Article

The intramuscular (IM) route is commonly used to administer medication in various clinical settings. Even when an IM medication is administered appropriately, patient factors such as high subcutaneous tissue, greater body mass index, and gender can lower the success rate of injections.¹ A key but infrequently discussed issue is the skill of the individual administering the IM medication. Incorrectly administering an IM medication can lead to complications, such as abscesses, nerve injury, and skeletal muscle fibrosis.² Poor IM injection technique can impact patient care and safety.¹ For example, a poorly administered antipsychotic medication might lead to the patient receiving a subtherapeutic dose, and could prompt a clinician to ask, “Does this agitated patient need more emergent medication because the medication being given is not effective, or because the medication is not being administered properly?”

This article offers 3 questions to ask when clinicians are evaluating how IM medications are being administered in their clinical setting.

1. Who is administering the medication?

Is the person a registered nurse, licensed psychiatric technician, certified nursing assistant, licensed vocational nurse, or medical assistant? What a specific clinician is permitted to do in one state may not be permitted in another state. For example, in the state of Washington, under certain conditions a medical assistant is allowed to administer an IM medication.³

2. What is the individual’s training in administering IM medications?

Has the person been trained in the proper technique, depending on the body location? Is the injection being properly prepared? Is the correct needle gauge being used?

3. What is the individual’s comfort level with administering IM medications?

Is the person comfortable administering medication only when a patient is calm? Or are they comfortable administering medication when a patient is agitated and being physically held or in 4-point restraints, such as in inpatient psychiatric units or emergency departments?

The intramuscular (IM) route is commonly used to administer medication in various clinical settings. Even when an IM medication is administered appropriately, patient factors such as high subcutaneous tissue, greater body mass index, and gender can lower the success rate of injections.¹ A key but infrequently discussed issue is the skill of the individual administering the IM medication. Incorrectly administering an IM medication can lead to complications, such as abscesses, nerve injury, and skeletal muscle fibrosis.² Poor IM injection technique can impact patient care and safety.¹ For example, a poorly administered antipsychotic medication might lead to the patient receiving a subtherapeutic dose, and could prompt a clinician to ask, “Does this agitated patient need more emergent medication because the medication being given is not effective, or because the medication is not being administered properly?”

This article offers 3 questions to ask when clinicians are evaluating how IM medications are being administered in their clinical setting.

1. Who is administering the medication?

Is the person a registered nurse, licensed psychiatric technician, certified nursing assistant, licensed vocational nurse, or medical assistant? What a specific clinician is permitted to do in one state may not be permitted in another state. For example, in the state of Washington, under certain conditions a medical assistant is allowed to administer an IM medication.³

2. What is the individual’s training in administering IM medications?

Has the person been trained in the proper technique, depending on the body location? Is the injection being properly prepared? Is the correct needle gauge being used?

3. What is the individual’s comfort level with administering IM medications?

Is the person comfortable administering medication only when a patient is calm? Or are they comfortable administering medication when a patient is agitated and being physically held or in 4-point restraints, such as in inpatient psychiatric units or emergency departments?

The intramuscular (IM) route is commonly used to administer medication in various clinical settings. Even when an IM medication is administered appropriately, patient factors such as high subcutaneous tissue, greater body mass index, and gender can lower the success rate of injections.¹ A key but infrequently discussed issue is the skill of the individual administering the IM medication. Incorrectly administering an IM medication can lead to complications, such as abscesses, nerve injury, and skeletal muscle fibrosis.² Poor IM injection technique can impact patient care and safety.¹ For example, a poorly administered antipsychotic medication might lead to the patient receiving a subtherapeutic dose, and could prompt a clinician to ask, “Does this agitated patient need more emergent medication because the medication being given is not effective, or because the medication is not being administered properly?”

This article offers 3 questions to ask when clinicians are evaluating how IM medications are being administered in their clinical setting.

1. Who is administering the medication?

Is the person a registered nurse, licensed psychiatric technician, certified nursing assistant, licensed vocational nurse, or medical assistant? What a specific clinician is permitted to do in one state may not be permitted in another state. For example, in the state of Washington, under certain conditions a medical assistant is allowed to administer an IM medication.³

2. What is the individual’s training in administering IM medications?

Has the person been trained in the proper technique, depending on the body location? Is the injection being properly prepared? Is the correct needle gauge being used?

3. What is the individual’s comfort level with administering IM medications?

Is the person comfortable administering medication only when a patient is calm? Or are they comfortable administering medication when a patient is agitated and being physically held or in 4-point restraints, such as in inpatient psychiatric units or emergency departments?

Intermittent fasting is the purposeful, restricted intake of food (and sometimes water), usually for health or religious reasons. Common forms are alternative-day fasting or time-restricted fasting, with variable ratios of days or hours for fasting and eating/drinking.¹ For example, fasting during Ramadan, the ninth month of the Islamic calendar, occurs from dawn to sunset, for a variable duration due to latitude and seasonal shifts.² Clinicians are likely to care for a patient who occasionally fasts. While there are potential benefits of fasting, clinicians need to consider the implications for patients who fast, particularly those receiving psychotropic medications.

Potential benefits for weight loss, mood

Some research suggests fasting is popular and may have benefits for an individual’s physical and mental health. In a 2020 online poll (N = 1,241), 24% of respondents said they had tried intermittent fasting, and 87% said the practice was very effective (50%) or somewhat effective (37%) in helping them lose weight.³ While more randomized control trials are needed to examine the practice’s effectiveness in promoting and maintaining weight loss, fasting has been linked to better glucose control in both humans and animals, and patients may have better adherence with fasting compared to caloric restriction alone.¹ Improved mood, alertness, tranquility, and sometimes euphoria have been documented among individuals who fast, but these benefits may not be sustained.⁴ A prospective study of 462 participants who fasted during Ramadan found the practice reduced depression in patients with diabetes, possibly due to mindfulness, decreased inflammation from improved insulin sensitivity, and/or social cohesion.⁵

Be aware of the potential risks

Fasting may either improve or destabilize mood in people with bipolar disorder by disrupting circadian rhythm and sleep.² Fasting might exacerbate underlying eating disorders.² Increased dehydration escalates the risk for orthostatic hypotension, which might require discontinuing clozapine.⁶ Hypotension and toxicity might arise during lithium pharmacotherapy. The Table⁴ summarizes things to consider when caring for a patient who fasts while receiving pharmacotherapy.

Provide patients with guidance

Advise patients not to fast if you believe it might exacerbate their mental illness, and encourage them to discuss with their primary care physicians any potential worsening of physical illnesses.² When caring for a patient who fasts for religious reasons, consider consulting with the patient’s religious leaders.² If patients choose to fast, monitor them for mood destabilization and/or medication adverse effects. If possible, avoid altering drug treatment regimens during fasting, and carefully monitor whenever a pharmaceutical change is necessary. When appropriate, the use of long-acting injectable medications may minimize adverse effects while maintaining mood stability. Encourage patients who fast to ensure they remain hydrated and practice sleep hygiene while they fast.⁷

Intermittent fasting is the purposeful, restricted intake of food (and sometimes water), usually for health or religious reasons. Common forms are alternative-day fasting or time-restricted fasting, with variable ratios of days or hours for fasting and eating/drinking.¹ For example, fasting during Ramadan, the ninth month of the Islamic calendar, occurs from dawn to sunset, for a variable duration due to latitude and seasonal shifts.² Clinicians are likely to care for a patient who occasionally fasts. While there are potential benefits of fasting, clinicians need to consider the implications for patients who fast, particularly those receiving psychotropic medications.

Potential benefits for weight loss, mood

Some research suggests fasting is popular and may have benefits for an individual’s physical and mental health. In a 2020 online poll (N = 1,241), 24% of respondents said they had tried intermittent fasting, and 87% said the practice was very effective (50%) or somewhat effective (37%) in helping them lose weight.³ While more randomized control trials are needed to examine the practice’s effectiveness in promoting and maintaining weight loss, fasting has been linked to better glucose control in both humans and animals, and patients may have better adherence with fasting compared to caloric restriction alone.¹ Improved mood, alertness, tranquility, and sometimes euphoria have been documented among individuals who fast, but these benefits may not be sustained.⁴ A prospective study of 462 participants who fasted during Ramadan found the practice reduced depression in patients with diabetes, possibly due to mindfulness, decreased inflammation from improved insulin sensitivity, and/or social cohesion.⁵

Be aware of the potential risks

Fasting may either improve or destabilize mood in people with bipolar disorder by disrupting circadian rhythm and sleep.² Fasting might exacerbate underlying eating disorders.² Increased dehydration escalates the risk for orthostatic hypotension, which might require discontinuing clozapine.⁶ Hypotension and toxicity might arise during lithium pharmacotherapy. The Table⁴ summarizes things to consider when caring for a patient who fasts while receiving pharmacotherapy.

Provide patients with guidance

Advise patients not to fast if you believe it might exacerbate their mental illness, and encourage them to discuss with their primary care physicians any potential worsening of physical illnesses.² When caring for a patient who fasts for religious reasons, consider consulting with the patient’s religious leaders.² If patients choose to fast, monitor them for mood destabilization and/or medication adverse effects. If possible, avoid altering drug treatment regimens during fasting, and carefully monitor whenever a pharmaceutical change is necessary. When appropriate, the use of long-acting injectable medications may minimize adverse effects while maintaining mood stability. Encourage patients who fast to ensure they remain hydrated and practice sleep hygiene while they fast.⁷

Intermittent fasting is the purposeful, restricted intake of food (and sometimes water), usually for health or religious reasons. Common forms are alternative-day fasting or time-restricted fasting, with variable ratios of days or hours for fasting and eating/drinking.¹ For example, fasting during Ramadan, the ninth month of the Islamic calendar, occurs from dawn to sunset, for a variable duration due to latitude and seasonal shifts.² Clinicians are likely to care for a patient who occasionally fasts. While there are potential benefits of fasting, clinicians need to consider the implications for patients who fast, particularly those receiving psychotropic medications.

Potential benefits for weight loss, mood

Some research suggests fasting is popular and may have benefits for an individual’s physical and mental health. In a 2020 online poll (N = 1,241), 24% of respondents said they had tried intermittent fasting, and 87% said the practice was very effective (50%) or somewhat effective (37%) in helping them lose weight.³ While more randomized control trials are needed to examine the practice’s effectiveness in promoting and maintaining weight loss, fasting has been linked to better glucose control in both humans and animals, and patients may have better adherence with fasting compared to caloric restriction alone.¹ Improved mood, alertness, tranquility, and sometimes euphoria have been documented among individuals who fast, but these benefits may not be sustained.⁴ A prospective study of 462 participants who fasted during Ramadan found the practice reduced depression in patients with diabetes, possibly due to mindfulness, decreased inflammation from improved insulin sensitivity, and/or social cohesion.⁵

Be aware of the potential risks

Fasting may either improve or destabilize mood in people with bipolar disorder by disrupting circadian rhythm and sleep.² Fasting might exacerbate underlying eating disorders.² Increased dehydration escalates the risk for orthostatic hypotension, which might require discontinuing clozapine.⁶ Hypotension and toxicity might arise during lithium pharmacotherapy. The Table⁴ summarizes things to consider when caring for a patient who fasts while receiving pharmacotherapy.

Provide patients with guidance

Advise patients not to fast if you believe it might exacerbate their mental illness, and encourage them to discuss with their primary care physicians any potential worsening of physical illnesses.² When caring for a patient who fasts for religious reasons, consider consulting with the patient’s religious leaders.² If patients choose to fast, monitor them for mood destabilization and/or medication adverse effects. If possible, avoid altering drug treatment regimens during fasting, and carefully monitor whenever a pharmaceutical change is necessary. When appropriate, the use of long-acting injectable medications may minimize adverse effects while maintaining mood stability. Encourage patients who fast to ensure they remain hydrated and practice sleep hygiene while they fast.⁷

Q2. Correct answer: B. He should undergo surveillance colonoscopy now and annually thereafter. 
 
Rationale  
PSC diagnosis is the most consistent risk factor for colorectal cancer (CRC) in patients with inflammatory bowel disease. Other identified risk factors include endoscopic extent of the disease (pancolitis), duration of the disease (more than 8 years), age at diagnosis (young), presence of pseudopolyps, and family history of CRC. The current guidelines recommend first surveillance colonoscopy 8-10 years after the diagnosis of ulcerative colitis or Crohn's disease that involves more than one-third of the colon with subsequent surveillance intervals at 1-3 years. However, for patients with a concomitant diagnosis of PSC, the recommendation is to initiate surveillance as soon as the coexisting diagnosis is established, with annual surveillance colonoscopy thereafter.  
High-dose UDCA (more than 28 mg/kg/day) is not recommended in patients with PSC because it was linked to adverse outcomes in this population including decompensated cirrhosis, death, and increased risk of colorectal neoplasia. On the other hand, low-dose UDCA may improve laboratory markers of cholestasis, but with no clear impact on survival or long-term outcomes, its role for chemoprophylaxis in colorectal cancer is still controversial.  
Yearly MRCP is recommended to screen for cholangiocarcinoma.  
 
References  
Lindor KD et al. Am J Gastroenterol. 2015 May;110(5):646-59; quiz 660.  
Lopez A et al. Best Pract Res Clin Gastroenterol. Feb-Apr 2018;32-33:103-109.

Q2. Correct answer: B. He should undergo surveillance colonoscopy now and annually thereafter. 
 
Rationale  
PSC diagnosis is the most consistent risk factor for colorectal cancer (CRC) in patients with inflammatory bowel disease. Other identified risk factors include endoscopic extent of the disease (pancolitis), duration of the disease (more than 8 years), age at diagnosis (young), presence of pseudopolyps, and family history of CRC. The current guidelines recommend first surveillance colonoscopy 8-10 years after the diagnosis of ulcerative colitis or Crohn's disease that involves more than one-third of the colon with subsequent surveillance intervals at 1-3 years. However, for patients with a concomitant diagnosis of PSC, the recommendation is to initiate surveillance as soon as the coexisting diagnosis is established, with annual surveillance colonoscopy thereafter.  
High-dose UDCA (more than 28 mg/kg/day) is not recommended in patients with PSC because it was linked to adverse outcomes in this population including decompensated cirrhosis, death, and increased risk of colorectal neoplasia. On the other hand, low-dose UDCA may improve laboratory markers of cholestasis, but with no clear impact on survival or long-term outcomes, its role for chemoprophylaxis in colorectal cancer is still controversial.  
Yearly MRCP is recommended to screen for cholangiocarcinoma.  
 
References  
Lindor KD et al. Am J Gastroenterol. 2015 May;110(5):646-59; quiz 660.  
Lopez A et al. Best Pract Res Clin Gastroenterol. Feb-Apr 2018;32-33:103-109.

Q2. Correct answer: B. He should undergo surveillance colonoscopy now and annually thereafter. 
 
Rationale  
PSC diagnosis is the most consistent risk factor for colorectal cancer (CRC) in patients with inflammatory bowel disease. Other identified risk factors include endoscopic extent of the disease (pancolitis), duration of the disease (more than 8 years), age at diagnosis (young), presence of pseudopolyps, and family history of CRC. The current guidelines recommend first surveillance colonoscopy 8-10 years after the diagnosis of ulcerative colitis or Crohn's disease that involves more than one-third of the colon with subsequent surveillance intervals at 1-3 years. However, for patients with a concomitant diagnosis of PSC, the recommendation is to initiate surveillance as soon as the coexisting diagnosis is established, with annual surveillance colonoscopy thereafter.  
High-dose UDCA (more than 28 mg/kg/day) is not recommended in patients with PSC because it was linked to adverse outcomes in this population including decompensated cirrhosis, death, and increased risk of colorectal neoplasia. On the other hand, low-dose UDCA may improve laboratory markers of cholestasis, but with no clear impact on survival or long-term outcomes, its role for chemoprophylaxis in colorectal cancer is still controversial.  
Yearly MRCP is recommended to screen for cholangiocarcinoma.  
 
References  
Lindor KD et al. Am J Gastroenterol. 2015 May;110(5):646-59; quiz 660.  
Lopez A et al. Best Pract Res Clin Gastroenterol. Feb-Apr 2018;32-33:103-109.

Q1. Correct answer: E. Emergent angiography 
 
Rationale  
This patient presents with a massive lower GI hemorrhage. After a brisk upper GI bleed was ruled-out with esophagogastroduodenoscopy, the patient continued to hemorrhage and remained hemodynamically unstable. In the setting of a patient with ongoing massive lower GI bleeding who has been ruled out for an upper GI bleed (negative upper endoscopy) and who continues to have hemodynamic instability despite resuscitation, emergent angiography should be pursued in an effort localize and control bleeding.  
Answer A is incorrect because an INR less than 2.5 does not require reversal prior to attempts at hemostasis. Answers B and C are incorrect because, given the patient's altered mental status and hemodynamic changes, she is unlikely to tolerate a bowel preparation and urgent colonoscopy. Also, there is no role for an unprepped colonoscopy in lower GI bleeding due to low yield and poor visualization. Answer D is incorrect because a nuclear-tagged red blood cell scan should be reserved for a patient who is hemodynamically stable.  
 
Reference  
Strate LL, Gralnek IM. Am J Gastroenterol. 2016 Apr;111(4):459-74.

Q1. Correct answer: E. Emergent angiography 
 
Rationale  
This patient presents with a massive lower GI hemorrhage. After a brisk upper GI bleed was ruled-out with esophagogastroduodenoscopy, the patient continued to hemorrhage and remained hemodynamically unstable. In the setting of a patient with ongoing massive lower GI bleeding who has been ruled out for an upper GI bleed (negative upper endoscopy) and who continues to have hemodynamic instability despite resuscitation, emergent angiography should be pursued in an effort localize and control bleeding.  
Answer A is incorrect because an INR less than 2.5 does not require reversal prior to attempts at hemostasis. Answers B and C are incorrect because, given the patient's altered mental status and hemodynamic changes, she is unlikely to tolerate a bowel preparation and urgent colonoscopy. Also, there is no role for an unprepped colonoscopy in lower GI bleeding due to low yield and poor visualization. Answer D is incorrect because a nuclear-tagged red blood cell scan should be reserved for a patient who is hemodynamically stable.  
 
Reference  
Strate LL, Gralnek IM. Am J Gastroenterol. 2016 Apr;111(4):459-74.

Q1. Correct answer: E. Emergent angiography 
 
Rationale  
This patient presents with a massive lower GI hemorrhage. After a brisk upper GI bleed was ruled-out with esophagogastroduodenoscopy, the patient continued to hemorrhage and remained hemodynamically unstable. In the setting of a patient with ongoing massive lower GI bleeding who has been ruled out for an upper GI bleed (negative upper endoscopy) and who continues to have hemodynamic instability despite resuscitation, emergent angiography should be pursued in an effort localize and control bleeding.  
Answer A is incorrect because an INR less than 2.5 does not require reversal prior to attempts at hemostasis. Answers B and C are incorrect because, given the patient's altered mental status and hemodynamic changes, she is unlikely to tolerate a bowel preparation and urgent colonoscopy. Also, there is no role for an unprepped colonoscopy in lower GI bleeding due to low yield and poor visualization. Answer D is incorrect because a nuclear-tagged red blood cell scan should be reserved for a patient who is hemodynamically stable.  
 
Reference  
Strate LL, Gralnek IM. Am J Gastroenterol. 2016 Apr;111(4):459-74.

Takayama et al evaluated 301 Japanese HCC patients who had a Child-Pugh score ≤ 7, no more than 3 HCC nodules (none more than 3 cm in greatest diameter), who were then randomly assigned to undergo either surgery (n=150) or RFA (n=151). The authors reported that though the median procedure duration was longer in the surgery group than in the RFA group (274 versus 40 minutes, P < 0.01) as was the median duration of hospital stay (17 days versus 10 days, P < 0.01), recurrence free survival (RFS) did not differ significantly between the groups. The median RFS was 3.5 years (95% confidence interval [CI], 2.6–5.1) in the surgery group and 3.0 years (95% CI, 2.4–5.6) in the RFA group (hazard ratio, 0.92; 95% CI, 0.67–1.25; P = 0.58). The overall survival (OS) data for this study are not yet mature.

Cao et al looked at outcomes of patients with periportal HCCs who were treated with RFA. They evaluated 233 patients who had a single nodular HCC that was ≤ 5 cm in greatest diameter who underwent RFA with or without transarterial chemoembolization (TACE) as first-line therapy. In that group, 56 patients had a periportal HCC. The authors reported that patients with periportal HCCs had worse outcomes. Local recurrence rates at 1, 3, and 5 years were significantly higher with periportal HCCs than with nonperiportal HCCs (15.7, 33.7, and 46.9% vs 6.0, 15.7, and 28.7%, respectively, P = 0.0067). The 1-, 3- and 5-year OS rates with periportal HCCs were significantly worse than with nonperiportal HCCs (81.3, 65.1 and 42.9% vs 99.3, 90.4 and 78.1%, respectively, P < 0.0001). In the subgroup of HCC ≤ 3 cm, patients with periportal HCCs showed significantly higher local recurrence rates (P = 0.0006) and OS (P < 0.0001) after RFA than patients with single nonperiportal HCCs. Subgroup analyses revealed that tumor size, periportal HCC and AFP ≥ 400ug/ml were independent prognostic factors for tumor progression after RFA. The authors concluded that periportal HCCs have a worse prognosis, and need better treatment options than are currently available.

Lee at al report a retrospective evaluation of Korean patients with HCC who were either treated with RFA or microwave ablation (MWA). Of 150 HCC patients (100 in the RFA group and 50 in the MWA group), the complete response rate, two-year survival rate, and complication rate were similar between the two groups. However, the MWA group had better one- and two-year disease-free survival than the RFA group (P = 0.035 and P = 0.032, respectively). In addition, there were fewer major complications in the MWA group (P = 0.043). In a subgroup analysis, patients with perivascular tumors, high risk of recurrence, and small tumor size (≤3 cm) were more suitable for MWA than RFA. The authors concluded that in patients with HCC, initial treatment with microwave ablation leads to better 1- and 2-year disease-free survival and a lower risk of major complications than RFA.

Takayama et al evaluated 301 Japanese HCC patients who had a Child-Pugh score ≤ 7, no more than 3 HCC nodules (none more than 3 cm in greatest diameter), who were then randomly assigned to undergo either surgery (n=150) or RFA (n=151). The authors reported that though the median procedure duration was longer in the surgery group than in the RFA group (274 versus 40 minutes, P < 0.01) as was the median duration of hospital stay (17 days versus 10 days, P < 0.01), recurrence free survival (RFS) did not differ significantly between the groups. The median RFS was 3.5 years (95% confidence interval [CI], 2.6–5.1) in the surgery group and 3.0 years (95% CI, 2.4–5.6) in the RFA group (hazard ratio, 0.92; 95% CI, 0.67–1.25; P = 0.58). The overall survival (OS) data for this study are not yet mature.

Cao et al looked at outcomes of patients with periportal HCCs who were treated with RFA. They evaluated 233 patients who had a single nodular HCC that was ≤ 5 cm in greatest diameter who underwent RFA with or without transarterial chemoembolization (TACE) as first-line therapy. In that group, 56 patients had a periportal HCC. The authors reported that patients with periportal HCCs had worse outcomes. Local recurrence rates at 1, 3, and 5 years were significantly higher with periportal HCCs than with nonperiportal HCCs (15.7, 33.7, and 46.9% vs 6.0, 15.7, and 28.7%, respectively, P = 0.0067). The 1-, 3- and 5-year OS rates with periportal HCCs were significantly worse than with nonperiportal HCCs (81.3, 65.1 and 42.9% vs 99.3, 90.4 and 78.1%, respectively, P < 0.0001). In the subgroup of HCC ≤ 3 cm, patients with periportal HCCs showed significantly higher local recurrence rates (P = 0.0006) and OS (P < 0.0001) after RFA than patients with single nonperiportal HCCs. Subgroup analyses revealed that tumor size, periportal HCC and AFP ≥ 400ug/ml were independent prognostic factors for tumor progression after RFA. The authors concluded that periportal HCCs have a worse prognosis, and need better treatment options than are currently available.

Lee at al report a retrospective evaluation of Korean patients with HCC who were either treated with RFA or microwave ablation (MWA). Of 150 HCC patients (100 in the RFA group and 50 in the MWA group), the complete response rate, two-year survival rate, and complication rate were similar between the two groups. However, the MWA group had better one- and two-year disease-free survival than the RFA group (P = 0.035 and P = 0.032, respectively). In addition, there were fewer major complications in the MWA group (P = 0.043). In a subgroup analysis, patients with perivascular tumors, high risk of recurrence, and small tumor size (≤3 cm) were more suitable for MWA than RFA. The authors concluded that in patients with HCC, initial treatment with microwave ablation leads to better 1- and 2-year disease-free survival and a lower risk of major complications than RFA.

Takayama et al evaluated 301 Japanese HCC patients who had a Child-Pugh score ≤ 7, no more than 3 HCC nodules (none more than 3 cm in greatest diameter), who were then randomly assigned to undergo either surgery (n=150) or RFA (n=151). The authors reported that though the median procedure duration was longer in the surgery group than in the RFA group (274 versus 40 minutes, P < 0.01) as was the median duration of hospital stay (17 days versus 10 days, P < 0.01), recurrence free survival (RFS) did not differ significantly between the groups. The median RFS was 3.5 years (95% confidence interval [CI], 2.6–5.1) in the surgery group and 3.0 years (95% CI, 2.4–5.6) in the RFA group (hazard ratio, 0.92; 95% CI, 0.67–1.25; P = 0.58). The overall survival (OS) data for this study are not yet mature.

Cao et al looked at outcomes of patients with periportal HCCs who were treated with RFA. They evaluated 233 patients who had a single nodular HCC that was ≤ 5 cm in greatest diameter who underwent RFA with or without transarterial chemoembolization (TACE) as first-line therapy. In that group, 56 patients had a periportal HCC. The authors reported that patients with periportal HCCs had worse outcomes. Local recurrence rates at 1, 3, and 5 years were significantly higher with periportal HCCs than with nonperiportal HCCs (15.7, 33.7, and 46.9% vs 6.0, 15.7, and 28.7%, respectively, P = 0.0067). The 1-, 3- and 5-year OS rates with periportal HCCs were significantly worse than with nonperiportal HCCs (81.3, 65.1 and 42.9% vs 99.3, 90.4 and 78.1%, respectively, P < 0.0001). In the subgroup of HCC ≤ 3 cm, patients with periportal HCCs showed significantly higher local recurrence rates (P = 0.0006) and OS (P < 0.0001) after RFA than patients with single nonperiportal HCCs. Subgroup analyses revealed that tumor size, periportal HCC and AFP ≥ 400ug/ml were independent prognostic factors for tumor progression after RFA. The authors concluded that periportal HCCs have a worse prognosis, and need better treatment options than are currently available.

Lee at al report a retrospective evaluation of Korean patients with HCC who were either treated with RFA or microwave ablation (MWA). Of 150 HCC patients (100 in the RFA group and 50 in the MWA group), the complete response rate, two-year survival rate, and complication rate were similar between the two groups. However, the MWA group had better one- and two-year disease-free survival than the RFA group (P = 0.035 and P = 0.032, respectively). In addition, there were fewer major complications in the MWA group (P = 0.043). In a subgroup analysis, patients with perivascular tumors, high risk of recurrence, and small tumor size (≤3 cm) were more suitable for MWA than RFA. The authors concluded that in patients with HCC, initial treatment with microwave ablation leads to better 1- and 2-year disease-free survival and a lower risk of major complications than RFA.

Takayama et al evaluated 301 Japanese HCC patients who had a Child-Pugh score ≤ 7, no more than 3 HCC nodules (none more than 3 cm in greatest diameter), who were then randomly assigned to undergo either surgery (n=150) or RFA (n=151). The authors reported that though the median procedure duration was longer in the surgery group than in the RFA group (274 versus 40 minutes, P < 0.01) as was the median duration of hospital stay (17 days versus 10 days, P < 0.01), recurrence free survival (RFS) did not differ significantly between the groups. The median RFS was 3.5 years (95% confidence interval [CI], 2.6–5.1) in the surgery group and 3.0 years (95% CI, 2.4–5.6) in the RFA group (hazard ratio, 0.92; 95% CI, 0.67–1.25; P = 0.58). The overall survival (OS) data for this study are not yet mature.

Cao et al looked at outcomes of patients with periportal HCCs who were treated with RFA. They evaluated 233 patients who had a single nodular HCC that was ≤ 5 cm in greatest diameter who underwent RFA with or without transarterial chemoembolization (TACE) as first-line therapy. In that group, 56 patients had a periportal HCC. The authors reported that patients with periportal HCCs had worse outcomes. Local recurrence rates at 1, 3, and 5 years were significantly higher with periportal HCCs than with nonperiportal HCCs (15.7, 33.7, and 46.9% vs 6.0, 15.7, and 28.7%, respectively, P = 0.0067). The 1-, 3- and 5-year OS rates with periportal HCCs were significantly worse than with nonperiportal HCCs (81.3, 65.1 and 42.9% vs 99.3, 90.4 and 78.1%, respectively, P < 0.0001). In the subgroup of HCC ≤ 3 cm, patients with periportal HCCs showed significantly higher local recurrence rates (P = 0.0006) and OS (P < 0.0001) after RFA than patients with single nonperiportal HCCs. Subgroup analyses revealed that tumor size, periportal HCC and AFP ≥ 400ug/ml were independent prognostic factors for tumor progression after RFA. The authors concluded that periportal HCCs have a worse prognosis, and need better treatment options than are currently available.

Lee at al report a retrospective evaluation of Korean patients with HCC who were either treated with RFA or microwave ablation (MWA). Of 150 HCC patients (100 in the RFA group and 50 in the MWA group), the complete response rate, two-year survival rate, and complication rate were similar between the two groups. However, the MWA group had better one- and two-year disease-free survival than the RFA group (P = 0.035 and P = 0.032, respectively). In addition, there were fewer major complications in the MWA group (P = 0.043). In a subgroup analysis, patients with perivascular tumors, high risk of recurrence, and small tumor size (≤3 cm) were more suitable for MWA than RFA. The authors concluded that in patients with HCC, initial treatment with microwave ablation leads to better 1- and 2-year disease-free survival and a lower risk of major complications than RFA.

Takayama et al evaluated 301 Japanese HCC patients who had a Child-Pugh score ≤ 7, no more than 3 HCC nodules (none more than 3 cm in greatest diameter), who were then randomly assigned to undergo either surgery (n=150) or RFA (n=151). The authors reported that though the median procedure duration was longer in the surgery group than in the RFA group (274 versus 40 minutes, P < 0.01) as was the median duration of hospital stay (17 days versus 10 days, P < 0.01), recurrence free survival (RFS) did not differ significantly between the groups. The median RFS was 3.5 years (95% confidence interval [CI], 2.6–5.1) in the surgery group and 3.0 years (95% CI, 2.4–5.6) in the RFA group (hazard ratio, 0.92; 95% CI, 0.67–1.25; P = 0.58). The overall survival (OS) data for this study are not yet mature.

Cao et al looked at outcomes of patients with periportal HCCs who were treated with RFA. They evaluated 233 patients who had a single nodular HCC that was ≤ 5 cm in greatest diameter who underwent RFA with or without transarterial chemoembolization (TACE) as first-line therapy. In that group, 56 patients had a periportal HCC. The authors reported that patients with periportal HCCs had worse outcomes. Local recurrence rates at 1, 3, and 5 years were significantly higher with periportal HCCs than with nonperiportal HCCs (15.7, 33.7, and 46.9% vs 6.0, 15.7, and 28.7%, respectively, P = 0.0067). The 1-, 3- and 5-year OS rates with periportal HCCs were significantly worse than with nonperiportal HCCs (81.3, 65.1 and 42.9% vs 99.3, 90.4 and 78.1%, respectively, P < 0.0001). In the subgroup of HCC ≤ 3 cm, patients with periportal HCCs showed significantly higher local recurrence rates (P = 0.0006) and OS (P < 0.0001) after RFA than patients with single nonperiportal HCCs. Subgroup analyses revealed that tumor size, periportal HCC and AFP ≥ 400ug/ml were independent prognostic factors for tumor progression after RFA. The authors concluded that periportal HCCs have a worse prognosis, and need better treatment options than are currently available.

Lee at al report a retrospective evaluation of Korean patients with HCC who were either treated with RFA or microwave ablation (MWA). Of 150 HCC patients (100 in the RFA group and 50 in the MWA group), the complete response rate, two-year survival rate, and complication rate were similar between the two groups. However, the MWA group had better one- and two-year disease-free survival than the RFA group (P = 0.035 and P = 0.032, respectively). In addition, there were fewer major complications in the MWA group (P = 0.043). In a subgroup analysis, patients with perivascular tumors, high risk of recurrence, and small tumor size (≤3 cm) were more suitable for MWA than RFA. The authors concluded that in patients with HCC, initial treatment with microwave ablation leads to better 1- and 2-year disease-free survival and a lower risk of major complications than RFA.

Takayama et al evaluated 301 Japanese HCC patients who had a Child-Pugh score ≤ 7, no more than 3 HCC nodules (none more than 3 cm in greatest diameter), who were then randomly assigned to undergo either surgery (n=150) or RFA (n=151). The authors reported that though the median procedure duration was longer in the surgery group than in the RFA group (274 versus 40 minutes, P < 0.01) as was the median duration of hospital stay (17 days versus 10 days, P < 0.01), recurrence free survival (RFS) did not differ significantly between the groups. The median RFS was 3.5 years (95% confidence interval [CI], 2.6–5.1) in the surgery group and 3.0 years (95% CI, 2.4–5.6) in the RFA group (hazard ratio, 0.92; 95% CI, 0.67–1.25; P = 0.58). The overall survival (OS) data for this study are not yet mature.

Cao et al looked at outcomes of patients with periportal HCCs who were treated with RFA. They evaluated 233 patients who had a single nodular HCC that was ≤ 5 cm in greatest diameter who underwent RFA with or without transarterial chemoembolization (TACE) as first-line therapy. In that group, 56 patients had a periportal HCC. The authors reported that patients with periportal HCCs had worse outcomes. Local recurrence rates at 1, 3, and 5 years were significantly higher with periportal HCCs than with nonperiportal HCCs (15.7, 33.7, and 46.9% vs 6.0, 15.7, and 28.7%, respectively, P = 0.0067). The 1-, 3- and 5-year OS rates with periportal HCCs were significantly worse than with nonperiportal HCCs (81.3, 65.1 and 42.9% vs 99.3, 90.4 and 78.1%, respectively, P < 0.0001). In the subgroup of HCC ≤ 3 cm, patients with periportal HCCs showed significantly higher local recurrence rates (P = 0.0006) and OS (P < 0.0001) after RFA than patients with single nonperiportal HCCs. Subgroup analyses revealed that tumor size, periportal HCC and AFP ≥ 400ug/ml were independent prognostic factors for tumor progression after RFA. The authors concluded that periportal HCCs have a worse prognosis, and need better treatment options than are currently available.

Lee at al report a retrospective evaluation of Korean patients with HCC who were either treated with RFA or microwave ablation (MWA). Of 150 HCC patients (100 in the RFA group and 50 in the MWA group), the complete response rate, two-year survival rate, and complication rate were similar between the two groups. However, the MWA group had better one- and two-year disease-free survival than the RFA group (P = 0.035 and P = 0.032, respectively). In addition, there were fewer major complications in the MWA group (P = 0.043). In a subgroup analysis, patients with perivascular tumors, high risk of recurrence, and small tumor size (≤3 cm) were more suitable for MWA than RFA. The authors concluded that in patients with HCC, initial treatment with microwave ablation leads to better 1- and 2-year disease-free survival and a lower risk of major complications than RFA.

The STAMPEDE platform included a multiple arm and multiple stage protocol to evaluate abiraterone and enzalutamide in high risk non-metastatic and metastatic disease in separate trials. In the accompanying article by Attard et. al, a meta-analysis of two separate trials conducted as part of the STAMPEDE platform was undertaken. In the first trial, patients with high-risk localized prostate cancer were randomized to androgen deprivation therapy (ADT) with or without abiraterone. In the second trial, similar patients were randomized to ADT versus ADT plus abiraterone plus enzalutamide. The primary outcome of metastasis-free survival and secondary outcome of overall survival [OS] were significantly longer for the treatment arms over ADT; however, the addition of enzalutamide to abiraterone did not result in additional benefit. In appropriately selected patients with high risk localized prostate cancer, abiraterone is a reasonable option to consider in appropriately selected patients.

While bone is the most frequent site of metastasis in men with prostate cancer, visceral metastases (predominantly liver or lung) has been associated with worse outcomes. However, lower incidence of visceral metastases makes conduct of studies focused on visceral disease challenging. Baciarello et al conducted a post-hoc analysis of the LATITUDE study (where men with metastatic castrate-sensitive disease were treated with ADT plus abiraterone or ADT alone) in participants with visceral disease. Overall, patients with visceral metastases derived OS benefit (55.4 versus 33 months). Patients with lung metastases had similar OS to the entire cohort; however, those with liver metastases still derived benefit but had lower OS (36.8 versus 25.6 months). These post-hoc findings suggest that liver metastases present unique challenges compare to other metastatic disease sites, but further study is needed.

In the ENZAMET trial, enzalutamide plus ADT was compared to ADT alone in patients with metastatic castrate-sensitive disease, and enzalutamide treatment was associated with improved OS. In the report by Stockler et al, quality of life metrics as assessed by periodic evaluation utilizing standard questionnaires were reported. Patients who received enzalutamide reported more fatigue and lower cognitive and physical function than those receiving placebo. However, the overall quality of life did not decrease. These important quality of life findings, which are increasingly being reported in similar studies, support the overall net benefit of utilization of enzalutamide in patients with metastatic castrate-sensitive disease.

The STAMPEDE platform included a multiple arm and multiple stage protocol to evaluate abiraterone and enzalutamide in high risk non-metastatic and metastatic disease in separate trials. In the accompanying article by Attard et. al, a meta-analysis of two separate trials conducted as part of the STAMPEDE platform was undertaken. In the first trial, patients with high-risk localized prostate cancer were randomized to androgen deprivation therapy (ADT) with or without abiraterone. In the second trial, similar patients were randomized to ADT versus ADT plus abiraterone plus enzalutamide. The primary outcome of metastasis-free survival and secondary outcome of overall survival [OS] were significantly longer for the treatment arms over ADT; however, the addition of enzalutamide to abiraterone did not result in additional benefit. In appropriately selected patients with high risk localized prostate cancer, abiraterone is a reasonable option to consider in appropriately selected patients.

While bone is the most frequent site of metastasis in men with prostate cancer, visceral metastases (predominantly liver or lung) has been associated with worse outcomes. However, lower incidence of visceral metastases makes conduct of studies focused on visceral disease challenging. Baciarello et al conducted a post-hoc analysis of the LATITUDE study (where men with metastatic castrate-sensitive disease were treated with ADT plus abiraterone or ADT alone) in participants with visceral disease. Overall, patients with visceral metastases derived OS benefit (55.4 versus 33 months). Patients with lung metastases had similar OS to the entire cohort; however, those with liver metastases still derived benefit but had lower OS (36.8 versus 25.6 months). These post-hoc findings suggest that liver metastases present unique challenges compare to other metastatic disease sites, but further study is needed.

In the ENZAMET trial, enzalutamide plus ADT was compared to ADT alone in patients with metastatic castrate-sensitive disease, and enzalutamide treatment was associated with improved OS. In the report by Stockler et al, quality of life metrics as assessed by periodic evaluation utilizing standard questionnaires were reported. Patients who received enzalutamide reported more fatigue and lower cognitive and physical function than those receiving placebo. However, the overall quality of life did not decrease. These important quality of life findings, which are increasingly being reported in similar studies, support the overall net benefit of utilization of enzalutamide in patients with metastatic castrate-sensitive disease.

The STAMPEDE platform included a multiple arm and multiple stage protocol to evaluate abiraterone and enzalutamide in high risk non-metastatic and metastatic disease in separate trials. In the accompanying article by Attard et. al, a meta-analysis of two separate trials conducted as part of the STAMPEDE platform was undertaken. In the first trial, patients with high-risk localized prostate cancer were randomized to androgen deprivation therapy (ADT) with or without abiraterone. In the second trial, similar patients were randomized to ADT versus ADT plus abiraterone plus enzalutamide. The primary outcome of metastasis-free survival and secondary outcome of overall survival [OS] were significantly longer for the treatment arms over ADT; however, the addition of enzalutamide to abiraterone did not result in additional benefit. In appropriately selected patients with high risk localized prostate cancer, abiraterone is a reasonable option to consider in appropriately selected patients.

While bone is the most frequent site of metastasis in men with prostate cancer, visceral metastases (predominantly liver or lung) has been associated with worse outcomes. However, lower incidence of visceral metastases makes conduct of studies focused on visceral disease challenging. Baciarello et al conducted a post-hoc analysis of the LATITUDE study (where men with metastatic castrate-sensitive disease were treated with ADT plus abiraterone or ADT alone) in participants with visceral disease. Overall, patients with visceral metastases derived OS benefit (55.4 versus 33 months). Patients with lung metastases had similar OS to the entire cohort; however, those with liver metastases still derived benefit but had lower OS (36.8 versus 25.6 months). These post-hoc findings suggest that liver metastases present unique challenges compare to other metastatic disease sites, but further study is needed.

In the ENZAMET trial, enzalutamide plus ADT was compared to ADT alone in patients with metastatic castrate-sensitive disease, and enzalutamide treatment was associated with improved OS. In the report by Stockler et al, quality of life metrics as assessed by periodic evaluation utilizing standard questionnaires were reported. Patients who received enzalutamide reported more fatigue and lower cognitive and physical function than those receiving placebo. However, the overall quality of life did not decrease. These important quality of life findings, which are increasingly being reported in similar studies, support the overall net benefit of utilization of enzalutamide in patients with metastatic castrate-sensitive disease.

What are the best office-based tests for the diagnosis of bacterial vaginosis?

Continue to the answer...

In patients with bacterial vaginosis, the vaginal pH typically is elevated in the range of 4.5. When a drop of potassium hydroxide solution is added to the vaginal secretions, a characteristic fishlike (amine) odor is liberated (positive “whiff test”). With saline microscopy, the key findings are a relative absence of lactobacilli in the background, an abundance of small cocci and bacilli, and the presence of clue cells, which are epithelial cells studded with bacteria along their outer margin.

What are the best office-based tests for the diagnosis of bacterial vaginosis?

Continue to the answer...

In patients with bacterial vaginosis, the vaginal pH typically is elevated in the range of 4.5. When a drop of potassium hydroxide solution is added to the vaginal secretions, a characteristic fishlike (amine) odor is liberated (positive “whiff test”). With saline microscopy, the key findings are a relative absence of lactobacilli in the background, an abundance of small cocci and bacilli, and the presence of clue cells, which are epithelial cells studded with bacteria along their outer margin.

What are the best office-based tests for the diagnosis of bacterial vaginosis?

Continue to the answer...

In patients with bacterial vaginosis, the vaginal pH typically is elevated in the range of 4.5. When a drop of potassium hydroxide solution is added to the vaginal secretions, a characteristic fishlike (amine) odor is liberated (positive “whiff test”). With saline microscopy, the key findings are a relative absence of lactobacilli in the background, an abundance of small cocci and bacilli, and the presence of clue cells, which are epithelial cells studded with bacteria along their outer margin.

Grouped vesicles on an erythematous base should prompt concern for herpes viruses including varicella zoster (VZV) and herpes simplex (HSV). Polymerase chain reaction (PCR) testing for both VZV and HSV revealed this to be sacral HSV.

VZV classically presents in a dermatomal distribution, whereas HSV more commonly manifests along a single peripheral sensory nerve. Zosteriform presentations of HSV, however, have been reported.

Nongenital and nonoral HSV aren’t uncommon and can be associated with genital herpes, whether from self-inoculation or viremia.¹ These outbreaks usually occur in the distribution of the pudendal nerve, which arises from the S2-S4 spinal nerves. There is an association of genital viral shedding even in the absence of lesions when sacral flaring manifests, and patients should be cautioned about sexual transmission or vertically transmitted perinatal infection in pregnant patients near term.

Treatment for an initial episode of genital infection with HSV is valacyclovir 1 g bid for 10 days. The regimen is ideally started within 48 to 72 hours of symptom onset.

This patient was empirically started on VZV dosing, then switched to HSV dosing when the PCR testing confirmed HSV. Knowledge of the exact pathogen is helpful in counseling the patient about the potential for spread and the risk of recurrence. With HSV, the patient may be prescribed a suppressive dose of valacyclovir 500 mg bid for 3 days, started at the onset of symptoms.

‌

Text courtesy of Jonathan Karnes, MD, medical director, MDFMR Dermatology Services, Augusta, ME. Photos courtesy of Jonathan Karnes, MD (copyright retained).

Grouped vesicles on an erythematous base should prompt concern for herpes viruses including varicella zoster (VZV) and herpes simplex (HSV). Polymerase chain reaction (PCR) testing for both VZV and HSV revealed this to be sacral HSV.

VZV classically presents in a dermatomal distribution, whereas HSV more commonly manifests along a single peripheral sensory nerve. Zosteriform presentations of HSV, however, have been reported.

Nongenital and nonoral HSV aren’t uncommon and can be associated with genital herpes, whether from self-inoculation or viremia.¹ These outbreaks usually occur in the distribution of the pudendal nerve, which arises from the S2-S4 spinal nerves. There is an association of genital viral shedding even in the absence of lesions when sacral flaring manifests, and patients should be cautioned about sexual transmission or vertically transmitted perinatal infection in pregnant patients near term.

Treatment for an initial episode of genital infection with HSV is valacyclovir 1 g bid for 10 days. The regimen is ideally started within 48 to 72 hours of symptom onset.

This patient was empirically started on VZV dosing, then switched to HSV dosing when the PCR testing confirmed HSV. Knowledge of the exact pathogen is helpful in counseling the patient about the potential for spread and the risk of recurrence. With HSV, the patient may be prescribed a suppressive dose of valacyclovir 500 mg bid for 3 days, started at the onset of symptoms.

‌

Text courtesy of Jonathan Karnes, MD, medical director, MDFMR Dermatology Services, Augusta, ME. Photos courtesy of Jonathan Karnes, MD (copyright retained).

Grouped vesicles on an erythematous base should prompt concern for herpes viruses including varicella zoster (VZV) and herpes simplex (HSV). Polymerase chain reaction (PCR) testing for both VZV and HSV revealed this to be sacral HSV.

VZV classically presents in a dermatomal distribution, whereas HSV more commonly manifests along a single peripheral sensory nerve. Zosteriform presentations of HSV, however, have been reported.

Nongenital and nonoral HSV aren’t uncommon and can be associated with genital herpes, whether from self-inoculation or viremia.¹ These outbreaks usually occur in the distribution of the pudendal nerve, which arises from the S2-S4 spinal nerves. There is an association of genital viral shedding even in the absence of lesions when sacral flaring manifests, and patients should be cautioned about sexual transmission or vertically transmitted perinatal infection in pregnant patients near term.

Treatment for an initial episode of genital infection with HSV is valacyclovir 1 g bid for 10 days. The regimen is ideally started within 48 to 72 hours of symptom onset.

This patient was empirically started on VZV dosing, then switched to HSV dosing when the PCR testing confirmed HSV. Knowledge of the exact pathogen is helpful in counseling the patient about the potential for spread and the risk of recurrence. With HSV, the patient may be prescribed a suppressive dose of valacyclovir 500 mg bid for 3 days, started at the onset of symptoms.

‌

Text courtesy of Jonathan Karnes, MD, medical director, MDFMR Dermatology Services, Augusta, ME. Photos courtesy of Jonathan Karnes, MD (copyright retained).

Several recent RA studies have addressed aspects of systemic illness other than joint pain and inflammation, including sleep, fatigue, psychosocial burden, and well-being. A cohort study by Lyne et al¹ evaluated sleep duration and quality in 3,265 patients in the Swedish EIRA registry from 1-12 years after RA diagnosis. About 40% had problems in at least one sleep domain and the frequency of sleep problems increased somewhat with disease duration, but the strongest correlations with poor sleep were pain and functional impairment, suggesting that the overall activity of the RA was most important. Further research on improving sleep quality with improved control of disease activity would be helpful in supporting this hypothesis.

A systematic review by Shamail et al² examined mental health outcomes in patients with RA taking Janus kinase (JAK) inhibitors, limiting the review to studies reporting SF-36 mental health outcomes. The resulting 19 studies encompassed over 14,000 patients and did demonstrate clinically meaningful changes in SF-36 scores compared to baseline in patients treated with JAK inhibitors. When compared to changes with placebo or disease-modifying antirheumatic drug (DMARD) treatment, JAK inhibitors appeared to have a benefit, though few studies showed a clinically meaningful difference. Given that other studies have shown improvement in mental health outcomes with other classes of RA treatments, it is not clear that this is an effect of the JAK inhibitor class rather than related to overall improvement in quality of life.

Fatigue is a prevalent concern among patients with RA and may significantly impact quality of life; its origins in RA are not well-understood but thought to be related to inflammation. A UK study of an inception cohort by Ifeseman et al³ examines fatigue in early RA; about 75% of participants reported a decreased vitality score compared to the mean in the UK general population. Of the approximately 729 study participants in the longitudinal analysis, trajectory modeling was used to identify two groups of people: one with an “average” vitality score and another with a score that was significantly reduced compared to average. This group had worse disease activity scores, Health Assessment Questionnaire (HAQ) scores, and pain, though as with the other studies mentioned above, it is not clear if fatigue is a feature of worse control of RA or related to ongoing central sensitization or “non-inflammatory” mechanisms.

Doumen et al⁴ analyzed interaction between psychosocial variables and disease activity in an early RA cohort and found that better baseline short form-36 (SF-36) scores as well as other measures of psychosocial burden and coping were associated with sustained Disease Activity Score 28 for Rheumatoid Arthritis with C-Reactive Protein (DAS-28-CRP) remission, while negative illness perception was associated with lower probability of sustained remission. Of the 287 patients who achieved DAS-28-CRP remission at week 16, the 231 patients who had a low psychosocial burden were more likely to remain in remission. Causality and direction are not established in this small study, so while evaluating psychosocial needs is relevant, as with the other studies mentioned above, caution must be used in attributing lack of improvement in disease activity to psychosocial burden or mood disorders.

References

1. Lyne L et al. Sleep problems in rheumatoid arthritis over 12 years from diagnosis: results from the Swedish EIRA study. RMD Open. 2022;8:e001800 (Jan 5).
2. Shamail GMH et al. Association between janus kinase inhibitors therapy and mental health outcome in rheumatoid arthritis: A systematic review and meta-analysis. Rheumatol Ther. 2021 (Dec 13).
3. Ifesemen OS et al. Fatigue in early rheumatoid arthritis: data from the Early Rheumatoid Arthritis Network. Rheumatology (Oxford). 2021;keab861 (Dec 27).
4. Doumen M et al. Psychosocial burden predicts sustained remission in early rheumatoid arthritis: unraveling the complex interplay of wellbeing and disease activity. Arthritis Care Res (Hoboken). 2021 (Dec 20).

Several recent RA studies have addressed aspects of systemic illness other than joint pain and inflammation, including sleep, fatigue, psychosocial burden, and well-being. A cohort study by Lyne et al¹ evaluated sleep duration and quality in 3,265 patients in the Swedish EIRA registry from 1-12 years after RA diagnosis. About 40% had problems in at least one sleep domain and the frequency of sleep problems increased somewhat with disease duration, but the strongest correlations with poor sleep were pain and functional impairment, suggesting that the overall activity of the RA was most important. Further research on improving sleep quality with improved control of disease activity would be helpful in supporting this hypothesis.

A systematic review by Shamail et al² examined mental health outcomes in patients with RA taking Janus kinase (JAK) inhibitors, limiting the review to studies reporting SF-36 mental health outcomes. The resulting 19 studies encompassed over 14,000 patients and did demonstrate clinically meaningful changes in SF-36 scores compared to baseline in patients treated with JAK inhibitors. When compared to changes with placebo or disease-modifying antirheumatic drug (DMARD) treatment, JAK inhibitors appeared to have a benefit, though few studies showed a clinically meaningful difference. Given that other studies have shown improvement in mental health outcomes with other classes of RA treatments, it is not clear that this is an effect of the JAK inhibitor class rather than related to overall improvement in quality of life.

Fatigue is a prevalent concern among patients with RA and may significantly impact quality of life; its origins in RA are not well-understood but thought to be related to inflammation. A UK study of an inception cohort by Ifeseman et al³ examines fatigue in early RA; about 75% of participants reported a decreased vitality score compared to the mean in the UK general population. Of the approximately 729 study participants in the longitudinal analysis, trajectory modeling was used to identify two groups of people: one with an “average” vitality score and another with a score that was significantly reduced compared to average. This group had worse disease activity scores, Health Assessment Questionnaire (HAQ) scores, and pain, though as with the other studies mentioned above, it is not clear if fatigue is a feature of worse control of RA or related to ongoing central sensitization or “non-inflammatory” mechanisms.

Doumen et al⁴ analyzed interaction between psychosocial variables and disease activity in an early RA cohort and found that better baseline short form-36 (SF-36) scores as well as other measures of psychosocial burden and coping were associated with sustained Disease Activity Score 28 for Rheumatoid Arthritis with C-Reactive Protein (DAS-28-CRP) remission, while negative illness perception was associated with lower probability of sustained remission. Of the 287 patients who achieved DAS-28-CRP remission at week 16, the 231 patients who had a low psychosocial burden were more likely to remain in remission. Causality and direction are not established in this small study, so while evaluating psychosocial needs is relevant, as with the other studies mentioned above, caution must be used in attributing lack of improvement in disease activity to psychosocial burden or mood disorders.

References

1. Lyne L et al. Sleep problems in rheumatoid arthritis over 12 years from diagnosis: results from the Swedish EIRA study. RMD Open. 2022;8:e001800 (Jan 5).
2. Shamail GMH et al. Association between janus kinase inhibitors therapy and mental health outcome in rheumatoid arthritis: A systematic review and meta-analysis. Rheumatol Ther. 2021 (Dec 13).
3. Ifesemen OS et al. Fatigue in early rheumatoid arthritis: data from the Early Rheumatoid Arthritis Network. Rheumatology (Oxford). 2021;keab861 (Dec 27).
4. Doumen M et al. Psychosocial burden predicts sustained remission in early rheumatoid arthritis: unraveling the complex interplay of wellbeing and disease activity. Arthritis Care Res (Hoboken). 2021 (Dec 20).

Several recent RA studies have addressed aspects of systemic illness other than joint pain and inflammation, including sleep, fatigue, psychosocial burden, and well-being. A cohort study by Lyne et al¹ evaluated sleep duration and quality in 3,265 patients in the Swedish EIRA registry from 1-12 years after RA diagnosis. About 40% had problems in at least one sleep domain and the frequency of sleep problems increased somewhat with disease duration, but the strongest correlations with poor sleep were pain and functional impairment, suggesting that the overall activity of the RA was most important. Further research on improving sleep quality with improved control of disease activity would be helpful in supporting this hypothesis.

A systematic review by Shamail et al² examined mental health outcomes in patients with RA taking Janus kinase (JAK) inhibitors, limiting the review to studies reporting SF-36 mental health outcomes. The resulting 19 studies encompassed over 14,000 patients and did demonstrate clinically meaningful changes in SF-36 scores compared to baseline in patients treated with JAK inhibitors. When compared to changes with placebo or disease-modifying antirheumatic drug (DMARD) treatment, JAK inhibitors appeared to have a benefit, though few studies showed a clinically meaningful difference. Given that other studies have shown improvement in mental health outcomes with other classes of RA treatments, it is not clear that this is an effect of the JAK inhibitor class rather than related to overall improvement in quality of life.

Fatigue is a prevalent concern among patients with RA and may significantly impact quality of life; its origins in RA are not well-understood but thought to be related to inflammation. A UK study of an inception cohort by Ifeseman et al³ examines fatigue in early RA; about 75% of participants reported a decreased vitality score compared to the mean in the UK general population. Of the approximately 729 study participants in the longitudinal analysis, trajectory modeling was used to identify two groups of people: one with an “average” vitality score and another with a score that was significantly reduced compared to average. This group had worse disease activity scores, Health Assessment Questionnaire (HAQ) scores, and pain, though as with the other studies mentioned above, it is not clear if fatigue is a feature of worse control of RA or related to ongoing central sensitization or “non-inflammatory” mechanisms.

Doumen et al⁴ analyzed interaction between psychosocial variables and disease activity in an early RA cohort and found that better baseline short form-36 (SF-36) scores as well as other measures of psychosocial burden and coping were associated with sustained Disease Activity Score 28 for Rheumatoid Arthritis with C-Reactive Protein (DAS-28-CRP) remission, while negative illness perception was associated with lower probability of sustained remission. Of the 287 patients who achieved DAS-28-CRP remission at week 16, the 231 patients who had a low psychosocial burden were more likely to remain in remission. Causality and direction are not established in this small study, so while evaluating psychosocial needs is relevant, as with the other studies mentioned above, caution must be used in attributing lack of improvement in disease activity to psychosocial burden or mood disorders.

References

1. Lyne L et al. Sleep problems in rheumatoid arthritis over 12 years from diagnosis: results from the Swedish EIRA study. RMD Open. 2022;8:e001800 (Jan 5).
2. Shamail GMH et al. Association between janus kinase inhibitors therapy and mental health outcome in rheumatoid arthritis: A systematic review and meta-analysis. Rheumatol Ther. 2021 (Dec 13).
3. Ifesemen OS et al. Fatigue in early rheumatoid arthritis: data from the Early Rheumatoid Arthritis Network. Rheumatology (Oxford). 2021;keab861 (Dec 27).
4. Doumen M et al. Psychosocial burden predicts sustained remission in early rheumatoid arthritis: unraveling the complex interplay of wellbeing and disease activity. Arthritis Care Res (Hoboken). 2021 (Dec 20).