Last week I saw a 35-year-old man for follow-up on a positive rapid plasma reagin (RPR). He thought he had syphilis, but he had never had any syphilis symptoms, so I suspected the RPR was a false positive. Because I seldom encounter this situation, it was time for some “point of care” research. I checked an online reference and found that the fluorescent treponemal antibody absorption (FTA-ABS) test is highly sensitive and would be sufficient to rule out syphilis. The good news: His subsequent FTA-ABS was negative. But the situation left me wondering why the FTA-ABS had not been done automatically after the positive RPR.

The question, “What is the best test to rule in or rule out X?” comes up frequently for family physicians (FPs), and sometimes we are uncertain about ordering the best test and interpreting the results correctly. According to a recent national survey sponsored by the Centers for Disease Control and Prevention¹—for which I was privileged to be the principal investigator—1768 FPs and general internists reported ordering diagnostic laboratory tests for an average of 31.4% of their patients per week. They were uncertain about the right test to order for 14.7% of these patients and uncertain about interpreting the results for 8.3%. That might not seem like a lot, but with more than 500 million primary care patient visits per year in the United States, this potentially affects 23 million patients each year.

In our EMR, 90% of the lab report details things I don't need to know to get to the 10% I do need, I have to scroll to click.We asked about problems with test ordering, too. I don’t think you will be surprised that physicians reported insurance company restrictions and costs to patients were the main barriers. They also reported difficulty with the variety of names for the same tests, which I certainly noticed when I moved from Cleveland Clinic to University of Illinois at Chicago. Not getting test results in a timely manner was a big problem, too, as was confusing report formats. In our electronic medical record, 90% of the lab report details things I don’t need to know and to get to the 10% I do need, I have to scroll or click.

In this issue, Tessier et al illustrate ways to avoid common lab testing pitfalls. I would argue that in addition to helpful articles like this one, we also need better electronic tools to help guide us when uncertain. Then again, the phone is still good technology; when in doubt, pick it up and call your lab.

Last week I saw a 35-year-old man for follow-up on a positive rapid plasma reagin (RPR). He thought he had syphilis, but he had never had any syphilis symptoms, so I suspected the RPR was a false positive. Because I seldom encounter this situation, it was time for some “point of care” research. I checked an online reference and found that the fluorescent treponemal antibody absorption (FTA-ABS) test is highly sensitive and would be sufficient to rule out syphilis. The good news: His subsequent FTA-ABS was negative. But the situation left me wondering why the FTA-ABS had not been done automatically after the positive RPR.

The question, “What is the best test to rule in or rule out X?” comes up frequently for family physicians (FPs), and sometimes we are uncertain about ordering the best test and interpreting the results correctly. According to a recent national survey sponsored by the Centers for Disease Control and Prevention¹—for which I was privileged to be the principal investigator—1768 FPs and general internists reported ordering diagnostic laboratory tests for an average of 31.4% of their patients per week. They were uncertain about the right test to order for 14.7% of these patients and uncertain about interpreting the results for 8.3%. That might not seem like a lot, but with more than 500 million primary care patient visits per year in the United States, this potentially affects 23 million patients each year.

In our EMR, 90% of the lab report details things I don't need to know to get to the 10% I do need, I have to scroll to click.We asked about problems with test ordering, too. I don’t think you will be surprised that physicians reported insurance company restrictions and costs to patients were the main barriers. They also reported difficulty with the variety of names for the same tests, which I certainly noticed when I moved from Cleveland Clinic to University of Illinois at Chicago. Not getting test results in a timely manner was a big problem, too, as was confusing report formats. In our electronic medical record, 90% of the lab report details things I don’t need to know and to get to the 10% I do need, I have to scroll or click.

In this issue, Tessier et al illustrate ways to avoid common lab testing pitfalls. I would argue that in addition to helpful articles like this one, we also need better electronic tools to help guide us when uncertain. Then again, the phone is still good technology; when in doubt, pick it up and call your lab.

Last week I saw a 35-year-old man for follow-up on a positive rapid plasma reagin (RPR). He thought he had syphilis, but he had never had any syphilis symptoms, so I suspected the RPR was a false positive. Because I seldom encounter this situation, it was time for some “point of care” research. I checked an online reference and found that the fluorescent treponemal antibody absorption (FTA-ABS) test is highly sensitive and would be sufficient to rule out syphilis. The good news: His subsequent FTA-ABS was negative. But the situation left me wondering why the FTA-ABS had not been done automatically after the positive RPR.

The question, “What is the best test to rule in or rule out X?” comes up frequently for family physicians (FPs), and sometimes we are uncertain about ordering the best test and interpreting the results correctly. According to a recent national survey sponsored by the Centers for Disease Control and Prevention¹—for which I was privileged to be the principal investigator—1768 FPs and general internists reported ordering diagnostic laboratory tests for an average of 31.4% of their patients per week. They were uncertain about the right test to order for 14.7% of these patients and uncertain about interpreting the results for 8.3%. That might not seem like a lot, but with more than 500 million primary care patient visits per year in the United States, this potentially affects 23 million patients each year.

In our EMR, 90% of the lab report details things I don't need to know to get to the 10% I do need, I have to scroll to click.We asked about problems with test ordering, too. I don’t think you will be surprised that physicians reported insurance company restrictions and costs to patients were the main barriers. They also reported difficulty with the variety of names for the same tests, which I certainly noticed when I moved from Cleveland Clinic to University of Illinois at Chicago. Not getting test results in a timely manner was a big problem, too, as was confusing report formats. In our electronic medical record, 90% of the lab report details things I don’t need to know and to get to the 10% I do need, I have to scroll or click.

In this issue, Tessier et al illustrate ways to avoid common lab testing pitfalls. I would argue that in addition to helpful articles like this one, we also need better electronic tools to help guide us when uncertain. Then again, the phone is still good technology; when in doubt, pick it up and call your lab.

We were happy to learn in “Time to routinely screen for intimate partner violence?” (PURLs. J Fam Pract. 2013;62:90-92) that the US Preventive Services Task Force (USPSTF) agrees with the Institute of Medicine (IOM) that all women of childbearing age should be screened for intimate partner violence (IPV).¹ Although the USPSTF recommendation comes 2 years after that of the IOM, it is truly better late than never.

Two populations with known IPV issues require special consideration: lesbian, gay, bisexual, transgender (LGBT) patients and heterosexual men. The rate of IPV is higher in the LGBT population than in heterosexual men and women cohabitating with their partners.² Despite high rates of IPV within the LGBT population, women in this group frequently are overlooked for IPV screening.²

We must remember to screen men in heterosexual relationships, as well. In 2000, the National Violence Against Women survey found that 7% of men reported having experienced IPV in their lifetime.² Given this data, we believe that all patients ages 14 years and older—regardless of gender or sexual orientation—should be screened for IPV. This would be a much-needed step towards addressing a major public health problem.

Barbara McMillan-Persaud, MD
Kyra P. Clark, MD
Riba Kelsey-Harris, MD
Folashade Omole, MD, FAAFP
Atlanta, Ga

We were happy to learn in “Time to routinely screen for intimate partner violence?” (PURLs. J Fam Pract. 2013;62:90-92) that the US Preventive Services Task Force (USPSTF) agrees with the Institute of Medicine (IOM) that all women of childbearing age should be screened for intimate partner violence (IPV).¹ Although the USPSTF recommendation comes 2 years after that of the IOM, it is truly better late than never.

Two populations with known IPV issues require special consideration: lesbian, gay, bisexual, transgender (LGBT) patients and heterosexual men. The rate of IPV is higher in the LGBT population than in heterosexual men and women cohabitating with their partners.² Despite high rates of IPV within the LGBT population, women in this group frequently are overlooked for IPV screening.²

We must remember to screen men in heterosexual relationships, as well. In 2000, the National Violence Against Women survey found that 7% of men reported having experienced IPV in their lifetime.² Given this data, we believe that all patients ages 14 years and older—regardless of gender or sexual orientation—should be screened for IPV. This would be a much-needed step towards addressing a major public health problem.

Barbara McMillan-Persaud, MD
Kyra P. Clark, MD
Riba Kelsey-Harris, MD
Folashade Omole, MD, FAAFP
Atlanta, Ga

We were happy to learn in “Time to routinely screen for intimate partner violence?” (PURLs. J Fam Pract. 2013;62:90-92) that the US Preventive Services Task Force (USPSTF) agrees with the Institute of Medicine (IOM) that all women of childbearing age should be screened for intimate partner violence (IPV).¹ Although the USPSTF recommendation comes 2 years after that of the IOM, it is truly better late than never.

Two populations with known IPV issues require special consideration: lesbian, gay, bisexual, transgender (LGBT) patients and heterosexual men. The rate of IPV is higher in the LGBT population than in heterosexual men and women cohabitating with their partners.² Despite high rates of IPV within the LGBT population, women in this group frequently are overlooked for IPV screening.²

We must remember to screen men in heterosexual relationships, as well. In 2000, the National Violence Against Women survey found that 7% of men reported having experienced IPV in their lifetime.² Given this data, we believe that all patients ages 14 years and older—regardless of gender or sexual orientation—should be screened for IPV. This would be a much-needed step towards addressing a major public health problem.

Barbara McMillan-Persaud, MD
Kyra P. Clark, MD
Riba Kelsey-Harris, MD
Folashade Omole, MD, FAAFP
Atlanta, Ga

THE CASE

A previously healthy 35-year-old man with a one-week history of left-sided neck pain and fever as high as 104°F sought care at our emergency department. He was given a diagnosis of viral pharyngitis and discharged. He returned the next day and indicated that he was now experiencing drenching night sweats and weakness.

The patient was anxious, but not distressed. His temperature was 100.1°F; blood pressure, 113/65 mm Hg; heart rate, 150 beats per minute; respiratory rate, 18 breaths per minute; and oxygen saturation, 95% on room air. Head and neck examination revealed bilateral cervical lymphadenopathy with pronounced tenderness on the left side of his neck. Oral exam revealed dry mucous membranes, halitosis, and bilateral tonsillar enlargement without exudate. The cardiopulmonary exam was within normal limits. Lab tests showed a white blood cell (WBC) count of 5.9 x 109/L. An ultrasound of the neck revealed thrombosis in the left submandibular branch of the left internal jugular vein (IJV) (FIGURE 1).

The next day, the patient remained febrile (102.8°F) and developed rigors, diarrhea, pleuritic chest pain, and an elevated WBC count (14.5). A blood culture grew gramnegative rods. The patient was started on piperacillin/tazobactam, and doxycycline was added to treat possible tick-borne infections. Computed tomography (CT) scans of the chest showed the presence of septic pulmonary emboli and small bilateral pleural effusions (FIGURE 2).

THE DIAGNOSIS

We made a diagnosis of Lemierre’s syndrome because our patient met all 4 criteria for the condition:^1,2
• a recent oropharyngeal infection
• clinical or radiological evidence of IJV thrombosis
• isolation of anaerobic pathogens (mainly Fusobacterium necrophorum)
• evidence of at least one septic focus, most commonly in the lungs.

We changed the patient’s antibiotic therapy to intravenous (IV) meropenem. His WBC and fever improved, and on Day 10 he was discharged to complete a 28-day course of IV meropenem via a peripherally inserted central catheter.

DISCUSSION

Lemierre’s—A “forgotten” condition that’s making a comeback

In 1936, French microbiologist Andrew Lemierre formally characterized the syndrome in a review of 20 patients who had sepsis, metastatic pulmonary lesions, and isolation of Bacillus funduliformis (now known as F necrophorum).^1,2 Other organisms that have been identified in this syndrome include Fusobacterium nucleatum, Candida, Staphylococcus, and Streptococcus.²

Before the antibiotic era, Lemierre’s syndrome was common and often fatal. But with the introduction of penicillin in the 1940s, the incidence of the syndrome dropped, and it eventually became known as “the forgotten disease.”² Since the 1990s, however, there has been a marked resurgence of Lemierre’s syndrome.³ The incidence of Lemierre’s syndrome today is 0.6 to 2.3 cases per 1 million people per year, with a mortality rate of up to 18%.^3,4

This resurgence of Lemierre’s syndrome has been linked to the restricted use of antibiotics for throat infections.3 (One study found the number of prescriptions written for antibiotics decreased by 23% from 1992 to 2000.⁵) Other factors cited for the increased incidence of Lemierre’s syndrome include improved identification of anaerobic organisms, more effective blood culture methods, and an increased awareness of this syndrome among clinical microbiologists.⁶

Diagnosis requires a high degree of suspicion

Lemierre’s syndrome typically occurs in healthy young adults. Pharyngitis is the most common initial symptom, occurring in 87% of patients.² This is followed by a fever (102.2°F - 105.8°F) usually 4 to 5 days after the onset of sore throat.³ Other common symptoms include chills, dysphagia, dyspnea, chest pain, hemoptysis, cervical neck discomfort, arthralgia, malaise, and night sweats.² Following suppurative thrombophlebitis of the IJV, infection spreads to other organ systems. Pulmonary involvement is the most common site (97% of cases).³ Other complications of this syndrome are listed in the TABLE.³

The differential includes mononucleosis

The differential diagnosis encompasses several common illnesses, including mononucleosis, Group A streptococcal pharyngitis, and peritonsillar abscess. However, while patients with these conditions might have a fever and an elevated WBC count, they typically would not have the pleuritic chest pain that is characteristic of Lemierre’s syndrome. In addition, while patients with peritonsillar abscess would have tonsillar exudates, patients with Lemierre’s syndrome would not likely have them.

Influenza is also part of the differential, although focal neck pain usually isn’t a finding in patients who have the flu.

Once other common illnesses have been ruled out, it’s important to have a high index of suspicion for Lemierre’s syndrome because the oropharyngeal infection may resolve by the time of presentation, and there may be few findings on physical exam.⁷ Therefore, suspect Lemierre’s if a patient comes in with neck pain and/or pleuritic chest pain and has a recent history of oropharyngeal infection and fever.

CT scan of the neck and chest with contrast is the optimal diagnostic modality because it allows physicians to visualize the IJV⁸ and detect pulmonary emboli.⁹ Doppler ultrasound also can be used to diagnose IJV thrombosis. Ultrasound findings would reveal an echogenic focus within a dilated IJV or a complex mass of cystic and solid components.¹⁰

Many case reports have demonstrated that complete recovery is possible without anticoagulation.Prompt antibiotic treatment is essential

Patients with Lemierre’s syndrome require prompt and appropriate antimicrobial therapy. Researchers have reported mortality rates of 25% among patients who received delayed antibiotic therapy, compared with rates of up to 18% with prompt therapy.³ Metronidazole is the most commonly prescribed antibiotic.⁸ When combined with ceftriaxone, it provides coverage for both F necrophorum and streptococci, a common copathogen. Monotherapy with a carbapenem antibiotic, clindamycin, ampicillin/sulbactam, or antipseudomonal penicillin also are appropriate options.⁵ Antimicrobial treatment for 3 to 6 weeks is recommended because relapses have been noted in patients treated for less than 2 weeks.¹¹

Anticoagulation is controversial.² Proponents of anticoagulation to treat Lemierre’s syndrome believe it may prevent formation of septic emboli and could expedite recovery.^4,12 Others believe that clots associated with Lemierre’s syndrome dissolve on their own and that anticoagulation may increase the likelihood of septic emboli.¹³ Many case reports, including this one, have demonstrated that complete recovery is possible without anticoagulation.^10,13-15 Anticoagulation therapy can be considered for patients with Lemierre’s syndrome in the absence of any contraindications such as gastrointestinal or intracranial bleeding.

THE TAKEAWAY

Suspect Lemierre’s syndrome when a patient complains of neck pain, high fever, rigors, dry cough, and pleuritic chest pain and mentions a sore throat that he or she had in the pretceding 7 days. Diagnosis can be confirmed by radiological findings and blood cultures positive for F. necrophorum. Patients with Lemierre’s syndrome should be promptly treated with antibiotics; evidence for anticoagulation is inconclusive.

THE CASE

A previously healthy 35-year-old man with a one-week history of left-sided neck pain and fever as high as 104°F sought care at our emergency department. He was given a diagnosis of viral pharyngitis and discharged. He returned the next day and indicated that he was now experiencing drenching night sweats and weakness.

The patient was anxious, but not distressed. His temperature was 100.1°F; blood pressure, 113/65 mm Hg; heart rate, 150 beats per minute; respiratory rate, 18 breaths per minute; and oxygen saturation, 95% on room air. Head and neck examination revealed bilateral cervical lymphadenopathy with pronounced tenderness on the left side of his neck. Oral exam revealed dry mucous membranes, halitosis, and bilateral tonsillar enlargement without exudate. The cardiopulmonary exam was within normal limits. Lab tests showed a white blood cell (WBC) count of 5.9 x 109/L. An ultrasound of the neck revealed thrombosis in the left submandibular branch of the left internal jugular vein (IJV) (FIGURE 1).

The next day, the patient remained febrile (102.8°F) and developed rigors, diarrhea, pleuritic chest pain, and an elevated WBC count (14.5). A blood culture grew gramnegative rods. The patient was started on piperacillin/tazobactam, and doxycycline was added to treat possible tick-borne infections. Computed tomography (CT) scans of the chest showed the presence of septic pulmonary emboli and small bilateral pleural effusions (FIGURE 2).

THE DIAGNOSIS

We made a diagnosis of Lemierre’s syndrome because our patient met all 4 criteria for the condition:^1,2
• a recent oropharyngeal infection
• clinical or radiological evidence of IJV thrombosis
• isolation of anaerobic pathogens (mainly Fusobacterium necrophorum)
• evidence of at least one septic focus, most commonly in the lungs.

We changed the patient’s antibiotic therapy to intravenous (IV) meropenem. His WBC and fever improved, and on Day 10 he was discharged to complete a 28-day course of IV meropenem via a peripherally inserted central catheter.

DISCUSSION

Lemierre’s—A “forgotten” condition that’s making a comeback

In 1936, French microbiologist Andrew Lemierre formally characterized the syndrome in a review of 20 patients who had sepsis, metastatic pulmonary lesions, and isolation of Bacillus funduliformis (now known as F necrophorum).^1,2 Other organisms that have been identified in this syndrome include Fusobacterium nucleatum, Candida, Staphylococcus, and Streptococcus.²

Before the antibiotic era, Lemierre’s syndrome was common and often fatal. But with the introduction of penicillin in the 1940s, the incidence of the syndrome dropped, and it eventually became known as “the forgotten disease.”² Since the 1990s, however, there has been a marked resurgence of Lemierre’s syndrome.³ The incidence of Lemierre’s syndrome today is 0.6 to 2.3 cases per 1 million people per year, with a mortality rate of up to 18%.^3,4

This resurgence of Lemierre’s syndrome has been linked to the restricted use of antibiotics for throat infections.3 (One study found the number of prescriptions written for antibiotics decreased by 23% from 1992 to 2000.⁵) Other factors cited for the increased incidence of Lemierre’s syndrome include improved identification of anaerobic organisms, more effective blood culture methods, and an increased awareness of this syndrome among clinical microbiologists.⁶

Diagnosis requires a high degree of suspicion

Lemierre’s syndrome typically occurs in healthy young adults. Pharyngitis is the most common initial symptom, occurring in 87% of patients.² This is followed by a fever (102.2°F - 105.8°F) usually 4 to 5 days after the onset of sore throat.³ Other common symptoms include chills, dysphagia, dyspnea, chest pain, hemoptysis, cervical neck discomfort, arthralgia, malaise, and night sweats.² Following suppurative thrombophlebitis of the IJV, infection spreads to other organ systems. Pulmonary involvement is the most common site (97% of cases).³ Other complications of this syndrome are listed in the TABLE.³

The differential includes mononucleosis

The differential diagnosis encompasses several common illnesses, including mononucleosis, Group A streptococcal pharyngitis, and peritonsillar abscess. However, while patients with these conditions might have a fever and an elevated WBC count, they typically would not have the pleuritic chest pain that is characteristic of Lemierre’s syndrome. In addition, while patients with peritonsillar abscess would have tonsillar exudates, patients with Lemierre’s syndrome would not likely have them.

Influenza is also part of the differential, although focal neck pain usually isn’t a finding in patients who have the flu.

Once other common illnesses have been ruled out, it’s important to have a high index of suspicion for Lemierre’s syndrome because the oropharyngeal infection may resolve by the time of presentation, and there may be few findings on physical exam.⁷ Therefore, suspect Lemierre’s if a patient comes in with neck pain and/or pleuritic chest pain and has a recent history of oropharyngeal infection and fever.

CT scan of the neck and chest with contrast is the optimal diagnostic modality because it allows physicians to visualize the IJV⁸ and detect pulmonary emboli.⁹ Doppler ultrasound also can be used to diagnose IJV thrombosis. Ultrasound findings would reveal an echogenic focus within a dilated IJV or a complex mass of cystic and solid components.¹⁰

Many case reports have demonstrated that complete recovery is possible without anticoagulation.Prompt antibiotic treatment is essential

Patients with Lemierre’s syndrome require prompt and appropriate antimicrobial therapy. Researchers have reported mortality rates of 25% among patients who received delayed antibiotic therapy, compared with rates of up to 18% with prompt therapy.³ Metronidazole is the most commonly prescribed antibiotic.⁸ When combined with ceftriaxone, it provides coverage for both F necrophorum and streptococci, a common copathogen. Monotherapy with a carbapenem antibiotic, clindamycin, ampicillin/sulbactam, or antipseudomonal penicillin also are appropriate options.⁵ Antimicrobial treatment for 3 to 6 weeks is recommended because relapses have been noted in patients treated for less than 2 weeks.¹¹

Anticoagulation is controversial.² Proponents of anticoagulation to treat Lemierre’s syndrome believe it may prevent formation of septic emboli and could expedite recovery.^4,12 Others believe that clots associated with Lemierre’s syndrome dissolve on their own and that anticoagulation may increase the likelihood of septic emboli.¹³ Many case reports, including this one, have demonstrated that complete recovery is possible without anticoagulation.^10,13-15 Anticoagulation therapy can be considered for patients with Lemierre’s syndrome in the absence of any contraindications such as gastrointestinal or intracranial bleeding.

THE TAKEAWAY

Suspect Lemierre’s syndrome when a patient complains of neck pain, high fever, rigors, dry cough, and pleuritic chest pain and mentions a sore throat that he or she had in the pretceding 7 days. Diagnosis can be confirmed by radiological findings and blood cultures positive for F. necrophorum. Patients with Lemierre’s syndrome should be promptly treated with antibiotics; evidence for anticoagulation is inconclusive.

THE CASE

A previously healthy 35-year-old man with a one-week history of left-sided neck pain and fever as high as 104°F sought care at our emergency department. He was given a diagnosis of viral pharyngitis and discharged. He returned the next day and indicated that he was now experiencing drenching night sweats and weakness.

The patient was anxious, but not distressed. His temperature was 100.1°F; blood pressure, 113/65 mm Hg; heart rate, 150 beats per minute; respiratory rate, 18 breaths per minute; and oxygen saturation, 95% on room air. Head and neck examination revealed bilateral cervical lymphadenopathy with pronounced tenderness on the left side of his neck. Oral exam revealed dry mucous membranes, halitosis, and bilateral tonsillar enlargement without exudate. The cardiopulmonary exam was within normal limits. Lab tests showed a white blood cell (WBC) count of 5.9 x 109/L. An ultrasound of the neck revealed thrombosis in the left submandibular branch of the left internal jugular vein (IJV) (FIGURE 1).

The next day, the patient remained febrile (102.8°F) and developed rigors, diarrhea, pleuritic chest pain, and an elevated WBC count (14.5). A blood culture grew gramnegative rods. The patient was started on piperacillin/tazobactam, and doxycycline was added to treat possible tick-borne infections. Computed tomography (CT) scans of the chest showed the presence of septic pulmonary emboli and small bilateral pleural effusions (FIGURE 2).

THE DIAGNOSIS

We made a diagnosis of Lemierre’s syndrome because our patient met all 4 criteria for the condition:^1,2
• a recent oropharyngeal infection
• clinical or radiological evidence of IJV thrombosis
• isolation of anaerobic pathogens (mainly Fusobacterium necrophorum)
• evidence of at least one septic focus, most commonly in the lungs.

We changed the patient’s antibiotic therapy to intravenous (IV) meropenem. His WBC and fever improved, and on Day 10 he was discharged to complete a 28-day course of IV meropenem via a peripherally inserted central catheter.

DISCUSSION

Lemierre’s—A “forgotten” condition that’s making a comeback

In 1936, French microbiologist Andrew Lemierre formally characterized the syndrome in a review of 20 patients who had sepsis, metastatic pulmonary lesions, and isolation of Bacillus funduliformis (now known as F necrophorum).^1,2 Other organisms that have been identified in this syndrome include Fusobacterium nucleatum, Candida, Staphylococcus, and Streptococcus.²

Before the antibiotic era, Lemierre’s syndrome was common and often fatal. But with the introduction of penicillin in the 1940s, the incidence of the syndrome dropped, and it eventually became known as “the forgotten disease.”² Since the 1990s, however, there has been a marked resurgence of Lemierre’s syndrome.³ The incidence of Lemierre’s syndrome today is 0.6 to 2.3 cases per 1 million people per year, with a mortality rate of up to 18%.^3,4

This resurgence of Lemierre’s syndrome has been linked to the restricted use of antibiotics for throat infections.3 (One study found the number of prescriptions written for antibiotics decreased by 23% from 1992 to 2000.⁵) Other factors cited for the increased incidence of Lemierre’s syndrome include improved identification of anaerobic organisms, more effective blood culture methods, and an increased awareness of this syndrome among clinical microbiologists.⁶

Diagnosis requires a high degree of suspicion

Lemierre’s syndrome typically occurs in healthy young adults. Pharyngitis is the most common initial symptom, occurring in 87% of patients.² This is followed by a fever (102.2°F - 105.8°F) usually 4 to 5 days after the onset of sore throat.³ Other common symptoms include chills, dysphagia, dyspnea, chest pain, hemoptysis, cervical neck discomfort, arthralgia, malaise, and night sweats.² Following suppurative thrombophlebitis of the IJV, infection spreads to other organ systems. Pulmonary involvement is the most common site (97% of cases).³ Other complications of this syndrome are listed in the TABLE.³

The differential includes mononucleosis

The differential diagnosis encompasses several common illnesses, including mononucleosis, Group A streptococcal pharyngitis, and peritonsillar abscess. However, while patients with these conditions might have a fever and an elevated WBC count, they typically would not have the pleuritic chest pain that is characteristic of Lemierre’s syndrome. In addition, while patients with peritonsillar abscess would have tonsillar exudates, patients with Lemierre’s syndrome would not likely have them.

Influenza is also part of the differential, although focal neck pain usually isn’t a finding in patients who have the flu.

Once other common illnesses have been ruled out, it’s important to have a high index of suspicion for Lemierre’s syndrome because the oropharyngeal infection may resolve by the time of presentation, and there may be few findings on physical exam.⁷ Therefore, suspect Lemierre’s if a patient comes in with neck pain and/or pleuritic chest pain and has a recent history of oropharyngeal infection and fever.

CT scan of the neck and chest with contrast is the optimal diagnostic modality because it allows physicians to visualize the IJV⁸ and detect pulmonary emboli.⁹ Doppler ultrasound also can be used to diagnose IJV thrombosis. Ultrasound findings would reveal an echogenic focus within a dilated IJV or a complex mass of cystic and solid components.¹⁰

Many case reports have demonstrated that complete recovery is possible without anticoagulation.Prompt antibiotic treatment is essential

Patients with Lemierre’s syndrome require prompt and appropriate antimicrobial therapy. Researchers have reported mortality rates of 25% among patients who received delayed antibiotic therapy, compared with rates of up to 18% with prompt therapy.³ Metronidazole is the most commonly prescribed antibiotic.⁸ When combined with ceftriaxone, it provides coverage for both F necrophorum and streptococci, a common copathogen. Monotherapy with a carbapenem antibiotic, clindamycin, ampicillin/sulbactam, or antipseudomonal penicillin also are appropriate options.⁵ Antimicrobial treatment for 3 to 6 weeks is recommended because relapses have been noted in patients treated for less than 2 weeks.¹¹

Anticoagulation is controversial.² Proponents of anticoagulation to treat Lemierre’s syndrome believe it may prevent formation of septic emboli and could expedite recovery.^4,12 Others believe that clots associated with Lemierre’s syndrome dissolve on their own and that anticoagulation may increase the likelihood of septic emboli.¹³ Many case reports, including this one, have demonstrated that complete recovery is possible without anticoagulation.^10,13-15 Anticoagulation therapy can be considered for patients with Lemierre’s syndrome in the absence of any contraindications such as gastrointestinal or intracranial bleeding.

THE TAKEAWAY

Suspect Lemierre’s syndrome when a patient complains of neck pain, high fever, rigors, dry cough, and pleuritic chest pain and mentions a sore throat that he or she had in the pretceding 7 days. Diagnosis can be confirmed by radiological findings and blood cultures positive for F. necrophorum. Patients with Lemierre’s syndrome should be promptly treated with antibiotics; evidence for anticoagulation is inconclusive.

ABSTRACT

Purpose Little is known about patients who present a written list during a medical consultation. In this preliminary study, we sought to examine and characterize patients who use a prepared list.

Methods The design was an open observational case-controlled study that took place at 2 urban primary care clinics. We enrolled patients consecutively as they arrived with a written list for consultation. Consecutive patients presenting without a list served as the control group. Physician interviews and completed questionnaires provided demographic and medical characteristics of this group and explanations for list preparation.

Results Fifty-four patients presented with a list and were compared with controls. Statistically, patients arriving with a list were significantly more likely to be older and retired, and less likely to be salaried workers or housewives. These patients had more chronic diseases and consumed more long-term medications. They had a greater number of doctor visits in the past year compared with controls, and perceived an increase in memory loss. There were no differences between the groups in terms of psychiatric disease or personality disorders.

Conclusions Aside from certain demographic and health characteristics, patients who use written lists do not differ substantially from those who don’t. They have no discernible ill intention, and the list serves as a memory aid to make the most of the visit.

Nonverbal communication is a significant part of the physician-patient encounter, in part revealing clues to underlying attitudes and emotions or indicating whether one agrees or disagrees with expressed statements.¹ Nonverbal communication exhibited by both doctor and patient strongly influences how each participant perceives the encounter and helps determine how the physician-patient relationship will develop.^2-4

Patients, for example, are affected by the amount of physician eye contact and computer use. Less eye contact and greater attention to the computer tend to lower patients’ opinions of the consultation.^1,5 These and other behaviors may contribute to the finding that 30% to 80% of patients feel their expectations are not met in routine primary care visits.⁶

Physicians, despite attempts to remain nonjudgmental, can be affected by a patient’s demeanor on entering the consulting room. Subtle prejudices may be evoked by age, gender, ethnicity, manner of dress, tone of voice, mannerisms, cell phone interruptions, and the like.^7,8 Negative reactions can create barriers to good communication. Awareness of them may be the first step to preventing or removing hindrances to meaningful dialogue.⁹

Patients who present lists at office visits tend to be older, have a number of chronic disorders, and think they have memory loss.One aspect of a patient’s presentation that may be viewed negatively is possession of a list. But this need not be the case. The list, if viewed as a patient-initiated agenda, can lead to a gratifying encounter for both patient and physician. In fact, there is reason to believe that a list representing a set agenda at the start of a visit may enhance patient satisfaction without increasing visit length.¹⁰ In fact, the Agency for Healthcare Research and Quality (AHRQ) advises patients to “Write down your questions before your visit. List the most important ones first to make sure they get asked and answered.”¹¹

To learn more about the people who arrive at a consultation with a written list, we conducted a study at 2 clinics in Clalit Health Services—Southern District (CHS-SD), which we designed to focus on answering the following questions:
1. Do patients with lists have a unique sociodemographic profile?
2. Do they present with specific medical ailments but have a high frequency of psychiatric disorders?
3. What are the underlying motives leading to list use?

METHODS

Design

This was an open observational case-controlled study, approved by the institutional review board and the clinical research board of the Department of Family Medicine, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel.

Setting

We conducted our study at 2 urban primary care clinics serving a population of 7000 people of diverse ages, 10% of whom are recent immigrants.

Selection of participants

We consecutively recruited patients who carried a list to use during the consultation. After obtaining patients’ informed consent to participate in the study, we asked them to spend the time necessary to disclose requested information. We excluded those who were not fluent in the language of their physicians.

Intervention

Family physicians at the participating clinics distributed a questionnaire to patients arriving with a written list, then conducted guided interviews. We defined “list use” as the patient’s choice to refer to a list as an agenda for that visit, whether to remind one’s self to cover all complaints, to accurately describe symptoms, to request medication prescriptions, or to ask about test results.

First, through interview or questionnaire, we gathered standard sociodemographic data. Second, we focused on general health issues, chronic medical disorders, psychiatric disorders, chronic medication consumption, and number of visits. We derived this information from computerized medical records. Third, through the questionnaire, we inquired about the reason patients used a list, and asked patients to subjectively rate their memory and give the general reasons for their visit.

The control group consisted of patients recruited consecutively at arbitrary points in time until its size matched that of the study group. These patients volunteered information to the same line of inquiry. Some members of the groups chose to complete the questionnaires in writing without the physician’s assistance.

Statistical analysis

We processed results using SPSS software. We applied the x2 test for statistical interpretation and set statistical significance at P<.05.

RESULTS

Twenty-five men and twenty-nine women ages 21 to 82 years of age comprised the group of patients presenting with a list. All patients who met inclusion criteria agreed to cooperate. TABLE 1 summarizes the sociodemographic data. The control group consisted of 30 men and 22 women ages 20 to 86 years of age.

There was no statistically meaningful difference in gender ratio between the groups. In the study and control groups, respectively, the average number of children of each subject was 4.1 and 3.5, years of formal education were 10.8 and 10.6, and years since immigration were 40.5 and 37.8 (P=.42). Marital status and average household income were also similar in both groups.

Statistically significant findings with the study group were relatively older ages and likelihood to be pensioners. The study group included fewer employed individuals and fewer housewives (P<.001). They also were more likely to have more than 3 chronic diseases (48.1% vs. 9.6%; P<.001) and took more long-term medications, including benzodiazepines (TABLE 2). They had a greater number of doctor visits in the past year compared with controls and reported a perceived increase in memory loss (TABLE 3). There were no significant differences between the groups in psychiatric or personality disorders, as determined by surveying patients’ electronic records.

Psychiatric disorders are no more common among list users than nonlist users. The reasons most commonly given for using a list indicated a desire to completely satisfy the objectives of the visit. Most of the individuals decided to prepare a list on their own initiative without persuasion from any external source.

DISCUSSION

In an survey of 216 family physicians and internists at the University of Wisconsin, >60% of respondents said their patients bring in lists very often or sometimes.¹¹ This figure seems much higher than would be found in our country (Israel). However, the practice is certainly common; although the actual frequency is unknown.

Other published observations about list use. Middleton et al¹² studied the effects of planned use of agenda forms, completed by patients and handed to physicians at the outset of a primary care visit. The written agenda significantly increased the number of problems identified in each consultation. Patient satisfaction increased and deepened the doctor-patient relationship. However, the duration of consultations also increased.

A commentary by Schrager et al¹¹ acknowledges that lists are dreaded by some physicians. Particularly if the expectation is for a patient to present with a single complaint, the appearance of a list may be an unwelcome surprise, suggesting a collection of separate complaints. And compulsive and somatizing patients can raise a series of overwhelming issues that encumber a short visit. But the commentary points out that, in general, fear of a list is unfounded, and that acceptance without prejudging can lead to a constructive outcome.

A number of researchers have examined the relationship between negative physician attitudes and certain patient attributes such as sociodemographic characteristics or a persistent emotional component to their ailments.¹³ Katz¹⁴ reported that patients who generated the most frustration were those who demanded a cure, those who added unrelated complaints at the end of the visit, malingerers, and those who refused to accept responsibility for their own maladies. List users, we believe, should not be lumped in with this group automatically.

One way for patients to become more involved in their care is to bring a list of questions to each visit, as advised by AHRQ.In our study, patients with lists did request more frequent consultations. However, this correlated closely with a heavier burden of disease. Using patient-centered communication to set the agenda for the visit and address the entirety of patients’ concerns has been shown to improve not only patient satisfaction but also adherence to treatment recommendations.^15,16 One way for patients to become more involved in their care is to bring a list of questions to each visit, as advised by AHRQ.

What our study revealed about list users. Our results show that those who made use of a list were older than the ones who did not, more likely to be pensioners, and less likely to be employed or be housewives. They had more chronic diseases, were receiving more medications including benzodiazepines, and had a significantly higher rate of medical appointments than did the controls. Psychiatric diagnoses were no more common among the list users, and reasons given for list use were congruent with aging and an increased burden of disease and medication. We could not discern the exact contribution of each independent factor of advanced age or disease burden. This would be an interesting issue to address in more elaborate research, as would be the actual frequency of list use.

The fact that the study group consumed more benzodiazepine medications may hint that its members suffer from greater levels of anxiety of depression. Limitations of our study. The weaknesses of our study include its questionable generalizability and the possibility that a number of list bearers may not have been recruited due to time constraints on patients or physicians. Randomization could have been improved if we had selected the controls consecutively after selecting the study patients, and not at a separate time. We did not time the length of the consultations, something that should be done in future studies.

The fact that the study group consumed more benzodiazepine medications may hint that its members suffer from greater levels of anxiety or depression. Nevertheless, we assumed that such conditions were likely of modest intensity since they were not included in the medical records.

Large-scale research could yield far more trustworthy results by adjusting for age, country of origin, and disease burden.

CORRESPONDENCE
Sody Naimer, MD, Department of Family Medicine, Faculty of Health Sciences, Ben-Gurion University of the Negev, POB 653, Beer-Sheva 84105, Israel; [email protected]

Acknowledgement
The authors thank Dr. Joseph Herman and Mrs. Barbra Schipper for their assistance in preparing this manuscript.

ABSTRACT

Purpose Little is known about patients who present a written list during a medical consultation. In this preliminary study, we sought to examine and characterize patients who use a prepared list.

Methods The design was an open observational case-controlled study that took place at 2 urban primary care clinics. We enrolled patients consecutively as they arrived with a written list for consultation. Consecutive patients presenting without a list served as the control group. Physician interviews and completed questionnaires provided demographic and medical characteristics of this group and explanations for list preparation.

Results Fifty-four patients presented with a list and were compared with controls. Statistically, patients arriving with a list were significantly more likely to be older and retired, and less likely to be salaried workers or housewives. These patients had more chronic diseases and consumed more long-term medications. They had a greater number of doctor visits in the past year compared with controls, and perceived an increase in memory loss. There were no differences between the groups in terms of psychiatric disease or personality disorders.

Conclusions Aside from certain demographic and health characteristics, patients who use written lists do not differ substantially from those who don’t. They have no discernible ill intention, and the list serves as a memory aid to make the most of the visit.

Nonverbal communication is a significant part of the physician-patient encounter, in part revealing clues to underlying attitudes and emotions or indicating whether one agrees or disagrees with expressed statements.¹ Nonverbal communication exhibited by both doctor and patient strongly influences how each participant perceives the encounter and helps determine how the physician-patient relationship will develop.^2-4

Patients, for example, are affected by the amount of physician eye contact and computer use. Less eye contact and greater attention to the computer tend to lower patients’ opinions of the consultation.^1,5 These and other behaviors may contribute to the finding that 30% to 80% of patients feel their expectations are not met in routine primary care visits.⁶

Physicians, despite attempts to remain nonjudgmental, can be affected by a patient’s demeanor on entering the consulting room. Subtle prejudices may be evoked by age, gender, ethnicity, manner of dress, tone of voice, mannerisms, cell phone interruptions, and the like.^7,8 Negative reactions can create barriers to good communication. Awareness of them may be the first step to preventing or removing hindrances to meaningful dialogue.⁹

Patients who present lists at office visits tend to be older, have a number of chronic disorders, and think they have memory loss.One aspect of a patient’s presentation that may be viewed negatively is possession of a list. But this need not be the case. The list, if viewed as a patient-initiated agenda, can lead to a gratifying encounter for both patient and physician. In fact, there is reason to believe that a list representing a set agenda at the start of a visit may enhance patient satisfaction without increasing visit length.¹⁰ In fact, the Agency for Healthcare Research and Quality (AHRQ) advises patients to “Write down your questions before your visit. List the most important ones first to make sure they get asked and answered.”¹¹

To learn more about the people who arrive at a consultation with a written list, we conducted a study at 2 clinics in Clalit Health Services—Southern District (CHS-SD), which we designed to focus on answering the following questions:
1. Do patients with lists have a unique sociodemographic profile?
2. Do they present with specific medical ailments but have a high frequency of psychiatric disorders?
3. What are the underlying motives leading to list use?

METHODS

Design

This was an open observational case-controlled study, approved by the institutional review board and the clinical research board of the Department of Family Medicine, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel.

Setting

We conducted our study at 2 urban primary care clinics serving a population of 7000 people of diverse ages, 10% of whom are recent immigrants.

Selection of participants

We consecutively recruited patients who carried a list to use during the consultation. After obtaining patients’ informed consent to participate in the study, we asked them to spend the time necessary to disclose requested information. We excluded those who were not fluent in the language of their physicians.

Intervention

Family physicians at the participating clinics distributed a questionnaire to patients arriving with a written list, then conducted guided interviews. We defined “list use” as the patient’s choice to refer to a list as an agenda for that visit, whether to remind one’s self to cover all complaints, to accurately describe symptoms, to request medication prescriptions, or to ask about test results.

First, through interview or questionnaire, we gathered standard sociodemographic data. Second, we focused on general health issues, chronic medical disorders, psychiatric disorders, chronic medication consumption, and number of visits. We derived this information from computerized medical records. Third, through the questionnaire, we inquired about the reason patients used a list, and asked patients to subjectively rate their memory and give the general reasons for their visit.

The control group consisted of patients recruited consecutively at arbitrary points in time until its size matched that of the study group. These patients volunteered information to the same line of inquiry. Some members of the groups chose to complete the questionnaires in writing without the physician’s assistance.

Statistical analysis

We processed results using SPSS software. We applied the x2 test for statistical interpretation and set statistical significance at P<.05.

RESULTS

Twenty-five men and twenty-nine women ages 21 to 82 years of age comprised the group of patients presenting with a list. All patients who met inclusion criteria agreed to cooperate. TABLE 1 summarizes the sociodemographic data. The control group consisted of 30 men and 22 women ages 20 to 86 years of age.

There was no statistically meaningful difference in gender ratio between the groups. In the study and control groups, respectively, the average number of children of each subject was 4.1 and 3.5, years of formal education were 10.8 and 10.6, and years since immigration were 40.5 and 37.8 (P=.42). Marital status and average household income were also similar in both groups.

Statistically significant findings with the study group were relatively older ages and likelihood to be pensioners. The study group included fewer employed individuals and fewer housewives (P<.001). They also were more likely to have more than 3 chronic diseases (48.1% vs. 9.6%; P<.001) and took more long-term medications, including benzodiazepines (TABLE 2). They had a greater number of doctor visits in the past year compared with controls and reported a perceived increase in memory loss (TABLE 3). There were no significant differences between the groups in psychiatric or personality disorders, as determined by surveying patients’ electronic records.

Psychiatric disorders are no more common among list users than nonlist users. The reasons most commonly given for using a list indicated a desire to completely satisfy the objectives of the visit. Most of the individuals decided to prepare a list on their own initiative without persuasion from any external source.

DISCUSSION

In an survey of 216 family physicians and internists at the University of Wisconsin, >60% of respondents said their patients bring in lists very often or sometimes.¹¹ This figure seems much higher than would be found in our country (Israel). However, the practice is certainly common; although the actual frequency is unknown.

Other published observations about list use. Middleton et al¹² studied the effects of planned use of agenda forms, completed by patients and handed to physicians at the outset of a primary care visit. The written agenda significantly increased the number of problems identified in each consultation. Patient satisfaction increased and deepened the doctor-patient relationship. However, the duration of consultations also increased.

A commentary by Schrager et al¹¹ acknowledges that lists are dreaded by some physicians. Particularly if the expectation is for a patient to present with a single complaint, the appearance of a list may be an unwelcome surprise, suggesting a collection of separate complaints. And compulsive and somatizing patients can raise a series of overwhelming issues that encumber a short visit. But the commentary points out that, in general, fear of a list is unfounded, and that acceptance without prejudging can lead to a constructive outcome.

A number of researchers have examined the relationship between negative physician attitudes and certain patient attributes such as sociodemographic characteristics or a persistent emotional component to their ailments.¹³ Katz¹⁴ reported that patients who generated the most frustration were those who demanded a cure, those who added unrelated complaints at the end of the visit, malingerers, and those who refused to accept responsibility for their own maladies. List users, we believe, should not be lumped in with this group automatically.

One way for patients to become more involved in their care is to bring a list of questions to each visit, as advised by AHRQ.In our study, patients with lists did request more frequent consultations. However, this correlated closely with a heavier burden of disease. Using patient-centered communication to set the agenda for the visit and address the entirety of patients’ concerns has been shown to improve not only patient satisfaction but also adherence to treatment recommendations.^15,16 One way for patients to become more involved in their care is to bring a list of questions to each visit, as advised by AHRQ.

What our study revealed about list users. Our results show that those who made use of a list were older than the ones who did not, more likely to be pensioners, and less likely to be employed or be housewives. They had more chronic diseases, were receiving more medications including benzodiazepines, and had a significantly higher rate of medical appointments than did the controls. Psychiatric diagnoses were no more common among the list users, and reasons given for list use were congruent with aging and an increased burden of disease and medication. We could not discern the exact contribution of each independent factor of advanced age or disease burden. This would be an interesting issue to address in more elaborate research, as would be the actual frequency of list use.

The fact that the study group consumed more benzodiazepine medications may hint that its members suffer from greater levels of anxiety of depression. Limitations of our study. The weaknesses of our study include its questionable generalizability and the possibility that a number of list bearers may not have been recruited due to time constraints on patients or physicians. Randomization could have been improved if we had selected the controls consecutively after selecting the study patients, and not at a separate time. We did not time the length of the consultations, something that should be done in future studies.

The fact that the study group consumed more benzodiazepine medications may hint that its members suffer from greater levels of anxiety or depression. Nevertheless, we assumed that such conditions were likely of modest intensity since they were not included in the medical records.

Large-scale research could yield far more trustworthy results by adjusting for age, country of origin, and disease burden.

CORRESPONDENCE
Sody Naimer, MD, Department of Family Medicine, Faculty of Health Sciences, Ben-Gurion University of the Negev, POB 653, Beer-Sheva 84105, Israel; [email protected]

Acknowledgement
The authors thank Dr. Joseph Herman and Mrs. Barbra Schipper for their assistance in preparing this manuscript.

ABSTRACT

Purpose Little is known about patients who present a written list during a medical consultation. In this preliminary study, we sought to examine and characterize patients who use a prepared list.

Methods The design was an open observational case-controlled study that took place at 2 urban primary care clinics. We enrolled patients consecutively as they arrived with a written list for consultation. Consecutive patients presenting without a list served as the control group. Physician interviews and completed questionnaires provided demographic and medical characteristics of this group and explanations for list preparation.

Results Fifty-four patients presented with a list and were compared with controls. Statistically, patients arriving with a list were significantly more likely to be older and retired, and less likely to be salaried workers or housewives. These patients had more chronic diseases and consumed more long-term medications. They had a greater number of doctor visits in the past year compared with controls, and perceived an increase in memory loss. There were no differences between the groups in terms of psychiatric disease or personality disorders.

Conclusions Aside from certain demographic and health characteristics, patients who use written lists do not differ substantially from those who don’t. They have no discernible ill intention, and the list serves as a memory aid to make the most of the visit.

Nonverbal communication is a significant part of the physician-patient encounter, in part revealing clues to underlying attitudes and emotions or indicating whether one agrees or disagrees with expressed statements.¹ Nonverbal communication exhibited by both doctor and patient strongly influences how each participant perceives the encounter and helps determine how the physician-patient relationship will develop.^2-4

Patients, for example, are affected by the amount of physician eye contact and computer use. Less eye contact and greater attention to the computer tend to lower patients’ opinions of the consultation.^1,5 These and other behaviors may contribute to the finding that 30% to 80% of patients feel their expectations are not met in routine primary care visits.⁶

Physicians, despite attempts to remain nonjudgmental, can be affected by a patient’s demeanor on entering the consulting room. Subtle prejudices may be evoked by age, gender, ethnicity, manner of dress, tone of voice, mannerisms, cell phone interruptions, and the like.^7,8 Negative reactions can create barriers to good communication. Awareness of them may be the first step to preventing or removing hindrances to meaningful dialogue.⁹

Patients who present lists at office visits tend to be older, have a number of chronic disorders, and think they have memory loss.One aspect of a patient’s presentation that may be viewed negatively is possession of a list. But this need not be the case. The list, if viewed as a patient-initiated agenda, can lead to a gratifying encounter for both patient and physician. In fact, there is reason to believe that a list representing a set agenda at the start of a visit may enhance patient satisfaction without increasing visit length.¹⁰ In fact, the Agency for Healthcare Research and Quality (AHRQ) advises patients to “Write down your questions before your visit. List the most important ones first to make sure they get asked and answered.”¹¹

To learn more about the people who arrive at a consultation with a written list, we conducted a study at 2 clinics in Clalit Health Services—Southern District (CHS-SD), which we designed to focus on answering the following questions:
1. Do patients with lists have a unique sociodemographic profile?
2. Do they present with specific medical ailments but have a high frequency of psychiatric disorders?
3. What are the underlying motives leading to list use?

METHODS

Design

This was an open observational case-controlled study, approved by the institutional review board and the clinical research board of the Department of Family Medicine, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel.

Setting

We conducted our study at 2 urban primary care clinics serving a population of 7000 people of diverse ages, 10% of whom are recent immigrants.

Selection of participants

We consecutively recruited patients who carried a list to use during the consultation. After obtaining patients’ informed consent to participate in the study, we asked them to spend the time necessary to disclose requested information. We excluded those who were not fluent in the language of their physicians.

Intervention

Family physicians at the participating clinics distributed a questionnaire to patients arriving with a written list, then conducted guided interviews. We defined “list use” as the patient’s choice to refer to a list as an agenda for that visit, whether to remind one’s self to cover all complaints, to accurately describe symptoms, to request medication prescriptions, or to ask about test results.

First, through interview or questionnaire, we gathered standard sociodemographic data. Second, we focused on general health issues, chronic medical disorders, psychiatric disorders, chronic medication consumption, and number of visits. We derived this information from computerized medical records. Third, through the questionnaire, we inquired about the reason patients used a list, and asked patients to subjectively rate their memory and give the general reasons for their visit.

The control group consisted of patients recruited consecutively at arbitrary points in time until its size matched that of the study group. These patients volunteered information to the same line of inquiry. Some members of the groups chose to complete the questionnaires in writing without the physician’s assistance.

Statistical analysis

We processed results using SPSS software. We applied the x2 test for statistical interpretation and set statistical significance at P<.05.

RESULTS

Twenty-five men and twenty-nine women ages 21 to 82 years of age comprised the group of patients presenting with a list. All patients who met inclusion criteria agreed to cooperate. TABLE 1 summarizes the sociodemographic data. The control group consisted of 30 men and 22 women ages 20 to 86 years of age.

There was no statistically meaningful difference in gender ratio between the groups. In the study and control groups, respectively, the average number of children of each subject was 4.1 and 3.5, years of formal education were 10.8 and 10.6, and years since immigration were 40.5 and 37.8 (P=.42). Marital status and average household income were also similar in both groups.

Statistically significant findings with the study group were relatively older ages and likelihood to be pensioners. The study group included fewer employed individuals and fewer housewives (P<.001). They also were more likely to have more than 3 chronic diseases (48.1% vs. 9.6%; P<.001) and took more long-term medications, including benzodiazepines (TABLE 2). They had a greater number of doctor visits in the past year compared with controls and reported a perceived increase in memory loss (TABLE 3). There were no significant differences between the groups in psychiatric or personality disorders, as determined by surveying patients’ electronic records.

Psychiatric disorders are no more common among list users than nonlist users. The reasons most commonly given for using a list indicated a desire to completely satisfy the objectives of the visit. Most of the individuals decided to prepare a list on their own initiative without persuasion from any external source.

DISCUSSION

In an survey of 216 family physicians and internists at the University of Wisconsin, >60% of respondents said their patients bring in lists very often or sometimes.¹¹ This figure seems much higher than would be found in our country (Israel). However, the practice is certainly common; although the actual frequency is unknown.

Other published observations about list use. Middleton et al¹² studied the effects of planned use of agenda forms, completed by patients and handed to physicians at the outset of a primary care visit. The written agenda significantly increased the number of problems identified in each consultation. Patient satisfaction increased and deepened the doctor-patient relationship. However, the duration of consultations also increased.

A commentary by Schrager et al¹¹ acknowledges that lists are dreaded by some physicians. Particularly if the expectation is for a patient to present with a single complaint, the appearance of a list may be an unwelcome surprise, suggesting a collection of separate complaints. And compulsive and somatizing patients can raise a series of overwhelming issues that encumber a short visit. But the commentary points out that, in general, fear of a list is unfounded, and that acceptance without prejudging can lead to a constructive outcome.

A number of researchers have examined the relationship between negative physician attitudes and certain patient attributes such as sociodemographic characteristics or a persistent emotional component to their ailments.¹³ Katz¹⁴ reported that patients who generated the most frustration were those who demanded a cure, those who added unrelated complaints at the end of the visit, malingerers, and those who refused to accept responsibility for their own maladies. List users, we believe, should not be lumped in with this group automatically.

One way for patients to become more involved in their care is to bring a list of questions to each visit, as advised by AHRQ.In our study, patients with lists did request more frequent consultations. However, this correlated closely with a heavier burden of disease. Using patient-centered communication to set the agenda for the visit and address the entirety of patients’ concerns has been shown to improve not only patient satisfaction but also adherence to treatment recommendations.^15,16 One way for patients to become more involved in their care is to bring a list of questions to each visit, as advised by AHRQ.

What our study revealed about list users. Our results show that those who made use of a list were older than the ones who did not, more likely to be pensioners, and less likely to be employed or be housewives. They had more chronic diseases, were receiving more medications including benzodiazepines, and had a significantly higher rate of medical appointments than did the controls. Psychiatric diagnoses were no more common among the list users, and reasons given for list use were congruent with aging and an increased burden of disease and medication. We could not discern the exact contribution of each independent factor of advanced age or disease burden. This would be an interesting issue to address in more elaborate research, as would be the actual frequency of list use.

The fact that the study group consumed more benzodiazepine medications may hint that its members suffer from greater levels of anxiety of depression. Limitations of our study. The weaknesses of our study include its questionable generalizability and the possibility that a number of list bearers may not have been recruited due to time constraints on patients or physicians. Randomization could have been improved if we had selected the controls consecutively after selecting the study patients, and not at a separate time. We did not time the length of the consultations, something that should be done in future studies.

The fact that the study group consumed more benzodiazepine medications may hint that its members suffer from greater levels of anxiety or depression. Nevertheless, we assumed that such conditions were likely of modest intensity since they were not included in the medical records.

Large-scale research could yield far more trustworthy results by adjusting for age, country of origin, and disease burden.

CORRESPONDENCE
Sody Naimer, MD, Department of Family Medicine, Faculty of Health Sciences, Ben-Gurion University of the Negev, POB 653, Beer-Sheva 84105, Israel; [email protected]

Acknowledgement
The authors thank Dr. Joseph Herman and Mrs. Barbra Schipper for their assistance in preparing this manuscript.

Little evidence suggests that most complementary or alternative medicine therapies treat the symptoms of multiple sclerosis (MS), according to an American Academy of Neurology guideline published March 25 in Neurology. Oral cannabis and oral medical marijuana spray, however, may ease patients’ reported symptoms of spasticity, pain related to spasticity, and frequent urination in MS. Not enough evidence is available to show whether smoking marijuana helps treat MS symptoms, according to the guideline. The authors concluded that magnetic therapy is probably effective for fatigue and probably ineffective for depression. Fish oil is probably ineffective for relapses, disability, fatigue, MRI lesions, and quality of life, according to the guideline. In addition, evidence indicates that ginkgo biloba is ineffective for cognition and possibly effective for fatigue, said the authors.

People who develop diabetes and high blood pressure in middle age are more likely to have brain cell loss and problems with memory and thinking skills than people who never have diabetes or high blood pressure or who develop them in old age, according to a study published online ahead of print March 19 in Neurology. Investigators evaluated the thinking and memory skills of 1,437 people (average age, 80), conducted brain scans, and reviewed participants’ medical records to determine whether the latter had been diagnosed with diabetes or high blood pressure in middle age or later. Midlife diabetes was associated with subcortical infarctions, reduced hippocampal volume, reduced whole brain volume, and prevalent mild cognitive impairment. Midlife hypertension was associated with infarctions and white matter hyperintensity volume.

Each 15-minute decrease in treatment delay may provide a patient an average equivalent of one month of additional disability-free life, according to a study published online ahead of print March 13 in Stroke. Researchers examined observational prospective data for 2,258 consecutive stroke patients treated with IV thrombolysis to determine distributions of age, sex, stroke severity, onset-to-treatment times, and three-month modified Rankin Scale score in daily clinical practice. The investigators found that for every one-minute reduction in onset-to-treatment time, patients gained an average 1.8 days of healthy life. Although all patients benefited from faster treatment, younger patients with longer life expectancies gained a little more than older patients. Women gained slightly more than men throughout their longer lifetimes. The awareness of the importance of speed could promote practice change, said the authors.

The FDA has approved extended-release Qudexy XR (topiramate) capsules as initial monotherapy in patients 10 or older with partial-onset seizures or primary generalized tonic-clonic seizures. The drug also received approval as adjunctive therapy in patients age 2 or older with partial-onset seizures, primary generalized tonic-clonic seizures, and seizures associated with Lennox–Gastaut syndrome. In a randomized, double-blind, placebo-controlled study, the drug demonstrated favorable safety and tolerability in patients with refractory partial-onset seizures. The extended-release formulation was associated with a significantly greater median percent reduction from baseline in seizure frequency, compared with placebo (39.5% vs 21.7%) after 11 weeks of treatment. Upsher-Smith Laboratories, headquartered in Maple Grove, Minnesota, manufactures the drug and expects it to be available during the second quarter of 2014.

The FDA has approved the Cefaly medical device as a preventive treatment for migraine headaches. The product is the first transcutaneous electrical nerve stimulation device specifically authorized for use before the onset of pain. The product is a small, portable, battery-powered unit resembling a plastic headband worn across the forehead once per day for 20 minutes. The device applies an electric current to the skin and underlying tissues to stimulate branches of the trigeminal nerve. In a study including 67 participants, patients who used Cefaly had significantly fewer days with migraines per month and used less migraine attack medication, compared with patients who used a placebo device. STX-Med, which is headquartered in Herstal, Liege, Belgium, manufactures the device, which is indicated for patients 18 and older.

Children with autism who are fed infant formula containing soy protein rather than milk protein may have a higher rate of seizures, according to research published March 12 in PLOS One. Researchers analyzed medical record data for 1,949 children with autism, including information on infant formula use, seizure incidence, the specific type of seizure exhibited, and IQ. Soy-based formula was given in 17.5% of the study population. About 13% of the subjects were female. The researchers found a 2.6-fold higher rate of febrile seizures (4.2% vs 1.6%), a 2.1-fold higher rate of epilepsy comorbidity (3.6% vs 1.7%), and a fourfold higher rate of simple partial seizures (1.2% vs 0.3%) in the children with autism who were fed soy-based formula. No statistically significant associations were found with other outcomes.

For patients with Alzheimer’s disease, levels of markers of neuronal injury in the spinal fluid may decrease as symptoms of memory loss and mental decline appear, according to research published March 5 in Science Translational Medicine. Investigators studied data from the Dominantly Inherited Alzheimer’s Network, which includes participants from families with genetic mutations that cause rare inherited forms of Alzheimer’s disease. The group examined levels of tau, p-tau, and visinin-like protein-1 (VILIP-1). Asymptomatic mutation carriers had elevated concentrations of CSF tau, p-tau181, and VILIP-1 10 to 20 years before their estimated age at symptom onset and before cognitive deficits were detected. The concentrations of CSF biomarkers of neuronal injury or death decreased after their estimated age at symptom onset, suggesting a slowing of acute neurodegenerative processes with symptomatic disease progression.

Men with poor cardiovascular fitness or a low IQ at age 18 are more likely to develop dementia before age 60, investigators reported online ahead of print March 6 in Brain. The researchers conducted a population-based cohort study of more than 1.1 million Swedish male conscripts (age 18) who underwent conscription exams between 1968 and 2005. Participants were followed for as long as 42 years. In fully adjusted models, low cardiovascular fitness and cognitive performance at age 18 were associated with increased risk for future early-onset dementia and mild cognitive impairment, compared with high cardiovascular fitness and cognitive performance. Poor performance on cardiovascular fitness and cognitive tests was associated with a greater-than-sevenfold and a greater than eightfold increased risk of early-onset dementia and early-onset mild cognitive impairment, respectively.

A test that detects low levels of prion protein in the blood may accurately screen for infection with the agent responsible for variant Creutzfeldt-Jakob disease (vCJD), according to a study published online ahead of print March 3 in JAMA Neurology. Researchers performed the test on samples from national blood collection and prion disease centers in the US and the UK. The samples were taken from healthy donors, patients with nonprion neurodegenerative disease, patients in whom a prion disease diagnosis was likely, and patients with confirmed vCJD. The assay’s specificity was confirmed as 100% in a healthy UK cohort. No potentially cross-reactive blood samples from patients with nonprion neurodegenerative diseases tested positive. Two patients with sporadic CJD tested positive. The authors’ previous sensitivity estimate was reconfirmed but not refined.

The FDA has approved Neuraceq (florbetaben F18 injection) for PET imaging of the brain to estimate beta-amyloid neuritic plaque density in adults with cognitive impairment who are being evaluated for Alzheimer’s disease and other causes of cognitive decline. The approval is based on safety data from 872 patients who participated in global clinical trials, and on three studies that examined images from adults with a range of cognitive function. Images were analyzed from 82 subjects with postmortem confirmation of the presence or absence of beta-amyloid neuritic plaques. Correlation of the visual PET interpretation with histopathology in these 82 brains demonstrated that Neuraceq (Piramal Imaging; Boston) accurately detects moderate to frequent beta-amyloid neuritic plaques in the brain.

A combination of human umbilical cord blood cells (hUCBs) and granulocyte colony stimulating factor (G-CSF) may provide more benefit for patients with traumatic brain injury (TBI) than either therapy alone, according to research published March 12 in PLOS One. Adult rats underwent moderate TBI and, seven days later, were treated with saline alone, G-CSF and saline, hUCB and saline, or hUCB and G-CSF. The rats treated with saline exhibited widespread neuroinflammation, impaired endogenous neurogenesis, and severe hippocampal cell loss. hUCB monotherapy suppressed neuroinflammation, nearly normalized neurogenesis, and reduced hippocampal cell loss, compared with saline alone. G-CSF monotherapy produced partial and short-lived benefits characterized by low levels of neuroinflammation, modest neurogenesis, and moderate reduction of hippocampal cell loss. Combined therapy robustly dampened neuroinflammation, enhanced endogenous neurogenesis, and reduced hippocampal cell loss.

The ability to learn new information may be significantly poorer among patients with Parkinson’s disease than among healthy individuals, according to research published online ahead of print February 24 in Movement Disorders. Investigators examined 27 patients with Parkinson’s disease without dementia and 27 age-, gender-, and education-matched healthy controls with a neuropsychologic test battery designed to assess new learning and memory. The researchers found a significant difference in the groups’ ability to learn a list of 10 semantically related words. Once the groups were equated on learning abilities, the investigators found no significant difference between patients with Parkinson’s disease and controls in recall or recognition of the newly learned material. The memory deficit in nondemented patients with Parkinson’s disease largely results from a deficit in learning new information, said the authors.

Chronic sleep loss may lead to irreversible physical damage to and loss of brain cells, according to research published March 19 in the Journal of Neuroscience. Investigators examined mice following periods of normal rest, short wakefulness, or extended wakefulness to model shift workers’ typical sleep patterns. In response to short-term sleep loss, locus coeruleus neurons upregulated the sirtuin type 3 (SirT3) protein, which protects neurons from metabolic injury. After several days of shift worker sleep patterns, locus coeruleus neurons in the mice had reduced SirT3 and increased cell death. In addition, oxidative stress and acetylation of mitochondrial proteins increased. The mice lost 25% of their locus coeruleus neurons. “This is the first report that sleep loss can actually result in a loss of neurons,” said the authors.

—Erik Greb

Little evidence suggests that most complementary or alternative medicine therapies treat the symptoms of multiple sclerosis (MS), according to an American Academy of Neurology guideline published March 25 in Neurology. Oral cannabis and oral medical marijuana spray, however, may ease patients’ reported symptoms of spasticity, pain related to spasticity, and frequent urination in MS. Not enough evidence is available to show whether smoking marijuana helps treat MS symptoms, according to the guideline. The authors concluded that magnetic therapy is probably effective for fatigue and probably ineffective for depression. Fish oil is probably ineffective for relapses, disability, fatigue, MRI lesions, and quality of life, according to the guideline. In addition, evidence indicates that ginkgo biloba is ineffective for cognition and possibly effective for fatigue, said the authors.

People who develop diabetes and high blood pressure in middle age are more likely to have brain cell loss and problems with memory and thinking skills than people who never have diabetes or high blood pressure or who develop them in old age, according to a study published online ahead of print March 19 in Neurology. Investigators evaluated the thinking and memory skills of 1,437 people (average age, 80), conducted brain scans, and reviewed participants’ medical records to determine whether the latter had been diagnosed with diabetes or high blood pressure in middle age or later. Midlife diabetes was associated with subcortical infarctions, reduced hippocampal volume, reduced whole brain volume, and prevalent mild cognitive impairment. Midlife hypertension was associated with infarctions and white matter hyperintensity volume.

Each 15-minute decrease in treatment delay may provide a patient an average equivalent of one month of additional disability-free life, according to a study published online ahead of print March 13 in Stroke. Researchers examined observational prospective data for 2,258 consecutive stroke patients treated with IV thrombolysis to determine distributions of age, sex, stroke severity, onset-to-treatment times, and three-month modified Rankin Scale score in daily clinical practice. The investigators found that for every one-minute reduction in onset-to-treatment time, patients gained an average 1.8 days of healthy life. Although all patients benefited from faster treatment, younger patients with longer life expectancies gained a little more than older patients. Women gained slightly more than men throughout their longer lifetimes. The awareness of the importance of speed could promote practice change, said the authors.

The FDA has approved extended-release Qudexy XR (topiramate) capsules as initial monotherapy in patients 10 or older with partial-onset seizures or primary generalized tonic-clonic seizures. The drug also received approval as adjunctive therapy in patients age 2 or older with partial-onset seizures, primary generalized tonic-clonic seizures, and seizures associated with Lennox–Gastaut syndrome. In a randomized, double-blind, placebo-controlled study, the drug demonstrated favorable safety and tolerability in patients with refractory partial-onset seizures. The extended-release formulation was associated with a significantly greater median percent reduction from baseline in seizure frequency, compared with placebo (39.5% vs 21.7%) after 11 weeks of treatment. Upsher-Smith Laboratories, headquartered in Maple Grove, Minnesota, manufactures the drug and expects it to be available during the second quarter of 2014.

The FDA has approved the Cefaly medical device as a preventive treatment for migraine headaches. The product is the first transcutaneous electrical nerve stimulation device specifically authorized for use before the onset of pain. The product is a small, portable, battery-powered unit resembling a plastic headband worn across the forehead once per day for 20 minutes. The device applies an electric current to the skin and underlying tissues to stimulate branches of the trigeminal nerve. In a study including 67 participants, patients who used Cefaly had significantly fewer days with migraines per month and used less migraine attack medication, compared with patients who used a placebo device. STX-Med, which is headquartered in Herstal, Liege, Belgium, manufactures the device, which is indicated for patients 18 and older.

Children with autism who are fed infant formula containing soy protein rather than milk protein may have a higher rate of seizures, according to research published March 12 in PLOS One. Researchers analyzed medical record data for 1,949 children with autism, including information on infant formula use, seizure incidence, the specific type of seizure exhibited, and IQ. Soy-based formula was given in 17.5% of the study population. About 13% of the subjects were female. The researchers found a 2.6-fold higher rate of febrile seizures (4.2% vs 1.6%), a 2.1-fold higher rate of epilepsy comorbidity (3.6% vs 1.7%), and a fourfold higher rate of simple partial seizures (1.2% vs 0.3%) in the children with autism who were fed soy-based formula. No statistically significant associations were found with other outcomes.

For patients with Alzheimer’s disease, levels of markers of neuronal injury in the spinal fluid may decrease as symptoms of memory loss and mental decline appear, according to research published March 5 in Science Translational Medicine. Investigators studied data from the Dominantly Inherited Alzheimer’s Network, which includes participants from families with genetic mutations that cause rare inherited forms of Alzheimer’s disease. The group examined levels of tau, p-tau, and visinin-like protein-1 (VILIP-1). Asymptomatic mutation carriers had elevated concentrations of CSF tau, p-tau181, and VILIP-1 10 to 20 years before their estimated age at symptom onset and before cognitive deficits were detected. The concentrations of CSF biomarkers of neuronal injury or death decreased after their estimated age at symptom onset, suggesting a slowing of acute neurodegenerative processes with symptomatic disease progression.

Men with poor cardiovascular fitness or a low IQ at age 18 are more likely to develop dementia before age 60, investigators reported online ahead of print March 6 in Brain. The researchers conducted a population-based cohort study of more than 1.1 million Swedish male conscripts (age 18) who underwent conscription exams between 1968 and 2005. Participants were followed for as long as 42 years. In fully adjusted models, low cardiovascular fitness and cognitive performance at age 18 were associated with increased risk for future early-onset dementia and mild cognitive impairment, compared with high cardiovascular fitness and cognitive performance. Poor performance on cardiovascular fitness and cognitive tests was associated with a greater-than-sevenfold and a greater than eightfold increased risk of early-onset dementia and early-onset mild cognitive impairment, respectively.

A test that detects low levels of prion protein in the blood may accurately screen for infection with the agent responsible for variant Creutzfeldt-Jakob disease (vCJD), according to a study published online ahead of print March 3 in JAMA Neurology. Researchers performed the test on samples from national blood collection and prion disease centers in the US and the UK. The samples were taken from healthy donors, patients with nonprion neurodegenerative disease, patients in whom a prion disease diagnosis was likely, and patients with confirmed vCJD. The assay’s specificity was confirmed as 100% in a healthy UK cohort. No potentially cross-reactive blood samples from patients with nonprion neurodegenerative diseases tested positive. Two patients with sporadic CJD tested positive. The authors’ previous sensitivity estimate was reconfirmed but not refined.

The FDA has approved Neuraceq (florbetaben F18 injection) for PET imaging of the brain to estimate beta-amyloid neuritic plaque density in adults with cognitive impairment who are being evaluated for Alzheimer’s disease and other causes of cognitive decline. The approval is based on safety data from 872 patients who participated in global clinical trials, and on three studies that examined images from adults with a range of cognitive function. Images were analyzed from 82 subjects with postmortem confirmation of the presence or absence of beta-amyloid neuritic plaques. Correlation of the visual PET interpretation with histopathology in these 82 brains demonstrated that Neuraceq (Piramal Imaging; Boston) accurately detects moderate to frequent beta-amyloid neuritic plaques in the brain.

A combination of human umbilical cord blood cells (hUCBs) and granulocyte colony stimulating factor (G-CSF) may provide more benefit for patients with traumatic brain injury (TBI) than either therapy alone, according to research published March 12 in PLOS One. Adult rats underwent moderate TBI and, seven days later, were treated with saline alone, G-CSF and saline, hUCB and saline, or hUCB and G-CSF. The rats treated with saline exhibited widespread neuroinflammation, impaired endogenous neurogenesis, and severe hippocampal cell loss. hUCB monotherapy suppressed neuroinflammation, nearly normalized neurogenesis, and reduced hippocampal cell loss, compared with saline alone. G-CSF monotherapy produced partial and short-lived benefits characterized by low levels of neuroinflammation, modest neurogenesis, and moderate reduction of hippocampal cell loss. Combined therapy robustly dampened neuroinflammation, enhanced endogenous neurogenesis, and reduced hippocampal cell loss.

The ability to learn new information may be significantly poorer among patients with Parkinson’s disease than among healthy individuals, according to research published online ahead of print February 24 in Movement Disorders. Investigators examined 27 patients with Parkinson’s disease without dementia and 27 age-, gender-, and education-matched healthy controls with a neuropsychologic test battery designed to assess new learning and memory. The researchers found a significant difference in the groups’ ability to learn a list of 10 semantically related words. Once the groups were equated on learning abilities, the investigators found no significant difference between patients with Parkinson’s disease and controls in recall or recognition of the newly learned material. The memory deficit in nondemented patients with Parkinson’s disease largely results from a deficit in learning new information, said the authors.

Chronic sleep loss may lead to irreversible physical damage to and loss of brain cells, according to research published March 19 in the Journal of Neuroscience. Investigators examined mice following periods of normal rest, short wakefulness, or extended wakefulness to model shift workers’ typical sleep patterns. In response to short-term sleep loss, locus coeruleus neurons upregulated the sirtuin type 3 (SirT3) protein, which protects neurons from metabolic injury. After several days of shift worker sleep patterns, locus coeruleus neurons in the mice had reduced SirT3 and increased cell death. In addition, oxidative stress and acetylation of mitochondrial proteins increased. The mice lost 25% of their locus coeruleus neurons. “This is the first report that sleep loss can actually result in a loss of neurons,” said the authors.

—Erik Greb

Little evidence suggests that most complementary or alternative medicine therapies treat the symptoms of multiple sclerosis (MS), according to an American Academy of Neurology guideline published March 25 in Neurology. Oral cannabis and oral medical marijuana spray, however, may ease patients’ reported symptoms of spasticity, pain related to spasticity, and frequent urination in MS. Not enough evidence is available to show whether smoking marijuana helps treat MS symptoms, according to the guideline. The authors concluded that magnetic therapy is probably effective for fatigue and probably ineffective for depression. Fish oil is probably ineffective for relapses, disability, fatigue, MRI lesions, and quality of life, according to the guideline. In addition, evidence indicates that ginkgo biloba is ineffective for cognition and possibly effective for fatigue, said the authors.

People who develop diabetes and high blood pressure in middle age are more likely to have brain cell loss and problems with memory and thinking skills than people who never have diabetes or high blood pressure or who develop them in old age, according to a study published online ahead of print March 19 in Neurology. Investigators evaluated the thinking and memory skills of 1,437 people (average age, 80), conducted brain scans, and reviewed participants’ medical records to determine whether the latter had been diagnosed with diabetes or high blood pressure in middle age or later. Midlife diabetes was associated with subcortical infarctions, reduced hippocampal volume, reduced whole brain volume, and prevalent mild cognitive impairment. Midlife hypertension was associated with infarctions and white matter hyperintensity volume.

Each 15-minute decrease in treatment delay may provide a patient an average equivalent of one month of additional disability-free life, according to a study published online ahead of print March 13 in Stroke. Researchers examined observational prospective data for 2,258 consecutive stroke patients treated with IV thrombolysis to determine distributions of age, sex, stroke severity, onset-to-treatment times, and three-month modified Rankin Scale score in daily clinical practice. The investigators found that for every one-minute reduction in onset-to-treatment time, patients gained an average 1.8 days of healthy life. Although all patients benefited from faster treatment, younger patients with longer life expectancies gained a little more than older patients. Women gained slightly more than men throughout their longer lifetimes. The awareness of the importance of speed could promote practice change, said the authors.

The FDA has approved extended-release Qudexy XR (topiramate) capsules as initial monotherapy in patients 10 or older with partial-onset seizures or primary generalized tonic-clonic seizures. The drug also received approval as adjunctive therapy in patients age 2 or older with partial-onset seizures, primary generalized tonic-clonic seizures, and seizures associated with Lennox–Gastaut syndrome. In a randomized, double-blind, placebo-controlled study, the drug demonstrated favorable safety and tolerability in patients with refractory partial-onset seizures. The extended-release formulation was associated with a significantly greater median percent reduction from baseline in seizure frequency, compared with placebo (39.5% vs 21.7%) after 11 weeks of treatment. Upsher-Smith Laboratories, headquartered in Maple Grove, Minnesota, manufactures the drug and expects it to be available during the second quarter of 2014.

The FDA has approved the Cefaly medical device as a preventive treatment for migraine headaches. The product is the first transcutaneous electrical nerve stimulation device specifically authorized for use before the onset of pain. The product is a small, portable, battery-powered unit resembling a plastic headband worn across the forehead once per day for 20 minutes. The device applies an electric current to the skin and underlying tissues to stimulate branches of the trigeminal nerve. In a study including 67 participants, patients who used Cefaly had significantly fewer days with migraines per month and used less migraine attack medication, compared with patients who used a placebo device. STX-Med, which is headquartered in Herstal, Liege, Belgium, manufactures the device, which is indicated for patients 18 and older.

Children with autism who are fed infant formula containing soy protein rather than milk protein may have a higher rate of seizures, according to research published March 12 in PLOS One. Researchers analyzed medical record data for 1,949 children with autism, including information on infant formula use, seizure incidence, the specific type of seizure exhibited, and IQ. Soy-based formula was given in 17.5% of the study population. About 13% of the subjects were female. The researchers found a 2.6-fold higher rate of febrile seizures (4.2% vs 1.6%), a 2.1-fold higher rate of epilepsy comorbidity (3.6% vs 1.7%), and a fourfold higher rate of simple partial seizures (1.2% vs 0.3%) in the children with autism who were fed soy-based formula. No statistically significant associations were found with other outcomes.

For patients with Alzheimer’s disease, levels of markers of neuronal injury in the spinal fluid may decrease as symptoms of memory loss and mental decline appear, according to research published March 5 in Science Translational Medicine. Investigators studied data from the Dominantly Inherited Alzheimer’s Network, which includes participants from families with genetic mutations that cause rare inherited forms of Alzheimer’s disease. The group examined levels of tau, p-tau, and visinin-like protein-1 (VILIP-1). Asymptomatic mutation carriers had elevated concentrations of CSF tau, p-tau181, and VILIP-1 10 to 20 years before their estimated age at symptom onset and before cognitive deficits were detected. The concentrations of CSF biomarkers of neuronal injury or death decreased after their estimated age at symptom onset, suggesting a slowing of acute neurodegenerative processes with symptomatic disease progression.

Men with poor cardiovascular fitness or a low IQ at age 18 are more likely to develop dementia before age 60, investigators reported online ahead of print March 6 in Brain. The researchers conducted a population-based cohort study of more than 1.1 million Swedish male conscripts (age 18) who underwent conscription exams between 1968 and 2005. Participants were followed for as long as 42 years. In fully adjusted models, low cardiovascular fitness and cognitive performance at age 18 were associated with increased risk for future early-onset dementia and mild cognitive impairment, compared with high cardiovascular fitness and cognitive performance. Poor performance on cardiovascular fitness and cognitive tests was associated with a greater-than-sevenfold and a greater than eightfold increased risk of early-onset dementia and early-onset mild cognitive impairment, respectively.

A test that detects low levels of prion protein in the blood may accurately screen for infection with the agent responsible for variant Creutzfeldt-Jakob disease (vCJD), according to a study published online ahead of print March 3 in JAMA Neurology. Researchers performed the test on samples from national blood collection and prion disease centers in the US and the UK. The samples were taken from healthy donors, patients with nonprion neurodegenerative disease, patients in whom a prion disease diagnosis was likely, and patients with confirmed vCJD. The assay’s specificity was confirmed as 100% in a healthy UK cohort. No potentially cross-reactive blood samples from patients with nonprion neurodegenerative diseases tested positive. Two patients with sporadic CJD tested positive. The authors’ previous sensitivity estimate was reconfirmed but not refined.

The FDA has approved Neuraceq (florbetaben F18 injection) for PET imaging of the brain to estimate beta-amyloid neuritic plaque density in adults with cognitive impairment who are being evaluated for Alzheimer’s disease and other causes of cognitive decline. The approval is based on safety data from 872 patients who participated in global clinical trials, and on three studies that examined images from adults with a range of cognitive function. Images were analyzed from 82 subjects with postmortem confirmation of the presence or absence of beta-amyloid neuritic plaques. Correlation of the visual PET interpretation with histopathology in these 82 brains demonstrated that Neuraceq (Piramal Imaging; Boston) accurately detects moderate to frequent beta-amyloid neuritic plaques in the brain.

A combination of human umbilical cord blood cells (hUCBs) and granulocyte colony stimulating factor (G-CSF) may provide more benefit for patients with traumatic brain injury (TBI) than either therapy alone, according to research published March 12 in PLOS One. Adult rats underwent moderate TBI and, seven days later, were treated with saline alone, G-CSF and saline, hUCB and saline, or hUCB and G-CSF. The rats treated with saline exhibited widespread neuroinflammation, impaired endogenous neurogenesis, and severe hippocampal cell loss. hUCB monotherapy suppressed neuroinflammation, nearly normalized neurogenesis, and reduced hippocampal cell loss, compared with saline alone. G-CSF monotherapy produced partial and short-lived benefits characterized by low levels of neuroinflammation, modest neurogenesis, and moderate reduction of hippocampal cell loss. Combined therapy robustly dampened neuroinflammation, enhanced endogenous neurogenesis, and reduced hippocampal cell loss.

The ability to learn new information may be significantly poorer among patients with Parkinson’s disease than among healthy individuals, according to research published online ahead of print February 24 in Movement Disorders. Investigators examined 27 patients with Parkinson’s disease without dementia and 27 age-, gender-, and education-matched healthy controls with a neuropsychologic test battery designed to assess new learning and memory. The researchers found a significant difference in the groups’ ability to learn a list of 10 semantically related words. Once the groups were equated on learning abilities, the investigators found no significant difference between patients with Parkinson’s disease and controls in recall or recognition of the newly learned material. The memory deficit in nondemented patients with Parkinson’s disease largely results from a deficit in learning new information, said the authors.

Chronic sleep loss may lead to irreversible physical damage to and loss of brain cells, according to research published March 19 in the Journal of Neuroscience. Investigators examined mice following periods of normal rest, short wakefulness, or extended wakefulness to model shift workers’ typical sleep patterns. In response to short-term sleep loss, locus coeruleus neurons upregulated the sirtuin type 3 (SirT3) protein, which protects neurons from metabolic injury. After several days of shift worker sleep patterns, locus coeruleus neurons in the mice had reduced SirT3 and increased cell death. In addition, oxidative stress and acetylation of mitochondrial proteins increased. The mice lost 25% of their locus coeruleus neurons. “This is the first report that sleep loss can actually result in a loss of neurons,” said the authors.

—Erik Greb