CASE › A 54-year-old man’s lab results following a routine annual examination reveal a level of IgM M-protein just under 1.5 g/dL. All other lab values, including free light chain (FLC) ratio and bone marrow exam, are normal. No clinical evidence of a related disorder is found. What is the risk that this patient’s condition could progress toward multiple myeloma, and how would you follow up?

The patient with a monoclonal gammopathy has an abnormal proliferation of monoclonal plasma cells that secrete an immunoglobulin, M-protein. This proliferation occurs most often in the bone marrow but can also be found in extra-medullary body tissue. The condition can begin insidiously, remain stable, or progress to frank malignancy causing bone and end-organ destruction. The major challenge is to separate stable, asymptomatic patients who require no treatment from patients with progressive, symptomatic myeloma who require immediate treatment.

Risk for MGUS progression increases markedly with a serum M-protein concentration ≥1.5 g/dL, a non-IgG isotype, or an abnormal serum FLC ratio (<0.26 or >1.65).

An increased, measurable level of serum monoclonal immunoglobulins or FLCs is called monoclonal gammopathy of undetermined significance (MGUS) when there is <3 g/dL monoclonal protein in the serum, <10% monoclonal plasma cells in the bone marrow, and an absence of beta-cell proliferative disorders, lytic bone lesions, anemia, hypercalcemia, or renal insufficiency (TABLE 1).^1,2 Serum and marrow measurements exceeding these values indicate progression of disease to a premalignancy stage. Continued proliferation of plasma cells in the bone marrow results in anemia and bone destruction, while the increase in M-protein leads to end-organ destruction. This final malignant state is multiple myeloma (MM).

Detailed classification of MGUS: A roadmap for monitoring patients

Extensive epidemiologic and clinical studies have refined the classification of MGUS^3-5 and related disorders (TABLES 2-4),³ providing physicians with guidance on how to monitor patients. There are 3 kinds of monoclonal gammopathies, each reflecting a particular type of immunoglobulin involvement—non-IgM, IgM, or light chain. Additionally, within each type of gammopathy, patient-specific characteristics determine 3 categories of clinical significance: premalignancy with low risk of progression (1%-2% per year³); premalignancy with high risk of progression (10% per year³); and malignancy.

Non-IgM MGUS with a high risk of progression is designated smoldering multiple myeloma (SMM) (TABLE 2).³ IgM MGUS with a high risk of progression is defined as smoldering Waldenström macroglobulinemia (SWM), with a predisposition to progress to Waldenström macroglobulinemia (WM) and, rarely, to IgM MM (TABLE 3).³

More recently, it has been reported that approximately 20% of the cases of MM belong to a new entity called light-chain MM that features an absence of heavy chain (IgG, IgA, IgM, IgD, or IgE) secretion in serum.⁶ The premalignant precursor is light-chain MGUS (LC-MGUS). The criteria for LC-MGUS and idiopathic Bence Jones proteinuria are found in TABLE 4.³ Idiopathic Bence Jones proteinuria is equivalent to SMM and SWM due to its higher risk of progression (10%/year)³ to light-chain MM.

Prevalence of MGUS

In general, the prevalence of all types of MGUS increases with age and is affected by race, sex, family history, immunosuppression, and pesticide exposure. The Caucasian American population >50 years exhibits a prevalence of MGUS of approximately 3.2%;⁷ the African American population exhibits a significantly higher prevalence of 5.9% to 8.4%.⁷ Native Asians have a lower rate of MM, and, as expected, a lower MGUS prevalence than is seen in the Western population (Thailand ≈2.3%;⁸ Korea ≈3.3%;⁹ Japan ≈2.1%;¹⁰ China ≈0.8%¹¹). The overall prevalence of the 3 types of MGUS is 4.2% in Caucasians.⁶

Distinguishing stable from progressive disease

The Mayo Clinic’s risk stratification model¹² further specifies risk of disease progression based on 3 indicators: serum M-protein concentration, Ig isotype of M-protein, and serum FLC ratio.

MGUS. A marked increase in risk for disease progression is associated with a serum M-protein concentration ≥1.5 g/dL, a non-IgG isotype, or an abnormal serum FLC ratio (<0.26 or >1.65, reflecting an increase in either the kappa or lambda light chain).¹² An MGUS patient exhibiting all 3 of these features has a 58% absolute risk of developing MM after 20 years of follow-up. A patient with 2 of the 3 abnormalities has a 37% risk of progressing to MM, and one who has just one abnormality has a 21% risk. In contrast, an MGUS patient who has an M-protein level <1.5 g/dL, an IgG isotype, and normal FLC range has only a 5% risk of progression to MM in the same 20 years.¹²

The Spanish Group risk stratification model¹³ is based on 2 risk factors: a high proportion of abnormal plasma cells (aPC) within the bone marrow plasma cell (BMPC) compartment (ie, ≥95% CD56+/CD19-); and an evolving subtype of the disease (defined as an increase in the level of serum M-protein by at least 10% during the first 6 months of follow-up, or a progressive and constant increase of the M-protein until overt MM develops). The 7-year cumulative probability of progression of MGUS to MM: 2% for patients with neither risk factor, 16% with one risk factor, and 72% with both risk factors.¹³

SMM. Classification of this progressive state is defined by a serum level of monoclonal protein (IgG, IgA, IgD, or IgE) ≥3 g/dL or a concentration of clonal bone marrow plasma cells ≥10%; and by an absence of end-organ damage such as hypercalcemia, renal insufficiency, anemia, and bone lesions (CRAB) that can be attributed to a plasma cell proliferative disorder (TABLE 2).³ Both laboratory and clinical criteria must be met.

According to the Mayo Clinic risk stratification model, likelihood of progression reflects combinations of 3 factors: bone marrow plasmacytosis ≥10%, a serum M-protein level ≥3 g/dL, and a serum FLC ratio ≤0.125 or ≥8.¹⁴ Using this stratification scheme, the risk over 10 years of progressing from SMM to MM is 84% for those with all 3 risk factors, 65% with 2 factors, and 52% with one factor.¹⁴ As SMM is defined, there is no upper limit of bone marrow involvement. However, Rajkumar et al¹⁵ found that progression time was significantly shorter (P<.001) among patients with ≥60% bone marrow involvement, compared with those having <60% involvement.

The Spanish Group risk stratification model¹³ uses the same model applied to MGUS: a proportion of abnormal plasma cells in the BMPC compartment ≥95% CD56+/CD19-; and an evolving subtype of disease. The 3-year cumulative probability of progression of SMM to MM is 46% for those with both risk factors, 12% for those with one factor, and <1% for those with no risk factors.¹³

LC-MGUS. The classification of LC-MGUS (TABLE 4)³ is primarily from a Mayo Clinic study⁶ and research on risk stratification is underway at 2 other institutions. False-positive results are possible in patients with renal¹⁶ and inflammatory¹⁷ disorders.

Applying risk stratification to patient management

The current approach to a patient with clearly defined MGUS is a prudent “watch and wait” strategy that specifies monitoring details based on risk category (ALGORITHM).^1,18

MGUS. In the low-risk MGUS group (IgG subtype, M-protein <1.5 g/dL, and normal FLC ratio)³ there is no need for bone marrow examination or skeletal radiography. Repeat the serum protein electrophoresis (SPE) in 6 months, and if there is no significant elevation of M-protein, repeat the SPE every 2 to 3 years.^1,19,20 However, if other findings are suggestive of plasma cell malignancy (anemia, renal insufficiency, hypercalcemia, or bone lesions), bone marrow examination and computed tomographic (CT) scan are advised. Further evaluation of an incidental detection of MGUS is also important since it is occasionally associated with bone diseases,²¹ arterial and venous thrombosis,²² and an increased risk (P<.05) of developing bacterial (pneumonia, osteomyelitis, septicemia, pyelonephritis, cellulitis, endocarditis, and meningitis) and viral (influenza and herpes zoster) infections.²³

Patients in the intermediate- and high-risk MGUS groups with serum monoclonal protein ≥1.5 g/dL, IgA or IgM subtype or an abnormal FLC ratio should undergo tests for CRAB and have bone marrow aspirate and biopsy with cytogenetics, flow cytometry, and fluorescence in situ hybridization (FISH). Patients with IgM MGUS should also undergo a CT scan of the abdomen to rule out the presence of asymptomatic retroperitoneal lymph nodes.^1,19 If the BM examination and CT scan yield negative results, repeat SPE and complete blood count (CBC) after 6 months and annually thereafter for life. IgD or IgE MGUS is rare, and patients exhibit a progression similar to the 20-year risk seen with MGUS generally.

SMM. Given the increased risk of progression from SMM to MM compared with MGUS (all risk groups), the 2010 International Myeloma Working Group (IMWG) has suggested monitoring SMM patients more frequently—ie, SPE every 2 to 3 months in the first year following diagnosis.¹ Repeat SPE in the second year every 4 to 6 months, and, if results are clinically stable, every 6 to 12 months thereafter. In addition to a baseline bone marrow examination (including cytogenetics, flow cytometry, and FISH studies), consider ordering magnetic resonance imaging of the spine and pelvis to detect occult lesions, as their presence predicts a more rapid progression to MM.²⁴ During the course of the follow-up, evaluate any unexplained anemia or renal function impairment for its origin. A report of MGUS progression over more than a decade to SMM and then to MM illustrates prudent monitoring of a patient.²⁵

LC-MGUS. Once LC-MGUS is detected, first rule out AL-amyloidosis, light-chain deposition disease, or cast nephropathy. If no malignant state is present, repeat the FLC serum assay every 6 months with renal function tests. Idiopathic Bence Jones proteinuria and LC-MGUS have some overlap and both entities put patients at risk for developing MM or amyloidosis. It is not uncommon for MGUS to be accompanied by Bence Jones proteinuria.

Likelihood of SMM progression varies with the combination of 3 factors: bone marrow plasmacytosis ≥10%, a serum M-protein level ≥3 g/dL, and a serum FLC ratio ≤0.125 or ≥8.

In addition to a thorough history and physical examination, recommended followup for both of these entities includes CBC, creatinine, serum FLC, and 24-hour urine protein electrophoresis.⁶ With idiopathic Bence Jones proteinuria, a monoclonal protein evident on urine protein electrophoresis at >500 mg/24 hr must be followed up with tests for other signs of malignancy (CRAB) and BM examination to exclude the possibility of MM.⁶

Treatment of MGUS to prevent progression

Multiple myeloma is still an incurable disease. Since MGUS is a precursor of MM, attempts have been made to either slow its progression or eradicate it. Several independent intervention studies²⁶ for the precursor diseases MGUS and SMM have been conducted or are ongoing. Thus far, no conclusive preventive treatment has been found and the 2010 IMWG guidelines do not recommend preventive therapy for MGUS and SMM patients by means of any drug, unless it is a part of a clinical trial.¹

CASE › The patient profiled at the start of this article has one abnormal risk factor (IgM isotype) and has a low risk of progression to MM. Management should follow the steps outlined in the ALGORITHM^1,18 for low-risk IgM MGUS: repeat SPE, CBC, and CT scan in 6 months and annually thereafter. If any abnormality is observed, rule out the possibilities of IgM SWM, IgM WM, or rapid progression to MM, and consider referral to an oncologist.

CORRESPONDENCE
John M. Boltri, MD, Department of Family and Community Medicine, Northeast Ohio Medical University, College of Medicine, 4209 St. Rt. 44, PO Box 95, Rootstown, Ohio 44272; [email protected].

ACKNOWLEDGEMENTS
The authors thank Kenneth F. Tucker, MD (Webber Cancer Center, St John Macomb-Oakland Hospital, Warren, Mich) and Elizabeth Sykes, MD (Professor, Oakland University, William Beaumont School of Medicine, Rochester, Mich) for their review of this article.

CASE › A 54-year-old man’s lab results following a routine annual examination reveal a level of IgM M-protein just under 1.5 g/dL. All other lab values, including free light chain (FLC) ratio and bone marrow exam, are normal. No clinical evidence of a related disorder is found. What is the risk that this patient’s condition could progress toward multiple myeloma, and how would you follow up?

The patient with a monoclonal gammopathy has an abnormal proliferation of monoclonal plasma cells that secrete an immunoglobulin, M-protein. This proliferation occurs most often in the bone marrow but can also be found in extra-medullary body tissue. The condition can begin insidiously, remain stable, or progress to frank malignancy causing bone and end-organ destruction. The major challenge is to separate stable, asymptomatic patients who require no treatment from patients with progressive, symptomatic myeloma who require immediate treatment.

Risk for MGUS progression increases markedly with a serum M-protein concentration ≥1.5 g/dL, a non-IgG isotype, or an abnormal serum FLC ratio (<0.26 or >1.65).

An increased, measurable level of serum monoclonal immunoglobulins or FLCs is called monoclonal gammopathy of undetermined significance (MGUS) when there is <3 g/dL monoclonal protein in the serum, <10% monoclonal plasma cells in the bone marrow, and an absence of beta-cell proliferative disorders, lytic bone lesions, anemia, hypercalcemia, or renal insufficiency (TABLE 1).^1,2 Serum and marrow measurements exceeding these values indicate progression of disease to a premalignancy stage. Continued proliferation of plasma cells in the bone marrow results in anemia and bone destruction, while the increase in M-protein leads to end-organ destruction. This final malignant state is multiple myeloma (MM).

Detailed classification of MGUS: A roadmap for monitoring patients

Extensive epidemiologic and clinical studies have refined the classification of MGUS^3-5 and related disorders (TABLES 2-4),³ providing physicians with guidance on how to monitor patients. There are 3 kinds of monoclonal gammopathies, each reflecting a particular type of immunoglobulin involvement—non-IgM, IgM, or light chain. Additionally, within each type of gammopathy, patient-specific characteristics determine 3 categories of clinical significance: premalignancy with low risk of progression (1%-2% per year³); premalignancy with high risk of progression (10% per year³); and malignancy.

Non-IgM MGUS with a high risk of progression is designated smoldering multiple myeloma (SMM) (TABLE 2).³ IgM MGUS with a high risk of progression is defined as smoldering Waldenström macroglobulinemia (SWM), with a predisposition to progress to Waldenström macroglobulinemia (WM) and, rarely, to IgM MM (TABLE 3).³

More recently, it has been reported that approximately 20% of the cases of MM belong to a new entity called light-chain MM that features an absence of heavy chain (IgG, IgA, IgM, IgD, or IgE) secretion in serum.⁶ The premalignant precursor is light-chain MGUS (LC-MGUS). The criteria for LC-MGUS and idiopathic Bence Jones proteinuria are found in TABLE 4.³ Idiopathic Bence Jones proteinuria is equivalent to SMM and SWM due to its higher risk of progression (10%/year)³ to light-chain MM.

Prevalence of MGUS

In general, the prevalence of all types of MGUS increases with age and is affected by race, sex, family history, immunosuppression, and pesticide exposure. The Caucasian American population >50 years exhibits a prevalence of MGUS of approximately 3.2%;⁷ the African American population exhibits a significantly higher prevalence of 5.9% to 8.4%.⁷ Native Asians have a lower rate of MM, and, as expected, a lower MGUS prevalence than is seen in the Western population (Thailand ≈2.3%;⁸ Korea ≈3.3%;⁹ Japan ≈2.1%;¹⁰ China ≈0.8%¹¹). The overall prevalence of the 3 types of MGUS is 4.2% in Caucasians.⁶

Distinguishing stable from progressive disease

The Mayo Clinic’s risk stratification model¹² further specifies risk of disease progression based on 3 indicators: serum M-protein concentration, Ig isotype of M-protein, and serum FLC ratio.

MGUS. A marked increase in risk for disease progression is associated with a serum M-protein concentration ≥1.5 g/dL, a non-IgG isotype, or an abnormal serum FLC ratio (<0.26 or >1.65, reflecting an increase in either the kappa or lambda light chain).¹² An MGUS patient exhibiting all 3 of these features has a 58% absolute risk of developing MM after 20 years of follow-up. A patient with 2 of the 3 abnormalities has a 37% risk of progressing to MM, and one who has just one abnormality has a 21% risk. In contrast, an MGUS patient who has an M-protein level <1.5 g/dL, an IgG isotype, and normal FLC range has only a 5% risk of progression to MM in the same 20 years.¹²

The Spanish Group risk stratification model¹³ is based on 2 risk factors: a high proportion of abnormal plasma cells (aPC) within the bone marrow plasma cell (BMPC) compartment (ie, ≥95% CD56+/CD19-); and an evolving subtype of the disease (defined as an increase in the level of serum M-protein by at least 10% during the first 6 months of follow-up, or a progressive and constant increase of the M-protein until overt MM develops). The 7-year cumulative probability of progression of MGUS to MM: 2% for patients with neither risk factor, 16% with one risk factor, and 72% with both risk factors.¹³

SMM. Classification of this progressive state is defined by a serum level of monoclonal protein (IgG, IgA, IgD, or IgE) ≥3 g/dL or a concentration of clonal bone marrow plasma cells ≥10%; and by an absence of end-organ damage such as hypercalcemia, renal insufficiency, anemia, and bone lesions (CRAB) that can be attributed to a plasma cell proliferative disorder (TABLE 2).³ Both laboratory and clinical criteria must be met.

According to the Mayo Clinic risk stratification model, likelihood of progression reflects combinations of 3 factors: bone marrow plasmacytosis ≥10%, a serum M-protein level ≥3 g/dL, and a serum FLC ratio ≤0.125 or ≥8.¹⁴ Using this stratification scheme, the risk over 10 years of progressing from SMM to MM is 84% for those with all 3 risk factors, 65% with 2 factors, and 52% with one factor.¹⁴ As SMM is defined, there is no upper limit of bone marrow involvement. However, Rajkumar et al¹⁵ found that progression time was significantly shorter (P<.001) among patients with ≥60% bone marrow involvement, compared with those having <60% involvement.

The Spanish Group risk stratification model¹³ uses the same model applied to MGUS: a proportion of abnormal plasma cells in the BMPC compartment ≥95% CD56+/CD19-; and an evolving subtype of disease. The 3-year cumulative probability of progression of SMM to MM is 46% for those with both risk factors, 12% for those with one factor, and <1% for those with no risk factors.¹³

LC-MGUS. The classification of LC-MGUS (TABLE 4)³ is primarily from a Mayo Clinic study⁶ and research on risk stratification is underway at 2 other institutions. False-positive results are possible in patients with renal¹⁶ and inflammatory¹⁷ disorders.

Applying risk stratification to patient management

The current approach to a patient with clearly defined MGUS is a prudent “watch and wait” strategy that specifies monitoring details based on risk category (ALGORITHM).^1,18

MGUS. In the low-risk MGUS group (IgG subtype, M-protein <1.5 g/dL, and normal FLC ratio)³ there is no need for bone marrow examination or skeletal radiography. Repeat the serum protein electrophoresis (SPE) in 6 months, and if there is no significant elevation of M-protein, repeat the SPE every 2 to 3 years.^1,19,20 However, if other findings are suggestive of plasma cell malignancy (anemia, renal insufficiency, hypercalcemia, or bone lesions), bone marrow examination and computed tomographic (CT) scan are advised. Further evaluation of an incidental detection of MGUS is also important since it is occasionally associated with bone diseases,²¹ arterial and venous thrombosis,²² and an increased risk (P<.05) of developing bacterial (pneumonia, osteomyelitis, septicemia, pyelonephritis, cellulitis, endocarditis, and meningitis) and viral (influenza and herpes zoster) infections.²³

Patients in the intermediate- and high-risk MGUS groups with serum monoclonal protein ≥1.5 g/dL, IgA or IgM subtype or an abnormal FLC ratio should undergo tests for CRAB and have bone marrow aspirate and biopsy with cytogenetics, flow cytometry, and fluorescence in situ hybridization (FISH). Patients with IgM MGUS should also undergo a CT scan of the abdomen to rule out the presence of asymptomatic retroperitoneal lymph nodes.^1,19 If the BM examination and CT scan yield negative results, repeat SPE and complete blood count (CBC) after 6 months and annually thereafter for life. IgD or IgE MGUS is rare, and patients exhibit a progression similar to the 20-year risk seen with MGUS generally.

SMM. Given the increased risk of progression from SMM to MM compared with MGUS (all risk groups), the 2010 International Myeloma Working Group (IMWG) has suggested monitoring SMM patients more frequently—ie, SPE every 2 to 3 months in the first year following diagnosis.¹ Repeat SPE in the second year every 4 to 6 months, and, if results are clinically stable, every 6 to 12 months thereafter. In addition to a baseline bone marrow examination (including cytogenetics, flow cytometry, and FISH studies), consider ordering magnetic resonance imaging of the spine and pelvis to detect occult lesions, as their presence predicts a more rapid progression to MM.²⁴ During the course of the follow-up, evaluate any unexplained anemia or renal function impairment for its origin. A report of MGUS progression over more than a decade to SMM and then to MM illustrates prudent monitoring of a patient.²⁵

LC-MGUS. Once LC-MGUS is detected, first rule out AL-amyloidosis, light-chain deposition disease, or cast nephropathy. If no malignant state is present, repeat the FLC serum assay every 6 months with renal function tests. Idiopathic Bence Jones proteinuria and LC-MGUS have some overlap and both entities put patients at risk for developing MM or amyloidosis. It is not uncommon for MGUS to be accompanied by Bence Jones proteinuria.

Likelihood of SMM progression varies with the combination of 3 factors: bone marrow plasmacytosis ≥10%, a serum M-protein level ≥3 g/dL, and a serum FLC ratio ≤0.125 or ≥8.

In addition to a thorough history and physical examination, recommended followup for both of these entities includes CBC, creatinine, serum FLC, and 24-hour urine protein electrophoresis.⁶ With idiopathic Bence Jones proteinuria, a monoclonal protein evident on urine protein electrophoresis at >500 mg/24 hr must be followed up with tests for other signs of malignancy (CRAB) and BM examination to exclude the possibility of MM.⁶

Treatment of MGUS to prevent progression

Multiple myeloma is still an incurable disease. Since MGUS is a precursor of MM, attempts have been made to either slow its progression or eradicate it. Several independent intervention studies²⁶ for the precursor diseases MGUS and SMM have been conducted or are ongoing. Thus far, no conclusive preventive treatment has been found and the 2010 IMWG guidelines do not recommend preventive therapy for MGUS and SMM patients by means of any drug, unless it is a part of a clinical trial.¹

CASE › The patient profiled at the start of this article has one abnormal risk factor (IgM isotype) and has a low risk of progression to MM. Management should follow the steps outlined in the ALGORITHM^1,18 for low-risk IgM MGUS: repeat SPE, CBC, and CT scan in 6 months and annually thereafter. If any abnormality is observed, rule out the possibilities of IgM SWM, IgM WM, or rapid progression to MM, and consider referral to an oncologist.

CORRESPONDENCE
John M. Boltri, MD, Department of Family and Community Medicine, Northeast Ohio Medical University, College of Medicine, 4209 St. Rt. 44, PO Box 95, Rootstown, Ohio 44272; [email protected].

ACKNOWLEDGEMENTS
The authors thank Kenneth F. Tucker, MD (Webber Cancer Center, St John Macomb-Oakland Hospital, Warren, Mich) and Elizabeth Sykes, MD (Professor, Oakland University, William Beaumont School of Medicine, Rochester, Mich) for their review of this article.

CASE › A 54-year-old man’s lab results following a routine annual examination reveal a level of IgM M-protein just under 1.5 g/dL. All other lab values, including free light chain (FLC) ratio and bone marrow exam, are normal. No clinical evidence of a related disorder is found. What is the risk that this patient’s condition could progress toward multiple myeloma, and how would you follow up?

The patient with a monoclonal gammopathy has an abnormal proliferation of monoclonal plasma cells that secrete an immunoglobulin, M-protein. This proliferation occurs most often in the bone marrow but can also be found in extra-medullary body tissue. The condition can begin insidiously, remain stable, or progress to frank malignancy causing bone and end-organ destruction. The major challenge is to separate stable, asymptomatic patients who require no treatment from patients with progressive, symptomatic myeloma who require immediate treatment.

Risk for MGUS progression increases markedly with a serum M-protein concentration ≥1.5 g/dL, a non-IgG isotype, or an abnormal serum FLC ratio (<0.26 or >1.65).

An increased, measurable level of serum monoclonal immunoglobulins or FLCs is called monoclonal gammopathy of undetermined significance (MGUS) when there is <3 g/dL monoclonal protein in the serum, <10% monoclonal plasma cells in the bone marrow, and an absence of beta-cell proliferative disorders, lytic bone lesions, anemia, hypercalcemia, or renal insufficiency (TABLE 1).^1,2 Serum and marrow measurements exceeding these values indicate progression of disease to a premalignancy stage. Continued proliferation of plasma cells in the bone marrow results in anemia and bone destruction, while the increase in M-protein leads to end-organ destruction. This final malignant state is multiple myeloma (MM).

Detailed classification of MGUS: A roadmap for monitoring patients

Extensive epidemiologic and clinical studies have refined the classification of MGUS^3-5 and related disorders (TABLES 2-4),³ providing physicians with guidance on how to monitor patients. There are 3 kinds of monoclonal gammopathies, each reflecting a particular type of immunoglobulin involvement—non-IgM, IgM, or light chain. Additionally, within each type of gammopathy, patient-specific characteristics determine 3 categories of clinical significance: premalignancy with low risk of progression (1%-2% per year³); premalignancy with high risk of progression (10% per year³); and malignancy.

Non-IgM MGUS with a high risk of progression is designated smoldering multiple myeloma (SMM) (TABLE 2).³ IgM MGUS with a high risk of progression is defined as smoldering Waldenström macroglobulinemia (SWM), with a predisposition to progress to Waldenström macroglobulinemia (WM) and, rarely, to IgM MM (TABLE 3).³

More recently, it has been reported that approximately 20% of the cases of MM belong to a new entity called light-chain MM that features an absence of heavy chain (IgG, IgA, IgM, IgD, or IgE) secretion in serum.⁶ The premalignant precursor is light-chain MGUS (LC-MGUS). The criteria for LC-MGUS and idiopathic Bence Jones proteinuria are found in TABLE 4.³ Idiopathic Bence Jones proteinuria is equivalent to SMM and SWM due to its higher risk of progression (10%/year)³ to light-chain MM.

Prevalence of MGUS

In general, the prevalence of all types of MGUS increases with age and is affected by race, sex, family history, immunosuppression, and pesticide exposure. The Caucasian American population >50 years exhibits a prevalence of MGUS of approximately 3.2%;⁷ the African American population exhibits a significantly higher prevalence of 5.9% to 8.4%.⁷ Native Asians have a lower rate of MM, and, as expected, a lower MGUS prevalence than is seen in the Western population (Thailand ≈2.3%;⁸ Korea ≈3.3%;⁹ Japan ≈2.1%;¹⁰ China ≈0.8%¹¹). The overall prevalence of the 3 types of MGUS is 4.2% in Caucasians.⁶

Distinguishing stable from progressive disease

The Mayo Clinic’s risk stratification model¹² further specifies risk of disease progression based on 3 indicators: serum M-protein concentration, Ig isotype of M-protein, and serum FLC ratio.

MGUS. A marked increase in risk for disease progression is associated with a serum M-protein concentration ≥1.5 g/dL, a non-IgG isotype, or an abnormal serum FLC ratio (<0.26 or >1.65, reflecting an increase in either the kappa or lambda light chain).¹² An MGUS patient exhibiting all 3 of these features has a 58% absolute risk of developing MM after 20 years of follow-up. A patient with 2 of the 3 abnormalities has a 37% risk of progressing to MM, and one who has just one abnormality has a 21% risk. In contrast, an MGUS patient who has an M-protein level <1.5 g/dL, an IgG isotype, and normal FLC range has only a 5% risk of progression to MM in the same 20 years.¹²

The Spanish Group risk stratification model¹³ is based on 2 risk factors: a high proportion of abnormal plasma cells (aPC) within the bone marrow plasma cell (BMPC) compartment (ie, ≥95% CD56+/CD19-); and an evolving subtype of the disease (defined as an increase in the level of serum M-protein by at least 10% during the first 6 months of follow-up, or a progressive and constant increase of the M-protein until overt MM develops). The 7-year cumulative probability of progression of MGUS to MM: 2% for patients with neither risk factor, 16% with one risk factor, and 72% with both risk factors.¹³

SMM. Classification of this progressive state is defined by a serum level of monoclonal protein (IgG, IgA, IgD, or IgE) ≥3 g/dL or a concentration of clonal bone marrow plasma cells ≥10%; and by an absence of end-organ damage such as hypercalcemia, renal insufficiency, anemia, and bone lesions (CRAB) that can be attributed to a plasma cell proliferative disorder (TABLE 2).³ Both laboratory and clinical criteria must be met.

According to the Mayo Clinic risk stratification model, likelihood of progression reflects combinations of 3 factors: bone marrow plasmacytosis ≥10%, a serum M-protein level ≥3 g/dL, and a serum FLC ratio ≤0.125 or ≥8.¹⁴ Using this stratification scheme, the risk over 10 years of progressing from SMM to MM is 84% for those with all 3 risk factors, 65% with 2 factors, and 52% with one factor.¹⁴ As SMM is defined, there is no upper limit of bone marrow involvement. However, Rajkumar et al¹⁵ found that progression time was significantly shorter (P<.001) among patients with ≥60% bone marrow involvement, compared with those having <60% involvement.

The Spanish Group risk stratification model¹³ uses the same model applied to MGUS: a proportion of abnormal plasma cells in the BMPC compartment ≥95% CD56+/CD19-; and an evolving subtype of disease. The 3-year cumulative probability of progression of SMM to MM is 46% for those with both risk factors, 12% for those with one factor, and <1% for those with no risk factors.¹³

LC-MGUS. The classification of LC-MGUS (TABLE 4)³ is primarily from a Mayo Clinic study⁶ and research on risk stratification is underway at 2 other institutions. False-positive results are possible in patients with renal¹⁶ and inflammatory¹⁷ disorders.

Applying risk stratification to patient management

The current approach to a patient with clearly defined MGUS is a prudent “watch and wait” strategy that specifies monitoring details based on risk category (ALGORITHM).^1,18

MGUS. In the low-risk MGUS group (IgG subtype, M-protein <1.5 g/dL, and normal FLC ratio)³ there is no need for bone marrow examination or skeletal radiography. Repeat the serum protein electrophoresis (SPE) in 6 months, and if there is no significant elevation of M-protein, repeat the SPE every 2 to 3 years.^1,19,20 However, if other findings are suggestive of plasma cell malignancy (anemia, renal insufficiency, hypercalcemia, or bone lesions), bone marrow examination and computed tomographic (CT) scan are advised. Further evaluation of an incidental detection of MGUS is also important since it is occasionally associated with bone diseases,²¹ arterial and venous thrombosis,²² and an increased risk (P<.05) of developing bacterial (pneumonia, osteomyelitis, septicemia, pyelonephritis, cellulitis, endocarditis, and meningitis) and viral (influenza and herpes zoster) infections.²³

Patients in the intermediate- and high-risk MGUS groups with serum monoclonal protein ≥1.5 g/dL, IgA or IgM subtype or an abnormal FLC ratio should undergo tests for CRAB and have bone marrow aspirate and biopsy with cytogenetics, flow cytometry, and fluorescence in situ hybridization (FISH). Patients with IgM MGUS should also undergo a CT scan of the abdomen to rule out the presence of asymptomatic retroperitoneal lymph nodes.^1,19 If the BM examination and CT scan yield negative results, repeat SPE and complete blood count (CBC) after 6 months and annually thereafter for life. IgD or IgE MGUS is rare, and patients exhibit a progression similar to the 20-year risk seen with MGUS generally.

SMM. Given the increased risk of progression from SMM to MM compared with MGUS (all risk groups), the 2010 International Myeloma Working Group (IMWG) has suggested monitoring SMM patients more frequently—ie, SPE every 2 to 3 months in the first year following diagnosis.¹ Repeat SPE in the second year every 4 to 6 months, and, if results are clinically stable, every 6 to 12 months thereafter. In addition to a baseline bone marrow examination (including cytogenetics, flow cytometry, and FISH studies), consider ordering magnetic resonance imaging of the spine and pelvis to detect occult lesions, as their presence predicts a more rapid progression to MM.²⁴ During the course of the follow-up, evaluate any unexplained anemia or renal function impairment for its origin. A report of MGUS progression over more than a decade to SMM and then to MM illustrates prudent monitoring of a patient.²⁵

LC-MGUS. Once LC-MGUS is detected, first rule out AL-amyloidosis, light-chain deposition disease, or cast nephropathy. If no malignant state is present, repeat the FLC serum assay every 6 months with renal function tests. Idiopathic Bence Jones proteinuria and LC-MGUS have some overlap and both entities put patients at risk for developing MM or amyloidosis. It is not uncommon for MGUS to be accompanied by Bence Jones proteinuria.

Likelihood of SMM progression varies with the combination of 3 factors: bone marrow plasmacytosis ≥10%, a serum M-protein level ≥3 g/dL, and a serum FLC ratio ≤0.125 or ≥8.

In addition to a thorough history and physical examination, recommended followup for both of these entities includes CBC, creatinine, serum FLC, and 24-hour urine protein electrophoresis.⁶ With idiopathic Bence Jones proteinuria, a monoclonal protein evident on urine protein electrophoresis at >500 mg/24 hr must be followed up with tests for other signs of malignancy (CRAB) and BM examination to exclude the possibility of MM.⁶

Treatment of MGUS to prevent progression

Multiple myeloma is still an incurable disease. Since MGUS is a precursor of MM, attempts have been made to either slow its progression or eradicate it. Several independent intervention studies²⁶ for the precursor diseases MGUS and SMM have been conducted or are ongoing. Thus far, no conclusive preventive treatment has been found and the 2010 IMWG guidelines do not recommend preventive therapy for MGUS and SMM patients by means of any drug, unless it is a part of a clinical trial.¹

CASE › The patient profiled at the start of this article has one abnormal risk factor (IgM isotype) and has a low risk of progression to MM. Management should follow the steps outlined in the ALGORITHM^1,18 for low-risk IgM MGUS: repeat SPE, CBC, and CT scan in 6 months and annually thereafter. If any abnormality is observed, rule out the possibilities of IgM SWM, IgM WM, or rapid progression to MM, and consider referral to an oncologist.

CORRESPONDENCE
John M. Boltri, MD, Department of Family and Community Medicine, Northeast Ohio Medical University, College of Medicine, 4209 St. Rt. 44, PO Box 95, Rootstown, Ohio 44272; [email protected].

ACKNOWLEDGEMENTS
The authors thank Kenneth F. Tucker, MD (Webber Cancer Center, St John Macomb-Oakland Hospital, Warren, Mich) and Elizabeth Sykes, MD (Professor, Oakland University, William Beaumont School of Medicine, Rochester, Mich) for their review of this article.

Active injections produce sustained improvement

A 2011 double-blind RCT randomized 68 female patients with both fibromyalgia and myofascial trigger points to either active trigger point injections with 1 mL 0.5% bupivacaine or placebo-like needle penetration with no medication to an area near the trigger point.¹ Patients were evaluated for both local and generalized fibromyalgia symptoms at 4 and 8 days (trial period) and after 30 days (follow-up). Injections occurred on Days 1 and 4, with an option of additional injections on Days 8 and 11.

Compared to baseline (7 days before the injection), patients receiving active trigger point injections had decreased myofascial pain episodes 7 days after the injection (5.6 vs 0.97 episodes; P<.001), decreased pain intensity (62 vs 19/100 mm Visual Analog Scale score; P<.001), and increased pressure threshold at the trigger point (1.5 vs 2.9 kg/cm²; P<.0001), whereas the control group showed no differences.

During Days 1 to 8, patients receiving active trigger point injections required less acetaminophen (0.2 vs 2.7 tablets/d; P<.0001). At Day 8, no patients in the active trigger point injection group requested additional injections, whereas all the patients in the control group requested an injection (P<.0001).

At Day 8, patients also had significantly decreased intensity of fibromyalgia pain, fewer tender points, and higher tender point pressure thresholds; none of these differences were statistically significant in the placebo injection group (data presented graphically). The improvements persisted at 30 days of follow-up (data presented graphically).

Small study shows improvement with injections after 2 weeks

An uncontrolled prospective before-after study in 1996 evaluated the effectiveness of 0.5% lidocaine trigger point injections in 9 patients with myofascial trigger points plus fibromyalgia compared with 9 patients with myofascial trigger points alone.²

Immediately after injection, patients with fibromyalgia had a nonsignificant worsening in pain intensity (pain scale 8.1 to 8.4/10; P>.1), but there was a significant improvement at 2 weeks (5.9; P<.01). The pressure threshold also decreased initially (1.7 to 1.4 kg/cm²; P>.1), but significantly increased at 2 weeks (2.4 kg/cm²; P<.01). In comparison, patients without fibromyalgia showed immediate improvement in all domains, which persisted at 2 weeks (P<.01).

What the guidelines say

Recent Canadian Fibromyalgia Guidelines discuss trigger point injections in the section on “off-label” medications, stating that they “may have some place in treatment of fibromyalgia.”³

Active injections produce sustained improvement

A 2011 double-blind RCT randomized 68 female patients with both fibromyalgia and myofascial trigger points to either active trigger point injections with 1 mL 0.5% bupivacaine or placebo-like needle penetration with no medication to an area near the trigger point.¹ Patients were evaluated for both local and generalized fibromyalgia symptoms at 4 and 8 days (trial period) and after 30 days (follow-up). Injections occurred on Days 1 and 4, with an option of additional injections on Days 8 and 11.

Compared to baseline (7 days before the injection), patients receiving active trigger point injections had decreased myofascial pain episodes 7 days after the injection (5.6 vs 0.97 episodes; P<.001), decreased pain intensity (62 vs 19/100 mm Visual Analog Scale score; P<.001), and increased pressure threshold at the trigger point (1.5 vs 2.9 kg/cm²; P<.0001), whereas the control group showed no differences.

During Days 1 to 8, patients receiving active trigger point injections required less acetaminophen (0.2 vs 2.7 tablets/d; P<.0001). At Day 8, no patients in the active trigger point injection group requested additional injections, whereas all the patients in the control group requested an injection (P<.0001).

At Day 8, patients also had significantly decreased intensity of fibromyalgia pain, fewer tender points, and higher tender point pressure thresholds; none of these differences were statistically significant in the placebo injection group (data presented graphically). The improvements persisted at 30 days of follow-up (data presented graphically).

Small study shows improvement with injections after 2 weeks

An uncontrolled prospective before-after study in 1996 evaluated the effectiveness of 0.5% lidocaine trigger point injections in 9 patients with myofascial trigger points plus fibromyalgia compared with 9 patients with myofascial trigger points alone.²

Immediately after injection, patients with fibromyalgia had a nonsignificant worsening in pain intensity (pain scale 8.1 to 8.4/10; P>.1), but there was a significant improvement at 2 weeks (5.9; P<.01). The pressure threshold also decreased initially (1.7 to 1.4 kg/cm²; P>.1), but significantly increased at 2 weeks (2.4 kg/cm²; P<.01). In comparison, patients without fibromyalgia showed immediate improvement in all domains, which persisted at 2 weeks (P<.01).

What the guidelines say

Recent Canadian Fibromyalgia Guidelines discuss trigger point injections in the section on “off-label” medications, stating that they “may have some place in treatment of fibromyalgia.”³

Active injections produce sustained improvement

A 2011 double-blind RCT randomized 68 female patients with both fibromyalgia and myofascial trigger points to either active trigger point injections with 1 mL 0.5% bupivacaine or placebo-like needle penetration with no medication to an area near the trigger point.¹ Patients were evaluated for both local and generalized fibromyalgia symptoms at 4 and 8 days (trial period) and after 30 days (follow-up). Injections occurred on Days 1 and 4, with an option of additional injections on Days 8 and 11.

Compared to baseline (7 days before the injection), patients receiving active trigger point injections had decreased myofascial pain episodes 7 days after the injection (5.6 vs 0.97 episodes; P<.001), decreased pain intensity (62 vs 19/100 mm Visual Analog Scale score; P<.001), and increased pressure threshold at the trigger point (1.5 vs 2.9 kg/cm²; P<.0001), whereas the control group showed no differences.

During Days 1 to 8, patients receiving active trigger point injections required less acetaminophen (0.2 vs 2.7 tablets/d; P<.0001). At Day 8, no patients in the active trigger point injection group requested additional injections, whereas all the patients in the control group requested an injection (P<.0001).

At Day 8, patients also had significantly decreased intensity of fibromyalgia pain, fewer tender points, and higher tender point pressure thresholds; none of these differences were statistically significant in the placebo injection group (data presented graphically). The improvements persisted at 30 days of follow-up (data presented graphically).

Small study shows improvement with injections after 2 weeks

An uncontrolled prospective before-after study in 1996 evaluated the effectiveness of 0.5% lidocaine trigger point injections in 9 patients with myofascial trigger points plus fibromyalgia compared with 9 patients with myofascial trigger points alone.²

Immediately after injection, patients with fibromyalgia had a nonsignificant worsening in pain intensity (pain scale 8.1 to 8.4/10; P>.1), but there was a significant improvement at 2 weeks (5.9; P<.01). The pressure threshold also decreased initially (1.7 to 1.4 kg/cm²; P>.1), but significantly increased at 2 weeks (2.4 kg/cm²; P<.01). In comparison, patients without fibromyalgia showed immediate improvement in all domains, which persisted at 2 weeks (P<.01).

What the guidelines say

Recent Canadian Fibromyalgia Guidelines discuss trigger point injections in the section on “off-label” medications, stating that they “may have some place in treatment of fibromyalgia.”³

WASHINGTON – Individuals suffering from migraine who also regularly experience insomnia are highly predisposed to developing anxiety and depression, according to a population-based study presented at the annual meeting of the American Headache Society.

“Treating comorbid conditions, such as anxiety and depression, is an essential part of optimal treatment of migraine,” explained Dr. Min Chu of Hallym University in Anyang, South Korea. “However, anxiety and depression, even in migraineurs, are usually underdiagnosed and undertreated, [and] the association between insomnia and anxiety and depression among migraineurs in a population-based setting is still unknown.”

© Karen Winton / iStockphoto.com

Dr. Chu and his coinvestigators selected a sample of 2,762 participants aged 19-69 years who underwent screening with the Insomnia Severity Index (ISI), Goldberg Anxiety Scale, and Patient Health Questionnaire–9 to determine each patient’s severity for each symptom. ISI scores equal to or greater than 15 were considered indicative of insomnia severe enough to potentially cause anxiety or depression. Evaluations for each subject were administered via a face-to-face, 60-item, semistructured interview.

Of 147 subjects found to have migraine in the previous year, 57 (38.8%) had insomnia, 45 (30.6%) had anxiety, and 26 (17.7%) had depression. Of the 57 migraineurs who also had insomnia, 50.9% had anxiety and 31.6% had depression. Logistic regression models ultimately showed that migraine and insomnia together create heightened odds for anxiety (odds ratio, 4.8; 95% confidence interval, 2.3-10.1) and depression (OR, 4.7; 95% CI, 1.9-11.8) (P < .001 for all). Out of the total population, 274 subjects (10.0%) had anxiety, 124 (4.5%) had depression, and 120 (4.3%) had insomnia.

“Insomnia, anxiety, and depression showed a close association in a population-based sample,” Dr. Chu said. “This association persisted among migraineurs, and more than two-thirds of migraineurs with insomnia have anxiety or depression.”

He added that it is critical for health care providers to assess insomnia in migraineurs to accurately treat anxiety and depression as well.

Dr. Chu did not report any relevant financial disclosures.

[email protected]

WASHINGTON – Individuals suffering from migraine who also regularly experience insomnia are highly predisposed to developing anxiety and depression, according to a population-based study presented at the annual meeting of the American Headache Society.

“Treating comorbid conditions, such as anxiety and depression, is an essential part of optimal treatment of migraine,” explained Dr. Min Chu of Hallym University in Anyang, South Korea. “However, anxiety and depression, even in migraineurs, are usually underdiagnosed and undertreated, [and] the association between insomnia and anxiety and depression among migraineurs in a population-based setting is still unknown.”

© Karen Winton / iStockphoto.com

Dr. Chu and his coinvestigators selected a sample of 2,762 participants aged 19-69 years who underwent screening with the Insomnia Severity Index (ISI), Goldberg Anxiety Scale, and Patient Health Questionnaire–9 to determine each patient’s severity for each symptom. ISI scores equal to or greater than 15 were considered indicative of insomnia severe enough to potentially cause anxiety or depression. Evaluations for each subject were administered via a face-to-face, 60-item, semistructured interview.

Of 147 subjects found to have migraine in the previous year, 57 (38.8%) had insomnia, 45 (30.6%) had anxiety, and 26 (17.7%) had depression. Of the 57 migraineurs who also had insomnia, 50.9% had anxiety and 31.6% had depression. Logistic regression models ultimately showed that migraine and insomnia together create heightened odds for anxiety (odds ratio, 4.8; 95% confidence interval, 2.3-10.1) and depression (OR, 4.7; 95% CI, 1.9-11.8) (P < .001 for all). Out of the total population, 274 subjects (10.0%) had anxiety, 124 (4.5%) had depression, and 120 (4.3%) had insomnia.

“Insomnia, anxiety, and depression showed a close association in a population-based sample,” Dr. Chu said. “This association persisted among migraineurs, and more than two-thirds of migraineurs with insomnia have anxiety or depression.”

He added that it is critical for health care providers to assess insomnia in migraineurs to accurately treat anxiety and depression as well.

Dr. Chu did not report any relevant financial disclosures.

[email protected]

WASHINGTON – Individuals suffering from migraine who also regularly experience insomnia are highly predisposed to developing anxiety and depression, according to a population-based study presented at the annual meeting of the American Headache Society.

“Treating comorbid conditions, such as anxiety and depression, is an essential part of optimal treatment of migraine,” explained Dr. Min Chu of Hallym University in Anyang, South Korea. “However, anxiety and depression, even in migraineurs, are usually underdiagnosed and undertreated, [and] the association between insomnia and anxiety and depression among migraineurs in a population-based setting is still unknown.”

© Karen Winton / iStockphoto.com

Dr. Chu and his coinvestigators selected a sample of 2,762 participants aged 19-69 years who underwent screening with the Insomnia Severity Index (ISI), Goldberg Anxiety Scale, and Patient Health Questionnaire–9 to determine each patient’s severity for each symptom. ISI scores equal to or greater than 15 were considered indicative of insomnia severe enough to potentially cause anxiety or depression. Evaluations for each subject were administered via a face-to-face, 60-item, semistructured interview.

Of 147 subjects found to have migraine in the previous year, 57 (38.8%) had insomnia, 45 (30.6%) had anxiety, and 26 (17.7%) had depression. Of the 57 migraineurs who also had insomnia, 50.9% had anxiety and 31.6% had depression. Logistic regression models ultimately showed that migraine and insomnia together create heightened odds for anxiety (odds ratio, 4.8; 95% confidence interval, 2.3-10.1) and depression (OR, 4.7; 95% CI, 1.9-11.8) (P < .001 for all). Out of the total population, 274 subjects (10.0%) had anxiety, 124 (4.5%) had depression, and 120 (4.3%) had insomnia.

“Insomnia, anxiety, and depression showed a close association in a population-based sample,” Dr. Chu said. “This association persisted among migraineurs, and more than two-thirds of migraineurs with insomnia have anxiety or depression.”

He added that it is critical for health care providers to assess insomnia in migraineurs to accurately treat anxiety and depression as well.

Dr. Chu did not report any relevant financial disclosures.

[email protected]

Follow-up of positive screening results lowers colorectal cancer mortality

No studies directly compare the need for colonoscopy when various numbers of stool samples are positive for occult blood on an FOBT. However, a Cochrane review of 4 randomized controlled trials (RCTs) with more than 300,000 patients examined the effectiveness of the FOBT for colorectal cancer screening.¹ Each study varied in its follow-up approach to a positive FOBT.

Two RCTs offered screening with FOBT or standard care (no screening) and immediately followed up any positive results with a colonoscopy. The screened group had lower colorectal cancer mortality (N=46,551; risk ratio [RR]=0.75; 95% confidence interval [CI], 0.62-0.91) than the unscreened group (N=61,933; RR=0.84; 95% CI, 0.73-0.96).

Another trial screened with FOBT or standard care and offered colonoscopy if 5 or more samples were positive on initial testing or one or more were positive on repeat testing. The screened group showed reduced colorectal cancer mortality (N=152,850; RR=0.87; 95% CI, 0.78-0.97).

The final trial examined screening with FOBT compared with standard care and inconsistently offered repeat FOBT or sigmoidoscopy with double-contrast barium enema if any samples were positive on initial testing, which resulted in decreased colorectal cancer mortality for the screened group (N=68,308; RR=0.84; 95% CI, 0.71-0.99).

Evidence-based guidelines recommend follow-up colonoscopy

Evidence-based guidelines from the United States Preventive Services Task Force, the European Commission, and the Canadian Task Force on Preventive Health Care state that FOBT should be used for colorectal cancer screening and that any positive screening test should be followed up with colonoscopy to further evaluate for neoplasm.^2-4

An evidence- and expert opinion-based guideline from the American Cancer Society, the US Multi-Society Task Force on Colorectal Cancer, and the American College of Radiology clarifies the issue further by emphasizing that any positive FOBT necessitates a colonoscopy and stating that repeat FOBT or other test is inappropriate as follow-up.⁵

Follow-up of positive screening results lowers colorectal cancer mortality

No studies directly compare the need for colonoscopy when various numbers of stool samples are positive for occult blood on an FOBT. However, a Cochrane review of 4 randomized controlled trials (RCTs) with more than 300,000 patients examined the effectiveness of the FOBT for colorectal cancer screening.¹ Each study varied in its follow-up approach to a positive FOBT.

Two RCTs offered screening with FOBT or standard care (no screening) and immediately followed up any positive results with a colonoscopy. The screened group had lower colorectal cancer mortality (N=46,551; risk ratio [RR]=0.75; 95% confidence interval [CI], 0.62-0.91) than the unscreened group (N=61,933; RR=0.84; 95% CI, 0.73-0.96).

Another trial screened with FOBT or standard care and offered colonoscopy if 5 or more samples were positive on initial testing or one or more were positive on repeat testing. The screened group showed reduced colorectal cancer mortality (N=152,850; RR=0.87; 95% CI, 0.78-0.97).

The final trial examined screening with FOBT compared with standard care and inconsistently offered repeat FOBT or sigmoidoscopy with double-contrast barium enema if any samples were positive on initial testing, which resulted in decreased colorectal cancer mortality for the screened group (N=68,308; RR=0.84; 95% CI, 0.71-0.99).

Evidence-based guidelines recommend follow-up colonoscopy

Evidence-based guidelines from the United States Preventive Services Task Force, the European Commission, and the Canadian Task Force on Preventive Health Care state that FOBT should be used for colorectal cancer screening and that any positive screening test should be followed up with colonoscopy to further evaluate for neoplasm.^2-4

An evidence- and expert opinion-based guideline from the American Cancer Society, the US Multi-Society Task Force on Colorectal Cancer, and the American College of Radiology clarifies the issue further by emphasizing that any positive FOBT necessitates a colonoscopy and stating that repeat FOBT or other test is inappropriate as follow-up.⁵

Follow-up of positive screening results lowers colorectal cancer mortality

No studies directly compare the need for colonoscopy when various numbers of stool samples are positive for occult blood on an FOBT. However, a Cochrane review of 4 randomized controlled trials (RCTs) with more than 300,000 patients examined the effectiveness of the FOBT for colorectal cancer screening.¹ Each study varied in its follow-up approach to a positive FOBT.

Two RCTs offered screening with FOBT or standard care (no screening) and immediately followed up any positive results with a colonoscopy. The screened group had lower colorectal cancer mortality (N=46,551; risk ratio [RR]=0.75; 95% confidence interval [CI], 0.62-0.91) than the unscreened group (N=61,933; RR=0.84; 95% CI, 0.73-0.96).

Another trial screened with FOBT or standard care and offered colonoscopy if 5 or more samples were positive on initial testing or one or more were positive on repeat testing. The screened group showed reduced colorectal cancer mortality (N=152,850; RR=0.87; 95% CI, 0.78-0.97).

The final trial examined screening with FOBT compared with standard care and inconsistently offered repeat FOBT or sigmoidoscopy with double-contrast barium enema if any samples were positive on initial testing, which resulted in decreased colorectal cancer mortality for the screened group (N=68,308; RR=0.84; 95% CI, 0.71-0.99).

Evidence-based guidelines recommend follow-up colonoscopy

Evidence-based guidelines from the United States Preventive Services Task Force, the European Commission, and the Canadian Task Force on Preventive Health Care state that FOBT should be used for colorectal cancer screening and that any positive screening test should be followed up with colonoscopy to further evaluate for neoplasm.^2-4

An evidence- and expert opinion-based guideline from the American Cancer Society, the US Multi-Society Task Force on Colorectal Cancer, and the American College of Radiology clarifies the issue further by emphasizing that any positive FOBT necessitates a colonoscopy and stating that repeat FOBT or other test is inappropriate as follow-up.⁵

THE CASE

A 21-year-old male college student sought care at our urology clinic for a 2-year history of progressive abdominal distention and loss of appetite due to abdominal pressure. On physical examination, his abdomen was distended and tense, but without any tenderness on palpation or any costovertebral angle tenderness. He had no abdominal or flank pain, and wasn’t in acute distress. His blood pressure was normal.

Initial lab test results were significant for elevated creatinine at 2.7 mg/dL (normal: 0.7-1.3 mg/dL) and blood urea nitrogen (BUN) at 31.1 mg/dL (normal: 6-20 mg/dL). Results of a complete blood count (CBC) were within normal ranges, including a white blood cell (WBC) count of 7900, hemoglobin level of 15.1 g/dL, and platelet count of 217,000/mcL. A urinalysis showed only a mild increase in the WBC count.

THE DIAGNOSIS

We performed a computed tomography (CT) scan of the patient’s abdomen, which revealed bilateral hydronephrosis secondary to ureteropelvic junction obstruction (UPJO). The patient’s right kidney was mildly to moderately enlarged, but the left kidney was massive (FIGURE 1A). The hydronephrotic left kidney had extended itself across the midline (FIGURE 1B), pushed the ipsilateral diaphragm upward, and displaced the bladder downward.

The patient underwent right-sided ureteral stent placement for temporary drainage and a complete left-sided nephrectomy. During the surgery, the left kidney was first aspirated, and more than 11,000 cc of clear urine was drained. (Aspiration reduced the kidney size, allowing the surgeon to make a smaller incision.) The removed kidney contained an additional 1200 cc of cloudy residual fluid (FIGURE 2). UPJO was confirmed by the pathological examination of the excised organ.

DISCUSSION

UPJO is the most common etiology for congenital hydronephrosis.¹ Because it can cause little to no pain, hydronephrosis secondary to UPJO can be asymptomatic and may not present until later in life. Frequently, an abdominal mass is the initial clinical presentation.

When the hydronephrotic fluid exceeds 1000 cc, the condition is referred to as giant hydronephrosis.² Although several cases of giant hydronephrosis secondary to UPJO have been reported in the medical literature,^3-5 the volume of the hydronephrotic fluid in these cases rarely exceeded 10,000 cc. We believe our patient may be the most severe case of hydronephrosis secondary to bilateral UPJO, with 12,200 cc of fluid. His condition reached this late stage only because his right kidney retained adequate function.

Diagnosis of hydronephrosis is straightforward with an abdominal ultrasound and/or CT scan. Widespread use of abdominal ultrasound as a screening tool has significantly increased the diagnosis of asymptomatic hydronephrosis, and many cases are secondary to UPJO.⁶ The true incidence of UPJO is unknown, but it is more prevalent in males than in females, and in 10% to 40% of cases, the condition is bilateral.⁷ Congenital UPJO typically results from intrinsic pathology of the ureter. The diseased segment is often fibrotic, strictured, and aperistaltic.⁸

Treatment choice depends on whether renal function can be preserved

Treatment of hydronephrosis is straightforward; when there is little or no salvageable renal function (<10%), a simple nephrectomy is indicated, as was the case for our patient. Nephrectomy can be accomplished by either an open or laparoscopic approach.

When there is salvageable renal function, treatment options include pyeloplasty and pyelotomy. Traditionally, open dismembered pyeloplasty has been the gold standard. However, with advances in endoscopic and laparoscopic techniques, there has been a shift toward minimally invasive procedures. Laparoscopic pyeloplasty—with or without robotic assistance—and endoscopic pyelotomy—with either a percutaneous or retrograde approach—are now typically performed. Ureteral stenting should only be used as a temporary measure.

Our patient. Four weeks after the nephrectomy, our patient underwent a right side pyeloplasty, which was successful. He had an uneventful recovery from both procedures. His renal function stabilized and other than routine follow-up, he required no additional treatment.

THE TAKEAWAY

Most cases of hydronephrosis in young people are due to congenital abnormalities, and UPJO is the leading cause. However, the condition can be asymptomatic and may not present until later in life. Whenever a patient presents with an asymptomatic abdominal mass, hydronephrosis should be part of the differential diagnosis. Treatment options include nephrectomy when there is no salvageable kidney function or pyeloplasty and pyelotomy when some kidney function can be preserved.

THE CASE

A 21-year-old male college student sought care at our urology clinic for a 2-year history of progressive abdominal distention and loss of appetite due to abdominal pressure. On physical examination, his abdomen was distended and tense, but without any tenderness on palpation or any costovertebral angle tenderness. He had no abdominal or flank pain, and wasn’t in acute distress. His blood pressure was normal.

Initial lab test results were significant for elevated creatinine at 2.7 mg/dL (normal: 0.7-1.3 mg/dL) and blood urea nitrogen (BUN) at 31.1 mg/dL (normal: 6-20 mg/dL). Results of a complete blood count (CBC) were within normal ranges, including a white blood cell (WBC) count of 7900, hemoglobin level of 15.1 g/dL, and platelet count of 217,000/mcL. A urinalysis showed only a mild increase in the WBC count.

THE DIAGNOSIS

We performed a computed tomography (CT) scan of the patient’s abdomen, which revealed bilateral hydronephrosis secondary to ureteropelvic junction obstruction (UPJO). The patient’s right kidney was mildly to moderately enlarged, but the left kidney was massive (FIGURE 1A). The hydronephrotic left kidney had extended itself across the midline (FIGURE 1B), pushed the ipsilateral diaphragm upward, and displaced the bladder downward.

The patient underwent right-sided ureteral stent placement for temporary drainage and a complete left-sided nephrectomy. During the surgery, the left kidney was first aspirated, and more than 11,000 cc of clear urine was drained. (Aspiration reduced the kidney size, allowing the surgeon to make a smaller incision.) The removed kidney contained an additional 1200 cc of cloudy residual fluid (FIGURE 2). UPJO was confirmed by the pathological examination of the excised organ.

DISCUSSION

UPJO is the most common etiology for congenital hydronephrosis.¹ Because it can cause little to no pain, hydronephrosis secondary to UPJO can be asymptomatic and may not present until later in life. Frequently, an abdominal mass is the initial clinical presentation.

When the hydronephrotic fluid exceeds 1000 cc, the condition is referred to as giant hydronephrosis.² Although several cases of giant hydronephrosis secondary to UPJO have been reported in the medical literature,^3-5 the volume of the hydronephrotic fluid in these cases rarely exceeded 10,000 cc. We believe our patient may be the most severe case of hydronephrosis secondary to bilateral UPJO, with 12,200 cc of fluid. His condition reached this late stage only because his right kidney retained adequate function.

Diagnosis of hydronephrosis is straightforward with an abdominal ultrasound and/or CT scan. Widespread use of abdominal ultrasound as a screening tool has significantly increased the diagnosis of asymptomatic hydronephrosis, and many cases are secondary to UPJO.⁶ The true incidence of UPJO is unknown, but it is more prevalent in males than in females, and in 10% to 40% of cases, the condition is bilateral.⁷ Congenital UPJO typically results from intrinsic pathology of the ureter. The diseased segment is often fibrotic, strictured, and aperistaltic.⁸

Treatment choice depends on whether renal function can be preserved

Treatment of hydronephrosis is straightforward; when there is little or no salvageable renal function (<10%), a simple nephrectomy is indicated, as was the case for our patient. Nephrectomy can be accomplished by either an open or laparoscopic approach.

When there is salvageable renal function, treatment options include pyeloplasty and pyelotomy. Traditionally, open dismembered pyeloplasty has been the gold standard. However, with advances in endoscopic and laparoscopic techniques, there has been a shift toward minimally invasive procedures. Laparoscopic pyeloplasty—with or without robotic assistance—and endoscopic pyelotomy—with either a percutaneous or retrograde approach—are now typically performed. Ureteral stenting should only be used as a temporary measure.

Our patient. Four weeks after the nephrectomy, our patient underwent a right side pyeloplasty, which was successful. He had an uneventful recovery from both procedures. His renal function stabilized and other than routine follow-up, he required no additional treatment.

THE TAKEAWAY

Most cases of hydronephrosis in young people are due to congenital abnormalities, and UPJO is the leading cause. However, the condition can be asymptomatic and may not present until later in life. Whenever a patient presents with an asymptomatic abdominal mass, hydronephrosis should be part of the differential diagnosis. Treatment options include nephrectomy when there is no salvageable kidney function or pyeloplasty and pyelotomy when some kidney function can be preserved.

THE CASE

A 21-year-old male college student sought care at our urology clinic for a 2-year history of progressive abdominal distention and loss of appetite due to abdominal pressure. On physical examination, his abdomen was distended and tense, but without any tenderness on palpation or any costovertebral angle tenderness. He had no abdominal or flank pain, and wasn’t in acute distress. His blood pressure was normal.

Initial lab test results were significant for elevated creatinine at 2.7 mg/dL (normal: 0.7-1.3 mg/dL) and blood urea nitrogen (BUN) at 31.1 mg/dL (normal: 6-20 mg/dL). Results of a complete blood count (CBC) were within normal ranges, including a white blood cell (WBC) count of 7900, hemoglobin level of 15.1 g/dL, and platelet count of 217,000/mcL. A urinalysis showed only a mild increase in the WBC count.

THE DIAGNOSIS

We performed a computed tomography (CT) scan of the patient’s abdomen, which revealed bilateral hydronephrosis secondary to ureteropelvic junction obstruction (UPJO). The patient’s right kidney was mildly to moderately enlarged, but the left kidney was massive (FIGURE 1A). The hydronephrotic left kidney had extended itself across the midline (FIGURE 1B), pushed the ipsilateral diaphragm upward, and displaced the bladder downward.

The patient underwent right-sided ureteral stent placement for temporary drainage and a complete left-sided nephrectomy. During the surgery, the left kidney was first aspirated, and more than 11,000 cc of clear urine was drained. (Aspiration reduced the kidney size, allowing the surgeon to make a smaller incision.) The removed kidney contained an additional 1200 cc of cloudy residual fluid (FIGURE 2). UPJO was confirmed by the pathological examination of the excised organ.

DISCUSSION

UPJO is the most common etiology for congenital hydronephrosis.¹ Because it can cause little to no pain, hydronephrosis secondary to UPJO can be asymptomatic and may not present until later in life. Frequently, an abdominal mass is the initial clinical presentation.

When the hydronephrotic fluid exceeds 1000 cc, the condition is referred to as giant hydronephrosis.² Although several cases of giant hydronephrosis secondary to UPJO have been reported in the medical literature,^3-5 the volume of the hydronephrotic fluid in these cases rarely exceeded 10,000 cc. We believe our patient may be the most severe case of hydronephrosis secondary to bilateral UPJO, with 12,200 cc of fluid. His condition reached this late stage only because his right kidney retained adequate function.

Diagnosis of hydronephrosis is straightforward with an abdominal ultrasound and/or CT scan. Widespread use of abdominal ultrasound as a screening tool has significantly increased the diagnosis of asymptomatic hydronephrosis, and many cases are secondary to UPJO.⁶ The true incidence of UPJO is unknown, but it is more prevalent in males than in females, and in 10% to 40% of cases, the condition is bilateral.⁷ Congenital UPJO typically results from intrinsic pathology of the ureter. The diseased segment is often fibrotic, strictured, and aperistaltic.⁸

Treatment choice depends on whether renal function can be preserved

Treatment of hydronephrosis is straightforward; when there is little or no salvageable renal function (<10%), a simple nephrectomy is indicated, as was the case for our patient. Nephrectomy can be accomplished by either an open or laparoscopic approach.

When there is salvageable renal function, treatment options include pyeloplasty and pyelotomy. Traditionally, open dismembered pyeloplasty has been the gold standard. However, with advances in endoscopic and laparoscopic techniques, there has been a shift toward minimally invasive procedures. Laparoscopic pyeloplasty—with or without robotic assistance—and endoscopic pyelotomy—with either a percutaneous or retrograde approach—are now typically performed. Ureteral stenting should only be used as a temporary measure.

Our patient. Four weeks after the nephrectomy, our patient underwent a right side pyeloplasty, which was successful. He had an uneventful recovery from both procedures. His renal function stabilized and other than routine follow-up, he required no additional treatment.

THE TAKEAWAY

Most cases of hydronephrosis in young people are due to congenital abnormalities, and UPJO is the leading cause. However, the condition can be asymptomatic and may not present until later in life. Whenever a patient presents with an asymptomatic abdominal mass, hydronephrosis should be part of the differential diagnosis. Treatment options include nephrectomy when there is no salvageable kidney function or pyeloplasty and pyelotomy when some kidney function can be preserved.

Clinical question: Can novel configured rapid response teams (RRTs) improve non-ICU cardiopulmonary arrest (CPA) and overall hospital mortality rate?

Background: RRTs are primarily executed in hospital settings to avert non-ICU CPA through early detection and intervention. Prevailing evidence has not shown consistent clear benefit of RRTs in this regard.

Study design: A parallel-controlled, before-after design.

Setting: Two urban university hospitals with approximately 500 medical/surgical beds.

Synopsis: Researchers compared annual non-ICU CPA rates from two university hospitals with newly configured RRTs (implemented in November 2007) from July 2005 through June 2011 and found a decline in the incidence of non-ICU CPA to 1.1 from 2.7 per 1000 discharges (P<0.0001) while comparing pre- (2005/2006 to 2006/2007) to post- RRT implementation (2007-2011), respectively. Post-implementation, the overall hospital mortality dropped to 1.74% from 2.12% (P<0.001). With year-over-year, the RRT activation was found to be inversely related to Code Blue activations (r=-0.68, P<0.001), while the case mix index coefficients were still high.

The study lacks internal validation and may carry bias by including just one pre-implementation year (2006) data. It demonstrates that the rounding of unit manager (charge nurse) on “at risk” patients might avert decompensation; however, there was no determination of their decision-making process, with regard to RRT activation. No comparison was done with other RRT configurations.

Bottom line: Novel configured RRTs may improve non-ICU CPA and overall hospital mortality rate.

Citation: Davis DP, Aguilar SA, Graham PG, et al. A novel configuration of a traditional rapid response team decreases non-intensive care unit arrests and overall hospital mortality. J Hosp Med. 2015;10(6):352-357.

Clinical question: Can novel configured rapid response teams (RRTs) improve non-ICU cardiopulmonary arrest (CPA) and overall hospital mortality rate?

Background: RRTs are primarily executed in hospital settings to avert non-ICU CPA through early detection and intervention. Prevailing evidence has not shown consistent clear benefit of RRTs in this regard.

Study design: A parallel-controlled, before-after design.

Setting: Two urban university hospitals with approximately 500 medical/surgical beds.

Synopsis: Researchers compared annual non-ICU CPA rates from two university hospitals with newly configured RRTs (implemented in November 2007) from July 2005 through June 2011 and found a decline in the incidence of non-ICU CPA to 1.1 from 2.7 per 1000 discharges (P<0.0001) while comparing pre- (2005/2006 to 2006/2007) to post- RRT implementation (2007-2011), respectively. Post-implementation, the overall hospital mortality dropped to 1.74% from 2.12% (P<0.001). With year-over-year, the RRT activation was found to be inversely related to Code Blue activations (r=-0.68, P<0.001), while the case mix index coefficients were still high.

The study lacks internal validation and may carry bias by including just one pre-implementation year (2006) data. It demonstrates that the rounding of unit manager (charge nurse) on “at risk” patients might avert decompensation; however, there was no determination of their decision-making process, with regard to RRT activation. No comparison was done with other RRT configurations.

Bottom line: Novel configured RRTs may improve non-ICU CPA and overall hospital mortality rate.

Citation: Davis DP, Aguilar SA, Graham PG, et al. A novel configuration of a traditional rapid response team decreases non-intensive care unit arrests and overall hospital mortality. J Hosp Med. 2015;10(6):352-357.

Clinical question: Can novel configured rapid response teams (RRTs) improve non-ICU cardiopulmonary arrest (CPA) and overall hospital mortality rate?

Background: RRTs are primarily executed in hospital settings to avert non-ICU CPA through early detection and intervention. Prevailing evidence has not shown consistent clear benefit of RRTs in this regard.

Study design: A parallel-controlled, before-after design.

Setting: Two urban university hospitals with approximately 500 medical/surgical beds.

Synopsis: Researchers compared annual non-ICU CPA rates from two university hospitals with newly configured RRTs (implemented in November 2007) from July 2005 through June 2011 and found a decline in the incidence of non-ICU CPA to 1.1 from 2.7 per 1000 discharges (P<0.0001) while comparing pre- (2005/2006 to 2006/2007) to post- RRT implementation (2007-2011), respectively. Post-implementation, the overall hospital mortality dropped to 1.74% from 2.12% (P<0.001). With year-over-year, the RRT activation was found to be inversely related to Code Blue activations (r=-0.68, P<0.001), while the case mix index coefficients were still high.

The study lacks internal validation and may carry bias by including just one pre-implementation year (2006) data. It demonstrates that the rounding of unit manager (charge nurse) on “at risk” patients might avert decompensation; however, there was no determination of their decision-making process, with regard to RRT activation. No comparison was done with other RRT configurations.

Bottom line: Novel configured RRTs may improve non-ICU CPA and overall hospital mortality rate.

Citation: Davis DP, Aguilar SA, Graham PG, et al. A novel configuration of a traditional rapid response team decreases non-intensive care unit arrests and overall hospital mortality. J Hosp Med. 2015;10(6):352-357.

Medication nonadherence is a major—and remediable—contributor to poor outcomes, leading to approximately 125,000 preventable deaths,¹ worsening of acute and chronic conditions, and billions of dollars in avoidable costs related to increased hospitalizations and emergency visits each year.^2,3 Nonadherence rates are 20% to 30% among patients being treated for cancer and acute illness³ and 50% to 60% for chronic conditions, with an average of 50% of all patients taking their medication incorrectly—or not at all.^2,4,5

What’s more, nonadherence disrupts the physician-patient relationship⁶—a serious problem, given that feeling understood is often the most critical component of recovery.^7-9

With that in mind, the words used to describe the problem have changed. Compliance and noncompliance, the older labels, were based on the assumptions that patients are passive recipients of medical advice that they should follow without question and that they are to blame for not doing so. Adherence and nonadherence, on the other hand, emphasize mutual agreement and the patient’s freedom to follow the doctor’s recommendations or not, without blame if he or she decides not to do so.¹⁰

Many systemic approaches have been tried to maximize adherence, including disease management (eg, Web-based assessment tools, clinical guidelines, and call center-based triage), smart phone apps¹¹ (for reminders and monitoring), and paying for or subsidizing the cost of drugs for those who can’t afford them. All have met with limited success.¹² Based on a thorough review of the literature, we suggest a different approach.

Evidence-based efforts by clinicians are the key to effective prescribing and maximal adherence. In the text and table that follow, we summarize physician and patient factors that influence adherence and present optimal prescribing guidelines.

Listen carefully, then respond

Whether patients are seeing a primary care physician or a specialist, they want their doctors to spend more time with them and to give them more comprehensive information about their condition.^13-15 The interaction should begin with the physician listening carefully to the patient before responding, but all too often this is not the case.

Family physicians have been found to interrupt patients 23 seconds after asking a question.¹⁶ To improve communication, listen quietly until the patient finishes presenting his or her complaints and agenda for the visit. Then ask, “Is there anything else that’s important for me to know?”¹⁷

Be more forthcoming

It is equally important for physicians to respond fully, but this is often not the case. A study involving internists found that in patient encounters lasting 20 minutes, physicians devoted little more than one minute, on average, to explaining the patient’s medical condition. The research showed that many physicians greatly overestimated the time they spent doing so.¹³

Studies have also shown that clinicians tell patients the name of the drug they’re prescribing 74% of the time and state its purpose 87% of the time, but discuss potential adverse effects and duration of treatment a mere 34% of the time. More than 4 in 10 patients are not told the frequency or timing of doses or the number of tablets to take.¹⁸

To improve communication, take the following steps when it’s your turn to talk:

Avoid medical jargon. Technical language (eg, edema) and medical shorthand (eg, history) is a significant barrier to patient understanding. In one study of more than 800 pediatrician visits, such speech was found to be detrimental more than half of the time. Although many mothers were confused by the terms, they rarely asked for clarification.¹⁹

Listen quietly until patients finish presenting their complaints and reason for the visit, then ask whether there is anything else that's important for you to know.

It has been suggested that doctors and patients have engaged in a “communication conspiracy.”²⁰ In one study, even after obstetricians and gynecologists had identified terms that they knew their patients did not understand, they continued to use them, and in only 15% of visits where unfamiliar terms were used did the patients admit that they did not understand them.²¹ Part of the problem may be that patients believe they must be seen as undemanding and compliant if they are to receive optimal attention from their physicians.²²

Compounding the problem is the fact that clinicians’ use of highly technical language doubles when they are pressured for time,²⁰ suggesting that this behavior could become more widespread as the demand for greater efficiency on the part of physicians increases.

Simplify the treatment regimen. It also helps to keep treatment regimens as straightforward as possible. Prescribing multiple medications simultaneously or giving patients a more complicated regimen decreases adherence. In one study, adherence rates of 84% were achieved when the regimen called for once-a-day dosing, but dropped to 59% when patients were instructed to take their medication 3 times a day.²³

Ask the patient to summarize. Using simple terms and clear, succinct explanations promotes understanding, but asking the patient to summarize what you’ve just said is an ideal way to find out just how much he or she grasped. “What will you tell your family about your diagnosis and treatment?” you might ask, or “Tell me what you plan to do to ensure that you follow the prescribed regimen.”

This is particularly important when patients are not native English speakers or when the news is bad. Patients find it particularly tough to understand difficult messages, such as a poor prognosis,²⁴ and are often unaware of their poor comprehension. This was underscored by a study of emergency department (ED) patients, in which 78% demonstrated deficient comprehension in at least one domain (eg, post-ED care, diagnosis, cause) but only 20% recognized their lack of understanding.²⁵

Asking patients if they have any other questions is a crucial step in ensuring complete understanding.^21,26

Take steps to maximize patient recall

Even when patients understand what they’ve heard, research suggests they may not retain it. Overall, 40% to 80% of medical information is forgotten immediately, and almost half of what is retained is incorrect.27,28 This is a serious problem, as understanding and accurate recall increase patient satisfaction and the likelihood of adherence to treatment (FIGURE W1).28,29

There are 3 basic explanations for poor recall: factors related to the clinician, such as the use of difficult medical terminology; the mode of communication (eg, spoken vs written); and factors related to the patient, such as a low level of education or learning disability.^29-32

Being as specific as possible and spending more time explaining the diagnosis and treatment has been shown to enhance patient recall. In an experiment in which patients read advice on how to develop self-control over their eating, the use of simple language and specific instructions, rather than general rules, increased recall.³³ Providing generic information by whatever means does little to improve recall and might even inhibit it.

Linking advice to the patient’s chief complaint, thereby creating a “teachable moment,” is also helpful.³⁴ For example, you might tell a patient with a kidney infection that “Your backache is also because of the kidney infection. Both the backache and the burning during urination should be better about 3 days after you start these pills.”

Watch your affect. How relaxed or worried you appear also influences patient recall. In a recent study, 40 women at risk for breast cancer viewed videotapes of an oncologist presenting mammogram results. Compared to women whose results were conveyed by a physician who appeared relaxed, those who had the same findings presented by a physician who seemed worried perceived their clinical situation to be more severe, developed higher anxiety, and recalled significantly less of what they were told.³⁵

Use multiple means of communication. In a comparison study, patients who received verbal lists of actions for managing fever and sore mouth accompanied by pictographs—images that represented the information presented—had a correct recall rate of 85%; those who received the verbal information alone had a recall rate of only 14%.^36,37

Clinicians tell patients the name of the drug they're prescribing 74% of the time and its purpose 87% of the time, but discuss potential adverse effects and duration of treatment a mere 34% of the time.

A review of recall in cancer patients also found that tailoring communication to the individual—providing an audiotape of the consultation, for instance, or having the patient bring a list of questions and addressing them one by one—is most effective.³⁶ Another study assessed the retention of pediatric patients and their parents when they received either a verbal report alone or a verbal report plus written information or visuals. The researchers concluded that children and their parents should receive verbal reports only when such reports are supplemented with written information or visuals.³⁷

The large body of research on learning and memory has proven useful in designing educational materials for those with poor reading skills. When images were used to convey meaning to 21 adults in a job training program—all with less than fifth grade reading skills—they had on average 85% correct recall immediately after the training and 71% recall 4 weeks later. Although the impact on symptom management and patient quality of life has yet to be studied, these findings suggest that pictures can help people with low literacy recall and retain complex information.³⁸

Overall, while written or recorded instructions appear to improve recall in most situations,³⁹ images have been shown to have the greatest impact.^36,37,40

Is the patient ready to adhere to treatment?

No matter how well or by what means you communicate, some patients are not ready for change. Patients in the “precontemplation” stage of change—who may not even recognize the need for change, let alone consider it—can benefit from supportive education and motivational interviewing, while those in the “contemplation” stage need support and convincing to reach the “preparation” stage. It is only in the “action” stage, however, that a patient is ready to collaborate with his or her physician in agreeing on and adhering to treatment.⁴⁰

Comorbid depression is a common condition, particularly in those with chronic illness, and one of the strongest predictors of nonadherence.^1,41 Thus, depression screening for all patients who are chronically or severely ill or nonadherent is strongly recommended, followed by treatment when appropriate.⁴¹

“Informed collaboration” is critical

Comorbid depression is particularly common among those with chronic illnesses, and one of the strongest predictors of nonadherence.

Research shows that if both physician and patient agree on the individual’s medical problem, it will be improved or resolved at follow-up in about half of all cases. In contrast, when the physician alone sees the patient’s condition as a problem, just over a quarter of cases improve, regardless of the severity.⁴² Compounding this difficulty is the finding that patients fail to report up to two-thirds of their most important health problems.⁴³ When physicians identify them, discord and denial typically result.⁴²

Thus, concordance (we prefer the term “informed collaboration”)—an overt agreement reached after a discussion in which the physician shares expert knowledge, then listens to and respects the feelings and beliefs of the patient with regard to how, when, or whether he or she will take the recommended treatment⁴⁴—is crucial.^42,43,45,46

One way to reach informed collaboration is to give patients problem lists or letters summarizing their health problems in simple and specific terms after each visit, in hopes that the written communication will encourage discussion and a physician-patient partnership in addressing them.⁴³ In a recent study of 967 psychiatric outpatients, adherence was significantly higher among those who cited concordance between their preferences and their treatment and felt that they had participated in decision making.⁴⁷

Problems can arise at any time

Even after a patient starts out fully adhering to his medication regimen, several issues can derail treatment. Inability to afford the medication is one potential problem.⁴⁸ Adverse effects are another major reason for discontinuation. Sexual dysfunction, caused by a number of drugs, is embarrassing to many patients and frequently goes unaddressed.⁴⁹ Thus, a patient may stop taking the medication without saying why—seemingly for no apparent reason. The best approach is to ask specifically why it was discontinued, including direct questions about sexual adverse effects.

Prescribing recommendations

Sexual dysfunction, caused by a number of drugs, is embarrassing to many patients and frequently goes unaddressed.

We believe that the outcome of treatment is being determined from the moment a patient steps into your office. Thus, we’ve compiled an evidence-based checklist (TABLE)^{24,33,40,41,47,49,50} with broad areas for discussion that constitute the art and science of prescribing. These fall into 3 main areas: 1) what to say before you write a prescription; 2) how to get patient buy-in (informed collaboration, rather than informed consent) when you’re ready to write the prescription; and 3) what to address to boost the likelihood of continued adherence at follow-up visits.

It is clear that allowing adequate patient participation and arriving at concordance and overt agreement lead to better clinical outcomes.⁵¹ The sequential steps we recommend may take a few extra minutes up front, but without them, nonadherence is highly likely. While physicians are supportive of shared decision making in theory, they are often less confident that this is achieved in practice.^52,53

It may help to keep in mind that every step need not be carried out by the physician. Using other members of the health care team, such as a nurse, medical assistant, or health coach, to provide patient education and support and take the patient through a number of the steps that are included in a physician visit has become increasingly necessary—and is easily accommodated in this case.

As the physician, you bear the final responsibility to ensure that the critical elements—particularly the overt agreement—are addressed. Ultimately supporting your patient's decision and reinforcing it will ensure continued adherence.

CORRESPONDENCE
Swati Shivale, MBBS, Department of Psychiatry, SUNY Upstate Medical University, 750 Adams Street, Syracuse, NY 13210; [email protected]

Medication nonadherence is a major—and remediable—contributor to poor outcomes, leading to approximately 125,000 preventable deaths,¹ worsening of acute and chronic conditions, and billions of dollars in avoidable costs related to increased hospitalizations and emergency visits each year.^2,3 Nonadherence rates are 20% to 30% among patients being treated for cancer and acute illness³ and 50% to 60% for chronic conditions, with an average of 50% of all patients taking their medication incorrectly—or not at all.^2,4,5

What’s more, nonadherence disrupts the physician-patient relationship⁶—a serious problem, given that feeling understood is often the most critical component of recovery.^7-9

With that in mind, the words used to describe the problem have changed. Compliance and noncompliance, the older labels, were based on the assumptions that patients are passive recipients of medical advice that they should follow without question and that they are to blame for not doing so. Adherence and nonadherence, on the other hand, emphasize mutual agreement and the patient’s freedom to follow the doctor’s recommendations or not, without blame if he or she decides not to do so.¹⁰

Many systemic approaches have been tried to maximize adherence, including disease management (eg, Web-based assessment tools, clinical guidelines, and call center-based triage), smart phone apps¹¹ (for reminders and monitoring), and paying for or subsidizing the cost of drugs for those who can’t afford them. All have met with limited success.¹² Based on a thorough review of the literature, we suggest a different approach.

Evidence-based efforts by clinicians are the key to effective prescribing and maximal adherence. In the text and table that follow, we summarize physician and patient factors that influence adherence and present optimal prescribing guidelines.

Listen carefully, then respond

Whether patients are seeing a primary care physician or a specialist, they want their doctors to spend more time with them and to give them more comprehensive information about their condition.^13-15 The interaction should begin with the physician listening carefully to the patient before responding, but all too often this is not the case.

Family physicians have been found to interrupt patients 23 seconds after asking a question.¹⁶ To improve communication, listen quietly until the patient finishes presenting his or her complaints and agenda for the visit. Then ask, “Is there anything else that’s important for me to know?”¹⁷

Be more forthcoming

It is equally important for physicians to respond fully, but this is often not the case. A study involving internists found that in patient encounters lasting 20 minutes, physicians devoted little more than one minute, on average, to explaining the patient’s medical condition. The research showed that many physicians greatly overestimated the time they spent doing so.¹³

Studies have also shown that clinicians tell patients the name of the drug they’re prescribing 74% of the time and state its purpose 87% of the time, but discuss potential adverse effects and duration of treatment a mere 34% of the time. More than 4 in 10 patients are not told the frequency or timing of doses or the number of tablets to take.¹⁸

To improve communication, take the following steps when it’s your turn to talk:

Avoid medical jargon. Technical language (eg, edema) and medical shorthand (eg, history) is a significant barrier to patient understanding. In one study of more than 800 pediatrician visits, such speech was found to be detrimental more than half of the time. Although many mothers were confused by the terms, they rarely asked for clarification.¹⁹

Listen quietly until patients finish presenting their complaints and reason for the visit, then ask whether there is anything else that's important for you to know.

It has been suggested that doctors and patients have engaged in a “communication conspiracy.”²⁰ In one study, even after obstetricians and gynecologists had identified terms that they knew their patients did not understand, they continued to use them, and in only 15% of visits where unfamiliar terms were used did the patients admit that they did not understand them.²¹ Part of the problem may be that patients believe they must be seen as undemanding and compliant if they are to receive optimal attention from their physicians.²²

Compounding the problem is the fact that clinicians’ use of highly technical language doubles when they are pressured for time,²⁰ suggesting that this behavior could become more widespread as the demand for greater efficiency on the part of physicians increases.

Simplify the treatment regimen. It also helps to keep treatment regimens as straightforward as possible. Prescribing multiple medications simultaneously or giving patients a more complicated regimen decreases adherence. In one study, adherence rates of 84% were achieved when the regimen called for once-a-day dosing, but dropped to 59% when patients were instructed to take their medication 3 times a day.²³

Ask the patient to summarize. Using simple terms and clear, succinct explanations promotes understanding, but asking the patient to summarize what you’ve just said is an ideal way to find out just how much he or she grasped. “What will you tell your family about your diagnosis and treatment?” you might ask, or “Tell me what you plan to do to ensure that you follow the prescribed regimen.”

This is particularly important when patients are not native English speakers or when the news is bad. Patients find it particularly tough to understand difficult messages, such as a poor prognosis,²⁴ and are often unaware of their poor comprehension. This was underscored by a study of emergency department (ED) patients, in which 78% demonstrated deficient comprehension in at least one domain (eg, post-ED care, diagnosis, cause) but only 20% recognized their lack of understanding.²⁵

Asking patients if they have any other questions is a crucial step in ensuring complete understanding.^21,26

Take steps to maximize patient recall

Even when patients understand what they’ve heard, research suggests they may not retain it. Overall, 40% to 80% of medical information is forgotten immediately, and almost half of what is retained is incorrect.27,28 This is a serious problem, as understanding and accurate recall increase patient satisfaction and the likelihood of adherence to treatment (FIGURE W1).28,29

There are 3 basic explanations for poor recall: factors related to the clinician, such as the use of difficult medical terminology; the mode of communication (eg, spoken vs written); and factors related to the patient, such as a low level of education or learning disability.^29-32

Being as specific as possible and spending more time explaining the diagnosis and treatment has been shown to enhance patient recall. In an experiment in which patients read advice on how to develop self-control over their eating, the use of simple language and specific instructions, rather than general rules, increased recall.³³ Providing generic information by whatever means does little to improve recall and might even inhibit it.

Linking advice to the patient’s chief complaint, thereby creating a “teachable moment,” is also helpful.³⁴ For example, you might tell a patient with a kidney infection that “Your backache is also because of the kidney infection. Both the backache and the burning during urination should be better about 3 days after you start these pills.”

Watch your affect. How relaxed or worried you appear also influences patient recall. In a recent study, 40 women at risk for breast cancer viewed videotapes of an oncologist presenting mammogram results. Compared to women whose results were conveyed by a physician who appeared relaxed, those who had the same findings presented by a physician who seemed worried perceived their clinical situation to be more severe, developed higher anxiety, and recalled significantly less of what they were told.³⁵

Use multiple means of communication. In a comparison study, patients who received verbal lists of actions for managing fever and sore mouth accompanied by pictographs—images that represented the information presented—had a correct recall rate of 85%; those who received the verbal information alone had a recall rate of only 14%.^36,37

Clinicians tell patients the name of the drug they're prescribing 74% of the time and its purpose 87% of the time, but discuss potential adverse effects and duration of treatment a mere 34% of the time.

A review of recall in cancer patients also found that tailoring communication to the individual—providing an audiotape of the consultation, for instance, or having the patient bring a list of questions and addressing them one by one—is most effective.³⁶ Another study assessed the retention of pediatric patients and their parents when they received either a verbal report alone or a verbal report plus written information or visuals. The researchers concluded that children and their parents should receive verbal reports only when such reports are supplemented with written information or visuals.³⁷

The large body of research on learning and memory has proven useful in designing educational materials for those with poor reading skills. When images were used to convey meaning to 21 adults in a job training program—all with less than fifth grade reading skills—they had on average 85% correct recall immediately after the training and 71% recall 4 weeks later. Although the impact on symptom management and patient quality of life has yet to be studied, these findings suggest that pictures can help people with low literacy recall and retain complex information.³⁸

Overall, while written or recorded instructions appear to improve recall in most situations,³⁹ images have been shown to have the greatest impact.^36,37,40

Is the patient ready to adhere to treatment?

No matter how well or by what means you communicate, some patients are not ready for change. Patients in the “precontemplation” stage of change—who may not even recognize the need for change, let alone consider it—can benefit from supportive education and motivational interviewing, while those in the “contemplation” stage need support and convincing to reach the “preparation” stage. It is only in the “action” stage, however, that a patient is ready to collaborate with his or her physician in agreeing on and adhering to treatment.⁴⁰

Comorbid depression is a common condition, particularly in those with chronic illness, and one of the strongest predictors of nonadherence.^1,41 Thus, depression screening for all patients who are chronically or severely ill or nonadherent is strongly recommended, followed by treatment when appropriate.⁴¹

“Informed collaboration” is critical

Comorbid depression is particularly common among those with chronic illnesses, and one of the strongest predictors of nonadherence.

Research shows that if both physician and patient agree on the individual’s medical problem, it will be improved or resolved at follow-up in about half of all cases. In contrast, when the physician alone sees the patient’s condition as a problem, just over a quarter of cases improve, regardless of the severity.⁴² Compounding this difficulty is the finding that patients fail to report up to two-thirds of their most important health problems.⁴³ When physicians identify them, discord and denial typically result.⁴²

Thus, concordance (we prefer the term “informed collaboration”)—an overt agreement reached after a discussion in which the physician shares expert knowledge, then listens to and respects the feelings and beliefs of the patient with regard to how, when, or whether he or she will take the recommended treatment⁴⁴—is crucial.^42,43,45,46

One way to reach informed collaboration is to give patients problem lists or letters summarizing their health problems in simple and specific terms after each visit, in hopes that the written communication will encourage discussion and a physician-patient partnership in addressing them.⁴³ In a recent study of 967 psychiatric outpatients, adherence was significantly higher among those who cited concordance between their preferences and their treatment and felt that they had participated in decision making.⁴⁷

Problems can arise at any time

Even after a patient starts out fully adhering to his medication regimen, several issues can derail treatment. Inability to afford the medication is one potential problem.⁴⁸ Adverse effects are another major reason for discontinuation. Sexual dysfunction, caused by a number of drugs, is embarrassing to many patients and frequently goes unaddressed.⁴⁹ Thus, a patient may stop taking the medication without saying why—seemingly for no apparent reason. The best approach is to ask specifically why it was discontinued, including direct questions about sexual adverse effects.

Prescribing recommendations

Sexual dysfunction, caused by a number of drugs, is embarrassing to many patients and frequently goes unaddressed.

We believe that the outcome of treatment is being determined from the moment a patient steps into your office. Thus, we’ve compiled an evidence-based checklist (TABLE)^{24,33,40,41,47,49,50} with broad areas for discussion that constitute the art and science of prescribing. These fall into 3 main areas: 1) what to say before you write a prescription; 2) how to get patient buy-in (informed collaboration, rather than informed consent) when you’re ready to write the prescription; and 3) what to address to boost the likelihood of continued adherence at follow-up visits.

It is clear that allowing adequate patient participation and arriving at concordance and overt agreement lead to better clinical outcomes.⁵¹ The sequential steps we recommend may take a few extra minutes up front, but without them, nonadherence is highly likely. While physicians are supportive of shared decision making in theory, they are often less confident that this is achieved in practice.^52,53

It may help to keep in mind that every step need not be carried out by the physician. Using other members of the health care team, such as a nurse, medical assistant, or health coach, to provide patient education and support and take the patient through a number of the steps that are included in a physician visit has become increasingly necessary—and is easily accommodated in this case.

As the physician, you bear the final responsibility to ensure that the critical elements—particularly the overt agreement—are addressed. Ultimately supporting your patient's decision and reinforcing it will ensure continued adherence.

CORRESPONDENCE
Swati Shivale, MBBS, Department of Psychiatry, SUNY Upstate Medical University, 750 Adams Street, Syracuse, NY 13210; [email protected]

Medication nonadherence is a major—and remediable—contributor to poor outcomes, leading to approximately 125,000 preventable deaths,¹ worsening of acute and chronic conditions, and billions of dollars in avoidable costs related to increased hospitalizations and emergency visits each year.^2,3 Nonadherence rates are 20% to 30% among patients being treated for cancer and acute illness³ and 50% to 60% for chronic conditions, with an average of 50% of all patients taking their medication incorrectly—or not at all.^2,4,5

What’s more, nonadherence disrupts the physician-patient relationship⁶—a serious problem, given that feeling understood is often the most critical component of recovery.^7-9

With that in mind, the words used to describe the problem have changed. Compliance and noncompliance, the older labels, were based on the assumptions that patients are passive recipients of medical advice that they should follow without question and that they are to blame for not doing so. Adherence and nonadherence, on the other hand, emphasize mutual agreement and the patient’s freedom to follow the doctor’s recommendations or not, without blame if he or she decides not to do so.¹⁰

Many systemic approaches have been tried to maximize adherence, including disease management (eg, Web-based assessment tools, clinical guidelines, and call center-based triage), smart phone apps¹¹ (for reminders and monitoring), and paying for or subsidizing the cost of drugs for those who can’t afford them. All have met with limited success.¹² Based on a thorough review of the literature, we suggest a different approach.

Evidence-based efforts by clinicians are the key to effective prescribing and maximal adherence. In the text and table that follow, we summarize physician and patient factors that influence adherence and present optimal prescribing guidelines.

Listen carefully, then respond

Whether patients are seeing a primary care physician or a specialist, they want their doctors to spend more time with them and to give them more comprehensive information about their condition.^13-15 The interaction should begin with the physician listening carefully to the patient before responding, but all too often this is not the case.

Family physicians have been found to interrupt patients 23 seconds after asking a question.¹⁶ To improve communication, listen quietly until the patient finishes presenting his or her complaints and agenda for the visit. Then ask, “Is there anything else that’s important for me to know?”¹⁷

Be more forthcoming

It is equally important for physicians to respond fully, but this is often not the case. A study involving internists found that in patient encounters lasting 20 minutes, physicians devoted little more than one minute, on average, to explaining the patient’s medical condition. The research showed that many physicians greatly overestimated the time they spent doing so.¹³

Studies have also shown that clinicians tell patients the name of the drug they’re prescribing 74% of the time and state its purpose 87% of the time, but discuss potential adverse effects and duration of treatment a mere 34% of the time. More than 4 in 10 patients are not told the frequency or timing of doses or the number of tablets to take.¹⁸

To improve communication, take the following steps when it’s your turn to talk:

Avoid medical jargon. Technical language (eg, edema) and medical shorthand (eg, history) is a significant barrier to patient understanding. In one study of more than 800 pediatrician visits, such speech was found to be detrimental more than half of the time. Although many mothers were confused by the terms, they rarely asked for clarification.¹⁹

Listen quietly until patients finish presenting their complaints and reason for the visit, then ask whether there is anything else that's important for you to know.

It has been suggested that doctors and patients have engaged in a “communication conspiracy.”²⁰ In one study, even after obstetricians and gynecologists had identified terms that they knew their patients did not understand, they continued to use them, and in only 15% of visits where unfamiliar terms were used did the patients admit that they did not understand them.²¹ Part of the problem may be that patients believe they must be seen as undemanding and compliant if they are to receive optimal attention from their physicians.²²

Compounding the problem is the fact that clinicians’ use of highly technical language doubles when they are pressured for time,²⁰ suggesting that this behavior could become more widespread as the demand for greater efficiency on the part of physicians increases.

Simplify the treatment regimen. It also helps to keep treatment regimens as straightforward as possible. Prescribing multiple medications simultaneously or giving patients a more complicated regimen decreases adherence. In one study, adherence rates of 84% were achieved when the regimen called for once-a-day dosing, but dropped to 59% when patients were instructed to take their medication 3 times a day.²³

Ask the patient to summarize. Using simple terms and clear, succinct explanations promotes understanding, but asking the patient to summarize what you’ve just said is an ideal way to find out just how much he or she grasped. “What will you tell your family about your diagnosis and treatment?” you might ask, or “Tell me what you plan to do to ensure that you follow the prescribed regimen.”

This is particularly important when patients are not native English speakers or when the news is bad. Patients find it particularly tough to understand difficult messages, such as a poor prognosis,²⁴ and are often unaware of their poor comprehension. This was underscored by a study of emergency department (ED) patients, in which 78% demonstrated deficient comprehension in at least one domain (eg, post-ED care, diagnosis, cause) but only 20% recognized their lack of understanding.²⁵

Asking patients if they have any other questions is a crucial step in ensuring complete understanding.^21,26

Take steps to maximize patient recall

Even when patients understand what they’ve heard, research suggests they may not retain it. Overall, 40% to 80% of medical information is forgotten immediately, and almost half of what is retained is incorrect.27,28 This is a serious problem, as understanding and accurate recall increase patient satisfaction and the likelihood of adherence to treatment (FIGURE W1).28,29

There are 3 basic explanations for poor recall: factors related to the clinician, such as the use of difficult medical terminology; the mode of communication (eg, spoken vs written); and factors related to the patient, such as a low level of education or learning disability.^29-32

Being as specific as possible and spending more time explaining the diagnosis and treatment has been shown to enhance patient recall. In an experiment in which patients read advice on how to develop self-control over their eating, the use of simple language and specific instructions, rather than general rules, increased recall.³³ Providing generic information by whatever means does little to improve recall and might even inhibit it.

Linking advice to the patient’s chief complaint, thereby creating a “teachable moment,” is also helpful.³⁴ For example, you might tell a patient with a kidney infection that “Your backache is also because of the kidney infection. Both the backache and the burning during urination should be better about 3 days after you start these pills.”

Watch your affect. How relaxed or worried you appear also influences patient recall. In a recent study, 40 women at risk for breast cancer viewed videotapes of an oncologist presenting mammogram results. Compared to women whose results were conveyed by a physician who appeared relaxed, those who had the same findings presented by a physician who seemed worried perceived their clinical situation to be more severe, developed higher anxiety, and recalled significantly less of what they were told.³⁵

Use multiple means of communication. In a comparison study, patients who received verbal lists of actions for managing fever and sore mouth accompanied by pictographs—images that represented the information presented—had a correct recall rate of 85%; those who received the verbal information alone had a recall rate of only 14%.^36,37

Clinicians tell patients the name of the drug they're prescribing 74% of the time and its purpose 87% of the time, but discuss potential adverse effects and duration of treatment a mere 34% of the time.

A review of recall in cancer patients also found that tailoring communication to the individual—providing an audiotape of the consultation, for instance, or having the patient bring a list of questions and addressing them one by one—is most effective.³⁶ Another study assessed the retention of pediatric patients and their parents when they received either a verbal report alone or a verbal report plus written information or visuals. The researchers concluded that children and their parents should receive verbal reports only when such reports are supplemented with written information or visuals.³⁷

The large body of research on learning and memory has proven useful in designing educational materials for those with poor reading skills. When images were used to convey meaning to 21 adults in a job training program—all with less than fifth grade reading skills—they had on average 85% correct recall immediately after the training and 71% recall 4 weeks later. Although the impact on symptom management and patient quality of life has yet to be studied, these findings suggest that pictures can help people with low literacy recall and retain complex information.³⁸

Overall, while written or recorded instructions appear to improve recall in most situations,³⁹ images have been shown to have the greatest impact.^36,37,40

Is the patient ready to adhere to treatment?

No matter how well or by what means you communicate, some patients are not ready for change. Patients in the “precontemplation” stage of change—who may not even recognize the need for change, let alone consider it—can benefit from supportive education and motivational interviewing, while those in the “contemplation” stage need support and convincing to reach the “preparation” stage. It is only in the “action” stage, however, that a patient is ready to collaborate with his or her physician in agreeing on and adhering to treatment.⁴⁰

Comorbid depression is a common condition, particularly in those with chronic illness, and one of the strongest predictors of nonadherence.^1,41 Thus, depression screening for all patients who are chronically or severely ill or nonadherent is strongly recommended, followed by treatment when appropriate.⁴¹

“Informed collaboration” is critical

Comorbid depression is particularly common among those with chronic illnesses, and one of the strongest predictors of nonadherence.

Research shows that if both physician and patient agree on the individual’s medical problem, it will be improved or resolved at follow-up in about half of all cases. In contrast, when the physician alone sees the patient’s condition as a problem, just over a quarter of cases improve, regardless of the severity.⁴² Compounding this difficulty is the finding that patients fail to report up to two-thirds of their most important health problems.⁴³ When physicians identify them, discord and denial typically result.⁴²

Thus, concordance (we prefer the term “informed collaboration”)—an overt agreement reached after a discussion in which the physician shares expert knowledge, then listens to and respects the feelings and beliefs of the patient with regard to how, when, or whether he or she will take the recommended treatment⁴⁴—is crucial.^42,43,45,46

One way to reach informed collaboration is to give patients problem lists or letters summarizing their health problems in simple and specific terms after each visit, in hopes that the written communication will encourage discussion and a physician-patient partnership in addressing them.⁴³ In a recent study of 967 psychiatric outpatients, adherence was significantly higher among those who cited concordance between their preferences and their treatment and felt that they had participated in decision making.⁴⁷

Problems can arise at any time

Even after a patient starts out fully adhering to his medication regimen, several issues can derail treatment. Inability to afford the medication is one potential problem.⁴⁸ Adverse effects are another major reason for discontinuation. Sexual dysfunction, caused by a number of drugs, is embarrassing to many patients and frequently goes unaddressed.⁴⁹ Thus, a patient may stop taking the medication without saying why—seemingly for no apparent reason. The best approach is to ask specifically why it was discontinued, including direct questions about sexual adverse effects.

Prescribing recommendations

Sexual dysfunction, caused by a number of drugs, is embarrassing to many patients and frequently goes unaddressed.

We believe that the outcome of treatment is being determined from the moment a patient steps into your office. Thus, we’ve compiled an evidence-based checklist (TABLE)^{24,33,40,41,47,49,50} with broad areas for discussion that constitute the art and science of prescribing. These fall into 3 main areas: 1) what to say before you write a prescription; 2) how to get patient buy-in (informed collaboration, rather than informed consent) when you’re ready to write the prescription; and 3) what to address to boost the likelihood of continued adherence at follow-up visits.

It is clear that allowing adequate patient participation and arriving at concordance and overt agreement lead to better clinical outcomes.⁵¹ The sequential steps we recommend may take a few extra minutes up front, but without them, nonadherence is highly likely. While physicians are supportive of shared decision making in theory, they are often less confident that this is achieved in practice.^52,53

It may help to keep in mind that every step need not be carried out by the physician. Using other members of the health care team, such as a nurse, medical assistant, or health coach, to provide patient education and support and take the patient through a number of the steps that are included in a physician visit has become increasingly necessary—and is easily accommodated in this case.

As the physician, you bear the final responsibility to ensure that the critical elements—particularly the overt agreement—are addressed. Ultimately supporting your patient's decision and reinforcing it will ensure continued adherence.

CORRESPONDENCE
Swati Shivale, MBBS, Department of Psychiatry, SUNY Upstate Medical University, 750 Adams Street, Syracuse, NY 13210; [email protected]

In this month's issue, our cover stories relay 11 things gastroenterologists think hospitalists should know about patients with gastroenterology disorders, and explore the intersection of post-acute care and hospital medicine. Elsewhere in this issue, we include tips for Choosing Wisely in HM, look at the hospitalist job search, and cover the latest in HM clinical literature.

[audio mp3="http://www.the-hospitalist.org/wp-content/uploads/2015/07/2015-July-Hospitalist-Highlights1.mp3"][/audio]

In this month's issue, our cover stories relay 11 things gastroenterologists think hospitalists should know about patients with gastroenterology disorders, and explore the intersection of post-acute care and hospital medicine. Elsewhere in this issue, we include tips for Choosing Wisely in HM, look at the hospitalist job search, and cover the latest in HM clinical literature.

[audio mp3="http://www.the-hospitalist.org/wp-content/uploads/2015/07/2015-July-Hospitalist-Highlights1.mp3"][/audio]

In this month's issue, our cover stories relay 11 things gastroenterologists think hospitalists should know about patients with gastroenterology disorders, and explore the intersection of post-acute care and hospital medicine. Elsewhere in this issue, we include tips for Choosing Wisely in HM, look at the hospitalist job search, and cover the latest in HM clinical literature.

[audio mp3="http://www.the-hospitalist.org/wp-content/uploads/2015/07/2015-July-Hospitalist-Highlights1.mp3"][/audio]

Q) I have been treating a 60-year-old man with a long history of microscopic hematuria and waxing/waning proteinuria. What could be the cause of his hematuria?

Hematuria is a consequence of erythrocytes, or red blood cells (RBCs), in the urine. This can cause a visible change in color, considered gross or macroscopic hematuria; or the blood may only be visible under microscopy or by urine dipstick (referred to as microscopic hematuria).

Both findings are followed up with urinalysis to quantify erythrocytes, protein, and presence of casts and to review RBC morphology. This information will assist in determining if the hematuria is glomerular or nonglomerular in origin.¹

The examination and treatment plan for nonglomerular hematuria will focus on urinary tract diseases. If the patient is found to have glomerular hematuria, the focus will be on diseases of the kidney. A thorough history and physical should be performed in addition to urinalysis.

Glomerular disease is suggested in those with micro- or macroscopic proteinuria, proteinuria > 1 g/24h, or an absence of casts. Our index patient has microscopic hematuria and “waxing/waning” (unquantified) proteinuria, suggesting glomerular origin.

There are a number of renal causes for glomerular bleeding, including primary glomerulonephritis, multisystem autoimmune disease, and hereditary or infective glomerulonephritis.² Renal biopsy is recommended for patients who have hypertension, proteinuria, and hematuria, to determine the cause and thus determine the appropriate treatment.

Amy L. Hazel, RN, MSN, CNP
Kidney & Hypertension Consultants, Canton, Ohio

REFERENCES
1. Greenberg A. Primer on Kidney Diseases. 5th ed. Philadelphia, PA: Elsevier Saunders; 2005.
2. Barratt J, Feehally J. IgA nephropathy [disease of the month]. J Am Soc Nephrol. 2005;16(7): 2088-2097.

Q) I have been treating a 60-year-old man with a long history of microscopic hematuria and waxing/waning proteinuria. What could be the cause of his hematuria?

Hematuria is a consequence of erythrocytes, or red blood cells (RBCs), in the urine. This can cause a visible change in color, considered gross or macroscopic hematuria; or the blood may only be visible under microscopy or by urine dipstick (referred to as microscopic hematuria).

Both findings are followed up with urinalysis to quantify erythrocytes, protein, and presence of casts and to review RBC morphology. This information will assist in determining if the hematuria is glomerular or nonglomerular in origin.¹

The examination and treatment plan for nonglomerular hematuria will focus on urinary tract diseases. If the patient is found to have glomerular hematuria, the focus will be on diseases of the kidney. A thorough history and physical should be performed in addition to urinalysis.

Glomerular disease is suggested in those with micro- or macroscopic proteinuria, proteinuria > 1 g/24h, or an absence of casts. Our index patient has microscopic hematuria and “waxing/waning” (unquantified) proteinuria, suggesting glomerular origin.

There are a number of renal causes for glomerular bleeding, including primary glomerulonephritis, multisystem autoimmune disease, and hereditary or infective glomerulonephritis.² Renal biopsy is recommended for patients who have hypertension, proteinuria, and hematuria, to determine the cause and thus determine the appropriate treatment.

Amy L. Hazel, RN, MSN, CNP
Kidney & Hypertension Consultants, Canton, Ohio

REFERENCES
1. Greenberg A. Primer on Kidney Diseases. 5th ed. Philadelphia, PA: Elsevier Saunders; 2005.
2. Barratt J, Feehally J. IgA nephropathy [disease of the month]. J Am Soc Nephrol. 2005;16(7): 2088-2097.

Q) I have been treating a 60-year-old man with a long history of microscopic hematuria and waxing/waning proteinuria. What could be the cause of his hematuria?

Hematuria is a consequence of erythrocytes, or red blood cells (RBCs), in the urine. This can cause a visible change in color, considered gross or macroscopic hematuria; or the blood may only be visible under microscopy or by urine dipstick (referred to as microscopic hematuria).

Both findings are followed up with urinalysis to quantify erythrocytes, protein, and presence of casts and to review RBC morphology. This information will assist in determining if the hematuria is glomerular or nonglomerular in origin.¹

The examination and treatment plan for nonglomerular hematuria will focus on urinary tract diseases. If the patient is found to have glomerular hematuria, the focus will be on diseases of the kidney. A thorough history and physical should be performed in addition to urinalysis.

Glomerular disease is suggested in those with micro- or macroscopic proteinuria, proteinuria > 1 g/24h, or an absence of casts. Our index patient has microscopic hematuria and “waxing/waning” (unquantified) proteinuria, suggesting glomerular origin.

There are a number of renal causes for glomerular bleeding, including primary glomerulonephritis, multisystem autoimmune disease, and hereditary or infective glomerulonephritis.² Renal biopsy is recommended for patients who have hypertension, proteinuria, and hematuria, to determine the cause and thus determine the appropriate treatment.

Amy L. Hazel, RN, MSN, CNP
Kidney & Hypertension Consultants, Canton, Ohio

REFERENCES
1. Greenberg A. Primer on Kidney Diseases. 5th ed. Philadelphia, PA: Elsevier Saunders; 2005.
2. Barratt J, Feehally J. IgA nephropathy [disease of the month]. J Am Soc Nephrol. 2005;16(7): 2088-2097.

ANSWER
The radiograph shows that the distal femur is medially dislocated relative to the tibial plateau. In addition, the patella is laterally dislocated. No obvious fractures are evident. 

Such injuries are typically associated with significant ligament injuries, especially of the medial collateral ligament (MCL), lateral collateral ligament (LCL), and anterior cruciate ligament (ACL). Orthopedics was consulted for reduction of the dislocation, as well as further workup (including MRI of the knee).

ANSWER
The radiograph shows that the distal femur is medially dislocated relative to the tibial plateau. In addition, the patella is laterally dislocated. No obvious fractures are evident. 

Such injuries are typically associated with significant ligament injuries, especially of the medial collateral ligament (MCL), lateral collateral ligament (LCL), and anterior cruciate ligament (ACL). Orthopedics was consulted for reduction of the dislocation, as well as further workup (including MRI of the knee).

ANSWER
The radiograph shows that the distal femur is medially dislocated relative to the tibial plateau. In addition, the patella is laterally dislocated. No obvious fractures are evident. 

Such injuries are typically associated with significant ligament injuries, especially of the medial collateral ligament (MCL), lateral collateral ligament (LCL), and anterior cruciate ligament (ACL). Orthopedics was consulted for reduction of the dislocation, as well as further workup (including MRI of the knee).