties with AstraZeneca, Teva, Eli Lilly, Boehringer Ingelheim, Sanofi, Sanofi Pasteur, GlaxoSmithKline, Merck, and Bayer. 

A version of this article appeared on Medscape.com.

This transcript has been edited for clarity. 

We often see urinary tract infections in primary care, so these guidelines for the prevention, diagnosis and management of urinary tract infection (UTI) are very helpful to reaffirm our knowledge in the areas where know what we’re doing and update our knowledge in areas of uncertainty. These guidelines are from a new group called the WikiGuidelines group. Ordinarily, I wouldn’t have considered reviewing one of these guidelines, but this one was published in JAMA Network Open. It is evidence based and covers the topic really well. 

Diagnosis. Order a urinalysis or a urine culture only if the patient is having symptoms of a UTI. This may seem obvious, but particularly among older individuals, in whom asymptomatic bacteriuria is very common and should not be treated, nonspecific symptoms such as just not feeling well for a day do not warrant obtaining a urinalysis and culture. With no clear way to distinguish between asymptomatic bacteriuria and a true UTI, the first step in making the diagnosis of a UTI accurately is ordering urine studies only in people who have a reasonable chance of having an infection.

The guideline suggests that the diagnosis of UTI should be primarily based on clinical symptoms. A urinalysis can provide further information, but the authors caution us against relying solely on the urinalysis. This is an incredibly important evidence-based recommendation. If you think about it, this supports the common practice of treating UTIs over the phone without having to see the patient or check a urinalysis. 

The rationale for this recommendation is that urinalysis is neither a sensitive nor specific test for UTI. The sensitivity of leukocyte esterase is only about 80%, and the specificity is even lower. For positive nitrite on urinalysis, the sensitivity is below 50%, meaning the test would be negative more than half the time when someone actually has a UTI. The specificity of urine nitrate is very high (more than 90%), so if the patient is nitrite positive, they clearly have a UTI. This means that a patient’s report of classic UTI symptoms — urinary burning, frequency, and urgency — is about as good if not a better indicator of a UTI than a urinalysis. 

The guidelines also say that in simple uncomplicated cystitis in healthy nonpregnant patients, routine urine cultures are not necessary. A fascinating meta-analysis in JAMA showed that, for women presenting to outpatient clinics with at least two symptoms of UTI and absence of vaginal discharge, there was a greater than 90% likelihood of having acute cystitis. A reminder here, however: If a woman is sexually active and at risk for sexually transmitted infections, then consider testing for STIs as well, because the symptoms of an STI can mimic those of a UTI.

Treatment. Treatment for UTI is usually empiric, with treatment initiated before the culture results are known and with cultures being done only for people with complicated infections, such as pyelonephritis, or with recurrent infections. Decisions about what to use for treatment can be influenced by local patterns of resistance and an individual’s risk factors for antimicrobial resistance. As a general rule, for uncomplicated cystitis, nitrofurantoin for 5 days is a reasonable first-line agent. Evidence of efficacy is good, and the risk for antimicrobial resistance is lower vs using antibiotics for other systemic infections. 

Other reasonable first-line agents for uncomplicated cystitis include trimethoprim-sulfamethoxazole (TMP-SMX) for 3 days; fosfomycin (oral) single dose; or a beta-lactam (most commonly a first generation cephalosporin), although evidence for duration is unclear. Also mentioned are two unfamiliar antibiotics: pivmecillinam (a beta-lactam agent recently approved by the Food and Drug Administration [FDA], given for 3 days) and gepotidacin (from a new class of antibiotic that is currently under FDA review). Fluoroquinolones should not usually be first-line agents unless other treatment options are not appropriate. 

It’s important to distinguish between uncomplicated cystitis and pyelonephritis. For pyelonephritis (infection of the upper urinary tract), the first decision has to do with setting for care, depending on how sick someone is, and the likelihood of gram-negative bacteremia — all of which help whether the patient needs to be hospitalized for intravenous antibiotics, or can be treated as an outpatient. Determine if they need to be admitted for intravenous antibiotics or whether they can be treated as an outpatient. For outpatient treatment of pyelonephritis, the guideline suggests that TMP-SMX or a first-generation cephalosporin are both reasonable first-line agents, with fluoroquinolones being a reasonable choice as well. Ceftriaxone is recommended for first-line therapy for patients who require intravenous treatment. 

People often forget that we can do a lot to prevent UTIs, particularly among women with recurrent UTIs. The prevention of UTIs has both nonpharmacologic and pharmacologic approaches.

Nonpharmacologic prevention. One nonpharmacologic strategy is increasing water intake. A randomized controlled trial in women with recurrent cystitis who drank less than 1.5 L of fluid a day showed that the women randomized to consume an additional 1.5 L of water daily had significantly reduced cystitis frequency — approximately 50%. Because this was the only randomized trial to show this effect, this is not a strong recommendation, but there is very little downside in healthy women, so increasing water intake is a reasonable recommendation.

Another commonly discussed intervention is the use of cranberry products. As it turns out, most prospective studies have shown that cranberry products can reduce the risk for symptomatic UTIs in women with recurrent UTI. 

Pharmacologic prevention. For postmenopausal women with recurrent UTI, topical vaginal estrogen has a strong base of evidence — more than 30 randomized trials — supporting its effectiveness in UTI: a 50%-90% reduction in the incidence of recurrent UTIs. Topical estrogen has minimal systemic absorption, and there are no concerning safety signals with respect to either thromboembolic disease or cancer (endometrial or breast). 

Methenamine hippurate is also recommended and is FDA-approved for prevention of UTIs. It works by releasing formaldehyde in the urine, leading to bacteriostasis, which is how it leads to a decrease in UTIs. Finally, postcoital or daily administration of TMP-SMX, nitrofurantoin, norfloxacin, and ciprofloxacin all have comparable efficacy for prophylaxis, with a meta-analysis showing a decrease in recurrence rate of approximately 85%. The guideline states that there is insufficient evidence to support the use of either probiotics or D-mannose to prevent UTIs. 

This is a wonderful update on a common problem. We all have a lot of clinical experience here.

Dr Skolnik, Department of Family Medicine, Sidney Kimmel Medical College of Thomas Jefferson University, Philadelphia; Associate Director, Department of Family Medicine, Abington Jefferson Health, Abington, Pennsylvania, disclosed ties with AstraZeneca, Teva, Eli Lilly, Boehringer Ingelheim, Sanofi, Sanofi Pasteur, GlaxoSmithKline, Merck, and Bayer. 

A version of this article appeared on Medscape.com.

An electronic nudge explaining the cardiovascular benefits of the influenza vaccine increased vaccination rates, particularly among people who had previously had a heart attack, showed the NUDGE FLU series of clinical trials.

Influenza has the potential to be a dangerous infection on its own, but it increases the risk for cardiovascular events among people with a history of heart attack, said the study’s lead author, Ankeet Bhatt, MD, a cardiologist at Kaiser Permanente San Francisco Medical Center, San Francisco.

“Yearly influenza vaccines help prevent influenza infection and, in patients with a heart attack, are potentially cardioprotective,” he said during his presentation at the American Heart Association (AHA) Scientific Sessions 2024 in Chicago. The NUDGE FLU results were simultaneously published online in JAMA Cardiology.

In Denmark, where the trials were conducted, about 80% of older adults get flu shots, but only about 40% of younger adults with chronic diseases do, Bhatt reported. In the United States, about 45% of adults and 55% of children received at least one dose of the flu vaccine in the 2023/24 flu season, according to the US Centers for Disease Control and Prevention (CDC).

 

The NUDGE FLU Trials

Bhatt and his colleagues conducted three related clinical trials during the 2022/23 and 2023/24 flu seasons: NUDGE-FLU and NUDGE-FLU-2 targeted older adults, whereas NUDGE-FLU-CHRONIC targeted younger adults with chronic diseases. Nearly 2 million people were involved in the three trials.

Participants were randomized to receive one of a series of different behavioral-science-informed letters, delivered through a government-run electronic communication system, or no reminder.

People who received any of the nudges had higher rates of vaccination; among heart attack survivors, there was a 1.8% improvement and among adults without a history of heart attack, there was a 1.3% improvement. But a nudge that explained the potential cardiovascular benefits of flu shots was even more effective, leading to a 3.9% increase among people with a history of heart attack and a 2% increase among those with no heart attack history.

“A simple sentence resulted in a durable improvement in the vaccination rate,” said Bhatt.

The effect was even greater among those who had not been vaccinated in the previous flu season. Among heart attack survivors, nearly 14% more people got the vaccine compared with just 1.5% more survivors who were previously vaccinated. And it was most effective among younger adults who had experienced a recent heart attack, resulting in a 26% increase.

“The impact was larger in patients with a history of acute myocardial infarction, in those who were vaccine-hesitant, and in younger people” — all groups with the most to gain from vaccination in terms of cardiovascular protection — Bhatt reported.

About 25% of people in the United States are unsure about whether to get a flu shot, said Orly Vardeny, PharmD, professor of medicine at the University of Minnesota Medical School in Minneapolis, who was not involved in the study. The fact that previously unvaccinated people were convinced by the nudges is reassuring. “That’s the group where this intervention is most likely to move the needle,” she said.

Around half of all people hospitalized for flu in the United States have cardiovascular disease, CDC data showed, so “even a small increase in the number of patients who get vaccinated has substantial public health benefits,” Vardeny said.

The NUDGE FLU series showed that nudges like this should be employed as a simple tool to improve vaccination rates, but the system would be much more difficult to implement in the United States, Bhatt said.

Denmark has a national health service and a preexisting government electronic communication system, whereas the US system is privately run and more fractured. It would be possible to make it work, he pointed out, but would take some effort.

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