Timothy Mott, MD

ILLUSTRATIVE CASE

A 43-year-old woman presents to the clinic with diffuse, intermittent abdominal discomfort, bloating, and diarrhea that has slowly but steadily worsened over the past few years to now-daily symptoms. She states her overall health is otherwise good. Her review of systems is pertinent only for 8 lbs of unintentional weight loss over the past year and increased fatigue. She takes no supplements or routine over-the-counter or prescription medications, except for low-dose combination oral contraceptives, and is unaware of any family history of gastrointestinal (GI) diseases. She does not drink or smoke. She is up to date with immunizations and with cervical and breast cancer screening. Her body mass index is 23, her vital signs are within normal limits, and her physical exam is normal except for mild, diffuse abdominal tenderness without any masses, organomegaly, or peritoneal signs.

Her diagnostic work-up includes a complete metabolic panel, magnesium level, complete blood count, thyroid-stimulating hormone measurement, cytomegalovirus IgG and IgM serology, and stool studies for fecal leukocytes, ova and parasites, and fecal fat, in addition to a kidney, ureter, and bladder noncontrast computed tomography scan. All diagnostic testing is negative except for slightly elevated fecal fat, thereby decreasing the likelihood of infection, thyroid disorder, electrolyte abnormalities, or malignancy as a source of her symptoms.

She says that based on her online searches, her symptoms seem consistent with CD—with which you concur. However, she is fearful of an endoscopic procedure and asks if there is any other way to diagnose CD.

CD is an immune-mediated disorder in genetically susceptible people that is triggered by dietary gluten, causing damage to the small intestine.^1-6 The estimated worldwide prevalence of CD is approximately 1%, with greater prevalence in females.^1-6 A strong genetic predisposition also has been noted: prevalence among first-degree relatives is 10% to 44%.^2,3,6 Although CD can be diagnosed at any age, in the United States the mean age at diagnosis is in the fifth decade of life.⁶

The incidence of CD is on the rise due to true increases in disease incidence and prevalence, increased detection through better diagnostic tools, and increased screening of at-risk populations (eg, first-degree relatives, those with specific human leukocyte antigen variant genotypes, and those with certain chromosomal disorders, such as Down syndrome and Turner syndrome).^2-6 However, despite the increasing prevalence of CD, most patients remain undiagnosed.¹

The consistently strong predictive value of tTG-IgA serum testing may enable celiac disease diagnosis at a much lower cost and reduced risk vs traditional invasive procedures.

The diagnosis of CD in adults is typically made with elevated serum tTG-IgA and endomysial IgA antibodies (EMAs) on initial screening, followed by a duodenal biopsy via EGD for confirmatory testing and/or elucidation of differential diagnoses.^7,8 In 2020, guidelines from the European Society for Paediatric Gastroenterology, Hepatology and Nutrition advised that the diagnosis of CD in children can be made without the need for biopsy.⁹ They stated that serum tTG-IgA antibodies ≥ 10 times the ULN, in conjunction with a positive serum EMA, effectively make the diagnosis without endoscopy. Although the gold standard of EGD with biopsy for diagnosing CD has its own inherent risks and can be expensive, a “no-biopsy” approach has yet to be adopted into guidelines for diagnosing CD in adults.^7,8

STUDY SUMMARY

tTG-IgA titers were highly predictive of CD in 3 distinct cohorts

This 2021 hybrid prospective/retrospective study with 3 distinct cohorts aimed to assess the utility of serum tTG-IgA titers compared to traditional EGD with duodenal biopsy for the diagnosis of CD in adult participants (defined as ≥ 16 years of age). A serum tTG-IgA titer ≥ 10 times the ULN was set as the minimal cutoff value, and standardized duodenal biopsy sampling and evaluation for histologic mucosal changes consistent with Marsh 3 lesions was used as the diagnostic reference standard.

Continue to: Cohort 1 was a...

Cohort 1 was a prospective analysis of adults (N = 740) considered to have a high suspicion for CD, recruited from a single CD subspecialty clinic in the United Kingdom. Patients with a previous diagnosis of CD, those adhering to a gluten-free diet, and those with IgA deficiency were excluded. Study patients had tTG-IgA titers drawn and, within 6 weeks, underwent endoscopy with ≥ 1 biopsy from the duodenal bulb and/or the second part of the duodenum. The PPV of tTG-IgA titers ≥ 10 times the ULN in patients with biopsy-proven CD was 98.7% (95% CI, 97%-99.4%).

Cohort 2 was a retrospective analysis of adult patients (N = 532) considered to have low suspicion for CD. These patients were referred for endoscopy for generalized GI complaints in the same hospital as Cohort 1, but not the subspecialty clinic. Exclusion criteria and timing of IgA titers and endoscopy were identical to those of Cohort 1. The PPV of tTG-IgA titers ≥ 10 times the ULN in patients with biopsy-proven CD was 100%.

Cohort 3 (which included patients in 8 countries) was a retrospective analysis of the performance of multiple assays to enhance the validity of this approach in a wide range of settings. Adult patients (N = 145) with tTG-IgA serology positive for celiac who then underwent endoscopy with 4 to 6 duodenal biopsy samples were included in this analysis. Eleven distinct laboratories performed the tTG-IgA assay. The PPV of tTG-IgA titers ≥ 10 times the ULN in patients with biopsy-proven CD was 95.2% (95% CI, 84.6%-98.6%).

In total, this study included 1417 adult patients; 431 (30%) had tTG-IgA titers ≥ 10 times the ULN. Of those patients, 424 (98%) had histopathologic findings on duodenal biopsy consistent with CD.

Of note, there was no standardization as to the assays used for the tTG-IgA titers: Cohort 1 used 2 different manufacturers’ assays, Cohort 2 used 1 assay, and Cohort 3 used 5 assays. Regardless, the “≥ 10 times the ULN” calculation was based on each manufacturer’s published assay ranges. The lack of assay standardization did create variance in false-positive rates, however: Across all 3 cohorts, the false-positive rate for trusting the “≥ 10 times the ULN” threshold as the sole marker for CD in adults increased from 1% (Cohorts 1 and 2) to 5% (all 3 cohorts).

Continue to: WHAT'S NEW

Less invasive, less costly diagnosis of celiac disease in adults

In adults with symptoms suggestive of CD, the diagnosis can be made with a high level of certainty if a serum tTG-IgA titer is ≥ 10 times the ULN. Through informed, shared decision making in the presence of such a finding, patients may accept a serologic diagnosis and forgo an invasive EGD with biopsy and its inherent costs and risks. Indeed, if the majority of patients with CD are undiagnosed or underdiagnosed, and there exists a minimally invasive blood test that is highly cost effective in the absence of “red flags,” the overall benefit of this path could be substantial.

CAVEATS

“No biopsy” does not mean no risk/benefit discussion

While the PPVs are quite high, the negative predictive value varied greatly: 13%, 98%, and 10% for Cohorts 1, 2, and 3, respectively. Therefore, although serum tTG-IgA titers ≥ 10 times the ULN are useful for diagnosis, a negative result (serum tTG-IgA titers < 10 times the ULN) should not be used to rule out CD, and other testing should be pursued.

Additionally (although rare), patients with CD who have IgA deficiency may obtain false-negative results using the tTG-IgA ≥ 10 times the ULN diagnostic criterion.^7,8

Also, both Cohorts 1 and 2 took place in general or subspecialty GI clinics (Cohort 3’s site types were not specified). However, the objective interpretation of tTG-IgA serology means it could be considered as an additional diagnostic tool for primary care physicians, as well.

If there are any potential “red flag” symptoms suggesting the possibility of a more concerning differential diagnosis, EGD evaluation should still be pursued.

Finally, if a primary care physician and their patient decide to go the “no-biopsy” route, it should be with a full discussion of the possible risks and benefits of not pursuing EGD. If there are any potential “red flag” symptoms suggesting the possibility of a more concerning differential diagnosis, EGD evaluation should still be pursued. Such symptoms might include (but not be limited to) chronic dyspepsia, dysphagia, weight loss, and unexplained anemia.⁷

Continue to: CHALLENGES TO IMPLEMENTATION

Diagnostic guidelines still favor EGD with biopsy for adults

The 2013 American College of Gastroenterology guidelines support the use of EGD and duodenal biopsy to diagnose CD in both low- and high-risk patients, regardless of serologic findings.⁷ In a 2019 Clinical Practice Update, the American Gastrointestinal Association (AGA) stated that when tTG-IgA titers are ≥ 10 times the ULN and EMAs are positive, the PPV is “virtually 100%” for CD. Yet they still state that in this scenario “EGD and duodenal biopsies may then be performed for purposes of differential diagnosis.”⁸ Furthermore, the AGA does not discuss informed and shared decision making with patients for the option of a “no-biopsy” diagnosis.⁸

Additionally, there may be challenges in finding commercial laboratories that report reference ranges with a clear ULN. Although costs for the serum tTG-IgA assay vary, they are less expensive than endoscopy with biopsy and histopathologic examination, and therefore may present less of a financial barrier.

ILLUSTRATIVE CASE

A 43-year-old woman presents to the clinic with diffuse, intermittent abdominal discomfort, bloating, and diarrhea that has slowly but steadily worsened over the past few years to now-daily symptoms. She states her overall health is otherwise good. Her review of systems is pertinent only for 8 lbs of unintentional weight loss over the past year and increased fatigue. She takes no supplements or routine over-the-counter or prescription medications, except for low-dose combination oral contraceptives, and is unaware of any family history of gastrointestinal (GI) diseases. She does not drink or smoke. She is up to date with immunizations and with cervical and breast cancer screening. Her body mass index is 23, her vital signs are within normal limits, and her physical exam is normal except for mild, diffuse abdominal tenderness without any masses, organomegaly, or peritoneal signs.

Her diagnostic work-up includes a complete metabolic panel, magnesium level, complete blood count, thyroid-stimulating hormone measurement, cytomegalovirus IgG and IgM serology, and stool studies for fecal leukocytes, ova and parasites, and fecal fat, in addition to a kidney, ureter, and bladder noncontrast computed tomography scan. All diagnostic testing is negative except for slightly elevated fecal fat, thereby decreasing the likelihood of infection, thyroid disorder, electrolyte abnormalities, or malignancy as a source of her symptoms.

She says that based on her online searches, her symptoms seem consistent with CD—with which you concur. However, she is fearful of an endoscopic procedure and asks if there is any other way to diagnose CD.

CD is an immune-mediated disorder in genetically susceptible people that is triggered by dietary gluten, causing damage to the small intestine.^1-6 The estimated worldwide prevalence of CD is approximately 1%, with greater prevalence in females.^1-6 A strong genetic predisposition also has been noted: prevalence among first-degree relatives is 10% to 44%.^2,3,6 Although CD can be diagnosed at any age, in the United States the mean age at diagnosis is in the fifth decade of life.⁶

The incidence of CD is on the rise due to true increases in disease incidence and prevalence, increased detection through better diagnostic tools, and increased screening of at-risk populations (eg, first-degree relatives, those with specific human leukocyte antigen variant genotypes, and those with certain chromosomal disorders, such as Down syndrome and Turner syndrome).^2-6 However, despite the increasing prevalence of CD, most patients remain undiagnosed.¹

The consistently strong predictive value of tTG-IgA serum testing may enable celiac disease diagnosis at a much lower cost and reduced risk vs traditional invasive procedures.

The diagnosis of CD in adults is typically made with elevated serum tTG-IgA and endomysial IgA antibodies (EMAs) on initial screening, followed by a duodenal biopsy via EGD for confirmatory testing and/or elucidation of differential diagnoses.^7,8 In 2020, guidelines from the European Society for Paediatric Gastroenterology, Hepatology and Nutrition advised that the diagnosis of CD in children can be made without the need for biopsy.⁹ They stated that serum tTG-IgA antibodies ≥ 10 times the ULN, in conjunction with a positive serum EMA, effectively make the diagnosis without endoscopy. Although the gold standard of EGD with biopsy for diagnosing CD has its own inherent risks and can be expensive, a “no-biopsy” approach has yet to be adopted into guidelines for diagnosing CD in adults.^7,8

STUDY SUMMARY

tTG-IgA titers were highly predictive of CD in 3 distinct cohorts

This 2021 hybrid prospective/retrospective study with 3 distinct cohorts aimed to assess the utility of serum tTG-IgA titers compared to traditional EGD with duodenal biopsy for the diagnosis of CD in adult participants (defined as ≥ 16 years of age). A serum tTG-IgA titer ≥ 10 times the ULN was set as the minimal cutoff value, and standardized duodenal biopsy sampling and evaluation for histologic mucosal changes consistent with Marsh 3 lesions was used as the diagnostic reference standard.

Continue to: Cohort 1 was a...

Cohort 1 was a prospective analysis of adults (N = 740) considered to have a high suspicion for CD, recruited from a single CD subspecialty clinic in the United Kingdom. Patients with a previous diagnosis of CD, those adhering to a gluten-free diet, and those with IgA deficiency were excluded. Study patients had tTG-IgA titers drawn and, within 6 weeks, underwent endoscopy with ≥ 1 biopsy from the duodenal bulb and/or the second part of the duodenum. The PPV of tTG-IgA titers ≥ 10 times the ULN in patients with biopsy-proven CD was 98.7% (95% CI, 97%-99.4%).

Cohort 2 was a retrospective analysis of adult patients (N = 532) considered to have low suspicion for CD. These patients were referred for endoscopy for generalized GI complaints in the same hospital as Cohort 1, but not the subspecialty clinic. Exclusion criteria and timing of IgA titers and endoscopy were identical to those of Cohort 1. The PPV of tTG-IgA titers ≥ 10 times the ULN in patients with biopsy-proven CD was 100%.

Cohort 3 (which included patients in 8 countries) was a retrospective analysis of the performance of multiple assays to enhance the validity of this approach in a wide range of settings. Adult patients (N = 145) with tTG-IgA serology positive for celiac who then underwent endoscopy with 4 to 6 duodenal biopsy samples were included in this analysis. Eleven distinct laboratories performed the tTG-IgA assay. The PPV of tTG-IgA titers ≥ 10 times the ULN in patients with biopsy-proven CD was 95.2% (95% CI, 84.6%-98.6%).

In total, this study included 1417 adult patients; 431 (30%) had tTG-IgA titers ≥ 10 times the ULN. Of those patients, 424 (98%) had histopathologic findings on duodenal biopsy consistent with CD.

Of note, there was no standardization as to the assays used for the tTG-IgA titers: Cohort 1 used 2 different manufacturers’ assays, Cohort 2 used 1 assay, and Cohort 3 used 5 assays. Regardless, the “≥ 10 times the ULN” calculation was based on each manufacturer’s published assay ranges. The lack of assay standardization did create variance in false-positive rates, however: Across all 3 cohorts, the false-positive rate for trusting the “≥ 10 times the ULN” threshold as the sole marker for CD in adults increased from 1% (Cohorts 1 and 2) to 5% (all 3 cohorts).

Continue to: WHAT'S NEW

Less invasive, less costly diagnosis of celiac disease in adults

In adults with symptoms suggestive of CD, the diagnosis can be made with a high level of certainty if a serum tTG-IgA titer is ≥ 10 times the ULN. Through informed, shared decision making in the presence of such a finding, patients may accept a serologic diagnosis and forgo an invasive EGD with biopsy and its inherent costs and risks. Indeed, if the majority of patients with CD are undiagnosed or underdiagnosed, and there exists a minimally invasive blood test that is highly cost effective in the absence of “red flags,” the overall benefit of this path could be substantial.

CAVEATS

“No biopsy” does not mean no risk/benefit discussion

While the PPVs are quite high, the negative predictive value varied greatly: 13%, 98%, and 10% for Cohorts 1, 2, and 3, respectively. Therefore, although serum tTG-IgA titers ≥ 10 times the ULN are useful for diagnosis, a negative result (serum tTG-IgA titers < 10 times the ULN) should not be used to rule out CD, and other testing should be pursued.

Additionally (although rare), patients with CD who have IgA deficiency may obtain false-negative results using the tTG-IgA ≥ 10 times the ULN diagnostic criterion.^7,8

Also, both Cohorts 1 and 2 took place in general or subspecialty GI clinics (Cohort 3’s site types were not specified). However, the objective interpretation of tTG-IgA serology means it could be considered as an additional diagnostic tool for primary care physicians, as well.

If there are any potential “red flag” symptoms suggesting the possibility of a more concerning differential diagnosis, EGD evaluation should still be pursued.

Finally, if a primary care physician and their patient decide to go the “no-biopsy” route, it should be with a full discussion of the possible risks and benefits of not pursuing EGD. If there are any potential “red flag” symptoms suggesting the possibility of a more concerning differential diagnosis, EGD evaluation should still be pursued. Such symptoms might include (but not be limited to) chronic dyspepsia, dysphagia, weight loss, and unexplained anemia.⁷

Continue to: CHALLENGES TO IMPLEMENTATION

Diagnostic guidelines still favor EGD with biopsy for adults

The 2013 American College of Gastroenterology guidelines support the use of EGD and duodenal biopsy to diagnose CD in both low- and high-risk patients, regardless of serologic findings.⁷ In a 2019 Clinical Practice Update, the American Gastrointestinal Association (AGA) stated that when tTG-IgA titers are ≥ 10 times the ULN and EMAs are positive, the PPV is “virtually 100%” for CD. Yet they still state that in this scenario “EGD and duodenal biopsies may then be performed for purposes of differential diagnosis.”⁸ Furthermore, the AGA does not discuss informed and shared decision making with patients for the option of a “no-biopsy” diagnosis.⁸

Additionally, there may be challenges in finding commercial laboratories that report reference ranges with a clear ULN. Although costs for the serum tTG-IgA assay vary, they are less expensive than endoscopy with biopsy and histopathologic examination, and therefore may present less of a financial barrier.

ILLUSTRATIVE CASE

A 43-year-old woman presents to the clinic with diffuse, intermittent abdominal discomfort, bloating, and diarrhea that has slowly but steadily worsened over the past few years to now-daily symptoms. She states her overall health is otherwise good. Her review of systems is pertinent only for 8 lbs of unintentional weight loss over the past year and increased fatigue. She takes no supplements or routine over-the-counter or prescription medications, except for low-dose combination oral contraceptives, and is unaware of any family history of gastrointestinal (GI) diseases. She does not drink or smoke. She is up to date with immunizations and with cervical and breast cancer screening. Her body mass index is 23, her vital signs are within normal limits, and her physical exam is normal except for mild, diffuse abdominal tenderness without any masses, organomegaly, or peritoneal signs.

Her diagnostic work-up includes a complete metabolic panel, magnesium level, complete blood count, thyroid-stimulating hormone measurement, cytomegalovirus IgG and IgM serology, and stool studies for fecal leukocytes, ova and parasites, and fecal fat, in addition to a kidney, ureter, and bladder noncontrast computed tomography scan. All diagnostic testing is negative except for slightly elevated fecal fat, thereby decreasing the likelihood of infection, thyroid disorder, electrolyte abnormalities, or malignancy as a source of her symptoms.

She says that based on her online searches, her symptoms seem consistent with CD—with which you concur. However, she is fearful of an endoscopic procedure and asks if there is any other way to diagnose CD.

CD is an immune-mediated disorder in genetically susceptible people that is triggered by dietary gluten, causing damage to the small intestine.^1-6 The estimated worldwide prevalence of CD is approximately 1%, with greater prevalence in females.^1-6 A strong genetic predisposition also has been noted: prevalence among first-degree relatives is 10% to 44%.^2,3,6 Although CD can be diagnosed at any age, in the United States the mean age at diagnosis is in the fifth decade of life.⁶

The incidence of CD is on the rise due to true increases in disease incidence and prevalence, increased detection through better diagnostic tools, and increased screening of at-risk populations (eg, first-degree relatives, those with specific human leukocyte antigen variant genotypes, and those with certain chromosomal disorders, such as Down syndrome and Turner syndrome).^2-6 However, despite the increasing prevalence of CD, most patients remain undiagnosed.¹

The consistently strong predictive value of tTG-IgA serum testing may enable celiac disease diagnosis at a much lower cost and reduced risk vs traditional invasive procedures.

The diagnosis of CD in adults is typically made with elevated serum tTG-IgA and endomysial IgA antibodies (EMAs) on initial screening, followed by a duodenal biopsy via EGD for confirmatory testing and/or elucidation of differential diagnoses.^7,8 In 2020, guidelines from the European Society for Paediatric Gastroenterology, Hepatology and Nutrition advised that the diagnosis of CD in children can be made without the need for biopsy.⁹ They stated that serum tTG-IgA antibodies ≥ 10 times the ULN, in conjunction with a positive serum EMA, effectively make the diagnosis without endoscopy. Although the gold standard of EGD with biopsy for diagnosing CD has its own inherent risks and can be expensive, a “no-biopsy” approach has yet to be adopted into guidelines for diagnosing CD in adults.^7,8

STUDY SUMMARY

tTG-IgA titers were highly predictive of CD in 3 distinct cohorts

This 2021 hybrid prospective/retrospective study with 3 distinct cohorts aimed to assess the utility of serum tTG-IgA titers compared to traditional EGD with duodenal biopsy for the diagnosis of CD in adult participants (defined as ≥ 16 years of age). A serum tTG-IgA titer ≥ 10 times the ULN was set as the minimal cutoff value, and standardized duodenal biopsy sampling and evaluation for histologic mucosal changes consistent with Marsh 3 lesions was used as the diagnostic reference standard.

Continue to: Cohort 1 was a...

Cohort 1 was a prospective analysis of adults (N = 740) considered to have a high suspicion for CD, recruited from a single CD subspecialty clinic in the United Kingdom. Patients with a previous diagnosis of CD, those adhering to a gluten-free diet, and those with IgA deficiency were excluded. Study patients had tTG-IgA titers drawn and, within 6 weeks, underwent endoscopy with ≥ 1 biopsy from the duodenal bulb and/or the second part of the duodenum. The PPV of tTG-IgA titers ≥ 10 times the ULN in patients with biopsy-proven CD was 98.7% (95% CI, 97%-99.4%).

Cohort 2 was a retrospective analysis of adult patients (N = 532) considered to have low suspicion for CD. These patients were referred for endoscopy for generalized GI complaints in the same hospital as Cohort 1, but not the subspecialty clinic. Exclusion criteria and timing of IgA titers and endoscopy were identical to those of Cohort 1. The PPV of tTG-IgA titers ≥ 10 times the ULN in patients with biopsy-proven CD was 100%.

Cohort 3 (which included patients in 8 countries) was a retrospective analysis of the performance of multiple assays to enhance the validity of this approach in a wide range of settings. Adult patients (N = 145) with tTG-IgA serology positive for celiac who then underwent endoscopy with 4 to 6 duodenal biopsy samples were included in this analysis. Eleven distinct laboratories performed the tTG-IgA assay. The PPV of tTG-IgA titers ≥ 10 times the ULN in patients with biopsy-proven CD was 95.2% (95% CI, 84.6%-98.6%).

In total, this study included 1417 adult patients; 431 (30%) had tTG-IgA titers ≥ 10 times the ULN. Of those patients, 424 (98%) had histopathologic findings on duodenal biopsy consistent with CD.

Of note, there was no standardization as to the assays used for the tTG-IgA titers: Cohort 1 used 2 different manufacturers’ assays, Cohort 2 used 1 assay, and Cohort 3 used 5 assays. Regardless, the “≥ 10 times the ULN” calculation was based on each manufacturer’s published assay ranges. The lack of assay standardization did create variance in false-positive rates, however: Across all 3 cohorts, the false-positive rate for trusting the “≥ 10 times the ULN” threshold as the sole marker for CD in adults increased from 1% (Cohorts 1 and 2) to 5% (all 3 cohorts).

Continue to: WHAT'S NEW

Less invasive, less costly diagnosis of celiac disease in adults

In adults with symptoms suggestive of CD, the diagnosis can be made with a high level of certainty if a serum tTG-IgA titer is ≥ 10 times the ULN. Through informed, shared decision making in the presence of such a finding, patients may accept a serologic diagnosis and forgo an invasive EGD with biopsy and its inherent costs and risks. Indeed, if the majority of patients with CD are undiagnosed or underdiagnosed, and there exists a minimally invasive blood test that is highly cost effective in the absence of “red flags,” the overall benefit of this path could be substantial.

CAVEATS

“No biopsy” does not mean no risk/benefit discussion

While the PPVs are quite high, the negative predictive value varied greatly: 13%, 98%, and 10% for Cohorts 1, 2, and 3, respectively. Therefore, although serum tTG-IgA titers ≥ 10 times the ULN are useful for diagnosis, a negative result (serum tTG-IgA titers < 10 times the ULN) should not be used to rule out CD, and other testing should be pursued.

Additionally (although rare), patients with CD who have IgA deficiency may obtain false-negative results using the tTG-IgA ≥ 10 times the ULN diagnostic criterion.^7,8

Also, both Cohorts 1 and 2 took place in general or subspecialty GI clinics (Cohort 3’s site types were not specified). However, the objective interpretation of tTG-IgA serology means it could be considered as an additional diagnostic tool for primary care physicians, as well.

If there are any potential “red flag” symptoms suggesting the possibility of a more concerning differential diagnosis, EGD evaluation should still be pursued.

Finally, if a primary care physician and their patient decide to go the “no-biopsy” route, it should be with a full discussion of the possible risks and benefits of not pursuing EGD. If there are any potential “red flag” symptoms suggesting the possibility of a more concerning differential diagnosis, EGD evaluation should still be pursued. Such symptoms might include (but not be limited to) chronic dyspepsia, dysphagia, weight loss, and unexplained anemia.⁷

Continue to: CHALLENGES TO IMPLEMENTATION

Diagnostic guidelines still favor EGD with biopsy for adults

The 2013 American College of Gastroenterology guidelines support the use of EGD and duodenal biopsy to diagnose CD in both low- and high-risk patients, regardless of serologic findings.⁷ In a 2019 Clinical Practice Update, the American Gastrointestinal Association (AGA) stated that when tTG-IgA titers are ≥ 10 times the ULN and EMAs are positive, the PPV is “virtually 100%” for CD. Yet they still state that in this scenario “EGD and duodenal biopsies may then be performed for purposes of differential diagnosis.”⁸ Furthermore, the AGA does not discuss informed and shared decision making with patients for the option of a “no-biopsy” diagnosis.⁸

Additionally, there may be challenges in finding commercial laboratories that report reference ranges with a clear ULN. Although costs for the serum tTG-IgA assay vary, they are less expensive than endoscopy with biopsy and histopathologic examination, and therefore may present less of a financial barrier.

ILLUSTRATIVE CASE

An otherwise healthy 56-year-old woman presents to the emergency department (ED) with a productive cough of 4 days’ duration. A review of her history is negative for recurrent upper respiratory infections, smoking, or environmental exposures. Her physical exam is unremarkable and, more specifically, her pulmonary exam and vital signs (temperature, respiratory rate, and heart rate) are within normal limits. The patient states that last year her friend had similar symptoms and was given a diagnosis of pneumonia. Is it necessary to order a chest x-ray in this patient to rule out community-acquired pneumonia (CAP)?

CAP is a common pulmonary condition seen in the outpatient setting in the United States, representing more than 4.5 million outpatient visits in the years 2009 to 2010.² Historically, a diagnosis of CAP has been based on clinical findings in conjunction with infiltrates seen on chest x-ray.

In 2017, more than 5 million visits to the ED were due to a cough.³ The use of radiographic imaging in EDs has been increasing. There were 49 million x-rays and 2.7 million noncardiac chest computed tomography (CT) scans performed in 2016, many of which were for patients with cough.^3,4 Although imaging is an extremely useful tool and indicated in many instances, the ability to rule out CAP in an adult who presents with a cough by using a set of simple, clinically based heuristics without requiring imaging would help to increase efficiency, limit cost, and decrease exposure of patients to unnecessary and potentially harmful diagnostic studies.

Clinical decision rules (CDRs) are simple heuristics that can stratify patients as either high risk or low risk for specific diseases. Two older large, prospective cross-­sectional studies developed CDRs to determine the probability of CAP based on symptoms (eg, night sweats, myalgias, and sputum production) and clinical findings (eg, temperature > 37.8 °C [100 °F], tachypnea, tachycardia, rales, and decreased breath sounds).^5,6 This meta-analysis includes these studies and more recent studies^7-9 used to develop a CDR that focuses solely on a few specific signs and symptoms that can reliably rule out CAP without imaging, and so prove highly useful for busy primary care clinicians.

STUDY SUMMARY

This simple approach rules out CAP in outpatients 99.6% of the time

This systematic review and meta-analysis included studies that used 2 or more signs, symptoms, or point-of-care tests to determine the patient’s risk for CAP.¹ Twelve studies (N = 10,254) met inclusion criteria by applying a CDR to adults or adolescents presenting with respiratory signs or symptoms potentially suggestive of CAP to either an outpatient setting or an ED. Prospective cohort, cross-sectional, and case-control studies were included when a chest x-ray or CT was utilized as the primary reference standard. Exclusion criteria included studies of military or nursing home populations and studies in which the majority of patients had hospital- or ventilator-associated pneumonia or were immunocompromised.

For adult outpatients who present with acute cough, this clinical decision rule can quickly and accurately rule out CAP without the need for diagnostic imaging.

A simple, highly useful CDR emerged from 3 of the studies (N = 1865).^7-9 Two of these studies were described as case-control studies with prospective enrollment of patients older than 17 years in both outpatient and ED settings.^7,8 One study was conducted in the United States (mean age, 65 years) and the other in Iran (mean age, 60 years). The third was a Chilean prospective cohort study of ED patients older than 15 years (mean age, 53 years).⁹ In each of these studies, the outpatient or ED physicians collected all clinical data and documented their physical exam prior to receiving the chest radiograph results. The radiologists were masked to the clinical findings at the time of their interpretation.

Results. From the meta-analysis, a simple CDR emerged for patients with normal vital signs (temperature, respiratory rate, and heart rate) and a normal pulmonary exam that virtually ruled out CAP (sensitivity = 96%; 95% CI, 92%–98%; and negative likelihood ratio = 0.10; 95% CI, 0.07–0.13). In patients presenting to an outpatient clinic with acute cough with a 4% baseline prevalence rate of pneumonia, this CDR ruled out CAP 99.6% of the time.

Continue to: WHAT'S NEW

A clinical decision rule validated for accuracy

This is the first validated CDR that accurately rules out CAP in the outpatient or ED setting using parameters easily obtainable during a clinical exam.

CAVEATS

Proceed with caution in the young and the very old

Two of the 3 studies in this CDR had an overall moderate risk of bias, whereas the third study was determined to be at low risk of bias, based on appraisal with the Quality Assessment Tool for Diagnostic Accuracy Studies (QUADAS-2) framework.¹⁰

The mean age range in these 3 studies was 53 to 66 years (without further data such as standard deviation), suggesting that application of the CDR to adults who fall at extremes of age should be done with a modicum of caution.

Additionally, although the symptom complex of COVID-19 pneumonia would suggest that this CDR would likely remain accurate today, it has not been validated in patients with COVID-19 infection.

CHALLENGES TO IMPLEMENTATION

Potential reluctance to forgo imaging

Beyond the caveats regarding COVID-19, the use of a simple CDR to reliably exclude pneumonia should have no barrier to implementation in an outpatient primary care setting or ED, although there could be reluctance on the part of both providers and patients to fully embrace this simple tool without a confirmatory chest x-ray.

ACKNOWLEDGEMENT

The PURLs Surveillance System was supported in part by Grant Number UL1RR024999 from the National Center for Research Resources, a Clinical Translational Science Award to the University of Chicago. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center for Research Resources or the National Institutes of Health.

ILLUSTRATIVE CASE

An otherwise healthy 56-year-old woman presents to the emergency department (ED) with a productive cough of 4 days’ duration. A review of her history is negative for recurrent upper respiratory infections, smoking, or environmental exposures. Her physical exam is unremarkable and, more specifically, her pulmonary exam and vital signs (temperature, respiratory rate, and heart rate) are within normal limits. The patient states that last year her friend had similar symptoms and was given a diagnosis of pneumonia. Is it necessary to order a chest x-ray in this patient to rule out community-acquired pneumonia (CAP)?

CAP is a common pulmonary condition seen in the outpatient setting in the United States, representing more than 4.5 million outpatient visits in the years 2009 to 2010.² Historically, a diagnosis of CAP has been based on clinical findings in conjunction with infiltrates seen on chest x-ray.

In 2017, more than 5 million visits to the ED were due to a cough.³ The use of radiographic imaging in EDs has been increasing. There were 49 million x-rays and 2.7 million noncardiac chest computed tomography (CT) scans performed in 2016, many of which were for patients with cough.^3,4 Although imaging is an extremely useful tool and indicated in many instances, the ability to rule out CAP in an adult who presents with a cough by using a set of simple, clinically based heuristics without requiring imaging would help to increase efficiency, limit cost, and decrease exposure of patients to unnecessary and potentially harmful diagnostic studies.

Clinical decision rules (CDRs) are simple heuristics that can stratify patients as either high risk or low risk for specific diseases. Two older large, prospective cross-­sectional studies developed CDRs to determine the probability of CAP based on symptoms (eg, night sweats, myalgias, and sputum production) and clinical findings (eg, temperature > 37.8 °C [100 °F], tachypnea, tachycardia, rales, and decreased breath sounds).^5,6 This meta-analysis includes these studies and more recent studies^7-9 used to develop a CDR that focuses solely on a few specific signs and symptoms that can reliably rule out CAP without imaging, and so prove highly useful for busy primary care clinicians.

STUDY SUMMARY

This simple approach rules out CAP in outpatients 99.6% of the time

This systematic review and meta-analysis included studies that used 2 or more signs, symptoms, or point-of-care tests to determine the patient’s risk for CAP.¹ Twelve studies (N = 10,254) met inclusion criteria by applying a CDR to adults or adolescents presenting with respiratory signs or symptoms potentially suggestive of CAP to either an outpatient setting or an ED. Prospective cohort, cross-sectional, and case-control studies were included when a chest x-ray or CT was utilized as the primary reference standard. Exclusion criteria included studies of military or nursing home populations and studies in which the majority of patients had hospital- or ventilator-associated pneumonia or were immunocompromised.

For adult outpatients who present with acute cough, this clinical decision rule can quickly and accurately rule out CAP without the need for diagnostic imaging.

A simple, highly useful CDR emerged from 3 of the studies (N = 1865).^7-9 Two of these studies were described as case-control studies with prospective enrollment of patients older than 17 years in both outpatient and ED settings.^7,8 One study was conducted in the United States (mean age, 65 years) and the other in Iran (mean age, 60 years). The third was a Chilean prospective cohort study of ED patients older than 15 years (mean age, 53 years).⁹ In each of these studies, the outpatient or ED physicians collected all clinical data and documented their physical exam prior to receiving the chest radiograph results. The radiologists were masked to the clinical findings at the time of their interpretation.

Results. From the meta-analysis, a simple CDR emerged for patients with normal vital signs (temperature, respiratory rate, and heart rate) and a normal pulmonary exam that virtually ruled out CAP (sensitivity = 96%; 95% CI, 92%–98%; and negative likelihood ratio = 0.10; 95% CI, 0.07–0.13). In patients presenting to an outpatient clinic with acute cough with a 4% baseline prevalence rate of pneumonia, this CDR ruled out CAP 99.6% of the time.

Continue to: WHAT'S NEW

A clinical decision rule validated for accuracy

This is the first validated CDR that accurately rules out CAP in the outpatient or ED setting using parameters easily obtainable during a clinical exam.

CAVEATS

Proceed with caution in the young and the very old

Two of the 3 studies in this CDR had an overall moderate risk of bias, whereas the third study was determined to be at low risk of bias, based on appraisal with the Quality Assessment Tool for Diagnostic Accuracy Studies (QUADAS-2) framework.¹⁰

The mean age range in these 3 studies was 53 to 66 years (without further data such as standard deviation), suggesting that application of the CDR to adults who fall at extremes of age should be done with a modicum of caution.

Additionally, although the symptom complex of COVID-19 pneumonia would suggest that this CDR would likely remain accurate today, it has not been validated in patients with COVID-19 infection.

CHALLENGES TO IMPLEMENTATION

Potential reluctance to forgo imaging

Beyond the caveats regarding COVID-19, the use of a simple CDR to reliably exclude pneumonia should have no barrier to implementation in an outpatient primary care setting or ED, although there could be reluctance on the part of both providers and patients to fully embrace this simple tool without a confirmatory chest x-ray.

ACKNOWLEDGEMENT

The PURLs Surveillance System was supported in part by Grant Number UL1RR024999 from the National Center for Research Resources, a Clinical Translational Science Award to the University of Chicago. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center for Research Resources or the National Institutes of Health.

ILLUSTRATIVE CASE

An otherwise healthy 56-year-old woman presents to the emergency department (ED) with a productive cough of 4 days’ duration. A review of her history is negative for recurrent upper respiratory infections, smoking, or environmental exposures. Her physical exam is unremarkable and, more specifically, her pulmonary exam and vital signs (temperature, respiratory rate, and heart rate) are within normal limits. The patient states that last year her friend had similar symptoms and was given a diagnosis of pneumonia. Is it necessary to order a chest x-ray in this patient to rule out community-acquired pneumonia (CAP)?

CAP is a common pulmonary condition seen in the outpatient setting in the United States, representing more than 4.5 million outpatient visits in the years 2009 to 2010.² Historically, a diagnosis of CAP has been based on clinical findings in conjunction with infiltrates seen on chest x-ray.

In 2017, more than 5 million visits to the ED were due to a cough.³ The use of radiographic imaging in EDs has been increasing. There were 49 million x-rays and 2.7 million noncardiac chest computed tomography (CT) scans performed in 2016, many of which were for patients with cough.^3,4 Although imaging is an extremely useful tool and indicated in many instances, the ability to rule out CAP in an adult who presents with a cough by using a set of simple, clinically based heuristics without requiring imaging would help to increase efficiency, limit cost, and decrease exposure of patients to unnecessary and potentially harmful diagnostic studies.

Clinical decision rules (CDRs) are simple heuristics that can stratify patients as either high risk or low risk for specific diseases. Two older large, prospective cross-­sectional studies developed CDRs to determine the probability of CAP based on symptoms (eg, night sweats, myalgias, and sputum production) and clinical findings (eg, temperature > 37.8 °C [100 °F], tachypnea, tachycardia, rales, and decreased breath sounds).^5,6 This meta-analysis includes these studies and more recent studies^7-9 used to develop a CDR that focuses solely on a few specific signs and symptoms that can reliably rule out CAP without imaging, and so prove highly useful for busy primary care clinicians.

STUDY SUMMARY

This simple approach rules out CAP in outpatients 99.6% of the time

This systematic review and meta-analysis included studies that used 2 or more signs, symptoms, or point-of-care tests to determine the patient’s risk for CAP.¹ Twelve studies (N = 10,254) met inclusion criteria by applying a CDR to adults or adolescents presenting with respiratory signs or symptoms potentially suggestive of CAP to either an outpatient setting or an ED. Prospective cohort, cross-sectional, and case-control studies were included when a chest x-ray or CT was utilized as the primary reference standard. Exclusion criteria included studies of military or nursing home populations and studies in which the majority of patients had hospital- or ventilator-associated pneumonia or were immunocompromised.

For adult outpatients who present with acute cough, this clinical decision rule can quickly and accurately rule out CAP without the need for diagnostic imaging.

A simple, highly useful CDR emerged from 3 of the studies (N = 1865).^7-9 Two of these studies were described as case-control studies with prospective enrollment of patients older than 17 years in both outpatient and ED settings.^7,8 One study was conducted in the United States (mean age, 65 years) and the other in Iran (mean age, 60 years). The third was a Chilean prospective cohort study of ED patients older than 15 years (mean age, 53 years).⁹ In each of these studies, the outpatient or ED physicians collected all clinical data and documented their physical exam prior to receiving the chest radiograph results. The radiologists were masked to the clinical findings at the time of their interpretation.

Results. From the meta-analysis, a simple CDR emerged for patients with normal vital signs (temperature, respiratory rate, and heart rate) and a normal pulmonary exam that virtually ruled out CAP (sensitivity = 96%; 95% CI, 92%–98%; and negative likelihood ratio = 0.10; 95% CI, 0.07–0.13). In patients presenting to an outpatient clinic with acute cough with a 4% baseline prevalence rate of pneumonia, this CDR ruled out CAP 99.6% of the time.

Continue to: WHAT'S NEW

A clinical decision rule validated for accuracy

This is the first validated CDR that accurately rules out CAP in the outpatient or ED setting using parameters easily obtainable during a clinical exam.

CAVEATS

Proceed with caution in the young and the very old

Two of the 3 studies in this CDR had an overall moderate risk of bias, whereas the third study was determined to be at low risk of bias, based on appraisal with the Quality Assessment Tool for Diagnostic Accuracy Studies (QUADAS-2) framework.¹⁰

The mean age range in these 3 studies was 53 to 66 years (without further data such as standard deviation), suggesting that application of the CDR to adults who fall at extremes of age should be done with a modicum of caution.

Additionally, although the symptom complex of COVID-19 pneumonia would suggest that this CDR would likely remain accurate today, it has not been validated in patients with COVID-19 infection.

CHALLENGES TO IMPLEMENTATION

Potential reluctance to forgo imaging

Beyond the caveats regarding COVID-19, the use of a simple CDR to reliably exclude pneumonia should have no barrier to implementation in an outpatient primary care setting or ED, although there could be reluctance on the part of both providers and patients to fully embrace this simple tool without a confirmatory chest x-ray.

ACKNOWLEDGEMENT

The PURLs Surveillance System was supported in part by Grant Number UL1RR024999 from the National Center for Research Resources, a Clinical Translational Science Award to the University of Chicago. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center for Research Resources or the National Institutes of Health.

Similar outcomes, except when it comes to return to work

A 2010 Cochrane review of 2 RCTs and one quasi-randomized trial (174 patients, 93% male, moderate to high risk of bias) compared surgical intervention with conservative management of acute AC separations of unspecified Rockwood classification.¹ Surgeries included coracoclavicular fixation with a cancellous screw or transfixation of the AC joint with Steinmann pins or Kirschner wires.

Conservative treatment included immobilization of the shoulder using an arm sling for 2 to 4 weeks. Patients were evaluated for a minimum of 12 months with a nonvalidated scoring system that measured pain, motion, and function or strength.

At one year, 63 of 76 patients (83%) in the post-surgical group and 74 of 84 patients (88%) in the conservative intervention group had either good or excellent results with no significant difference in unsatisfactory outcomes (relative risk [RR]=1.49; 95% confidence interval [CI], 0.75-2.95). (Fourteen patients—7 in each group—were lost to follow-up.) Moreover, the review found no significant difference in treatment failures requiring a subsequent operation between the groups—11 of 83 (13%) surgical patients and 7 of 91 (8%) conservatively managed patients (RR=1.72; 95% CI, 0.72-4.12).

Notably, regardless of activity level, surgical patients consistently returned to previous work functions later than patients managed conservatively. The mean convalescence time ranged from 8 to 11 weeks for surgical patients and 4 to 6 weeks for conservatively managed patients (P<.05).

A look at cosmetic results and risk of infection

A 2011 meta-analysis of 6 retrospective case series (379 patients, approximately 88% male) compared operative with nonoperative management in patients with acute, closed Rockwood grade III AC dislocations.² Operative techniques varied; nonoperative patients each received physiotherapy or rehabilitation therapy and most were treated with a sling. Patient follow-up varied from 32 months to 10.8 years.

Four of the included studies suggested that nonoperative management resulted in poorer cosmetic results (methods not defined) compared with the operative group (11 of 115 surgical patients [10%], 74 of 88 nonoperative patients [84%]; risk difference [RD]=−0.79; 95% CI, −0.92 to −0.66; number needed to harm [NNH]=>2). Two of the studies evaluated the duration of sick leave and found a longer leave with operative management (50 operative and 54 nonoperative patients; mean difference=3.3; 95% CI, 2.1-4.5).

Five of the studies observed an increased risk of infection following operative management (8 of 175 [5%] operative patients compared with 0 of 152 [0%] nonoperative patients; RD=0.05; 95% CI, 0.01-0.09; NNH=20).

Recommendations depend on the grade of the injury

The American College of Occupational and Environmental Medicine recommends against routine surgical repair for Grade III AC joint separations.³ The College also recommends nonoperative management for patients with grade I to II AC dislocations and surgical repair for patients with grades IV to VI and select grade III AC dislocations.

Similar outcomes, except when it comes to return to work

A 2010 Cochrane review of 2 RCTs and one quasi-randomized trial (174 patients, 93% male, moderate to high risk of bias) compared surgical intervention with conservative management of acute AC separations of unspecified Rockwood classification.¹ Surgeries included coracoclavicular fixation with a cancellous screw or transfixation of the AC joint with Steinmann pins or Kirschner wires.

Conservative treatment included immobilization of the shoulder using an arm sling for 2 to 4 weeks. Patients were evaluated for a minimum of 12 months with a nonvalidated scoring system that measured pain, motion, and function or strength.

At one year, 63 of 76 patients (83%) in the post-surgical group and 74 of 84 patients (88%) in the conservative intervention group had either good or excellent results with no significant difference in unsatisfactory outcomes (relative risk [RR]=1.49; 95% confidence interval [CI], 0.75-2.95). (Fourteen patients—7 in each group—were lost to follow-up.) Moreover, the review found no significant difference in treatment failures requiring a subsequent operation between the groups—11 of 83 (13%) surgical patients and 7 of 91 (8%) conservatively managed patients (RR=1.72; 95% CI, 0.72-4.12).

Notably, regardless of activity level, surgical patients consistently returned to previous work functions later than patients managed conservatively. The mean convalescence time ranged from 8 to 11 weeks for surgical patients and 4 to 6 weeks for conservatively managed patients (P<.05).

A look at cosmetic results and risk of infection

A 2011 meta-analysis of 6 retrospective case series (379 patients, approximately 88% male) compared operative with nonoperative management in patients with acute, closed Rockwood grade III AC dislocations.² Operative techniques varied; nonoperative patients each received physiotherapy or rehabilitation therapy and most were treated with a sling. Patient follow-up varied from 32 months to 10.8 years.

Four of the included studies suggested that nonoperative management resulted in poorer cosmetic results (methods not defined) compared with the operative group (11 of 115 surgical patients [10%], 74 of 88 nonoperative patients [84%]; risk difference [RD]=−0.79; 95% CI, −0.92 to −0.66; number needed to harm [NNH]=>2). Two of the studies evaluated the duration of sick leave and found a longer leave with operative management (50 operative and 54 nonoperative patients; mean difference=3.3; 95% CI, 2.1-4.5).

Five of the studies observed an increased risk of infection following operative management (8 of 175 [5%] operative patients compared with 0 of 152 [0%] nonoperative patients; RD=0.05; 95% CI, 0.01-0.09; NNH=20).

Recommendations depend on the grade of the injury

The American College of Occupational and Environmental Medicine recommends against routine surgical repair for Grade III AC joint separations.³ The College also recommends nonoperative management for patients with grade I to II AC dislocations and surgical repair for patients with grades IV to VI and select grade III AC dislocations.

Similar outcomes, except when it comes to return to work

A 2010 Cochrane review of 2 RCTs and one quasi-randomized trial (174 patients, 93% male, moderate to high risk of bias) compared surgical intervention with conservative management of acute AC separations of unspecified Rockwood classification.¹ Surgeries included coracoclavicular fixation with a cancellous screw or transfixation of the AC joint with Steinmann pins or Kirschner wires.

Conservative treatment included immobilization of the shoulder using an arm sling for 2 to 4 weeks. Patients were evaluated for a minimum of 12 months with a nonvalidated scoring system that measured pain, motion, and function or strength.

At one year, 63 of 76 patients (83%) in the post-surgical group and 74 of 84 patients (88%) in the conservative intervention group had either good or excellent results with no significant difference in unsatisfactory outcomes (relative risk [RR]=1.49; 95% confidence interval [CI], 0.75-2.95). (Fourteen patients—7 in each group—were lost to follow-up.) Moreover, the review found no significant difference in treatment failures requiring a subsequent operation between the groups—11 of 83 (13%) surgical patients and 7 of 91 (8%) conservatively managed patients (RR=1.72; 95% CI, 0.72-4.12).

Notably, regardless of activity level, surgical patients consistently returned to previous work functions later than patients managed conservatively. The mean convalescence time ranged from 8 to 11 weeks for surgical patients and 4 to 6 weeks for conservatively managed patients (P<.05).

A look at cosmetic results and risk of infection

A 2011 meta-analysis of 6 retrospective case series (379 patients, approximately 88% male) compared operative with nonoperative management in patients with acute, closed Rockwood grade III AC dislocations.² Operative techniques varied; nonoperative patients each received physiotherapy or rehabilitation therapy and most were treated with a sling. Patient follow-up varied from 32 months to 10.8 years.

Four of the included studies suggested that nonoperative management resulted in poorer cosmetic results (methods not defined) compared with the operative group (11 of 115 surgical patients [10%], 74 of 88 nonoperative patients [84%]; risk difference [RD]=−0.79; 95% CI, −0.92 to −0.66; number needed to harm [NNH]=>2). Two of the studies evaluated the duration of sick leave and found a longer leave with operative management (50 operative and 54 nonoperative patients; mean difference=3.3; 95% CI, 2.1-4.5).

Five of the studies observed an increased risk of infection following operative management (8 of 175 [5%] operative patients compared with 0 of 152 [0%] nonoperative patients; RD=0.05; 95% CI, 0.01-0.09; NNH=20).

Recommendations depend on the grade of the injury

The American College of Occupational and Environmental Medicine recommends against routine surgical repair for Grade III AC joint separations.³ The College also recommends nonoperative management for patients with grade I to II AC dislocations and surgical repair for patients with grades IV to VI and select grade III AC dislocations.

EVIDENCE SUMMARY

A 2012 Cochrane review of 52 studies (44 RCTs and 8 cluster-randomized trials; N=56,451) assessed the overall effectiveness of multiple supportive measures on decreasing cessation of “any” (partial and exclusive) and “exclusive” breastfeeding compared with usual care.¹ Participants were healthy breastfeeding mothers of healthy term babies. Support interventions were defined broadly but included individual and group interactions, as well as contact in person or over the phone by professionals or lay volunteers. Patients were approached proactively or reactively upon request, and the interventions occurred one or more times.

The interventions reduced discontinuation rates among both “exclusive” and “any” breastfeeding mothers (TABLE¹). The review found lay and professional support to be equally effective at promoting continuation of breastfeeding. Limitations include a moderate to high amount of heterogeneity, as well as the inherent difficulty of blinding subjects in the studies.

Lay support can make a significant difference in the short term

A 2008 systematic review of 38 RCTs (N=29,020) compared any counseling or behavioral intervention initiated from a clinician’s practice (office or hospital) with usual care.² The review excluded community and peer-initiated interventions. The reviewers defined breastfeeding duration as follows: initiation (up to 2 weeks), short-term (one to 3 months), intermediate-term (4 to 5 months), long-term (6 to 8 months), and prolonged (9 or more months). Investigators also analyzed breastfeeding rates by “exclusive” and “nonexclusive” (formula supplementation) regimens.

For nonexclusive breastfeeding, the review found interventions to promote breastfeeding improved rates only at initiation (18 RCTs, N=7688; relative risk [RR] for cessation of breastfeeding=1.04; 95% confidence interval [CI], 1.0-1.08; number needed to treat [NNT]=38) and in the short term (18 RCTs, N= 19,358; RR=1.10; 95% CI, 1.02-1.19; NNT=7). For exclusive breastfeeding, interventions improved rates only in the short term (17 RCTs, N=20,552; RR=1.72; 95% CI, 1.0-2.97; NNT=3).

The review found that lay support (defined as counseling or social support from peers) but not professional support was significantly associated with improving rates of both “nonexclusive” and “exclusive’ breastfeeding, but only over the short term (5 RCTs, N not provided; RR=1.22; 95% CI, 1.08-1.37; and 4 RCTs, N not provided; RR=1.65; 95% CI, 1.03-2.63; respectively). As with the Cochrane review, the results for all study groups demonstrated moderate to significant heterogeneity.

RECOMMENDATIONS

The Surgeon General, the American Academy of Family Physicians, the American Academy of Pediatrics, and the American College of Obstetricians and Gynecologists all recommend that women be educated about the benefits of breastfeeding and receive supportive interventions before and after delivery.^3-6

EVIDENCE SUMMARY

A 2012 Cochrane review of 52 studies (44 RCTs and 8 cluster-randomized trials; N=56,451) assessed the overall effectiveness of multiple supportive measures on decreasing cessation of “any” (partial and exclusive) and “exclusive” breastfeeding compared with usual care.¹ Participants were healthy breastfeeding mothers of healthy term babies. Support interventions were defined broadly but included individual and group interactions, as well as contact in person or over the phone by professionals or lay volunteers. Patients were approached proactively or reactively upon request, and the interventions occurred one or more times.

The interventions reduced discontinuation rates among both “exclusive” and “any” breastfeeding mothers (TABLE¹). The review found lay and professional support to be equally effective at promoting continuation of breastfeeding. Limitations include a moderate to high amount of heterogeneity, as well as the inherent difficulty of blinding subjects in the studies.

Lay support can make a significant difference in the short term

A 2008 systematic review of 38 RCTs (N=29,020) compared any counseling or behavioral intervention initiated from a clinician’s practice (office or hospital) with usual care.² The review excluded community and peer-initiated interventions. The reviewers defined breastfeeding duration as follows: initiation (up to 2 weeks), short-term (one to 3 months), intermediate-term (4 to 5 months), long-term (6 to 8 months), and prolonged (9 or more months). Investigators also analyzed breastfeeding rates by “exclusive” and “nonexclusive” (formula supplementation) regimens.

For nonexclusive breastfeeding, the review found interventions to promote breastfeeding improved rates only at initiation (18 RCTs, N=7688; relative risk [RR] for cessation of breastfeeding=1.04; 95% confidence interval [CI], 1.0-1.08; number needed to treat [NNT]=38) and in the short term (18 RCTs, N= 19,358; RR=1.10; 95% CI, 1.02-1.19; NNT=7). For exclusive breastfeeding, interventions improved rates only in the short term (17 RCTs, N=20,552; RR=1.72; 95% CI, 1.0-2.97; NNT=3).

The review found that lay support (defined as counseling or social support from peers) but not professional support was significantly associated with improving rates of both “nonexclusive” and “exclusive’ breastfeeding, but only over the short term (5 RCTs, N not provided; RR=1.22; 95% CI, 1.08-1.37; and 4 RCTs, N not provided; RR=1.65; 95% CI, 1.03-2.63; respectively). As with the Cochrane review, the results for all study groups demonstrated moderate to significant heterogeneity.

RECOMMENDATIONS

The Surgeon General, the American Academy of Family Physicians, the American Academy of Pediatrics, and the American College of Obstetricians and Gynecologists all recommend that women be educated about the benefits of breastfeeding and receive supportive interventions before and after delivery.^3-6

EVIDENCE SUMMARY

A 2012 Cochrane review of 52 studies (44 RCTs and 8 cluster-randomized trials; N=56,451) assessed the overall effectiveness of multiple supportive measures on decreasing cessation of “any” (partial and exclusive) and “exclusive” breastfeeding compared with usual care.¹ Participants were healthy breastfeeding mothers of healthy term babies. Support interventions were defined broadly but included individual and group interactions, as well as contact in person or over the phone by professionals or lay volunteers. Patients were approached proactively or reactively upon request, and the interventions occurred one or more times.

The interventions reduced discontinuation rates among both “exclusive” and “any” breastfeeding mothers (TABLE¹). The review found lay and professional support to be equally effective at promoting continuation of breastfeeding. Limitations include a moderate to high amount of heterogeneity, as well as the inherent difficulty of blinding subjects in the studies.

Lay support can make a significant difference in the short term

A 2008 systematic review of 38 RCTs (N=29,020) compared any counseling or behavioral intervention initiated from a clinician’s practice (office or hospital) with usual care.² The review excluded community and peer-initiated interventions. The reviewers defined breastfeeding duration as follows: initiation (up to 2 weeks), short-term (one to 3 months), intermediate-term (4 to 5 months), long-term (6 to 8 months), and prolonged (9 or more months). Investigators also analyzed breastfeeding rates by “exclusive” and “nonexclusive” (formula supplementation) regimens.

For nonexclusive breastfeeding, the review found interventions to promote breastfeeding improved rates only at initiation (18 RCTs, N=7688; relative risk [RR] for cessation of breastfeeding=1.04; 95% confidence interval [CI], 1.0-1.08; number needed to treat [NNT]=38) and in the short term (18 RCTs, N= 19,358; RR=1.10; 95% CI, 1.02-1.19; NNT=7). For exclusive breastfeeding, interventions improved rates only in the short term (17 RCTs, N=20,552; RR=1.72; 95% CI, 1.0-2.97; NNT=3).

The review found that lay support (defined as counseling or social support from peers) but not professional support was significantly associated with improving rates of both “nonexclusive” and “exclusive’ breastfeeding, but only over the short term (5 RCTs, N not provided; RR=1.22; 95% CI, 1.08-1.37; and 4 RCTs, N not provided; RR=1.65; 95% CI, 1.03-2.63; respectively). As with the Cochrane review, the results for all study groups demonstrated moderate to significant heterogeneity.

RECOMMENDATIONS

The Surgeon General, the American Academy of Family Physicians, the American Academy of Pediatrics, and the American College of Obstetricians and Gynecologists all recommend that women be educated about the benefits of breastfeeding and receive supportive interventions before and after delivery.^3-6