Illustrative case

A 23-year-old woman who was diagnosed with irritable bowel syndrome (IBS) comes to your clinic with complaints of increased frequency of defecation with watery stools and generalized, cramping abdominal pain. She also notes increased passage of mucus and a sensation of incomplete evacuation. She says the only thing that relieves her pain is defecation. She has tried loperamide, acetaminophen, and ibuprofen without relief. She does not have Crohn’s disease or ulcerative colitis. What else can you offer her that is safe and effective?

IBS is a chronic, episodic functional gastrointestinal disorder characterized by abdominal pain or discomfort and altered bowel habits (constipation [IBS-C], diarrhea [IBS-D], or alternating periods of both—mixed [IBS-M]).² It is diagnosed based on Rome III criteria—recurrent abdominal pain or discomfort at least 3 days/month in the last 3 months associated with ≥2 of the following: improvement with defecation, onset associated with a change in frequency of stool, and onset associated with a change in form (appearance) of stool.³ IBS often is unrecognized or untreated, and as few as 25% of patients with IBS seek care.⁴

IBS-D affects approximately 5% of the general population in North America.^5,6 IBS-D is associated with a considerably decreased quality of life and is a common cause of work absenteeism.^7,8 Because many conditions can cause diarrhea, patients typically undergo numerous tests before receiving an accurate diagnosis, which creates a financial burden.⁹

For many patients, current IBS treatments, which include fiber supplements, laxatives, antidiarrheal medications, antispasmodics, and antidepressants such as tricyclics and selective serotonin reuptake inhibitors, are unsatisfactory.¹⁰ Alosetron, a 5-hydroxytryptamine 3 (5HT3) receptor antagonist, has been used to treat IBS-D,¹¹ but this medication was voluntarily withdrawn from the US market in 2000 due to concerns of ischemic colitis and severe constipation.¹² It was reintroduced in 2002, but can be prescribed only by physicians who enroll in a prescribing program provided by the manufacturer, and the drug has restrictions on its use.

Ondansetron—a different 5HT3 receptor antagonist used to treat nausea and vomiting caused by chemotherapy—may be another option for treating IBS-D. Garsed et al¹ recently conducted a RCT to evaluate the efficacy of ondansetron for patients with IBS-D.

STUDY SUMMARY: Ondansetron improves stool consistency, severity of IBS symptoms


In a 5-week, double-blind crossover RCT, Garsed et al¹ compared ondansetron vs placebo for symptom relief in 120 patients who met Rome III criteria for IBS-D. All patients were ages 18 to 75 and had no evidence of inflammatory bowel disease. Exclusion criteria were pregnancy or breastfeeding, unwillingness to stop antidiarrheal medication, prior abdominal surgery other than appendectomy or cholecystectomy, or being in another trial. Patients were started on ondansetron 4 mg/d with dose titration up to 24 mg/d based on response; no dose adjustments were allowed during the last 2 weeks of the study. There was a 2- to 3-week washout between treatment periods.

The primary endpoint was average stool consistency in the last 2 weeks of treatment, as measured by the Bristol Stool Form (BSF) scale.¹³ The BSF is a visual scale that depicts stool as hard (Type 1) to watery (Type 7); types 3 and 4 describe normal stools. The study also looked at urgency and frequency of defecation, bowel transit time, and pain scores.

Treatment with ondansetron resulted in a small but statistically significant improvement in stool consistency. The mean difference in BSF score between ondansetron and placebo was -0.9 (95% confidence interval [CI], -1.1 to -0.6; P<.001), indicating slightly more formed stool with use of ondansetron. The IBS Severity Scoring System score (maximum score 500 points, with mild, moderate, and severe cases indicated by scores of 75-175, 175-300, and >300, respectively) was reduced by more points with ondansetron than placebo (83 ± 9.8 vs 37 ± 9.7; P=.001). Although this mean difference of 46 points fell just short of the 50-point threshold that is considered clinically significant, many patients exceeded this threshold.

For patients with IBS-D, ondansetron reduced frequency of defecation and bloating, but did not relieve pain. Compared to those who received placebo, patients who took ondansetron also had less frequent defecation (P=.002) and lower urgency scores (P<.001). Gut transit time was lengthened in the ondansetron group by 10 hours more than in the placebo group (95% CI, 6-14 hours; P<.001). Pain scores did not change significantly for patients taking ondansetron, although they experienced significantly fewer days of urgency and bloating. Symptoms typically improved in as little as 7 days but returned after stopping ondansetron, typically within 2 weeks. Sixty-five percent of patients reported adequate relief with ondansetron, compared to 14% with placebo.

Patients whose diarrhea was more severe at baseline didn’t respond as well to ondansetron as did those whose diarrhea was less severe. The only frequent adverse effect was constipation, which occurred in 9% of patients receiving ondansetron and 2% of those on placebo.

WHAT’S NEW: Another option for IBS patients
 with diarrhea


A prior, smaller study of ondansetron that used a lower dosage (12 mg/d) suggested benefit in IBS-D.¹⁴ In that study, ondansetron decreased diarrhea and functional dyspepsia. The study by Garsed et al¹ is the first large RCT to show significantly improved stool consistency, less frequent defecation, and less urgency and bloating from using ondansetron to treat IBS-D.

CAVEATS: Ondansetron doesn’t appear 
to reduce pain


In Garsed et al,¹ patients who received ondansetron did not experience relief from pain, which is one of the main complaints of IBS. However, this study did find slight improvement in formed stools, symptom relief that approached—but did not quite reach—clinical significance, fewer days with urgency and bloating, and less frequent defecation. This study did not evaluate the long-term effects of ondansetron use. However, ondansetron has been used for other indications for more than 25 years and has been reported to have a low risk of adverse effects.¹⁵

CHALLENGES TO IMPLEMENTATION: Remember ondansetron 
is not for IBS patients with constipation

Proper use of this drug among patients with IBS is key. The primary benefits of ondansetron are limited to IBS patients who suffer from diarrhea, and not constipation. Ondansetron should not be prescribed to IBS patients who experience constipation, or those with mixed symptoms.

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.

Click here to view PURL METHODOLOGY

Illustrative case

A 23-year-old woman who was diagnosed with irritable bowel syndrome (IBS) comes to your clinic with complaints of increased frequency of defecation with watery stools and generalized, cramping abdominal pain. She also notes increased passage of mucus and a sensation of incomplete evacuation. She says the only thing that relieves her pain is defecation. She has tried loperamide, acetaminophen, and ibuprofen without relief. She does not have Crohn’s disease or ulcerative colitis. What else can you offer her that is safe and effective?

IBS is a chronic, episodic functional gastrointestinal disorder characterized by abdominal pain or discomfort and altered bowel habits (constipation [IBS-C], diarrhea [IBS-D], or alternating periods of both—mixed [IBS-M]).² It is diagnosed based on Rome III criteria—recurrent abdominal pain or discomfort at least 3 days/month in the last 3 months associated with ≥2 of the following: improvement with defecation, onset associated with a change in frequency of stool, and onset associated with a change in form (appearance) of stool.³ IBS often is unrecognized or untreated, and as few as 25% of patients with IBS seek care.⁴

IBS-D affects approximately 5% of the general population in North America.^5,6 IBS-D is associated with a considerably decreased quality of life and is a common cause of work absenteeism.^7,8 Because many conditions can cause diarrhea, patients typically undergo numerous tests before receiving an accurate diagnosis, which creates a financial burden.⁹

For many patients, current IBS treatments, which include fiber supplements, laxatives, antidiarrheal medications, antispasmodics, and antidepressants such as tricyclics and selective serotonin reuptake inhibitors, are unsatisfactory.¹⁰ Alosetron, a 5-hydroxytryptamine 3 (5HT3) receptor antagonist, has been used to treat IBS-D,¹¹ but this medication was voluntarily withdrawn from the US market in 2000 due to concerns of ischemic colitis and severe constipation.¹² It was reintroduced in 2002, but can be prescribed only by physicians who enroll in a prescribing program provided by the manufacturer, and the drug has restrictions on its use.

Ondansetron—a different 5HT3 receptor antagonist used to treat nausea and vomiting caused by chemotherapy—may be another option for treating IBS-D. Garsed et al¹ recently conducted a RCT to evaluate the efficacy of ondansetron for patients with IBS-D.

STUDY SUMMARY: Ondansetron improves stool consistency, severity of IBS symptoms


In a 5-week, double-blind crossover RCT, Garsed et al¹ compared ondansetron vs placebo for symptom relief in 120 patients who met Rome III criteria for IBS-D. All patients were ages 18 to 75 and had no evidence of inflammatory bowel disease. Exclusion criteria were pregnancy or breastfeeding, unwillingness to stop antidiarrheal medication, prior abdominal surgery other than appendectomy or cholecystectomy, or being in another trial. Patients were started on ondansetron 4 mg/d with dose titration up to 24 mg/d based on response; no dose adjustments were allowed during the last 2 weeks of the study. There was a 2- to 3-week washout between treatment periods.

The primary endpoint was average stool consistency in the last 2 weeks of treatment, as measured by the Bristol Stool Form (BSF) scale.¹³ The BSF is a visual scale that depicts stool as hard (Type 1) to watery (Type 7); types 3 and 4 describe normal stools. The study also looked at urgency and frequency of defecation, bowel transit time, and pain scores.

Treatment with ondansetron resulted in a small but statistically significant improvement in stool consistency. The mean difference in BSF score between ondansetron and placebo was -0.9 (95% confidence interval [CI], -1.1 to -0.6; P<.001), indicating slightly more formed stool with use of ondansetron. The IBS Severity Scoring System score (maximum score 500 points, with mild, moderate, and severe cases indicated by scores of 75-175, 175-300, and >300, respectively) was reduced by more points with ondansetron than placebo (83 ± 9.8 vs 37 ± 9.7; P=.001). Although this mean difference of 46 points fell just short of the 50-point threshold that is considered clinically significant, many patients exceeded this threshold.

For patients with IBS-D, ondansetron reduced frequency of defecation and bloating, but did not relieve pain. Compared to those who received placebo, patients who took ondansetron also had less frequent defecation (P=.002) and lower urgency scores (P<.001). Gut transit time was lengthened in the ondansetron group by 10 hours more than in the placebo group (95% CI, 6-14 hours; P<.001). Pain scores did not change significantly for patients taking ondansetron, although they experienced significantly fewer days of urgency and bloating. Symptoms typically improved in as little as 7 days but returned after stopping ondansetron, typically within 2 weeks. Sixty-five percent of patients reported adequate relief with ondansetron, compared to 14% with placebo.

Patients whose diarrhea was more severe at baseline didn’t respond as well to ondansetron as did those whose diarrhea was less severe. The only frequent adverse effect was constipation, which occurred in 9% of patients receiving ondansetron and 2% of those on placebo.

WHAT’S NEW: Another option for IBS patients
 with diarrhea


A prior, smaller study of ondansetron that used a lower dosage (12 mg/d) suggested benefit in IBS-D.¹⁴ In that study, ondansetron decreased diarrhea and functional dyspepsia. The study by Garsed et al¹ is the first large RCT to show significantly improved stool consistency, less frequent defecation, and less urgency and bloating from using ondansetron to treat IBS-D.

CAVEATS: Ondansetron doesn’t appear 
to reduce pain


In Garsed et al,¹ patients who received ondansetron did not experience relief from pain, which is one of the main complaints of IBS. However, this study did find slight improvement in formed stools, symptom relief that approached—but did not quite reach—clinical significance, fewer days with urgency and bloating, and less frequent defecation. This study did not evaluate the long-term effects of ondansetron use. However, ondansetron has been used for other indications for more than 25 years and has been reported to have a low risk of adverse effects.¹⁵

CHALLENGES TO IMPLEMENTATION: Remember ondansetron 
is not for IBS patients with constipation

Proper use of this drug among patients with IBS is key. The primary benefits of ondansetron are limited to IBS patients who suffer from diarrhea, and not constipation. Ondansetron should not be prescribed to IBS patients who experience constipation, or those with mixed symptoms.

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.

Click here to view PURL METHODOLOGY

Illustrative case

A 23-year-old woman who was diagnosed with irritable bowel syndrome (IBS) comes to your clinic with complaints of increased frequency of defecation with watery stools and generalized, cramping abdominal pain. She also notes increased passage of mucus and a sensation of incomplete evacuation. She says the only thing that relieves her pain is defecation. She has tried loperamide, acetaminophen, and ibuprofen without relief. She does not have Crohn’s disease or ulcerative colitis. What else can you offer her that is safe and effective?

IBS is a chronic, episodic functional gastrointestinal disorder characterized by abdominal pain or discomfort and altered bowel habits (constipation [IBS-C], diarrhea [IBS-D], or alternating periods of both—mixed [IBS-M]).² It is diagnosed based on Rome III criteria—recurrent abdominal pain or discomfort at least 3 days/month in the last 3 months associated with ≥2 of the following: improvement with defecation, onset associated with a change in frequency of stool, and onset associated with a change in form (appearance) of stool.³ IBS often is unrecognized or untreated, and as few as 25% of patients with IBS seek care.⁴

IBS-D affects approximately 5% of the general population in North America.^5,6 IBS-D is associated with a considerably decreased quality of life and is a common cause of work absenteeism.^7,8 Because many conditions can cause diarrhea, patients typically undergo numerous tests before receiving an accurate diagnosis, which creates a financial burden.⁹

For many patients, current IBS treatments, which include fiber supplements, laxatives, antidiarrheal medications, antispasmodics, and antidepressants such as tricyclics and selective serotonin reuptake inhibitors, are unsatisfactory.¹⁰ Alosetron, a 5-hydroxytryptamine 3 (5HT3) receptor antagonist, has been used to treat IBS-D,¹¹ but this medication was voluntarily withdrawn from the US market in 2000 due to concerns of ischemic colitis and severe constipation.¹² It was reintroduced in 2002, but can be prescribed only by physicians who enroll in a prescribing program provided by the manufacturer, and the drug has restrictions on its use.

Ondansetron—a different 5HT3 receptor antagonist used to treat nausea and vomiting caused by chemotherapy—may be another option for treating IBS-D. Garsed et al¹ recently conducted a RCT to evaluate the efficacy of ondansetron for patients with IBS-D.

STUDY SUMMARY: Ondansetron improves stool consistency, severity of IBS symptoms


In a 5-week, double-blind crossover RCT, Garsed et al¹ compared ondansetron vs placebo for symptom relief in 120 patients who met Rome III criteria for IBS-D. All patients were ages 18 to 75 and had no evidence of inflammatory bowel disease. Exclusion criteria were pregnancy or breastfeeding, unwillingness to stop antidiarrheal medication, prior abdominal surgery other than appendectomy or cholecystectomy, or being in another trial. Patients were started on ondansetron 4 mg/d with dose titration up to 24 mg/d based on response; no dose adjustments were allowed during the last 2 weeks of the study. There was a 2- to 3-week washout between treatment periods.

The primary endpoint was average stool consistency in the last 2 weeks of treatment, as measured by the Bristol Stool Form (BSF) scale.¹³ The BSF is a visual scale that depicts stool as hard (Type 1) to watery (Type 7); types 3 and 4 describe normal stools. The study also looked at urgency and frequency of defecation, bowel transit time, and pain scores.

Treatment with ondansetron resulted in a small but statistically significant improvement in stool consistency. The mean difference in BSF score between ondansetron and placebo was -0.9 (95% confidence interval [CI], -1.1 to -0.6; P<.001), indicating slightly more formed stool with use of ondansetron. The IBS Severity Scoring System score (maximum score 500 points, with mild, moderate, and severe cases indicated by scores of 75-175, 175-300, and >300, respectively) was reduced by more points with ondansetron than placebo (83 ± 9.8 vs 37 ± 9.7; P=.001). Although this mean difference of 46 points fell just short of the 50-point threshold that is considered clinically significant, many patients exceeded this threshold.

For patients with IBS-D, ondansetron reduced frequency of defecation and bloating, but did not relieve pain. Compared to those who received placebo, patients who took ondansetron also had less frequent defecation (P=.002) and lower urgency scores (P<.001). Gut transit time was lengthened in the ondansetron group by 10 hours more than in the placebo group (95% CI, 6-14 hours; P<.001). Pain scores did not change significantly for patients taking ondansetron, although they experienced significantly fewer days of urgency and bloating. Symptoms typically improved in as little as 7 days but returned after stopping ondansetron, typically within 2 weeks. Sixty-five percent of patients reported adequate relief with ondansetron, compared to 14% with placebo.

Patients whose diarrhea was more severe at baseline didn’t respond as well to ondansetron as did those whose diarrhea was less severe. The only frequent adverse effect was constipation, which occurred in 9% of patients receiving ondansetron and 2% of those on placebo.

WHAT’S NEW: Another option for IBS patients
 with diarrhea


A prior, smaller study of ondansetron that used a lower dosage (12 mg/d) suggested benefit in IBS-D.¹⁴ In that study, ondansetron decreased diarrhea and functional dyspepsia. The study by Garsed et al¹ is the first large RCT to show significantly improved stool consistency, less frequent defecation, and less urgency and bloating from using ondansetron to treat IBS-D.

CAVEATS: Ondansetron doesn’t appear 
to reduce pain


In Garsed et al,¹ patients who received ondansetron did not experience relief from pain, which is one of the main complaints of IBS. However, this study did find slight improvement in formed stools, symptom relief that approached—but did not quite reach—clinical significance, fewer days with urgency and bloating, and less frequent defecation. This study did not evaluate the long-term effects of ondansetron use. However, ondansetron has been used for other indications for more than 25 years and has been reported to have a low risk of adverse effects.¹⁵

CHALLENGES TO IMPLEMENTATION: Remember ondansetron 
is not for IBS patients with constipation

Proper use of this drug among patients with IBS is key. The primary benefits of ondansetron are limited to IBS patients who suffer from diarrhea, and not constipation. Ondansetron should not be prescribed to IBS patients who experience constipation, or those with mixed symptoms.

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.

Click here to view PURL METHODOLOGY

The first medical management guidelines for treating the bacteria listeria during pregnancy were recently released by the American College of Obstetricians and Gynecologists (ACOG).¹

The new guidelines were developed in response to recent reports of recalls of listeria-contaminated food and concern because data show the incidence of listeriosis among pregnant women is approximately 13 times higher than in the general population.¹ Maternal listeriosis can cause significant fetal and perinatal complications, including miscarriage, preterm labor, stillbirth, as well as neonatal listeriosis and neonatal death.²

“It is essential for ObGyns not only to be aware of the best ways to manage the care of a pregnant patient who has been exposed to listeria bacteria, but, just as important, to counsel pregnant women regarding how to avoid potential exposure,” said Jeffrey L. Ecker, MD, chair of the ACOG Committee on Obstetric Practice.²

Symptoms of listeriosis are similar to a flu-like infection and can include fever, muscle pain, backache, headache, and gastrointestinal symptoms, including diarrhea.²

The Committee Opinion offers management recommendations for three scenarios¹:

• Asymptomatic women who have been exposed to listeria: No testing is necessary unless symptoms develop within 2 months of exposure. Listeriosis-related fetal surveillance is unnecessary.
• No fever, with mild symptoms consistent with listeriosis: A pregnant woman who has been exposed to a listeria-containing food and is displaying mild symptoms, but does not have a fever, does not require culture testing (although it may be done). If her blood is tested, the laboratory should be informed about the listeriosis threat so that the bacteria is not confused with a contaminant.
• Fever, with or without symptoms consistent with listeriosis: A pregnant woman who has been exposed and has a fever exceeding 100.6°F should undergo blood culture testing. Because results will not be available for several days, the Committee Opinion recommends simultaneous listeriosis treatment for the patient and surveillance of the fetus.

Preventive measures to avoid listeria exposure include not eating the following foods¹:

• hot dogs, lunch meats, cold cuts served cold or heated to less than 165°F
• refrigerated pate and meat spreads
• refrigerated smoked seafood
• raw (unpasteurized) milk
• unpasteurized soft cheese (feta, queso blanco, Brie, blue-veined cheeses)
• unwashed raw produce (when eating raw fruits and vegetables, skin should be washed thoroughly in running tap water, even if it will be peeled or cut).

Share your thoughts on this news! Send your Letter to the Editor to [email protected]. Please include your name, and the city and state in which you practice.

The first medical management guidelines for treating the bacteria listeria during pregnancy were recently released by the American College of Obstetricians and Gynecologists (ACOG).¹

The new guidelines were developed in response to recent reports of recalls of listeria-contaminated food and concern because data show the incidence of listeriosis among pregnant women is approximately 13 times higher than in the general population.¹ Maternal listeriosis can cause significant fetal and perinatal complications, including miscarriage, preterm labor, stillbirth, as well as neonatal listeriosis and neonatal death.²

“It is essential for ObGyns not only to be aware of the best ways to manage the care of a pregnant patient who has been exposed to listeria bacteria, but, just as important, to counsel pregnant women regarding how to avoid potential exposure,” said Jeffrey L. Ecker, MD, chair of the ACOG Committee on Obstetric Practice.²

Symptoms of listeriosis are similar to a flu-like infection and can include fever, muscle pain, backache, headache, and gastrointestinal symptoms, including diarrhea.²

The Committee Opinion offers management recommendations for three scenarios¹:

• Asymptomatic women who have been exposed to listeria: No testing is necessary unless symptoms develop within 2 months of exposure. Listeriosis-related fetal surveillance is unnecessary.
• No fever, with mild symptoms consistent with listeriosis: A pregnant woman who has been exposed to a listeria-containing food and is displaying mild symptoms, but does not have a fever, does not require culture testing (although it may be done). If her blood is tested, the laboratory should be informed about the listeriosis threat so that the bacteria is not confused with a contaminant.
• Fever, with or without symptoms consistent with listeriosis: A pregnant woman who has been exposed and has a fever exceeding 100.6°F should undergo blood culture testing. Because results will not be available for several days, the Committee Opinion recommends simultaneous listeriosis treatment for the patient and surveillance of the fetus.

Preventive measures to avoid listeria exposure include not eating the following foods¹:

• hot dogs, lunch meats, cold cuts served cold or heated to less than 165°F
• refrigerated pate and meat spreads
• refrigerated smoked seafood
• raw (unpasteurized) milk
• unpasteurized soft cheese (feta, queso blanco, Brie, blue-veined cheeses)
• unwashed raw produce (when eating raw fruits and vegetables, skin should be washed thoroughly in running tap water, even if it will be peeled or cut).

Share your thoughts on this news! Send your Letter to the Editor to [email protected]. Please include your name, and the city and state in which you practice.

The first medical management guidelines for treating the bacteria listeria during pregnancy were recently released by the American College of Obstetricians and Gynecologists (ACOG).¹

The new guidelines were developed in response to recent reports of recalls of listeria-contaminated food and concern because data show the incidence of listeriosis among pregnant women is approximately 13 times higher than in the general population.¹ Maternal listeriosis can cause significant fetal and perinatal complications, including miscarriage, preterm labor, stillbirth, as well as neonatal listeriosis and neonatal death.²

“It is essential for ObGyns not only to be aware of the best ways to manage the care of a pregnant patient who has been exposed to listeria bacteria, but, just as important, to counsel pregnant women regarding how to avoid potential exposure,” said Jeffrey L. Ecker, MD, chair of the ACOG Committee on Obstetric Practice.²

Symptoms of listeriosis are similar to a flu-like infection and can include fever, muscle pain, backache, headache, and gastrointestinal symptoms, including diarrhea.²

The Committee Opinion offers management recommendations for three scenarios¹:

• Asymptomatic women who have been exposed to listeria: No testing is necessary unless symptoms develop within 2 months of exposure. Listeriosis-related fetal surveillance is unnecessary.
• No fever, with mild symptoms consistent with listeriosis: A pregnant woman who has been exposed to a listeria-containing food and is displaying mild symptoms, but does not have a fever, does not require culture testing (although it may be done). If her blood is tested, the laboratory should be informed about the listeriosis threat so that the bacteria is not confused with a contaminant.
• Fever, with or without symptoms consistent with listeriosis: A pregnant woman who has been exposed and has a fever exceeding 100.6°F should undergo blood culture testing. Because results will not be available for several days, the Committee Opinion recommends simultaneous listeriosis treatment for the patient and surveillance of the fetus.

Preventive measures to avoid listeria exposure include not eating the following foods¹:

• hot dogs, lunch meats, cold cuts served cold or heated to less than 165°F
• refrigerated pate and meat spreads
• refrigerated smoked seafood
• raw (unpasteurized) milk
• unpasteurized soft cheese (feta, queso blanco, Brie, blue-veined cheeses)
• unwashed raw produce (when eating raw fruits and vegetables, skin should be washed thoroughly in running tap water, even if it will be peeled or cut).

Share your thoughts on this news! Send your Letter to the Editor to [email protected]. Please include your name, and the city and state in which you practice.

I think today’s EHRs are like an old-fashioned crank phone and what we really need is an iPhone. Clicking on a checklist of symptoms seldom provides sufficient information about the patient’s illness. “Hypertension” and “type 2 diabetes” are not assessments; they are diagnoses that do not tell the person reading the electronic health record (EHR) how the patient is doing. A diagnosis of “abdominal pain” without a prioritized differential is inadequate, especially in court.

Why is visit documentation too often inadequate? I am convinced it is rarely due to clinician incompetence, laziness, or lack of knowledge, but nearly always due to a combination of inadequate EHR formats and billing documentation requirements that encourage quantity rather than quality. Documentation is no longer driven by the essential need to record the care provided.

I’m sure a lot of you are nodding your heads in agreement. You all know what those EHR notes look like—cluttered with cut-and-pasted information drawn from prior encounters that document no end of details regarding medical, family, and social histories, facts that are often completely irrelevant to the reason the patient is in the office today. And unless one meticulously updates those other elements of the patient’s record, this information pulled into the note may be inaccurate.

I am not the only one complaining. The American Medical Association just published Improving Care: Priorities to Improve Electronic Health Record Usability,¹ which outlines 8 priorities for EHR improvement. The first is to “Enhance physicians’ ability to provide high-quality patient care.” I could not agree more. I think today’s EHRs are like an old-fashioned crank phone and what we really need is an iPhone.

Something has got to change.

So tell me: Have any of you figured out how to use your EHR to enhance the quality of your documentation?

I think today’s EHRs are like an old-fashioned crank phone and what we really need is an iPhone. Clicking on a checklist of symptoms seldom provides sufficient information about the patient’s illness. “Hypertension” and “type 2 diabetes” are not assessments; they are diagnoses that do not tell the person reading the electronic health record (EHR) how the patient is doing. A diagnosis of “abdominal pain” without a prioritized differential is inadequate, especially in court.

Why is visit documentation too often inadequate? I am convinced it is rarely due to clinician incompetence, laziness, or lack of knowledge, but nearly always due to a combination of inadequate EHR formats and billing documentation requirements that encourage quantity rather than quality. Documentation is no longer driven by the essential need to record the care provided.

I’m sure a lot of you are nodding your heads in agreement. You all know what those EHR notes look like—cluttered with cut-and-pasted information drawn from prior encounters that document no end of details regarding medical, family, and social histories, facts that are often completely irrelevant to the reason the patient is in the office today. And unless one meticulously updates those other elements of the patient’s record, this information pulled into the note may be inaccurate.

I am not the only one complaining. The American Medical Association just published Improving Care: Priorities to Improve Electronic Health Record Usability,¹ which outlines 8 priorities for EHR improvement. The first is to “Enhance physicians’ ability to provide high-quality patient care.” I could not agree more. I think today’s EHRs are like an old-fashioned crank phone and what we really need is an iPhone.

Something has got to change.

So tell me: Have any of you figured out how to use your EHR to enhance the quality of your documentation?

I think today’s EHRs are like an old-fashioned crank phone and what we really need is an iPhone. Clicking on a checklist of symptoms seldom provides sufficient information about the patient’s illness. “Hypertension” and “type 2 diabetes” are not assessments; they are diagnoses that do not tell the person reading the electronic health record (EHR) how the patient is doing. A diagnosis of “abdominal pain” without a prioritized differential is inadequate, especially in court.

Why is visit documentation too often inadequate? I am convinced it is rarely due to clinician incompetence, laziness, or lack of knowledge, but nearly always due to a combination of inadequate EHR formats and billing documentation requirements that encourage quantity rather than quality. Documentation is no longer driven by the essential need to record the care provided.

I’m sure a lot of you are nodding your heads in agreement. You all know what those EHR notes look like—cluttered with cut-and-pasted information drawn from prior encounters that document no end of details regarding medical, family, and social histories, facts that are often completely irrelevant to the reason the patient is in the office today. And unless one meticulously updates those other elements of the patient’s record, this information pulled into the note may be inaccurate.

I am not the only one complaining. The American Medical Association just published Improving Care: Priorities to Improve Electronic Health Record Usability,¹ which outlines 8 priorities for EHR improvement. The first is to “Enhance physicians’ ability to provide high-quality patient care.” I could not agree more. I think today’s EHRs are like an old-fashioned crank phone and what we really need is an iPhone.

Something has got to change.

So tell me: Have any of you figured out how to use your EHR to enhance the quality of your documentation?

Uterine rupture, child stillborn: $3.8M net award
At 35 weeks' gestation, a woman went to the emergency department (ED) with abdominal pain, fast heartbeat, and irregular contractions. Her history included three cesarean deliveries, including one with a vertical incision. She was admitted, and a cesarean delivery was planned for the next day. After 8 hours, during which the patient’s condition worsened, an emergency cesarean delivery was undertaken. A full rupture of the uterus was found; the baby’s body had extruded into the mother’s abdomen. The child was stillborn.

PARENTS’ CLAIM The stillbirth could have been avoided if the nurses had communicated the mother’s worsening condition to the physicians.

DEFENDANTS’ DEFENSE After the hospital and physicians settled prior to trial, the case continued against the nurse in charge of the mother’s care and the nurse-staffing group. Negligence was denied; all protocols were followed.

VERDICT A $2.9 million Illinois verdict was returned. With a $900,000 settlement from the hospital and physicians, the net award was $3.8 million.

_______________

Where did rare strep A infection come from?
A 36-year-old woman reported heavy vaginal bleeding to her ObGyn. She underwent endometrial ablation in her physician’s office.

The next day, the woman called the office to report abdominal pain. She was told to stop the medication she was taking, and if the pain continued to the next day, to go to an ED. The next day, the patient went to the ED and was found to be in septic shock. During emergency laparotomy, 50 mL of purulent fluid were drained and an emergency hysterectomy was performed. Three days later, the patient died from pulmonary arrest caused by toxic shock syndrome. An autopsy revealed that the patient’s sepsis was caused by group A streptococci (GAS) infection.

ESTATE’S CLAIM The patient was not a proper candidate for endometrial ablation because of her history of chronic cervical infection. The ObGyn perforated the cervix during the procedure and tried to conceal it. At autopsy, bone wax was found in the rectal lumen that had been used to cover up damage to the cervix. The ObGyn introduced GAS bacteria into the patient’s system. The ObGyn’s staff failed to ask the proper questions when she called the day after the procedure. She should have been told to go directly to the ED.

DEFENDANTS’ DEFENSE The ObGyn did not perforate the cervix or uterus during the procedure. GAS infection is so rare that it would have been difficult to foresee or diagnose. Potentially, the patient had a chronic
cervical infection before ablation.

VERDICT A Texas defense verdict was returned.

_______________

DURING INSERTION, IUD PERFORATES UTERINE WALL; LATER FOUND BELOW LIVER
On July 21, a 46-year-old woman went to an ObGyn for placement of an intrauterine device (IUD). Shortly after the ObGyn inserted the levonorgestrel-releasing intrauterine system (Mirena, Bayer HealthCare), the patient reported severe pelvic and abdominal pain. On July 26, the patient underwent surgical removal of the IUD.

She was discharged on July 29 but continued to report pain. She was readmitted to the hospital the next day and treated for pain. She was bed ridden for 3 weeks after IUD-removal surgery, and had a 3-month recovery before feeling pain free.

PATIENT’S CLAIM The ObGyn was negligent in perforating the patient’s uterine wall during IUD insertion, causing the device to ultimately migrate under the patient’s liver.

DEFENDANTS’ DEFENSE Uterine perforation is a known complication of IUD insertion. The IUD escaped from the patient’s uterus at a later time and not during the insertion procedure.

VERDICT A Florida verdict of $208,839 was returned; the amount was reduced to $161,058 because the medical expenses were written off by the health-care providers.

_______________

Was travel appropriate for this pregnant woman?
A woman with a history of two premature deliveries and one miscarriage became pregnant again. She received prenatal care at an Army hospital. She traveled to Spain, where the baby was born at 31 weeks’ gestation. The baby required treatment in a neonatal intensive care unit (NICU) for 17 days. The child has cerebral palsy, with tetraplegia of all four extremities. She cannot walk without assistance and suffers severe cognitive and vision impairment.

PARENTS’ CLAIM The ObGyn at the Army hospital should not have approved the mother’s request for travel; he did so, despite knowing that the mother was at high risk for premature birth. The military medical hospital to which she was assigned in Spain could not manage a high-risk pregnancy, didn’t have a NICU, and didn’t have specialists to treat premature infants.

DEFENDANTS’ DEFENSE The ObGyn argued that he did not have access to the medical records showing the mother’s history. The patient countered that the ObGyn did indeed have the patient’s records, as he had discussed them with her.

VERDICT A $10,409,700 California verdict was returned against the ObGyn and the government facility.

_______________

Triple-negative BrCa not diagnosed until metastasized: $5.2M
After finding lumps in both breasts, a woman in her 30s saw a nurse practitioner (NP) at an Army hospital. A radiologist reported no mass in the right breast and multiple benign-appearing anechoic lesions in the left breast after bilateral mammography and ultrasonography (US) in July 2008. The Chief of Mammography Services recommended referral to a breast surgeon, but the patient never received the letter. It was placed in her mammography file, not in the treatment file.

In November 2008, the patient returned to the clinic. Bilateral diagnostic mammography and US were ordered, but for unknown reasons, cancelled. US of the left breast was interpreted as benign in January 2009.

After imaging in March 2010, followed by a needle biopsy of the right breast, a radiologist reported finding intermediate-grade infiltrating ductal carcinoma.

The patient sought care outside the military medical system at a large university hospital. In April 2010, stage 3 triple-negative invasive ductal carcinoma (IDC) was identified. The patient underwent chemotherapy, a double mastectomy, removal of 21 lymph nodes, and breast reconstruction. She was given a 60% chance of recurrence in 5–7 years.

PATIENT’S CLAIM It was negligent to not inform her of imaging results. Biopsy should have been performed in 2008, when the IDC was likely at stage 1; treatment would have been far less aggressive. Electronic medical records showed that the 2008 mammography and US results had been “signed off” by an NP at the clinic.

DEFENDANTS’ DEFENSE While unable to concede liability, the government agency did not contest the point.

VERDICT A $5.2 million Tennessee federal court bench verdict was returned, citing failures in communication, poor and improper record keeping and retention, failure to follow-up, and an unexplained cancellation of a medical order.

_______________

Woman dies from cervical cancer: $2.3M
In 2001, a 41-year-old woman had abnormal Pap smear results but her gynecologist did not order more testing. The patient was told to return in 3 months, but she did not return until 2007—reporting abnormal bleeding, vaginal discharge, and pain. Her Pap results were normal, however, and the gynecologist did not order further testing. In 2009, the patient was found to have advanced cervical cancer. She died 2 years later.

ESTATE’S CLAIM Further testing should have been ordered in 2001, which would have likely revealed dysplasia, which can lead to cancer. The laboratory incorrectly interpreted the 2007 Pap test; if the results had been properly reported, additional testing could have been ordered.

DEFENDANTS’ DEFENSE The laboratory and patient’s estate settled for a confidential amount before trial. The gynecologist denied negligence.

VERDICT A New Jersey jury found the gynecologist 40% at fault for his actions in 2007. The jury found the laboratory 50% at fault, and the patient 10% at fault. A gross verdict of $2.33 million was returned.

_______________
 

Bowel injury after cesarean delivery; mother dies of sepsis
At 40 4/7 weeks' gestation, a 37-year-old woman gave birth to a healthy child by cesarean delivery. The next day, the patient had an elevated white blood cell (WBC) count with a left shift, her abdomen was tympanic but soft, and she was passing flatus and belching. The ObGyn ordered a Fleet enema; only flatus was released. A covering ObGyn ordered an abdominal radiograph, which the radiologist reported as showing postoperative ileus and mild constipation. The patient was given a second Fleet enema the next day, resulting in watery stool. She vomited 300 mL of dark green fluid.

After a rectal tube was placed 2 days later, one hard brown stool and several brown, pasty, loose, and liquid stools were returned. She vomited several times that day, and was found to have hypoactive bowel sounds with continued tympanic quality in the upper quadrants. Laboratory testing revealed continued elevated WBC count with left shift. The next day, she had hypoactive bowel sounds with brown liquid stools. Later that morning, she was able to tolerate clear liquids. The ObGyn decided to discharge her home with instructions to continue on a clear liquid diet for 2 more days before advancing her diet.

The day after discharge, she was found unresponsive at home. She was taken to the hospital, but resuscitation attempts failed. She died. An autopsy revealed that the cause of death was sepsis.

ESTATE’S CLAIM The ObGyn was negligent in failing to diagnose and treat a postoperative intra-abdominal infection caused by bowel perforation. A surgical consult should have been obtained. The woman was prematurely discharged. The radiologist failed to report the presence of free air on the abdominal x-ray.

DEFENDANTS’ DEFENSE The case was settled during trial.

VERDICT A $1 million Maryland settlement was reached. 

_______________

Right ureter injury detected and repaired
During laparoscopic-assisted vaginal hysterectomy, the ObGyn detected and repaired an injury to the right ureter. The patient’s recovery was delayed by the injury.

PATIENT’S CLAIM The ObGyn was negligent in using a Kleppinger bipolar cauterizing instrument to cauterize the vaginal cuff. Thermal overspray from the instrument or the instrument itself damaged the ureter. The ObGyn was also negligent in not performing diagnostic cystoscopy to confirm patency of the ureter after the repair was made.

PHYSICIAN’S DEFENSE Ureter injury is a known risk of the procedure. All procedures were performed according to protocol.

VERDICT A Florida defense verdict was returned.

_______________

Failure to detect inflammatory BrCa; woman dies
A 42-year-old woman underwent mammography in February 2002 after reporting pain, discoloration, inflammation, and swelling in her left breast. The radiologist who interpreted the mammography suggested a biopsy for a differential diagnosis of mastitis or inflammatory carcinoma. The biopsy results were negative.

The patient’s symptoms persisted, and she underwent US in late May 2002. Another radiologist interpreted the US, noting that the patient could not tolerate compression, which led to less than optimal evaluation. The radiologist suggested that mastitis was the likely cause of the patient’s symptoms.

The patient then consulted a surgeon, who ordered mammography and magnetic resonance imaging (MRI) followed by biopsy, which indicated cancer. The patient underwent a mastectomy but metastasis had already occurred. She died at age 50 prior to the trial.

ESTATE’S CLAIM If the cancer had been diagnosed earlier, the outcome would have been better. Both radiologists misinterpreted the mammographies.

DEFENDANTS’ DEFENSE The mammographies had been properly interpreted. Any missed diagnosis would not have impacted the outcome due to the type of cancer. The scans had been released to the patient, but were subsequently lost; an adverse interference instruction was given to the jury.

VERDICT A New York defense verdict was returned.

These cases were selected by the editors of OBG Management from Medical Malpractice Verdicts, Settlements & Experts, with permission of the editor, Lewis Laska (www.verdictslaska.com). The information available to the editors about the cases presented here is sometimes incomplete. Moreover, the cases may or may not have merit. Nevertheless, these cases represent the types of clinical situations that typically result in litigation and are meant to illustrate nationwide variation in jury verdicts and awards.

Share your thoughts on this article! Send your Letter to the Editor to [email protected]. Please include your name and the city and state in which you practice.

Uterine rupture, child stillborn: $3.8M net award
At 35 weeks' gestation, a woman went to the emergency department (ED) with abdominal pain, fast heartbeat, and irregular contractions. Her history included three cesarean deliveries, including one with a vertical incision. She was admitted, and a cesarean delivery was planned for the next day. After 8 hours, during which the patient’s condition worsened, an emergency cesarean delivery was undertaken. A full rupture of the uterus was found; the baby’s body had extruded into the mother’s abdomen. The child was stillborn.

PARENTS’ CLAIM The stillbirth could have been avoided if the nurses had communicated the mother’s worsening condition to the physicians.

DEFENDANTS’ DEFENSE After the hospital and physicians settled prior to trial, the case continued against the nurse in charge of the mother’s care and the nurse-staffing group. Negligence was denied; all protocols were followed.

VERDICT A $2.9 million Illinois verdict was returned. With a $900,000 settlement from the hospital and physicians, the net award was $3.8 million.

_______________

Where did rare strep A infection come from?
A 36-year-old woman reported heavy vaginal bleeding to her ObGyn. She underwent endometrial ablation in her physician’s office.

The next day, the woman called the office to report abdominal pain. She was told to stop the medication she was taking, and if the pain continued to the next day, to go to an ED. The next day, the patient went to the ED and was found to be in septic shock. During emergency laparotomy, 50 mL of purulent fluid were drained and an emergency hysterectomy was performed. Three days later, the patient died from pulmonary arrest caused by toxic shock syndrome. An autopsy revealed that the patient’s sepsis was caused by group A streptococci (GAS) infection.

ESTATE’S CLAIM The patient was not a proper candidate for endometrial ablation because of her history of chronic cervical infection. The ObGyn perforated the cervix during the procedure and tried to conceal it. At autopsy, bone wax was found in the rectal lumen that had been used to cover up damage to the cervix. The ObGyn introduced GAS bacteria into the patient’s system. The ObGyn’s staff failed to ask the proper questions when she called the day after the procedure. She should have been told to go directly to the ED.

DEFENDANTS’ DEFENSE The ObGyn did not perforate the cervix or uterus during the procedure. GAS infection is so rare that it would have been difficult to foresee or diagnose. Potentially, the patient had a chronic
cervical infection before ablation.

VERDICT A Texas defense verdict was returned.

_______________

DURING INSERTION, IUD PERFORATES UTERINE WALL; LATER FOUND BELOW LIVER
On July 21, a 46-year-old woman went to an ObGyn for placement of an intrauterine device (IUD). Shortly after the ObGyn inserted the levonorgestrel-releasing intrauterine system (Mirena, Bayer HealthCare), the patient reported severe pelvic and abdominal pain. On July 26, the patient underwent surgical removal of the IUD.

She was discharged on July 29 but continued to report pain. She was readmitted to the hospital the next day and treated for pain. She was bed ridden for 3 weeks after IUD-removal surgery, and had a 3-month recovery before feeling pain free.

PATIENT’S CLAIM The ObGyn was negligent in perforating the patient’s uterine wall during IUD insertion, causing the device to ultimately migrate under the patient’s liver.

DEFENDANTS’ DEFENSE Uterine perforation is a known complication of IUD insertion. The IUD escaped from the patient’s uterus at a later time and not during the insertion procedure.

VERDICT A Florida verdict of $208,839 was returned; the amount was reduced to $161,058 because the medical expenses were written off by the health-care providers.

_______________

Was travel appropriate for this pregnant woman?
A woman with a history of two premature deliveries and one miscarriage became pregnant again. She received prenatal care at an Army hospital. She traveled to Spain, where the baby was born at 31 weeks’ gestation. The baby required treatment in a neonatal intensive care unit (NICU) for 17 days. The child has cerebral palsy, with tetraplegia of all four extremities. She cannot walk without assistance and suffers severe cognitive and vision impairment.

PARENTS’ CLAIM The ObGyn at the Army hospital should not have approved the mother’s request for travel; he did so, despite knowing that the mother was at high risk for premature birth. The military medical hospital to which she was assigned in Spain could not manage a high-risk pregnancy, didn’t have a NICU, and didn’t have specialists to treat premature infants.

DEFENDANTS’ DEFENSE The ObGyn argued that he did not have access to the medical records showing the mother’s history. The patient countered that the ObGyn did indeed have the patient’s records, as he had discussed them with her.

VERDICT A $10,409,700 California verdict was returned against the ObGyn and the government facility.

_______________

Triple-negative BrCa not diagnosed until metastasized: $5.2M
After finding lumps in both breasts, a woman in her 30s saw a nurse practitioner (NP) at an Army hospital. A radiologist reported no mass in the right breast and multiple benign-appearing anechoic lesions in the left breast after bilateral mammography and ultrasonography (US) in July 2008. The Chief of Mammography Services recommended referral to a breast surgeon, but the patient never received the letter. It was placed in her mammography file, not in the treatment file.

In November 2008, the patient returned to the clinic. Bilateral diagnostic mammography and US were ordered, but for unknown reasons, cancelled. US of the left breast was interpreted as benign in January 2009.

After imaging in March 2010, followed by a needle biopsy of the right breast, a radiologist reported finding intermediate-grade infiltrating ductal carcinoma.

The patient sought care outside the military medical system at a large university hospital. In April 2010, stage 3 triple-negative invasive ductal carcinoma (IDC) was identified. The patient underwent chemotherapy, a double mastectomy, removal of 21 lymph nodes, and breast reconstruction. She was given a 60% chance of recurrence in 5–7 years.

PATIENT’S CLAIM It was negligent to not inform her of imaging results. Biopsy should have been performed in 2008, when the IDC was likely at stage 1; treatment would have been far less aggressive. Electronic medical records showed that the 2008 mammography and US results had been “signed off” by an NP at the clinic.

DEFENDANTS’ DEFENSE While unable to concede liability, the government agency did not contest the point.

VERDICT A $5.2 million Tennessee federal court bench verdict was returned, citing failures in communication, poor and improper record keeping and retention, failure to follow-up, and an unexplained cancellation of a medical order.

_______________

Woman dies from cervical cancer: $2.3M
In 2001, a 41-year-old woman had abnormal Pap smear results but her gynecologist did not order more testing. The patient was told to return in 3 months, but she did not return until 2007—reporting abnormal bleeding, vaginal discharge, and pain. Her Pap results were normal, however, and the gynecologist did not order further testing. In 2009, the patient was found to have advanced cervical cancer. She died 2 years later.

ESTATE’S CLAIM Further testing should have been ordered in 2001, which would have likely revealed dysplasia, which can lead to cancer. The laboratory incorrectly interpreted the 2007 Pap test; if the results had been properly reported, additional testing could have been ordered.

DEFENDANTS’ DEFENSE The laboratory and patient’s estate settled for a confidential amount before trial. The gynecologist denied negligence.

VERDICT A New Jersey jury found the gynecologist 40% at fault for his actions in 2007. The jury found the laboratory 50% at fault, and the patient 10% at fault. A gross verdict of $2.33 million was returned.

_______________
 

Bowel injury after cesarean delivery; mother dies of sepsis
At 40 4/7 weeks' gestation, a 37-year-old woman gave birth to a healthy child by cesarean delivery. The next day, the patient had an elevated white blood cell (WBC) count with a left shift, her abdomen was tympanic but soft, and she was passing flatus and belching. The ObGyn ordered a Fleet enema; only flatus was released. A covering ObGyn ordered an abdominal radiograph, which the radiologist reported as showing postoperative ileus and mild constipation. The patient was given a second Fleet enema the next day, resulting in watery stool. She vomited 300 mL of dark green fluid.

After a rectal tube was placed 2 days later, one hard brown stool and several brown, pasty, loose, and liquid stools were returned. She vomited several times that day, and was found to have hypoactive bowel sounds with continued tympanic quality in the upper quadrants. Laboratory testing revealed continued elevated WBC count with left shift. The next day, she had hypoactive bowel sounds with brown liquid stools. Later that morning, she was able to tolerate clear liquids. The ObGyn decided to discharge her home with instructions to continue on a clear liquid diet for 2 more days before advancing her diet.

The day after discharge, she was found unresponsive at home. She was taken to the hospital, but resuscitation attempts failed. She died. An autopsy revealed that the cause of death was sepsis.

ESTATE’S CLAIM The ObGyn was negligent in failing to diagnose and treat a postoperative intra-abdominal infection caused by bowel perforation. A surgical consult should have been obtained. The woman was prematurely discharged. The radiologist failed to report the presence of free air on the abdominal x-ray.

DEFENDANTS’ DEFENSE The case was settled during trial.

VERDICT A $1 million Maryland settlement was reached. 

_______________

Right ureter injury detected and repaired
During laparoscopic-assisted vaginal hysterectomy, the ObGyn detected and repaired an injury to the right ureter. The patient’s recovery was delayed by the injury.

PATIENT’S CLAIM The ObGyn was negligent in using a Kleppinger bipolar cauterizing instrument to cauterize the vaginal cuff. Thermal overspray from the instrument or the instrument itself damaged the ureter. The ObGyn was also negligent in not performing diagnostic cystoscopy to confirm patency of the ureter after the repair was made.

PHYSICIAN’S DEFENSE Ureter injury is a known risk of the procedure. All procedures were performed according to protocol.

VERDICT A Florida defense verdict was returned.

_______________

Failure to detect inflammatory BrCa; woman dies
A 42-year-old woman underwent mammography in February 2002 after reporting pain, discoloration, inflammation, and swelling in her left breast. The radiologist who interpreted the mammography suggested a biopsy for a differential diagnosis of mastitis or inflammatory carcinoma. The biopsy results were negative.

The patient’s symptoms persisted, and she underwent US in late May 2002. Another radiologist interpreted the US, noting that the patient could not tolerate compression, which led to less than optimal evaluation. The radiologist suggested that mastitis was the likely cause of the patient’s symptoms.

The patient then consulted a surgeon, who ordered mammography and magnetic resonance imaging (MRI) followed by biopsy, which indicated cancer. The patient underwent a mastectomy but metastasis had already occurred. She died at age 50 prior to the trial.

ESTATE’S CLAIM If the cancer had been diagnosed earlier, the outcome would have been better. Both radiologists misinterpreted the mammographies.

DEFENDANTS’ DEFENSE The mammographies had been properly interpreted. Any missed diagnosis would not have impacted the outcome due to the type of cancer. The scans had been released to the patient, but were subsequently lost; an adverse interference instruction was given to the jury.

VERDICT A New York defense verdict was returned.

These cases were selected by the editors of OBG Management from Medical Malpractice Verdicts, Settlements & Experts, with permission of the editor, Lewis Laska (www.verdictslaska.com). The information available to the editors about the cases presented here is sometimes incomplete. Moreover, the cases may or may not have merit. Nevertheless, these cases represent the types of clinical situations that typically result in litigation and are meant to illustrate nationwide variation in jury verdicts and awards.

Share your thoughts on this article! Send your Letter to the Editor to [email protected]. Please include your name and the city and state in which you practice.

Uterine rupture, child stillborn: $3.8M net award
At 35 weeks' gestation, a woman went to the emergency department (ED) with abdominal pain, fast heartbeat, and irregular contractions. Her history included three cesarean deliveries, including one with a vertical incision. She was admitted, and a cesarean delivery was planned for the next day. After 8 hours, during which the patient’s condition worsened, an emergency cesarean delivery was undertaken. A full rupture of the uterus was found; the baby’s body had extruded into the mother’s abdomen. The child was stillborn.

PARENTS’ CLAIM The stillbirth could have been avoided if the nurses had communicated the mother’s worsening condition to the physicians.

DEFENDANTS’ DEFENSE After the hospital and physicians settled prior to trial, the case continued against the nurse in charge of the mother’s care and the nurse-staffing group. Negligence was denied; all protocols were followed.

VERDICT A $2.9 million Illinois verdict was returned. With a $900,000 settlement from the hospital and physicians, the net award was $3.8 million.

_______________

Where did rare strep A infection come from?
A 36-year-old woman reported heavy vaginal bleeding to her ObGyn. She underwent endometrial ablation in her physician’s office.

The next day, the woman called the office to report abdominal pain. She was told to stop the medication she was taking, and if the pain continued to the next day, to go to an ED. The next day, the patient went to the ED and was found to be in septic shock. During emergency laparotomy, 50 mL of purulent fluid were drained and an emergency hysterectomy was performed. Three days later, the patient died from pulmonary arrest caused by toxic shock syndrome. An autopsy revealed that the patient’s sepsis was caused by group A streptococci (GAS) infection.

ESTATE’S CLAIM The patient was not a proper candidate for endometrial ablation because of her history of chronic cervical infection. The ObGyn perforated the cervix during the procedure and tried to conceal it. At autopsy, bone wax was found in the rectal lumen that had been used to cover up damage to the cervix. The ObGyn introduced GAS bacteria into the patient’s system. The ObGyn’s staff failed to ask the proper questions when she called the day after the procedure. She should have been told to go directly to the ED.

DEFENDANTS’ DEFENSE The ObGyn did not perforate the cervix or uterus during the procedure. GAS infection is so rare that it would have been difficult to foresee or diagnose. Potentially, the patient had a chronic
cervical infection before ablation.

VERDICT A Texas defense verdict was returned.

_______________

DURING INSERTION, IUD PERFORATES UTERINE WALL; LATER FOUND BELOW LIVER
On July 21, a 46-year-old woman went to an ObGyn for placement of an intrauterine device (IUD). Shortly after the ObGyn inserted the levonorgestrel-releasing intrauterine system (Mirena, Bayer HealthCare), the patient reported severe pelvic and abdominal pain. On July 26, the patient underwent surgical removal of the IUD.

She was discharged on July 29 but continued to report pain. She was readmitted to the hospital the next day and treated for pain. She was bed ridden for 3 weeks after IUD-removal surgery, and had a 3-month recovery before feeling pain free.

PATIENT’S CLAIM The ObGyn was negligent in perforating the patient’s uterine wall during IUD insertion, causing the device to ultimately migrate under the patient’s liver.

DEFENDANTS’ DEFENSE Uterine perforation is a known complication of IUD insertion. The IUD escaped from the patient’s uterus at a later time and not during the insertion procedure.

VERDICT A Florida verdict of $208,839 was returned; the amount was reduced to $161,058 because the medical expenses were written off by the health-care providers.

_______________

Was travel appropriate for this pregnant woman?
A woman with a history of two premature deliveries and one miscarriage became pregnant again. She received prenatal care at an Army hospital. She traveled to Spain, where the baby was born at 31 weeks’ gestation. The baby required treatment in a neonatal intensive care unit (NICU) for 17 days. The child has cerebral palsy, with tetraplegia of all four extremities. She cannot walk without assistance and suffers severe cognitive and vision impairment.

PARENTS’ CLAIM The ObGyn at the Army hospital should not have approved the mother’s request for travel; he did so, despite knowing that the mother was at high risk for premature birth. The military medical hospital to which she was assigned in Spain could not manage a high-risk pregnancy, didn’t have a NICU, and didn’t have specialists to treat premature infants.

DEFENDANTS’ DEFENSE The ObGyn argued that he did not have access to the medical records showing the mother’s history. The patient countered that the ObGyn did indeed have the patient’s records, as he had discussed them with her.

VERDICT A $10,409,700 California verdict was returned against the ObGyn and the government facility.

_______________

Triple-negative BrCa not diagnosed until metastasized: $5.2M
After finding lumps in both breasts, a woman in her 30s saw a nurse practitioner (NP) at an Army hospital. A radiologist reported no mass in the right breast and multiple benign-appearing anechoic lesions in the left breast after bilateral mammography and ultrasonography (US) in July 2008. The Chief of Mammography Services recommended referral to a breast surgeon, but the patient never received the letter. It was placed in her mammography file, not in the treatment file.

In November 2008, the patient returned to the clinic. Bilateral diagnostic mammography and US were ordered, but for unknown reasons, cancelled. US of the left breast was interpreted as benign in January 2009.

After imaging in March 2010, followed by a needle biopsy of the right breast, a radiologist reported finding intermediate-grade infiltrating ductal carcinoma.

The patient sought care outside the military medical system at a large university hospital. In April 2010, stage 3 triple-negative invasive ductal carcinoma (IDC) was identified. The patient underwent chemotherapy, a double mastectomy, removal of 21 lymph nodes, and breast reconstruction. She was given a 60% chance of recurrence in 5–7 years.

PATIENT’S CLAIM It was negligent to not inform her of imaging results. Biopsy should have been performed in 2008, when the IDC was likely at stage 1; treatment would have been far less aggressive. Electronic medical records showed that the 2008 mammography and US results had been “signed off” by an NP at the clinic.

DEFENDANTS’ DEFENSE While unable to concede liability, the government agency did not contest the point.

VERDICT A $5.2 million Tennessee federal court bench verdict was returned, citing failures in communication, poor and improper record keeping and retention, failure to follow-up, and an unexplained cancellation of a medical order.

_______________

Woman dies from cervical cancer: $2.3M
In 2001, a 41-year-old woman had abnormal Pap smear results but her gynecologist did not order more testing. The patient was told to return in 3 months, but she did not return until 2007—reporting abnormal bleeding, vaginal discharge, and pain. Her Pap results were normal, however, and the gynecologist did not order further testing. In 2009, the patient was found to have advanced cervical cancer. She died 2 years later.

ESTATE’S CLAIM Further testing should have been ordered in 2001, which would have likely revealed dysplasia, which can lead to cancer. The laboratory incorrectly interpreted the 2007 Pap test; if the results had been properly reported, additional testing could have been ordered.

DEFENDANTS’ DEFENSE The laboratory and patient’s estate settled for a confidential amount before trial. The gynecologist denied negligence.

VERDICT A New Jersey jury found the gynecologist 40% at fault for his actions in 2007. The jury found the laboratory 50% at fault, and the patient 10% at fault. A gross verdict of $2.33 million was returned.

_______________
 

Bowel injury after cesarean delivery; mother dies of sepsis
At 40 4/7 weeks' gestation, a 37-year-old woman gave birth to a healthy child by cesarean delivery. The next day, the patient had an elevated white blood cell (WBC) count with a left shift, her abdomen was tympanic but soft, and she was passing flatus and belching. The ObGyn ordered a Fleet enema; only flatus was released. A covering ObGyn ordered an abdominal radiograph, which the radiologist reported as showing postoperative ileus and mild constipation. The patient was given a second Fleet enema the next day, resulting in watery stool. She vomited 300 mL of dark green fluid.

After a rectal tube was placed 2 days later, one hard brown stool and several brown, pasty, loose, and liquid stools were returned. She vomited several times that day, and was found to have hypoactive bowel sounds with continued tympanic quality in the upper quadrants. Laboratory testing revealed continued elevated WBC count with left shift. The next day, she had hypoactive bowel sounds with brown liquid stools. Later that morning, she was able to tolerate clear liquids. The ObGyn decided to discharge her home with instructions to continue on a clear liquid diet for 2 more days before advancing her diet.

The day after discharge, she was found unresponsive at home. She was taken to the hospital, but resuscitation attempts failed. She died. An autopsy revealed that the cause of death was sepsis.

ESTATE’S CLAIM The ObGyn was negligent in failing to diagnose and treat a postoperative intra-abdominal infection caused by bowel perforation. A surgical consult should have been obtained. The woman was prematurely discharged. The radiologist failed to report the presence of free air on the abdominal x-ray.

DEFENDANTS’ DEFENSE The case was settled during trial.

VERDICT A $1 million Maryland settlement was reached. 

_______________

Right ureter injury detected and repaired
During laparoscopic-assisted vaginal hysterectomy, the ObGyn detected and repaired an injury to the right ureter. The patient’s recovery was delayed by the injury.

PATIENT’S CLAIM The ObGyn was negligent in using a Kleppinger bipolar cauterizing instrument to cauterize the vaginal cuff. Thermal overspray from the instrument or the instrument itself damaged the ureter. The ObGyn was also negligent in not performing diagnostic cystoscopy to confirm patency of the ureter after the repair was made.

PHYSICIAN’S DEFENSE Ureter injury is a known risk of the procedure. All procedures were performed according to protocol.

VERDICT A Florida defense verdict was returned.

_______________

Failure to detect inflammatory BrCa; woman dies
A 42-year-old woman underwent mammography in February 2002 after reporting pain, discoloration, inflammation, and swelling in her left breast. The radiologist who interpreted the mammography suggested a biopsy for a differential diagnosis of mastitis or inflammatory carcinoma. The biopsy results were negative.

The patient’s symptoms persisted, and she underwent US in late May 2002. Another radiologist interpreted the US, noting that the patient could not tolerate compression, which led to less than optimal evaluation. The radiologist suggested that mastitis was the likely cause of the patient’s symptoms.

The patient then consulted a surgeon, who ordered mammography and magnetic resonance imaging (MRI) followed by biopsy, which indicated cancer. The patient underwent a mastectomy but metastasis had already occurred. She died at age 50 prior to the trial.

ESTATE’S CLAIM If the cancer had been diagnosed earlier, the outcome would have been better. Both radiologists misinterpreted the mammographies.

DEFENDANTS’ DEFENSE The mammographies had been properly interpreted. Any missed diagnosis would not have impacted the outcome due to the type of cancer. The scans had been released to the patient, but were subsequently lost; an adverse interference instruction was given to the jury.

VERDICT A New York defense verdict was returned.

These cases were selected by the editors of OBG Management from Medical Malpractice Verdicts, Settlements & Experts, with permission of the editor, Lewis Laska (www.verdictslaska.com). The information available to the editors about the cases presented here is sometimes incomplete. Moreover, the cases may or may not have merit. Nevertheless, these cases represent the types of clinical situations that typically result in litigation and are meant to illustrate nationwide variation in jury verdicts and awards.

Share your thoughts on this article! Send your Letter to the Editor to [email protected]. Please include your name and the city and state in which you practice.

EVIDENCE SUMMARY

A systematic review of pharmacotherapy for joint pain in patients with SLE found 4 poor-quality RCTs that evaluated hydroxychloroquine, chloroquine, and methotrexate.¹ Of the 2 studies that examined the effect of hydroxychloroquine, one (47 patients) showed a statistically significant 50% reduction in SLE flares (including arthritis, pleuritis, and cutaneous symptoms) over 24 weeks in patients treated with hydroxychloroquine compared with placebo (TABLE^1-8). The second study (71 subjects) found a nonquantified decrease in self-reported pain when hydroxychloroquine was compared with placebo, although some of the patients were also taking prednisone (10 mg/d).

An RCT that evaluated the effect of chloroquine showed a statistically significant reduction in unspecified “articular involvement” compared with placebo.

The authors of the review noted that consensus opinion holds that oral corticosteroids and NSAIDs reduce SLE-associated joint pain, but they found no studies that objectively evaluated either of these interventions.¹

Fish oil also helps arthritis

Two RCTs on the effects of 3 g/d of omega-3 polyunsaturated fatty acids (fish oil) for 24 weeks in SLE patients with mild disease found a reduction in Systemic Lupus Activity Measure-Revised (SLAM-R) scores.^2,3 SLAM-R is a validated measure of SLE disease activity, rated on a scale from 0 to 81, including 23 clinical and 7 laboratory manifestations of disease.

In the first study (52 subjects), disease activity decreased from an average SLAM-R score of 6.1 at baseline to 4.7 (P<.05). The second study (60 subjects) found a similar reduction in mean SLAM-R scores from 9.4 to 6.3 (P<.001) and joint pain scores from 1.27 to 0.83 (P=.047).

Drug treatments don’t significantly relieve fatigue


An industry-sponsored RCT that compared abatacept with placebo found improvements in fatigue that weren’t clinically meaningful in posthoc analysis (-9.45 points difference on a self-reported 0-to-100 visual analog scale; 95% confidence interval, -17.65 to -1.25, with a 10-point reduction considered to be clinically meaningful). Abatacept also had a high rate of serious adverse events, including facial edema, polyneuropathy, and serious infections (24/121 with abatacept vs 4/59 placebo; NNH=8).⁴

Another RCT found no effect of dehydroepiandrosterone on fatigue in women with inactive SLE.⁵


Studies of nondrug treatment of SLE-associated fatigue show inconsistent results. A systematic review of nonpharmacologic interventions for fatigue in several chronic diseases found 2 RCTs and 4 quasi-experimental studies that included 324 patients with SLE.⁶ Of 4 studies that evaluated the effect of exercise, 2 showed improvement and 2 didn’t. Neither group self-management nor relaxation therapy and telephone counseling significantly relieved fatigue.^6-8 A small RCT (24 patients) found no benefit for acupuncture over sham needling in treating pain and fatigue in SLE.⁹

RECOMMENDATIONS

Methotrexate reduced arthralgias by as much as 79%, but produced adverse effects in up to 70% of patients. The American College of Rheumatology guideline for referral and management of SLE states that “NSAIDs are sometimes helpful for control of fever, arthritis, and mild serositis. Antimalarial agents (eg, hydroxychloroquine) are useful for skin and joint manifestations of SLE, for preventing flares, and for other constitutional symptoms of the disease. They may also reduce fatigue.”¹⁰

The European League Against Rheumatism recommends antimalarials or glucocorticoids to treat patients with SLE without major organ manifestations. They also say clinicians may try NSAIDs for limited periods of time in patients at low risk for the drugs’ complications.¹¹

EVIDENCE SUMMARY

A systematic review of pharmacotherapy for joint pain in patients with SLE found 4 poor-quality RCTs that evaluated hydroxychloroquine, chloroquine, and methotrexate.¹ Of the 2 studies that examined the effect of hydroxychloroquine, one (47 patients) showed a statistically significant 50% reduction in SLE flares (including arthritis, pleuritis, and cutaneous symptoms) over 24 weeks in patients treated with hydroxychloroquine compared with placebo (TABLE^1-8). The second study (71 subjects) found a nonquantified decrease in self-reported pain when hydroxychloroquine was compared with placebo, although some of the patients were also taking prednisone (10 mg/d).

An RCT that evaluated the effect of chloroquine showed a statistically significant reduction in unspecified “articular involvement” compared with placebo.

The authors of the review noted that consensus opinion holds that oral corticosteroids and NSAIDs reduce SLE-associated joint pain, but they found no studies that objectively evaluated either of these interventions.¹

Fish oil also helps arthritis

Two RCTs on the effects of 3 g/d of omega-3 polyunsaturated fatty acids (fish oil) for 24 weeks in SLE patients with mild disease found a reduction in Systemic Lupus Activity Measure-Revised (SLAM-R) scores.^2,3 SLAM-R is a validated measure of SLE disease activity, rated on a scale from 0 to 81, including 23 clinical and 7 laboratory manifestations of disease.

In the first study (52 subjects), disease activity decreased from an average SLAM-R score of 6.1 at baseline to 4.7 (P<.05). The second study (60 subjects) found a similar reduction in mean SLAM-R scores from 9.4 to 6.3 (P<.001) and joint pain scores from 1.27 to 0.83 (P=.047).

Drug treatments don’t significantly relieve fatigue


An industry-sponsored RCT that compared abatacept with placebo found improvements in fatigue that weren’t clinically meaningful in posthoc analysis (-9.45 points difference on a self-reported 0-to-100 visual analog scale; 95% confidence interval, -17.65 to -1.25, with a 10-point reduction considered to be clinically meaningful). Abatacept also had a high rate of serious adverse events, including facial edema, polyneuropathy, and serious infections (24/121 with abatacept vs 4/59 placebo; NNH=8).⁴

Another RCT found no effect of dehydroepiandrosterone on fatigue in women with inactive SLE.⁵


Studies of nondrug treatment of SLE-associated fatigue show inconsistent results. A systematic review of nonpharmacologic interventions for fatigue in several chronic diseases found 2 RCTs and 4 quasi-experimental studies that included 324 patients with SLE.⁶ Of 4 studies that evaluated the effect of exercise, 2 showed improvement and 2 didn’t. Neither group self-management nor relaxation therapy and telephone counseling significantly relieved fatigue.^6-8 A small RCT (24 patients) found no benefit for acupuncture over sham needling in treating pain and fatigue in SLE.⁹

RECOMMENDATIONS

Methotrexate reduced arthralgias by as much as 79%, but produced adverse effects in up to 70% of patients. The American College of Rheumatology guideline for referral and management of SLE states that “NSAIDs are sometimes helpful for control of fever, arthritis, and mild serositis. Antimalarial agents (eg, hydroxychloroquine) are useful for skin and joint manifestations of SLE, for preventing flares, and for other constitutional symptoms of the disease. They may also reduce fatigue.”¹⁰

The European League Against Rheumatism recommends antimalarials or glucocorticoids to treat patients with SLE without major organ manifestations. They also say clinicians may try NSAIDs for limited periods of time in patients at low risk for the drugs’ complications.¹¹

EVIDENCE SUMMARY

A systematic review of pharmacotherapy for joint pain in patients with SLE found 4 poor-quality RCTs that evaluated hydroxychloroquine, chloroquine, and methotrexate.¹ Of the 2 studies that examined the effect of hydroxychloroquine, one (47 patients) showed a statistically significant 50% reduction in SLE flares (including arthritis, pleuritis, and cutaneous symptoms) over 24 weeks in patients treated with hydroxychloroquine compared with placebo (TABLE^1-8). The second study (71 subjects) found a nonquantified decrease in self-reported pain when hydroxychloroquine was compared with placebo, although some of the patients were also taking prednisone (10 mg/d).

An RCT that evaluated the effect of chloroquine showed a statistically significant reduction in unspecified “articular involvement” compared with placebo.

The authors of the review noted that consensus opinion holds that oral corticosteroids and NSAIDs reduce SLE-associated joint pain, but they found no studies that objectively evaluated either of these interventions.¹

Fish oil also helps arthritis

Two RCTs on the effects of 3 g/d of omega-3 polyunsaturated fatty acids (fish oil) for 24 weeks in SLE patients with mild disease found a reduction in Systemic Lupus Activity Measure-Revised (SLAM-R) scores.^2,3 SLAM-R is a validated measure of SLE disease activity, rated on a scale from 0 to 81, including 23 clinical and 7 laboratory manifestations of disease.

In the first study (52 subjects), disease activity decreased from an average SLAM-R score of 6.1 at baseline to 4.7 (P<.05). The second study (60 subjects) found a similar reduction in mean SLAM-R scores from 9.4 to 6.3 (P<.001) and joint pain scores from 1.27 to 0.83 (P=.047).

Drug treatments don’t significantly relieve fatigue


An industry-sponsored RCT that compared abatacept with placebo found improvements in fatigue that weren’t clinically meaningful in posthoc analysis (-9.45 points difference on a self-reported 0-to-100 visual analog scale; 95% confidence interval, -17.65 to -1.25, with a 10-point reduction considered to be clinically meaningful). Abatacept also had a high rate of serious adverse events, including facial edema, polyneuropathy, and serious infections (24/121 with abatacept vs 4/59 placebo; NNH=8).⁴

Another RCT found no effect of dehydroepiandrosterone on fatigue in women with inactive SLE.⁵


Studies of nondrug treatment of SLE-associated fatigue show inconsistent results. A systematic review of nonpharmacologic interventions for fatigue in several chronic diseases found 2 RCTs and 4 quasi-experimental studies that included 324 patients with SLE.⁶ Of 4 studies that evaluated the effect of exercise, 2 showed improvement and 2 didn’t. Neither group self-management nor relaxation therapy and telephone counseling significantly relieved fatigue.^6-8 A small RCT (24 patients) found no benefit for acupuncture over sham needling in treating pain and fatigue in SLE.⁹

RECOMMENDATIONS

Methotrexate reduced arthralgias by as much as 79%, but produced adverse effects in up to 70% of patients. The American College of Rheumatology guideline for referral and management of SLE states that “NSAIDs are sometimes helpful for control of fever, arthritis, and mild serositis. Antimalarial agents (eg, hydroxychloroquine) are useful for skin and joint manifestations of SLE, for preventing flares, and for other constitutional symptoms of the disease. They may also reduce fatigue.”¹⁰

The European League Against Rheumatism recommends antimalarials or glucocorticoids to treat patients with SLE without major organ manifestations. They also say clinicians may try NSAIDs for limited periods of time in patients at low risk for the drugs’ complications.¹¹

THE CASE

A 57-year-old Hispanic man sought treatment because he had been feeling tired for a few weeks. He had not seen a physician for 15 years. When he came in, his temperature was 98.8°F, blood pressure was 132/82 mm Hg, pulse was 82 beats/min, respiration rate was 16 breaths/min, and oxygen saturation was 93% on room air. Examination of the head, neck, and respiratory and cardiovascular systems was normal. Skin examination showed petechiae and bruising on his abdomen, left ankle, right thigh, and bilateral shin area. His abdomen was nontender with no organomegaly. There was no focal neurological finding or spinal tenderness. Our patient had no chills, chest pains, shortness of breath, headache, dizziness, or loss of consciousness. There was no hematemesis, melena, hematuria, edema, or weight loss. He had no medical or surgical history and denied substance abuse or taking any medications recently; he did use alcohol previously.

Results of some initial lab tests were abnormal, including a decreased white blood cell count (5.82/mcL), platelet count (29 x 10³/mcL), hemoglobin (8.6 g/dL), and hematocrit (27%) (TABLE). A peripheral blood smear showed decreased normocytic red blood cells and scattered schistocytes. His prostate-specific antigen (PSA) level was elevated at 212 ng/mL.

The patient’s coagulation profile was normal, and his von Willebrand factor (vWF) protease (ADAMTS-13) level was within normal limits (13.83). Antineutrophil cytoplasmic antibody and antinuclear antibody tests were negative. Testing for pulmonary embolism was negative, as was testing for human immunodeficiency virus. An abdominal ultrasound was normal, as well.

THE DIAGNOSIS

Based on our patient’s abnormal blood test results and the presence of petechiae and bruising, we diagnosed thrombotic thrombocytopenic purpura (TTP). The patient’s elevated PSA prompted us to order computed tomography of the chest and abdomen, which showed an enlarged prostate gland and mixed lytic sclerotic lesions in T3 to T5 and T9 vertebrae and in his ribs. A bone marrow biopsy revealed metastatic prostatic adenocarcinoma and a bone scan confirmed multiple metastases in the spine, pelvis, and shoulders.

DISCUSSION

TTP is a rare disorder of increased clotting in small blood vessels throughout the body that can include thrombocytopenia, microangiopathic hemolytic anemia (MAHA), fever, renal dysfunction, and neurological deficits.¹ It’s important to maintain a high index of suspicion for TTP because the condition is a hematologic medical emergency that can quickly cause multiorgan failure and death.²

Cancer-associated TTP could be a complication from chemotherapy or a manifestation of the cancer itself. Almost always an acquired condition, TTP can be idiopathic or secondary to another condition, such as collagen vascular diseases, transplants, certain drugs, infections, pregnancy, or cancer.³ In idiopathic TTP, the cause of the condition is believed to be reduced activity of ADAMTS-13, the protease that breaks vWF into smaller pieces—thus preventing the formation of unnecessary blood clots.

In cancer-associated TTP, which could be a complication resulting from chemotherapy or a manifestation of cancer itself,³ ADAMTS-13 level is normal and the condition is likely the result of an increased tumor cell load, which leads to endothelial damage and fragmentation of red blood cells (RBC) as they traverse the injured microvasculature.⁴ In an analysis of 154 cases of “solid” cancer-related MAHA, Lechner and Obermeier⁵ found 23 cases were related to prostate cancer, as was the case with our patient.

Treatment for TTP is plasma exchange. The mortality rate of untreated TTP can exceed 90%, but plasma exchange therapy has reduced that rate to <20%.⁶ It has been suggested that proteolysis of vWF may play a central role in the efficacy of plasma exchange for TTP.⁷

Our patient was hospitalized and received 2 units of packed RBCs. He also received plasma exchange for 9 days with minimal response. On Day 5, our patient was started on leuprorelin and parenteral steroids. Soon after, his platelet count rose to 33 × 10³/mcL and lactate dehydrogenase decreased. He was discharged approximately one week after the steroids were started.

After several months of outpatient treatment with leuprorelin and bicalutamide, the patient’s platelet count normalized to 212 × 10³/mcL (from 29 × 10³/mcL), alkaline phosphatase decreased to 402 U/L (from 1919 U/L), and PSA levels trended downward to 8.63 ng/mL (from 212 ng/mL). He continued to receive care from our oncology clinic for the next several months and his PSA level continued to decline. However, at his last few visits, his PSA level had trended up, suggesting progression of his prostate cancer. The patient has not followed up with our clinic recently.

THE TAKEAWAY

Suspect TTP in patients who present with unexplained petechiae and bruising, and whose blood work reveals thrombocytopenia and MAHA.² Patients with TTP who do not respond to plasma exchange should be evaluated for underlying cancer or other potential secondary causes.³ Patients with cancer-associated TTP may respond to steroid therapy.

THE CASE

A 57-year-old Hispanic man sought treatment because he had been feeling tired for a few weeks. He had not seen a physician for 15 years. When he came in, his temperature was 98.8°F, blood pressure was 132/82 mm Hg, pulse was 82 beats/min, respiration rate was 16 breaths/min, and oxygen saturation was 93% on room air. Examination of the head, neck, and respiratory and cardiovascular systems was normal. Skin examination showed petechiae and bruising on his abdomen, left ankle, right thigh, and bilateral shin area. His abdomen was nontender with no organomegaly. There was no focal neurological finding or spinal tenderness. Our patient had no chills, chest pains, shortness of breath, headache, dizziness, or loss of consciousness. There was no hematemesis, melena, hematuria, edema, or weight loss. He had no medical or surgical history and denied substance abuse or taking any medications recently; he did use alcohol previously.

Results of some initial lab tests were abnormal, including a decreased white blood cell count (5.82/mcL), platelet count (29 x 10³/mcL), hemoglobin (8.6 g/dL), and hematocrit (27%) (TABLE). A peripheral blood smear showed decreased normocytic red blood cells and scattered schistocytes. His prostate-specific antigen (PSA) level was elevated at 212 ng/mL.

The patient’s coagulation profile was normal, and his von Willebrand factor (vWF) protease (ADAMTS-13) level was within normal limits (13.83). Antineutrophil cytoplasmic antibody and antinuclear antibody tests were negative. Testing for pulmonary embolism was negative, as was testing for human immunodeficiency virus. An abdominal ultrasound was normal, as well.

THE DIAGNOSIS

Based on our patient’s abnormal blood test results and the presence of petechiae and bruising, we diagnosed thrombotic thrombocytopenic purpura (TTP). The patient’s elevated PSA prompted us to order computed tomography of the chest and abdomen, which showed an enlarged prostate gland and mixed lytic sclerotic lesions in T3 to T5 and T9 vertebrae and in his ribs. A bone marrow biopsy revealed metastatic prostatic adenocarcinoma and a bone scan confirmed multiple metastases in the spine, pelvis, and shoulders.

DISCUSSION

TTP is a rare disorder of increased clotting in small blood vessels throughout the body that can include thrombocytopenia, microangiopathic hemolytic anemia (MAHA), fever, renal dysfunction, and neurological deficits.¹ It’s important to maintain a high index of suspicion for TTP because the condition is a hematologic medical emergency that can quickly cause multiorgan failure and death.²

Cancer-associated TTP could be a complication from chemotherapy or a manifestation of the cancer itself. Almost always an acquired condition, TTP can be idiopathic or secondary to another condition, such as collagen vascular diseases, transplants, certain drugs, infections, pregnancy, or cancer.³ In idiopathic TTP, the cause of the condition is believed to be reduced activity of ADAMTS-13, the protease that breaks vWF into smaller pieces—thus preventing the formation of unnecessary blood clots.

In cancer-associated TTP, which could be a complication resulting from chemotherapy or a manifestation of cancer itself,³ ADAMTS-13 level is normal and the condition is likely the result of an increased tumor cell load, which leads to endothelial damage and fragmentation of red blood cells (RBC) as they traverse the injured microvasculature.⁴ In an analysis of 154 cases of “solid” cancer-related MAHA, Lechner and Obermeier⁵ found 23 cases were related to prostate cancer, as was the case with our patient.

Treatment for TTP is plasma exchange. The mortality rate of untreated TTP can exceed 90%, but plasma exchange therapy has reduced that rate to <20%.⁶ It has been suggested that proteolysis of vWF may play a central role in the efficacy of plasma exchange for TTP.⁷

Our patient was hospitalized and received 2 units of packed RBCs. He also received plasma exchange for 9 days with minimal response. On Day 5, our patient was started on leuprorelin and parenteral steroids. Soon after, his platelet count rose to 33 × 10³/mcL and lactate dehydrogenase decreased. He was discharged approximately one week after the steroids were started.

After several months of outpatient treatment with leuprorelin and bicalutamide, the patient’s platelet count normalized to 212 × 10³/mcL (from 29 × 10³/mcL), alkaline phosphatase decreased to 402 U/L (from 1919 U/L), and PSA levels trended downward to 8.63 ng/mL (from 212 ng/mL). He continued to receive care from our oncology clinic for the next several months and his PSA level continued to decline. However, at his last few visits, his PSA level had trended up, suggesting progression of his prostate cancer. The patient has not followed up with our clinic recently.

THE TAKEAWAY

Suspect TTP in patients who present with unexplained petechiae and bruising, and whose blood work reveals thrombocytopenia and MAHA.² Patients with TTP who do not respond to plasma exchange should be evaluated for underlying cancer or other potential secondary causes.³ Patients with cancer-associated TTP may respond to steroid therapy.

THE CASE

A 57-year-old Hispanic man sought treatment because he had been feeling tired for a few weeks. He had not seen a physician for 15 years. When he came in, his temperature was 98.8°F, blood pressure was 132/82 mm Hg, pulse was 82 beats/min, respiration rate was 16 breaths/min, and oxygen saturation was 93% on room air. Examination of the head, neck, and respiratory and cardiovascular systems was normal. Skin examination showed petechiae and bruising on his abdomen, left ankle, right thigh, and bilateral shin area. His abdomen was nontender with no organomegaly. There was no focal neurological finding or spinal tenderness. Our patient had no chills, chest pains, shortness of breath, headache, dizziness, or loss of consciousness. There was no hematemesis, melena, hematuria, edema, or weight loss. He had no medical or surgical history and denied substance abuse or taking any medications recently; he did use alcohol previously.

Results of some initial lab tests were abnormal, including a decreased white blood cell count (5.82/mcL), platelet count (29 x 10³/mcL), hemoglobin (8.6 g/dL), and hematocrit (27%) (TABLE). A peripheral blood smear showed decreased normocytic red blood cells and scattered schistocytes. His prostate-specific antigen (PSA) level was elevated at 212 ng/mL.

The patient’s coagulation profile was normal, and his von Willebrand factor (vWF) protease (ADAMTS-13) level was within normal limits (13.83). Antineutrophil cytoplasmic antibody and antinuclear antibody tests were negative. Testing for pulmonary embolism was negative, as was testing for human immunodeficiency virus. An abdominal ultrasound was normal, as well.

THE DIAGNOSIS

Based on our patient’s abnormal blood test results and the presence of petechiae and bruising, we diagnosed thrombotic thrombocytopenic purpura (TTP). The patient’s elevated PSA prompted us to order computed tomography of the chest and abdomen, which showed an enlarged prostate gland and mixed lytic sclerotic lesions in T3 to T5 and T9 vertebrae and in his ribs. A bone marrow biopsy revealed metastatic prostatic adenocarcinoma and a bone scan confirmed multiple metastases in the spine, pelvis, and shoulders.

DISCUSSION

TTP is a rare disorder of increased clotting in small blood vessels throughout the body that can include thrombocytopenia, microangiopathic hemolytic anemia (MAHA), fever, renal dysfunction, and neurological deficits.¹ It’s important to maintain a high index of suspicion for TTP because the condition is a hematologic medical emergency that can quickly cause multiorgan failure and death.²

Cancer-associated TTP could be a complication from chemotherapy or a manifestation of the cancer itself. Almost always an acquired condition, TTP can be idiopathic or secondary to another condition, such as collagen vascular diseases, transplants, certain drugs, infections, pregnancy, or cancer.³ In idiopathic TTP, the cause of the condition is believed to be reduced activity of ADAMTS-13, the protease that breaks vWF into smaller pieces—thus preventing the formation of unnecessary blood clots.

In cancer-associated TTP, which could be a complication resulting from chemotherapy or a manifestation of cancer itself,³ ADAMTS-13 level is normal and the condition is likely the result of an increased tumor cell load, which leads to endothelial damage and fragmentation of red blood cells (RBC) as they traverse the injured microvasculature.⁴ In an analysis of 154 cases of “solid” cancer-related MAHA, Lechner and Obermeier⁵ found 23 cases were related to prostate cancer, as was the case with our patient.

Treatment for TTP is plasma exchange. The mortality rate of untreated TTP can exceed 90%, but plasma exchange therapy has reduced that rate to <20%.⁶ It has been suggested that proteolysis of vWF may play a central role in the efficacy of plasma exchange for TTP.⁷

Our patient was hospitalized and received 2 units of packed RBCs. He also received plasma exchange for 9 days with minimal response. On Day 5, our patient was started on leuprorelin and parenteral steroids. Soon after, his platelet count rose to 33 × 10³/mcL and lactate dehydrogenase decreased. He was discharged approximately one week after the steroids were started.

After several months of outpatient treatment with leuprorelin and bicalutamide, the patient’s platelet count normalized to 212 × 10³/mcL (from 29 × 10³/mcL), alkaline phosphatase decreased to 402 U/L (from 1919 U/L), and PSA levels trended downward to 8.63 ng/mL (from 212 ng/mL). He continued to receive care from our oncology clinic for the next several months and his PSA level continued to decline. However, at his last few visits, his PSA level had trended up, suggesting progression of his prostate cancer. The patient has not followed up with our clinic recently.

THE TAKEAWAY

Suspect TTP in patients who present with unexplained petechiae and bruising, and whose blood work reveals thrombocytopenia and MAHA.² Patients with TTP who do not respond to plasma exchange should be evaluated for underlying cancer or other potential secondary causes.³ Patients with cancer-associated TTP may respond to steroid therapy.

THE CASE

A 63-year-old multiparous woman visited her general practitioner because of nausea, vomiting, and general malaise. A proton pump inhibitor was prescribed, which temporarily relieved her symptoms. Two weeks later, however, her symptoms worsened and she was admitted to the hospital.

The patient’s physical examination on admission was normal, but laboratory findings revealed severe renal failure with a creatinine level of 7.4 mg/dL (normal, 0.6-1.1 mg/dL), potassium level of 7.4 mmol/L (3.5-5 mmol/L), and a sodium level of 123 mmol/L (135-145 mmol/L). A renal ultrasound revealed severe bilateral hydronephrosis with hydroureteronephrosis caused by obstructive uropathy. A radiologist examined the patient and determined that she had a total uterine prolapse; the cervix was 11 cm outside of the vagina (FIGURE 1). Our patient’s untreated pelvic organ prolapse (POP) had caused chronic renal failure. The patient was referred to a urogynecologist.

Previous attempts at treatment. It appeared that our patient had POP for years and there had been a previous attempt to treat it with a pessary. However, because of an unpleasant experience at her initial appointment and because her biggest complaint (until recently) had been the need to urinate frequently, she had not returned for follow-up appointments.

DISCUSSION

POP is not life-threatening, but the condition lowers the quality of life for 50% of parous women age >50 years.¹ It can present as stress urinary incontinence, fecal incontinence, sexual dysfunction, and mechanical problems due to vaginal bulging or pelvic pressure.² With the exception of vaginal bulging, symptoms are not specific for POP and there is no linear relationship between the severity of the prolapse and the symptoms.^3,4

The condition is staged using the POP-Quantification (POP-Q) system⁵:

    1. Stage 0: no prolapse
    2. Stage I: the most distal portion of the prolapse is >1 cm above the hymen
    3. Stage II: the prolapse is ≤1 cm proximal or distal to the plane of the hymen
    4. Stage III: the prolapse is >1 cm below the plane of the hymen, but protrudes no farther 
than 2 cm less than the total vaginal length
    5. Stage IV: complete eversion of the lower genital tract.

As was the case with our patient, it is possible for a woman with severe total uterine prolapse (Stage IV) to have no major problems with urination or defecation.

The link between POP and hydronephrosis

Hydronephrosis appears to be a frequent finding in women with POP.4 A recent prospective observational study reported an overall prevalence of 10.3% (95% confidence interval, 6%-14%) in women with POP.⁴ Patients with advanced stages of POP (POP-Q Stage III or IV)⁴ who also had diabetes mellitus and hypertension were at particularly high risk, with a prevalence of about 20%. An analysis of factors, including age, parity, diabetes, hypertension, and type of prolapse, found that severity of POP was the strongest predictor of hydronephrosis: Patients with a Stage III to IV prolapse are 3.4 times more likely to have hydronephrosis than those with a Stage I or II prolapse.^4,6

Possible causes of hydronephrosis in POP patients. Some researchers have proposed that hydronephrosis in patients with uterine prolapse may be due to a kinking of the ureters by the extrinsic compression of the prolapsed uterus. In patients with vaginal vault prolapse, the cause of the hydronephrosis could be a weakening or disintegration of the cardinal ligaments after hysterectomy.^4,7

Patients may not complain. When hydronephrosis caused by POP occurs, it may develop slowly, causing little or no discomfort. As time passes, patients may complain of dull pain in the flank, suffer from urinary tract infections, or develop kidney stones before progressive renal dysfunction or renal failure occurs.⁴

There are 2 other cases in the literature of women who, like our patient, had uterine prolapse that went untreated until they were in renal failure.^8,9 The patients noticed only mechanical problems due to the POP; bilateral hydroureteronephrosis and renal failure had developed undetected. In the end, both women needed lifelong hemodialysis.

Treatment options

Treatment options for POP include supervised pelvic floor exercise programs, pessary insertion, or reconstructive pelvic surgery. If POP is treated adequately, an estimated 95% of the hydronephrosis can resolve, regardless of its severity at presentation.⁴

Our patient was treated with a 95 mm Falk pessary. After 24 hours, renal ultrasonography showed a decrease in both the hydroureteronephrosis and the hydronephrosis (FIGURE 2A and 2B). Four weeks later, her serum creatinine level had decreased to 3.3 mg/dL. Four years later, our patient continues to wear the pessary but has chronic renal failure.

THE TAKEAWAY

When hydronephrosis occurs as a result of uterine prolapse, it may cause little or no discomfort.

POP often is viewed as a minor problem, but it can cause obstructive uropathy with unilateral or bilateral hydronephrosis or renal dysfunction and/or failure. The delay often seen with reporting genital prolapse may be due to the mild symptoms or feelings of shame or fear. Combining screening for cervical pathology in general practice with a screening for genital prolapse could identify these problems.

Monitoring renal function is advised in patients with a Stage III or IV POP and any patients with POP who also have hypertension or diabetes mellitus. Because only minor changes in laboratory findings may be observed in patients with unilateral hydronephrosis, consider renal ultrasonography.

Treatment options for POP includes pelvic floor exercises, pessary insertion, and reconstructive surgery. Early treatment can resolve hydronephrosis and possibly prevent irreversible renal damage.

ACKNOWLEDGEMENTS
The authors thank Wilhelm Van Dorp, MD, Rob A. van de Beek, MD, and Alan Brind for their help with this manuscript.

THE CASE

A 63-year-old multiparous woman visited her general practitioner because of nausea, vomiting, and general malaise. A proton pump inhibitor was prescribed, which temporarily relieved her symptoms. Two weeks later, however, her symptoms worsened and she was admitted to the hospital.

The patient’s physical examination on admission was normal, but laboratory findings revealed severe renal failure with a creatinine level of 7.4 mg/dL (normal, 0.6-1.1 mg/dL), potassium level of 7.4 mmol/L (3.5-5 mmol/L), and a sodium level of 123 mmol/L (135-145 mmol/L). A renal ultrasound revealed severe bilateral hydronephrosis with hydroureteronephrosis caused by obstructive uropathy. A radiologist examined the patient and determined that she had a total uterine prolapse; the cervix was 11 cm outside of the vagina (FIGURE 1). Our patient’s untreated pelvic organ prolapse (POP) had caused chronic renal failure. The patient was referred to a urogynecologist.

Previous attempts at treatment. It appeared that our patient had POP for years and there had been a previous attempt to treat it with a pessary. However, because of an unpleasant experience at her initial appointment and because her biggest complaint (until recently) had been the need to urinate frequently, she had not returned for follow-up appointments.

DISCUSSION

POP is not life-threatening, but the condition lowers the quality of life for 50% of parous women age >50 years.¹ It can present as stress urinary incontinence, fecal incontinence, sexual dysfunction, and mechanical problems due to vaginal bulging or pelvic pressure.² With the exception of vaginal bulging, symptoms are not specific for POP and there is no linear relationship between the severity of the prolapse and the symptoms.^3,4

The condition is staged using the POP-Quantification (POP-Q) system⁵:

    1. Stage 0: no prolapse
    2. Stage I: the most distal portion of the prolapse is >1 cm above the hymen
    3. Stage II: the prolapse is ≤1 cm proximal or distal to the plane of the hymen
    4. Stage III: the prolapse is >1 cm below the plane of the hymen, but protrudes no farther 
than 2 cm less than the total vaginal length
    5. Stage IV: complete eversion of the lower genital tract.

As was the case with our patient, it is possible for a woman with severe total uterine prolapse (Stage IV) to have no major problems with urination or defecation.

The link between POP and hydronephrosis

Hydronephrosis appears to be a frequent finding in women with POP.4 A recent prospective observational study reported an overall prevalence of 10.3% (95% confidence interval, 6%-14%) in women with POP.⁴ Patients with advanced stages of POP (POP-Q Stage III or IV)⁴ who also had diabetes mellitus and hypertension were at particularly high risk, with a prevalence of about 20%. An analysis of factors, including age, parity, diabetes, hypertension, and type of prolapse, found that severity of POP was the strongest predictor of hydronephrosis: Patients with a Stage III to IV prolapse are 3.4 times more likely to have hydronephrosis than those with a Stage I or II prolapse.^4,6

Possible causes of hydronephrosis in POP patients. Some researchers have proposed that hydronephrosis in patients with uterine prolapse may be due to a kinking of the ureters by the extrinsic compression of the prolapsed uterus. In patients with vaginal vault prolapse, the cause of the hydronephrosis could be a weakening or disintegration of the cardinal ligaments after hysterectomy.^4,7

Patients may not complain. When hydronephrosis caused by POP occurs, it may develop slowly, causing little or no discomfort. As time passes, patients may complain of dull pain in the flank, suffer from urinary tract infections, or develop kidney stones before progressive renal dysfunction or renal failure occurs.⁴

There are 2 other cases in the literature of women who, like our patient, had uterine prolapse that went untreated until they were in renal failure.^8,9 The patients noticed only mechanical problems due to the POP; bilateral hydroureteronephrosis and renal failure had developed undetected. In the end, both women needed lifelong hemodialysis.

Treatment options

Treatment options for POP include supervised pelvic floor exercise programs, pessary insertion, or reconstructive pelvic surgery. If POP is treated adequately, an estimated 95% of the hydronephrosis can resolve, regardless of its severity at presentation.⁴

Our patient was treated with a 95 mm Falk pessary. After 24 hours, renal ultrasonography showed a decrease in both the hydroureteronephrosis and the hydronephrosis (FIGURE 2A and 2B). Four weeks later, her serum creatinine level had decreased to 3.3 mg/dL. Four years later, our patient continues to wear the pessary but has chronic renal failure.

THE TAKEAWAY

When hydronephrosis occurs as a result of uterine prolapse, it may cause little or no discomfort.

POP often is viewed as a minor problem, but it can cause obstructive uropathy with unilateral or bilateral hydronephrosis or renal dysfunction and/or failure. The delay often seen with reporting genital prolapse may be due to the mild symptoms or feelings of shame or fear. Combining screening for cervical pathology in general practice with a screening for genital prolapse could identify these problems.

Monitoring renal function is advised in patients with a Stage III or IV POP and any patients with POP who also have hypertension or diabetes mellitus. Because only minor changes in laboratory findings may be observed in patients with unilateral hydronephrosis, consider renal ultrasonography.

Treatment options for POP includes pelvic floor exercises, pessary insertion, and reconstructive surgery. Early treatment can resolve hydronephrosis and possibly prevent irreversible renal damage.

ACKNOWLEDGEMENTS
The authors thank Wilhelm Van Dorp, MD, Rob A. van de Beek, MD, and Alan Brind for their help with this manuscript.

THE CASE

A 63-year-old multiparous woman visited her general practitioner because of nausea, vomiting, and general malaise. A proton pump inhibitor was prescribed, which temporarily relieved her symptoms. Two weeks later, however, her symptoms worsened and she was admitted to the hospital.

The patient’s physical examination on admission was normal, but laboratory findings revealed severe renal failure with a creatinine level of 7.4 mg/dL (normal, 0.6-1.1 mg/dL), potassium level of 7.4 mmol/L (3.5-5 mmol/L), and a sodium level of 123 mmol/L (135-145 mmol/L). A renal ultrasound revealed severe bilateral hydronephrosis with hydroureteronephrosis caused by obstructive uropathy. A radiologist examined the patient and determined that she had a total uterine prolapse; the cervix was 11 cm outside of the vagina (FIGURE 1). Our patient’s untreated pelvic organ prolapse (POP) had caused chronic renal failure. The patient was referred to a urogynecologist.

Previous attempts at treatment. It appeared that our patient had POP for years and there had been a previous attempt to treat it with a pessary. However, because of an unpleasant experience at her initial appointment and because her biggest complaint (until recently) had been the need to urinate frequently, she had not returned for follow-up appointments.

DISCUSSION

POP is not life-threatening, but the condition lowers the quality of life for 50% of parous women age >50 years.¹ It can present as stress urinary incontinence, fecal incontinence, sexual dysfunction, and mechanical problems due to vaginal bulging or pelvic pressure.² With the exception of vaginal bulging, symptoms are not specific for POP and there is no linear relationship between the severity of the prolapse and the symptoms.^3,4

The condition is staged using the POP-Quantification (POP-Q) system⁵:

    1. Stage 0: no prolapse
    2. Stage I: the most distal portion of the prolapse is >1 cm above the hymen
    3. Stage II: the prolapse is ≤1 cm proximal or distal to the plane of the hymen
    4. Stage III: the prolapse is >1 cm below the plane of the hymen, but protrudes no farther 
than 2 cm less than the total vaginal length
    5. Stage IV: complete eversion of the lower genital tract.

As was the case with our patient, it is possible for a woman with severe total uterine prolapse (Stage IV) to have no major problems with urination or defecation.

The link between POP and hydronephrosis

Hydronephrosis appears to be a frequent finding in women with POP.4 A recent prospective observational study reported an overall prevalence of 10.3% (95% confidence interval, 6%-14%) in women with POP.⁴ Patients with advanced stages of POP (POP-Q Stage III or IV)⁴ who also had diabetes mellitus and hypertension were at particularly high risk, with a prevalence of about 20%. An analysis of factors, including age, parity, diabetes, hypertension, and type of prolapse, found that severity of POP was the strongest predictor of hydronephrosis: Patients with a Stage III to IV prolapse are 3.4 times more likely to have hydronephrosis than those with a Stage I or II prolapse.^4,6

Possible causes of hydronephrosis in POP patients. Some researchers have proposed that hydronephrosis in patients with uterine prolapse may be due to a kinking of the ureters by the extrinsic compression of the prolapsed uterus. In patients with vaginal vault prolapse, the cause of the hydronephrosis could be a weakening or disintegration of the cardinal ligaments after hysterectomy.^4,7

Patients may not complain. When hydronephrosis caused by POP occurs, it may develop slowly, causing little or no discomfort. As time passes, patients may complain of dull pain in the flank, suffer from urinary tract infections, or develop kidney stones before progressive renal dysfunction or renal failure occurs.⁴

There are 2 other cases in the literature of women who, like our patient, had uterine prolapse that went untreated until they were in renal failure.^8,9 The patients noticed only mechanical problems due to the POP; bilateral hydroureteronephrosis and renal failure had developed undetected. In the end, both women needed lifelong hemodialysis.

Treatment options

Treatment options for POP include supervised pelvic floor exercise programs, pessary insertion, or reconstructive pelvic surgery. If POP is treated adequately, an estimated 95% of the hydronephrosis can resolve, regardless of its severity at presentation.⁴

Our patient was treated with a 95 mm Falk pessary. After 24 hours, renal ultrasonography showed a decrease in both the hydroureteronephrosis and the hydronephrosis (FIGURE 2A and 2B). Four weeks later, her serum creatinine level had decreased to 3.3 mg/dL. Four years later, our patient continues to wear the pessary but has chronic renal failure.

THE TAKEAWAY

When hydronephrosis occurs as a result of uterine prolapse, it may cause little or no discomfort.

POP often is viewed as a minor problem, but it can cause obstructive uropathy with unilateral or bilateral hydronephrosis or renal dysfunction and/or failure. The delay often seen with reporting genital prolapse may be due to the mild symptoms or feelings of shame or fear. Combining screening for cervical pathology in general practice with a screening for genital prolapse could identify these problems.

Monitoring renal function is advised in patients with a Stage III or IV POP and any patients with POP who also have hypertension or diabetes mellitus. Because only minor changes in laboratory findings may be observed in patients with unilateral hydronephrosis, consider renal ultrasonography.

Treatment options for POP includes pelvic floor exercises, pessary insertion, and reconstructive surgery. Early treatment can resolve hydronephrosis and possibly prevent irreversible renal damage.

ACKNOWLEDGEMENTS
The authors thank Wilhelm Van Dorp, MD, Rob A. van de Beek, MD, and Alan Brind for their help with this manuscript.

I recently attended the International Interscience Conference of Infectious Diseases and Vaccines, and I would like to share some of the presentations from the session entitled “Hot Topics in Vaccines.”

CNS complications of varicella-zoster virus infection

Dr. Michelle Science of the Hospital for Sick Children, Toronto, and her associates described the spectrum of CNS complications of varicella-zoster virus (VZV) in children admitted to the hospital during 1999-2012 (J. Pediatr. 2014;165:779-85). Clinical syndromes included 26 cases of acute cerebellar ataxia, 17 of encephalitis, 16 isolated seizures, 10 strokes, 10 cases of meningitis, 2 cases of Guillain-Barré syndrome, 2 cases of acute disseminated encephalomyelitis, and 1 case of Ramsay Hunt syndrome. In children with acute nonstroke complications, neurologic symptoms occurred a median 5 days after the onset of rash, but neurologic symptoms predated the onset of rash in five cases and in two cases there were no exanthems. Time between rash onset and stroke ranged from 2 to 26 weeks (median 16 weeks). There were three deaths among the 17 (18%) children with encephalitis. Among the 39 children with follow-up at 1 year, residual neurologic sequelae occurred in 9 (23%). Only four of the children had received a VZV vaccine. Although an effective vaccine exists, neurologic complications of VZV infection continue to occur.

Timely versus delayed early childhood vaccination and seizures

Dr. Simon J. Hambidge of Denver Health, Colorado, and his associates studied a cohort of 323,247 U.S. children from the Vaccine Safety Datalink born during 2004-2008 for an association between the timing of childhood vaccination and the first occurrence of seizures (Pediatrics 2014;133(6):e1492-9). In the first year, there was no association between the timing of infant vaccination and postvaccination seizures. In the second year, the incidence rate ratio for seizures after receiving the first MMR dose at 12-15 months was 2.7, compared with a rate of 6.5 after an MMR dose at 16-23 months; thus there were more seizures when MMR was delayed. The incidence rate ratio for seizures after receiving the first measles-mumps-rubella-varicella vaccine (MMRV) dose at 12-15 months was 4.95, compared with 9.80 after an MMRV dose at 16-23 months. Again, there were more seizures when MMRV was delayed. These findings suggest that on-time vaccination is as safe with regard to seizures as delayed vaccination in year 1, and that delayed vaccination in year 2 is linked to more postvaccination seizures than on-time vaccination with MMR and that risk is doubled with MMRV.

Effective messages in vaccine promotion: a randomized trial

Brendan Nyhan, Ph.D., of Dartmouth College, Hanover, N.H., and his associates tested the efficacy of various informational messages tailored to reduce misperceptions about vaccines and increase MMR vaccination rates (Pediatrics 2014;133:e835-42). Nearly 1,800 parents were randomly assigned to receive one of four interventions: information explaining the lack of evidence that MMR causes autism from the Centers for Disease Control and Prevention; information about the danger of the diseases prevented by MMR from the Vaccine Information Statement; photos of children with diseases prevented by the MMR vaccine; a dramatic narrative about an infant who almost died of measles from a CDC fact sheet. In addition there was a control group. None of the four interventions increased parents’ intention to vaccinate another child if they had one in the future. Although refuting claims of an MMR/autism link did reduce misperceptions that vaccines cause autism, it decreased intent to vaccinate among parents who had the least favorable attitudes toward vaccines. Also, photos of sick children increased belief in an association between vaccines and autism, and the dramatic narrative about an infant in danger increased belief in serious vaccine side effects. Attempts to rectify misperceptions about vaccines may be counterproductive in some populations, so public health communications about vaccines should be tested before being widely disseminated.

Silent reintroduction of wild-type poliovirus to Israel, 2013

Dr. E. Kaliner of the Israeli Ministry of Health, Jerusalem, and associates, reported that Israel has been certified as polio-free by the World Health Organization for decades and its routine immunization schedule, like the United States, consists of inactivated poliovirus vaccine only (Euro. Surveill. 2014;19:20703). At the end of May 2013, the Israeli Ministry of Health confirmed the reintroduction of wild-type poliovirus 1 into the country. Documented ongoing human-to-human transmission required a thorough risk assessment followed by a supplemental immunization campaign using oral polio vaccine.

Trends in otitis media–related health care use in the United States, 2001-2011

Dr. Tal Marom of the University of Texas, Galveston, and associates studied the trend in otitis media–related health care use in the United States during the pneumococcal conjugate vaccine (PCV) era in 2001-2011 (JAMA Pediatr. 2014;168:68-75). An analysis of an insurance claims database of a large, nationwide managed health care plan was conducted; 7.82 million children aged 6 years and under had 6.21 million primary otitis media (OM) visits. There was an overall downward trend in OM-related health care use across the 10-year study. Recurrent OM rates (defined as greater than or equal to three OM visits within 6 months) decreased at 0.003 per child-year in 2001-2009 and at 0.018 per child-year in 2010-2011. Prior to the pneumococcal conjugate vaccine (PCV-13), there was a stable rate ratio of 1.38 between OM visit rates. During the transition year 2010, the RR decreased significantly to 1.32, and in 2011 the RR decreased further to 1.01. Mastoiditis rates significantly decreased from 61 per 100,000 child-years in 2008 to 37 per 100,000 child-years in 2011. The ventilating tube insertion rate decreased by 19% from 2010 to 2011. Tympanic membrane perforation/otorrhea rates increased gradually and significantly from 3,721 per 100,000 OM child-years in 2001 to 4,542 per 100,000 OM child-years in 2011; the reasons for this are unclear.

Dr. Pichichero, a specialist in pediatric infectious diseases, is director of the Research Institute, Rochester (N.Y.) General Hospital. He is also a pediatrician at Legacy Pediatrics in Rochester. Dr. Pichichero said he had no financial disclosures relevant to this article. To comment, e-mail him at [email protected].

I recently attended the International Interscience Conference of Infectious Diseases and Vaccines, and I would like to share some of the presentations from the session entitled “Hot Topics in Vaccines.”

CNS complications of varicella-zoster virus infection

Dr. Michelle Science of the Hospital for Sick Children, Toronto, and her associates described the spectrum of CNS complications of varicella-zoster virus (VZV) in children admitted to the hospital during 1999-2012 (J. Pediatr. 2014;165:779-85). Clinical syndromes included 26 cases of acute cerebellar ataxia, 17 of encephalitis, 16 isolated seizures, 10 strokes, 10 cases of meningitis, 2 cases of Guillain-Barré syndrome, 2 cases of acute disseminated encephalomyelitis, and 1 case of Ramsay Hunt syndrome. In children with acute nonstroke complications, neurologic symptoms occurred a median 5 days after the onset of rash, but neurologic symptoms predated the onset of rash in five cases and in two cases there were no exanthems. Time between rash onset and stroke ranged from 2 to 26 weeks (median 16 weeks). There were three deaths among the 17 (18%) children with encephalitis. Among the 39 children with follow-up at 1 year, residual neurologic sequelae occurred in 9 (23%). Only four of the children had received a VZV vaccine. Although an effective vaccine exists, neurologic complications of VZV infection continue to occur.

Timely versus delayed early childhood vaccination and seizures

Dr. Simon J. Hambidge of Denver Health, Colorado, and his associates studied a cohort of 323,247 U.S. children from the Vaccine Safety Datalink born during 2004-2008 for an association between the timing of childhood vaccination and the first occurrence of seizures (Pediatrics 2014;133(6):e1492-9). In the first year, there was no association between the timing of infant vaccination and postvaccination seizures. In the second year, the incidence rate ratio for seizures after receiving the first MMR dose at 12-15 months was 2.7, compared with a rate of 6.5 after an MMR dose at 16-23 months; thus there were more seizures when MMR was delayed. The incidence rate ratio for seizures after receiving the first measles-mumps-rubella-varicella vaccine (MMRV) dose at 12-15 months was 4.95, compared with 9.80 after an MMRV dose at 16-23 months. Again, there were more seizures when MMRV was delayed. These findings suggest that on-time vaccination is as safe with regard to seizures as delayed vaccination in year 1, and that delayed vaccination in year 2 is linked to more postvaccination seizures than on-time vaccination with MMR and that risk is doubled with MMRV.

Effective messages in vaccine promotion: a randomized trial

Brendan Nyhan, Ph.D., of Dartmouth College, Hanover, N.H., and his associates tested the efficacy of various informational messages tailored to reduce misperceptions about vaccines and increase MMR vaccination rates (Pediatrics 2014;133:e835-42). Nearly 1,800 parents were randomly assigned to receive one of four interventions: information explaining the lack of evidence that MMR causes autism from the Centers for Disease Control and Prevention; information about the danger of the diseases prevented by MMR from the Vaccine Information Statement; photos of children with diseases prevented by the MMR vaccine; a dramatic narrative about an infant who almost died of measles from a CDC fact sheet. In addition there was a control group. None of the four interventions increased parents’ intention to vaccinate another child if they had one in the future. Although refuting claims of an MMR/autism link did reduce misperceptions that vaccines cause autism, it decreased intent to vaccinate among parents who had the least favorable attitudes toward vaccines. Also, photos of sick children increased belief in an association between vaccines and autism, and the dramatic narrative about an infant in danger increased belief in serious vaccine side effects. Attempts to rectify misperceptions about vaccines may be counterproductive in some populations, so public health communications about vaccines should be tested before being widely disseminated.

Silent reintroduction of wild-type poliovirus to Israel, 2013

Dr. E. Kaliner of the Israeli Ministry of Health, Jerusalem, and associates, reported that Israel has been certified as polio-free by the World Health Organization for decades and its routine immunization schedule, like the United States, consists of inactivated poliovirus vaccine only (Euro. Surveill. 2014;19:20703). At the end of May 2013, the Israeli Ministry of Health confirmed the reintroduction of wild-type poliovirus 1 into the country. Documented ongoing human-to-human transmission required a thorough risk assessment followed by a supplemental immunization campaign using oral polio vaccine.

Trends in otitis media–related health care use in the United States, 2001-2011

Dr. Tal Marom of the University of Texas, Galveston, and associates studied the trend in otitis media–related health care use in the United States during the pneumococcal conjugate vaccine (PCV) era in 2001-2011 (JAMA Pediatr. 2014;168:68-75). An analysis of an insurance claims database of a large, nationwide managed health care plan was conducted; 7.82 million children aged 6 years and under had 6.21 million primary otitis media (OM) visits. There was an overall downward trend in OM-related health care use across the 10-year study. Recurrent OM rates (defined as greater than or equal to three OM visits within 6 months) decreased at 0.003 per child-year in 2001-2009 and at 0.018 per child-year in 2010-2011. Prior to the pneumococcal conjugate vaccine (PCV-13), there was a stable rate ratio of 1.38 between OM visit rates. During the transition year 2010, the RR decreased significantly to 1.32, and in 2011 the RR decreased further to 1.01. Mastoiditis rates significantly decreased from 61 per 100,000 child-years in 2008 to 37 per 100,000 child-years in 2011. The ventilating tube insertion rate decreased by 19% from 2010 to 2011. Tympanic membrane perforation/otorrhea rates increased gradually and significantly from 3,721 per 100,000 OM child-years in 2001 to 4,542 per 100,000 OM child-years in 2011; the reasons for this are unclear.

Dr. Pichichero, a specialist in pediatric infectious diseases, is director of the Research Institute, Rochester (N.Y.) General Hospital. He is also a pediatrician at Legacy Pediatrics in Rochester. Dr. Pichichero said he had no financial disclosures relevant to this article. To comment, e-mail him at [email protected].

I recently attended the International Interscience Conference of Infectious Diseases and Vaccines, and I would like to share some of the presentations from the session entitled “Hot Topics in Vaccines.”

CNS complications of varicella-zoster virus infection

Dr. Michelle Science of the Hospital for Sick Children, Toronto, and her associates described the spectrum of CNS complications of varicella-zoster virus (VZV) in children admitted to the hospital during 1999-2012 (J. Pediatr. 2014;165:779-85). Clinical syndromes included 26 cases of acute cerebellar ataxia, 17 of encephalitis, 16 isolated seizures, 10 strokes, 10 cases of meningitis, 2 cases of Guillain-Barré syndrome, 2 cases of acute disseminated encephalomyelitis, and 1 case of Ramsay Hunt syndrome. In children with acute nonstroke complications, neurologic symptoms occurred a median 5 days after the onset of rash, but neurologic symptoms predated the onset of rash in five cases and in two cases there were no exanthems. Time between rash onset and stroke ranged from 2 to 26 weeks (median 16 weeks). There were three deaths among the 17 (18%) children with encephalitis. Among the 39 children with follow-up at 1 year, residual neurologic sequelae occurred in 9 (23%). Only four of the children had received a VZV vaccine. Although an effective vaccine exists, neurologic complications of VZV infection continue to occur.

Timely versus delayed early childhood vaccination and seizures

Dr. Simon J. Hambidge of Denver Health, Colorado, and his associates studied a cohort of 323,247 U.S. children from the Vaccine Safety Datalink born during 2004-2008 for an association between the timing of childhood vaccination and the first occurrence of seizures (Pediatrics 2014;133(6):e1492-9). In the first year, there was no association between the timing of infant vaccination and postvaccination seizures. In the second year, the incidence rate ratio for seizures after receiving the first MMR dose at 12-15 months was 2.7, compared with a rate of 6.5 after an MMR dose at 16-23 months; thus there were more seizures when MMR was delayed. The incidence rate ratio for seizures after receiving the first measles-mumps-rubella-varicella vaccine (MMRV) dose at 12-15 months was 4.95, compared with 9.80 after an MMRV dose at 16-23 months. Again, there were more seizures when MMRV was delayed. These findings suggest that on-time vaccination is as safe with regard to seizures as delayed vaccination in year 1, and that delayed vaccination in year 2 is linked to more postvaccination seizures than on-time vaccination with MMR and that risk is doubled with MMRV.

Effective messages in vaccine promotion: a randomized trial

Brendan Nyhan, Ph.D., of Dartmouth College, Hanover, N.H., and his associates tested the efficacy of various informational messages tailored to reduce misperceptions about vaccines and increase MMR vaccination rates (Pediatrics 2014;133:e835-42). Nearly 1,800 parents were randomly assigned to receive one of four interventions: information explaining the lack of evidence that MMR causes autism from the Centers for Disease Control and Prevention; information about the danger of the diseases prevented by MMR from the Vaccine Information Statement; photos of children with diseases prevented by the MMR vaccine; a dramatic narrative about an infant who almost died of measles from a CDC fact sheet. In addition there was a control group. None of the four interventions increased parents’ intention to vaccinate another child if they had one in the future. Although refuting claims of an MMR/autism link did reduce misperceptions that vaccines cause autism, it decreased intent to vaccinate among parents who had the least favorable attitudes toward vaccines. Also, photos of sick children increased belief in an association between vaccines and autism, and the dramatic narrative about an infant in danger increased belief in serious vaccine side effects. Attempts to rectify misperceptions about vaccines may be counterproductive in some populations, so public health communications about vaccines should be tested before being widely disseminated.

Silent reintroduction of wild-type poliovirus to Israel, 2013

Dr. E. Kaliner of the Israeli Ministry of Health, Jerusalem, and associates, reported that Israel has been certified as polio-free by the World Health Organization for decades and its routine immunization schedule, like the United States, consists of inactivated poliovirus vaccine only (Euro. Surveill. 2014;19:20703). At the end of May 2013, the Israeli Ministry of Health confirmed the reintroduction of wild-type poliovirus 1 into the country. Documented ongoing human-to-human transmission required a thorough risk assessment followed by a supplemental immunization campaign using oral polio vaccine.

Trends in otitis media–related health care use in the United States, 2001-2011

Dr. Tal Marom of the University of Texas, Galveston, and associates studied the trend in otitis media–related health care use in the United States during the pneumococcal conjugate vaccine (PCV) era in 2001-2011 (JAMA Pediatr. 2014;168:68-75). An analysis of an insurance claims database of a large, nationwide managed health care plan was conducted; 7.82 million children aged 6 years and under had 6.21 million primary otitis media (OM) visits. There was an overall downward trend in OM-related health care use across the 10-year study. Recurrent OM rates (defined as greater than or equal to three OM visits within 6 months) decreased at 0.003 per child-year in 2001-2009 and at 0.018 per child-year in 2010-2011. Prior to the pneumococcal conjugate vaccine (PCV-13), there was a stable rate ratio of 1.38 between OM visit rates. During the transition year 2010, the RR decreased significantly to 1.32, and in 2011 the RR decreased further to 1.01. Mastoiditis rates significantly decreased from 61 per 100,000 child-years in 2008 to 37 per 100,000 child-years in 2011. The ventilating tube insertion rate decreased by 19% from 2010 to 2011. Tympanic membrane perforation/otorrhea rates increased gradually and significantly from 3,721 per 100,000 OM child-years in 2001 to 4,542 per 100,000 OM child-years in 2011; the reasons for this are unclear.

Dr. Pichichero, a specialist in pediatric infectious diseases, is director of the Research Institute, Rochester (N.Y.) General Hospital. He is also a pediatrician at Legacy Pediatrics in Rochester. Dr. Pichichero said he had no financial disclosures relevant to this article. To comment, e-mail him at [email protected].

To the Editor: In their article about the care of patients with advanced chronic kidney disease, Sakhuja et al¹ mentioned that metformin is contraindicated in chronic kidney disease.

Metformin is a good and useful drug. Not only is it one of the cheapest antidiabetic medications, it is the only one shown to reduce cardiovascular mortality rates in type 2 diabetes mellitus.

Although metformin is thought to increase the risk of lactic acidosis, a Cochrane review² found that the incidence of lactic acidosis was only 4.3 cases per 100,000 patient-years in patients taking metformin, compared with 5.4 cases per 100,000 patient-years in patients not taking metformin. Furthermore, in a large registry of patients with type 2 diabetes and atherothrombosis,³ the rate of all-cause mortality was 24% lower in metformin users than in nonusers, and in those who had moderate renal impairment (creatinine clearance 30–59 mL/min/1.73 m²) the difference was 36%.³

A trial by Rachmani et al⁴ raised questions about the standard contraindications to metformin. The authors reviewed 393 patients who had at least one contraindication to metformin but who were receiving it anyway. Their serum creatinine levels ranged from 1.5 to 2.5 mg/dL. There were no cases of lactic acidosis reported. The patients were then randomized either to continue taking metformin or to stop taking it. At 2 years, the group that had stopped taking it had gained more weight, and their glycemic control was worse.

In the Cochrane analysis,² although individual creatinine levels were not available, 53% of the studies reviewed did not exclude patients with serum creatinine levels higher than 1.5 mg/dL. This equated to 37,360 patient-years of metformin use in studies that included patients with chronic kidney disease, and did not lead to lactic acidosis.

Even though metformin’s US package insert says that it is contraindicated if the serum creatinine level is 1.5 mg/dL or higher in men or 1.4 mg/dL or higher in women or if the creatinine clearance is “abnormal,” in view of the available evidence, many countries (eg, the United Kingdom, Australia, the Netherlands) now allow metformin to be used in patients with glomerular filtration rates as low as 30 mL/min/1.73m², with lower doses if the glomerular filtration rate is lower than 45.⁵

The current contraindication to metformin in chronic kidney disease needs to be reviewed. In poor countries like India, this cheap medicine may be the only option available for treating type 2 diabetes mellitus, and it remains the first-line therapy for type 2 diabetes mellitus as recommended by the International Diabetes Federation, the American Diabetes Association, and the European Association for the Study of Diabetes.⁵

To the Editor: In their article about the care of patients with advanced chronic kidney disease, Sakhuja et al¹ mentioned that metformin is contraindicated in chronic kidney disease.

Metformin is a good and useful drug. Not only is it one of the cheapest antidiabetic medications, it is the only one shown to reduce cardiovascular mortality rates in type 2 diabetes mellitus.

Although metformin is thought to increase the risk of lactic acidosis, a Cochrane review² found that the incidence of lactic acidosis was only 4.3 cases per 100,000 patient-years in patients taking metformin, compared with 5.4 cases per 100,000 patient-years in patients not taking metformin. Furthermore, in a large registry of patients with type 2 diabetes and atherothrombosis,³ the rate of all-cause mortality was 24% lower in metformin users than in nonusers, and in those who had moderate renal impairment (creatinine clearance 30–59 mL/min/1.73 m²) the difference was 36%.³

A trial by Rachmani et al⁴ raised questions about the standard contraindications to metformin. The authors reviewed 393 patients who had at least one contraindication to metformin but who were receiving it anyway. Their serum creatinine levels ranged from 1.5 to 2.5 mg/dL. There were no cases of lactic acidosis reported. The patients were then randomized either to continue taking metformin or to stop taking it. At 2 years, the group that had stopped taking it had gained more weight, and their glycemic control was worse.

In the Cochrane analysis,² although individual creatinine levels were not available, 53% of the studies reviewed did not exclude patients with serum creatinine levels higher than 1.5 mg/dL. This equated to 37,360 patient-years of metformin use in studies that included patients with chronic kidney disease, and did not lead to lactic acidosis.

Even though metformin’s US package insert says that it is contraindicated if the serum creatinine level is 1.5 mg/dL or higher in men or 1.4 mg/dL or higher in women or if the creatinine clearance is “abnormal,” in view of the available evidence, many countries (eg, the United Kingdom, Australia, the Netherlands) now allow metformin to be used in patients with glomerular filtration rates as low as 30 mL/min/1.73m², with lower doses if the glomerular filtration rate is lower than 45.⁵

The current contraindication to metformin in chronic kidney disease needs to be reviewed. In poor countries like India, this cheap medicine may be the only option available for treating type 2 diabetes mellitus, and it remains the first-line therapy for type 2 diabetes mellitus as recommended by the International Diabetes Federation, the American Diabetes Association, and the European Association for the Study of Diabetes.⁵

To the Editor: In their article about the care of patients with advanced chronic kidney disease, Sakhuja et al¹ mentioned that metformin is contraindicated in chronic kidney disease.

Metformin is a good and useful drug. Not only is it one of the cheapest antidiabetic medications, it is the only one shown to reduce cardiovascular mortality rates in type 2 diabetes mellitus.

Although metformin is thought to increase the risk of lactic acidosis, a Cochrane review² found that the incidence of lactic acidosis was only 4.3 cases per 100,000 patient-years in patients taking metformin, compared with 5.4 cases per 100,000 patient-years in patients not taking metformin. Furthermore, in a large registry of patients with type 2 diabetes and atherothrombosis,³ the rate of all-cause mortality was 24% lower in metformin users than in nonusers, and in those who had moderate renal impairment (creatinine clearance 30–59 mL/min/1.73 m²) the difference was 36%.³

A trial by Rachmani et al⁴ raised questions about the standard contraindications to metformin. The authors reviewed 393 patients who had at least one contraindication to metformin but who were receiving it anyway. Their serum creatinine levels ranged from 1.5 to 2.5 mg/dL. There were no cases of lactic acidosis reported. The patients were then randomized either to continue taking metformin or to stop taking it. At 2 years, the group that had stopped taking it had gained more weight, and their glycemic control was worse.

In the Cochrane analysis,² although individual creatinine levels were not available, 53% of the studies reviewed did not exclude patients with serum creatinine levels higher than 1.5 mg/dL. This equated to 37,360 patient-years of metformin use in studies that included patients with chronic kidney disease, and did not lead to lactic acidosis.

Even though metformin’s US package insert says that it is contraindicated if the serum creatinine level is 1.5 mg/dL or higher in men or 1.4 mg/dL or higher in women or if the creatinine clearance is “abnormal,” in view of the available evidence, many countries (eg, the United Kingdom, Australia, the Netherlands) now allow metformin to be used in patients with glomerular filtration rates as low as 30 mL/min/1.73m², with lower doses if the glomerular filtration rate is lower than 45.⁵

The current contraindication to metformin in chronic kidney disease needs to be reviewed. In poor countries like India, this cheap medicine may be the only option available for treating type 2 diabetes mellitus, and it remains the first-line therapy for type 2 diabetes mellitus as recommended by the International Diabetes Federation, the American Diabetes Association, and the European Association for the Study of Diabetes.⁵