There are many controversial topics relating to renal disease in hospitalized patients. The aim of this review is to shed light on some important and often debated issues. We will first discuss topics related to electrolytes disorder commonly seen in hospitalized patients (hyponatremia, hyperkalemia, metabolic acidosis) then the use of diuretics in patients with allergy to sulfa containing antibiotics.

Hypothyroidism and Hyponatremia

Hyponatremia is common in hospitalized patients and is associated with worse outcomes.1 It can be seen with a variety of conditions ranging from congestive heart failure to volume depletion. Careful history and physical examination are paramount and the initial work‐up usually includes serum and urine osmolality and urine sodium concentration.

For euvolemic hyponatremia, the differential diagnosis includes the syndrome of inappropriate adenine dinucleotide (ADH) secretion (SIADH), hypoadrenalism, and beer potomania. Additionally, many authorities also include hypothyroidism.

Although the simultaneous finding of hypothyroidism and hyponatremia can occur in patients as both diseases are widely prevalent in the general population, causation has yet to be convincingly demonstrated.

ADH is released in response to effective volume depletion; consequently when hypothyroidism is encountered in the setting of complete pituitary failure there is often hyponatremia.2, 3 Alternatively, with myxedema, the ability of the kidney to handle a water load and concentrate urine can be impaired.4

However, the observation that thyroid hormone administration did not raise sodium values in newborns with congenital hypothyroidism or in adults supports the absence of causal effect.5, 6And in addition, large studies done in the hospital and outpatient setting showed no differences between the serum sodium values of hypothyroid patients and that of controls.7, 8 In the study of outpatients, among those with hypothyroidism, for every increase of 10 mU/L of thyroid‐stimulating hormone (TSH), there was a drop of only 0.14 mmol/L of Na concentration.8 Thus, the elevation of TSH required for a clinically meaningful drop in sodium to occur was considerable.

Hence in patients with hyponatremia, the hospitalist should look for etiologies other than hypothyroidism and should only consider thyroid hypofunction as a culprit in cases of myxedema, or panhypopituitarism.

Sodium Bicarbonate for Hyperkalemia

Hyperkalemia is one of the most feared electrolyte disorders encountered in hospitalized patients and can lead to dire outcomes.9, 10

Potassium (K+) homeostasis is maintained in the body by 2 complimentary systems: a short‐term system that regulates K+ variation by modifying translocation across the cellular membrane and a long‐term system that adjusts overall K+ balance. The translocation system is regulated primarily by insulin and ‐2 stimulation. Overall K+ balance is mainly controlled by the kidney (90‐95%) although the gastrointestinal (GI) tract can have a more preponderant role in anephric patients.

Hyperkalemia can ensue by either a dysregulation of the translocation system (as in diabetic Ketoacidosis secondary to insulin deficiency) or impairment of K+ elimination.

Acid‐base status was previously thought to have a prominent influence on K+ concentration, based on studies that demonstrated that. However, studies looking at metabolic acidosis revealed that contrary to the effect of mineral acidosis (excess of nonmetabolizable anions)11 where there is an inverse correlation between potassium concentration and pH; organic acidosis (excess of metabolizable anions)11 was not associated with hyperkalemia.1214 However, organic acidosis can be seen simultaneously and induced by a same underlying disease (such as organ ischemia with lactic acidosis or insulin deficiency complicated by ketoacidosis). Also, when changes in pH are induced by respiratory variations or with alkalosis, the impact on serum K+ concentration is less remarkable.15 Hence, it seems that it is the nature of the acid‐base disturbance that impacts K+ concentration more than the change in pH itself.

In the kidney, the main site for regulation of K+ balance is the collecting duct. Factors that affect elimination include urinary sodium delivery, urine flow, and aldosterone.16 In order to adequately eliminate K+ these factors must be optimized in conjunction.

Treatment of hyperkalemia includes the sequential administration of agents that stabilize the cardiac membrane (calcium gluconate), shift the potassium intracellularly (insulin, ‐2 agonists), and remove the potassium (diuretics, sodium polystyrene, or dialysis).

The use of sodium bicarbonate for treatment of hyperkalemia has been long advocated.17 It was thought to act by translocation of potassium hence could be used to quickly lower K+ concentration. However, this dogma has been challenged recently.

To assess the true impact of sodium bicarbonate on potassium translocation, studies have been conducted on anephric patients with hyperkalemia. Bicarbonate infusion failed to elicit a significant rapid change in serum K+ concentration despite increase in bicarbonate concentration, arguing against a translocation mechanism.1821 After 60 minutes of treatment, neither isotonic nor hypertonic bicarbonate infusion affected Serum K+ levels in end‐stage renal disease (ESRD) patients.19, 20 On the contrary, hypertonic sodium bicarbonate increased the K+ concentration after 180 minutes of treatment,20 and it took a prolonged infusion of 4 hours to see a significant decrease in K+ concentration (0.6 mmol/L); half of which could be accounted for solely by volume administration. Moreover, this reduction was highly variable.

Rather, sodium bicarbonate seems to enhance potassium elimination by increasing sodium delivery to the distal tubule, increasing urinary pH and negative luminal charge and potentiating the action of diuretics.23 In an elegant study on normovolemic patients, the induction of bicarbonaturia practically doubled potassium excretion.23 However, such an effect is heterogeneous and usually takes place over 4 hours to 6 hours.17

At the cellular level, 2 ion exchange pumps cooperate to handle Na/K/H movement across the cellular membrane: an Na⁺/H⁺ exchanger (NHE) and the Na⁺/K⁺ ATP‐ase pump (Figure 1). The NHE is normally inactive and is only upregulated in cases of severe intracellular acidosis.24 The infusion of sodium bicarbonate to patients with severe metabolic acidosis could possibly decrease the serum potassium concentration by translocation if the NHE was significantly upregulated. However, this treatment can be associated with a drop in the ionized calcium level, a worsening of the intracellular acidosis, and a decreased peripheral oxygen delivery.25 Thus, the benefits should be balanced with the potential adverse effects and, even in cases of severe metabolic acidosis with hyperkalemia, we would advise the clinician to restrictively administer sodium bicarbonate.

Figure 1

In addition, in ESRD patients, the administration of sodium bicarbonate can be problematic owing to the osmotic and volume burden it carries. It should also be avoided in patients who are volume overload or in those with decreased ability to eliminate potassium.

When treating hyperkalemic patients, hospitalists should use sodium bicarbonate to potentiate urinary elimination of potassium and should consider administering it either with acetazolamide or a loop diuretic, anticipating a lowering effect after a few hours.26 It should be avoided in patients with volume overload and anuria. Immediate translocation of potassium into cells is best achieved by insulin and ‐2 agonists.

5‐Oxoprolinuria: A Newly Recognized Cause of High Anion Gap Metabolic Acidosis

There are several causes of metabolic high anion gap acidosis in hospitalized patients. However, despite careful investigations, the cause of that disorder is not always apparent.27 Recently, 5‐oxoprolinuria (also called pyroglutamic acidosis) has become increasingly recognized as a potential etiology.2832

The metabolism of glutamate (though the ‐Glutamyl cycle) generates glutathione which provides negative feedback to the ‐Glutamyl‐cysteine synthetase enzyme. The depletion of glutathione increases 5‐oxoproline production owing to the loss of that inhibition (Figures 2 and 3). Low glutathione levels can be seen with liver disease,33 chronic alcohol intake,34 acetaminophen use,35 malnutrition,36 renal dysfunction,29 use of vigabatrim (an antiepileptic that received Food and Drug Administration [FDA] approval for use in April 2009)37 and sepsis.38 Most of the reported cases were female and had more than one risk factor.39

Figure 2

Figure 3

Typically, patients present with high anion gap acidosis (often more than 20)28 with normal acetaminophen levels and all usual tests being negative. A history of chronic acetaminophen use with or without other risk factors can frequently be found. The true independent impact of this type of acidosis on outcomes is difficult to determine as all of the reported cases had many confounding factors.

A urinary organic acid level is diagnostic and will reveal increased levels of pyroglutamic acid. Alternatively, the finding of a positive urinary anion gap (U_Na +U_K U_Cl) with a positive urinary osmolar gap (Uosm_measured‐Uosm_calculated) in the appropriate clinical setting (unexplained high anion gap acidosis with negative workup and presence of risk factors for 5‐oxoproliniuria) can point towards the diagnosis.40

A study of patients with unexplained metabolic acidosis did not find any cases of 5‐oxoprolinuria.41 Although this might suggest that the incidence of this disease is low, very few of those patients were actually taking acetaminophen (therefore had a reduced propensity for developing pyroglutamic acidosis).41 Thus, the actual incidence of 5‐oxoprolinuria is hard to determine.

Once recognized, acetaminophen should be withheld and N‐acetylcysteine (NAC) can be used to replete glutathione levels although there is no convincing evidence for this use.42 It is important for hospitalists to be aware of this disorder as it can pose a diagnostic challenge (negative usual work‐up), is easy to treat by stopping acetaminophen, and can (possibly) negatively affect outcomes.

Furosemide and Patients With Sulfa Allergy

Allergic reactions are a common occurrence with sulfa‐containing antibiotics (SCA) and reports estimates the incidence to be approximately 3% to 5%.43, 44

One misbelief is that patients who are allergic to SCAs should not receive sulfa containing diuretics or other sulfa‐containing medications.45 This leads some physicians to substitute commonly used diuretics (such as furosemide or thiazides) for ethacrynic acid. The use of ethacrynic acid has several challenges: the limited supply of the intravenous form, the discontinuation of the oral form, the increased cost, and the risk of permanent ototoxicity.

The evidence for potential allergic cross‐reactivity among medications containing the sulfa moiety has been primarily derived from Case Reports.4649

The molecular structures of sulfamethoxazole and furosemide are shown below. The allergic antigen is most often the N1 component,45 and sometimes N4 but not the sulfa moiety. Both of the incriminated antigens are not present in the furosemide structure (as well as all other sulfa containing diuretics) (Figures 4 and 5).

Figure 4

Figure 5

Experimental data showed that serum from patients allergic to SCAs did not bind to diuretics.50 In addition, clinical reports failed to demonstrate cross‐reactivity.5153 In a large clinical trial, Strom et al.53 showed that although there was a higher risk for allergic reaction to sulfa containing medications (SCM) in patients allergic to SCA (compared to those who were not), it was lower among patients with an allergy to sulfa antibiotic than among patients with a history of hypersensitivity to penicillins, suggesting this was due to a predisposition to allergic reactions in general rather than true cross‐reactivity. In another report, patients who were receiving ethacrynic acid for many years were successfully and uneventfully switched to furosemide.54

Taken together, these findings suggest that there is no evidence for withholding sulfa nonantibiotics in patients allergic to sulfa containing antibiotics.

Conclusion

Hypothyroidism, unlike myxedema, is not a cause of hyponatremia (although it can be sometimes seen in conjunction with the latter) and additional investigations should be done to determine its etiology. Sodium bicarbonate is effective for treatment of hyperkalemia by enhancing renal potassium elimination, rather than from shifting potassium into cells. The 5‐oxoprolinuria is a newly recognized cause of high anion‐gap metabolic acidosis and should be considered in patients who have taken acetaminophen. Furosemide (and sulfa containing diuretics) can be used safely in patients with an allergy to SCA.

There are many controversial topics relating to renal disease in hospitalized patients. The aim of this review is to shed light on some important and often debated issues. We will first discuss topics related to electrolytes disorder commonly seen in hospitalized patients (hyponatremia, hyperkalemia, metabolic acidosis) then the use of diuretics in patients with allergy to sulfa containing antibiotics.

Hypothyroidism and Hyponatremia

Hyponatremia is common in hospitalized patients and is associated with worse outcomes.1 It can be seen with a variety of conditions ranging from congestive heart failure to volume depletion. Careful history and physical examination are paramount and the initial work‐up usually includes serum and urine osmolality and urine sodium concentration.

For euvolemic hyponatremia, the differential diagnosis includes the syndrome of inappropriate adenine dinucleotide (ADH) secretion (SIADH), hypoadrenalism, and beer potomania. Additionally, many authorities also include hypothyroidism.

Although the simultaneous finding of hypothyroidism and hyponatremia can occur in patients as both diseases are widely prevalent in the general population, causation has yet to be convincingly demonstrated.

ADH is released in response to effective volume depletion; consequently when hypothyroidism is encountered in the setting of complete pituitary failure there is often hyponatremia.2, 3 Alternatively, with myxedema, the ability of the kidney to handle a water load and concentrate urine can be impaired.4

However, the observation that thyroid hormone administration did not raise sodium values in newborns with congenital hypothyroidism or in adults supports the absence of causal effect.5, 6And in addition, large studies done in the hospital and outpatient setting showed no differences between the serum sodium values of hypothyroid patients and that of controls.7, 8 In the study of outpatients, among those with hypothyroidism, for every increase of 10 mU/L of thyroid‐stimulating hormone (TSH), there was a drop of only 0.14 mmol/L of Na concentration.8 Thus, the elevation of TSH required for a clinically meaningful drop in sodium to occur was considerable.

Hence in patients with hyponatremia, the hospitalist should look for etiologies other than hypothyroidism and should only consider thyroid hypofunction as a culprit in cases of myxedema, or panhypopituitarism.

Sodium Bicarbonate for Hyperkalemia

Hyperkalemia is one of the most feared electrolyte disorders encountered in hospitalized patients and can lead to dire outcomes.9, 10

Potassium (K+) homeostasis is maintained in the body by 2 complimentary systems: a short‐term system that regulates K+ variation by modifying translocation across the cellular membrane and a long‐term system that adjusts overall K+ balance. The translocation system is regulated primarily by insulin and ‐2 stimulation. Overall K+ balance is mainly controlled by the kidney (90‐95%) although the gastrointestinal (GI) tract can have a more preponderant role in anephric patients.

Hyperkalemia can ensue by either a dysregulation of the translocation system (as in diabetic Ketoacidosis secondary to insulin deficiency) or impairment of K+ elimination.

Acid‐base status was previously thought to have a prominent influence on K+ concentration, based on studies that demonstrated that. However, studies looking at metabolic acidosis revealed that contrary to the effect of mineral acidosis (excess of nonmetabolizable anions)11 where there is an inverse correlation between potassium concentration and pH; organic acidosis (excess of metabolizable anions)11 was not associated with hyperkalemia.1214 However, organic acidosis can be seen simultaneously and induced by a same underlying disease (such as organ ischemia with lactic acidosis or insulin deficiency complicated by ketoacidosis). Also, when changes in pH are induced by respiratory variations or with alkalosis, the impact on serum K+ concentration is less remarkable.15 Hence, it seems that it is the nature of the acid‐base disturbance that impacts K+ concentration more than the change in pH itself.

In the kidney, the main site for regulation of K+ balance is the collecting duct. Factors that affect elimination include urinary sodium delivery, urine flow, and aldosterone.16 In order to adequately eliminate K+ these factors must be optimized in conjunction.

Treatment of hyperkalemia includes the sequential administration of agents that stabilize the cardiac membrane (calcium gluconate), shift the potassium intracellularly (insulin, ‐2 agonists), and remove the potassium (diuretics, sodium polystyrene, or dialysis).

The use of sodium bicarbonate for treatment of hyperkalemia has been long advocated.17 It was thought to act by translocation of potassium hence could be used to quickly lower K+ concentration. However, this dogma has been challenged recently.

To assess the true impact of sodium bicarbonate on potassium translocation, studies have been conducted on anephric patients with hyperkalemia. Bicarbonate infusion failed to elicit a significant rapid change in serum K+ concentration despite increase in bicarbonate concentration, arguing against a translocation mechanism.1821 After 60 minutes of treatment, neither isotonic nor hypertonic bicarbonate infusion affected Serum K+ levels in end‐stage renal disease (ESRD) patients.19, 20 On the contrary, hypertonic sodium bicarbonate increased the K+ concentration after 180 minutes of treatment,20 and it took a prolonged infusion of 4 hours to see a significant decrease in K+ concentration (0.6 mmol/L); half of which could be accounted for solely by volume administration. Moreover, this reduction was highly variable.

Rather, sodium bicarbonate seems to enhance potassium elimination by increasing sodium delivery to the distal tubule, increasing urinary pH and negative luminal charge and potentiating the action of diuretics.23 In an elegant study on normovolemic patients, the induction of bicarbonaturia practically doubled potassium excretion.23 However, such an effect is heterogeneous and usually takes place over 4 hours to 6 hours.17

At the cellular level, 2 ion exchange pumps cooperate to handle Na/K/H movement across the cellular membrane: an Na⁺/H⁺ exchanger (NHE) and the Na⁺/K⁺ ATP‐ase pump (Figure 1). The NHE is normally inactive and is only upregulated in cases of severe intracellular acidosis.24 The infusion of sodium bicarbonate to patients with severe metabolic acidosis could possibly decrease the serum potassium concentration by translocation if the NHE was significantly upregulated. However, this treatment can be associated with a drop in the ionized calcium level, a worsening of the intracellular acidosis, and a decreased peripheral oxygen delivery.25 Thus, the benefits should be balanced with the potential adverse effects and, even in cases of severe metabolic acidosis with hyperkalemia, we would advise the clinician to restrictively administer sodium bicarbonate.

Figure 1

In addition, in ESRD patients, the administration of sodium bicarbonate can be problematic owing to the osmotic and volume burden it carries. It should also be avoided in patients who are volume overload or in those with decreased ability to eliminate potassium.

When treating hyperkalemic patients, hospitalists should use sodium bicarbonate to potentiate urinary elimination of potassium and should consider administering it either with acetazolamide or a loop diuretic, anticipating a lowering effect after a few hours.26 It should be avoided in patients with volume overload and anuria. Immediate translocation of potassium into cells is best achieved by insulin and ‐2 agonists.

5‐Oxoprolinuria: A Newly Recognized Cause of High Anion Gap Metabolic Acidosis

There are several causes of metabolic high anion gap acidosis in hospitalized patients. However, despite careful investigations, the cause of that disorder is not always apparent.27 Recently, 5‐oxoprolinuria (also called pyroglutamic acidosis) has become increasingly recognized as a potential etiology.2832

The metabolism of glutamate (though the ‐Glutamyl cycle) generates glutathione which provides negative feedback to the ‐Glutamyl‐cysteine synthetase enzyme. The depletion of glutathione increases 5‐oxoproline production owing to the loss of that inhibition (Figures 2 and 3). Low glutathione levels can be seen with liver disease,33 chronic alcohol intake,34 acetaminophen use,35 malnutrition,36 renal dysfunction,29 use of vigabatrim (an antiepileptic that received Food and Drug Administration [FDA] approval for use in April 2009)37 and sepsis.38 Most of the reported cases were female and had more than one risk factor.39

Figure 2

Figure 3

Typically, patients present with high anion gap acidosis (often more than 20)28 with normal acetaminophen levels and all usual tests being negative. A history of chronic acetaminophen use with or without other risk factors can frequently be found. The true independent impact of this type of acidosis on outcomes is difficult to determine as all of the reported cases had many confounding factors.

A urinary organic acid level is diagnostic and will reveal increased levels of pyroglutamic acid. Alternatively, the finding of a positive urinary anion gap (U_Na +U_K U_Cl) with a positive urinary osmolar gap (Uosm_measured‐Uosm_calculated) in the appropriate clinical setting (unexplained high anion gap acidosis with negative workup and presence of risk factors for 5‐oxoproliniuria) can point towards the diagnosis.40

A study of patients with unexplained metabolic acidosis did not find any cases of 5‐oxoprolinuria.41 Although this might suggest that the incidence of this disease is low, very few of those patients were actually taking acetaminophen (therefore had a reduced propensity for developing pyroglutamic acidosis).41 Thus, the actual incidence of 5‐oxoprolinuria is hard to determine.

Once recognized, acetaminophen should be withheld and N‐acetylcysteine (NAC) can be used to replete glutathione levels although there is no convincing evidence for this use.42 It is important for hospitalists to be aware of this disorder as it can pose a diagnostic challenge (negative usual work‐up), is easy to treat by stopping acetaminophen, and can (possibly) negatively affect outcomes.

Furosemide and Patients With Sulfa Allergy

Allergic reactions are a common occurrence with sulfa‐containing antibiotics (SCA) and reports estimates the incidence to be approximately 3% to 5%.43, 44

One misbelief is that patients who are allergic to SCAs should not receive sulfa containing diuretics or other sulfa‐containing medications.45 This leads some physicians to substitute commonly used diuretics (such as furosemide or thiazides) for ethacrynic acid. The use of ethacrynic acid has several challenges: the limited supply of the intravenous form, the discontinuation of the oral form, the increased cost, and the risk of permanent ototoxicity.

The evidence for potential allergic cross‐reactivity among medications containing the sulfa moiety has been primarily derived from Case Reports.4649

The molecular structures of sulfamethoxazole and furosemide are shown below. The allergic antigen is most often the N1 component,45 and sometimes N4 but not the sulfa moiety. Both of the incriminated antigens are not present in the furosemide structure (as well as all other sulfa containing diuretics) (Figures 4 and 5).

Figure 4

Figure 5

Experimental data showed that serum from patients allergic to SCAs did not bind to diuretics.50 In addition, clinical reports failed to demonstrate cross‐reactivity.5153 In a large clinical trial, Strom et al.53 showed that although there was a higher risk for allergic reaction to sulfa containing medications (SCM) in patients allergic to SCA (compared to those who were not), it was lower among patients with an allergy to sulfa antibiotic than among patients with a history of hypersensitivity to penicillins, suggesting this was due to a predisposition to allergic reactions in general rather than true cross‐reactivity. In another report, patients who were receiving ethacrynic acid for many years were successfully and uneventfully switched to furosemide.54

Taken together, these findings suggest that there is no evidence for withholding sulfa nonantibiotics in patients allergic to sulfa containing antibiotics.

Conclusion

Hypothyroidism, unlike myxedema, is not a cause of hyponatremia (although it can be sometimes seen in conjunction with the latter) and additional investigations should be done to determine its etiology. Sodium bicarbonate is effective for treatment of hyperkalemia by enhancing renal potassium elimination, rather than from shifting potassium into cells. The 5‐oxoprolinuria is a newly recognized cause of high anion‐gap metabolic acidosis and should be considered in patients who have taken acetaminophen. Furosemide (and sulfa containing diuretics) can be used safely in patients with an allergy to SCA.

There are many controversial topics relating to renal disease in hospitalized patients. The aim of this review is to shed light on some important and often debated issues. We will first discuss topics related to electrolytes disorder commonly seen in hospitalized patients (hyponatremia, hyperkalemia, metabolic acidosis) then the use of diuretics in patients with allergy to sulfa containing antibiotics.

Hypothyroidism and Hyponatremia

Hyponatremia is common in hospitalized patients and is associated with worse outcomes.1 It can be seen with a variety of conditions ranging from congestive heart failure to volume depletion. Careful history and physical examination are paramount and the initial work‐up usually includes serum and urine osmolality and urine sodium concentration.

For euvolemic hyponatremia, the differential diagnosis includes the syndrome of inappropriate adenine dinucleotide (ADH) secretion (SIADH), hypoadrenalism, and beer potomania. Additionally, many authorities also include hypothyroidism.

Although the simultaneous finding of hypothyroidism and hyponatremia can occur in patients as both diseases are widely prevalent in the general population, causation has yet to be convincingly demonstrated.

ADH is released in response to effective volume depletion; consequently when hypothyroidism is encountered in the setting of complete pituitary failure there is often hyponatremia.2, 3 Alternatively, with myxedema, the ability of the kidney to handle a water load and concentrate urine can be impaired.4

However, the observation that thyroid hormone administration did not raise sodium values in newborns with congenital hypothyroidism or in adults supports the absence of causal effect.5, 6And in addition, large studies done in the hospital and outpatient setting showed no differences between the serum sodium values of hypothyroid patients and that of controls.7, 8 In the study of outpatients, among those with hypothyroidism, for every increase of 10 mU/L of thyroid‐stimulating hormone (TSH), there was a drop of only 0.14 mmol/L of Na concentration.8 Thus, the elevation of TSH required for a clinically meaningful drop in sodium to occur was considerable.

Hence in patients with hyponatremia, the hospitalist should look for etiologies other than hypothyroidism and should only consider thyroid hypofunction as a culprit in cases of myxedema, or panhypopituitarism.

Sodium Bicarbonate for Hyperkalemia

Hyperkalemia is one of the most feared electrolyte disorders encountered in hospitalized patients and can lead to dire outcomes.9, 10

Potassium (K+) homeostasis is maintained in the body by 2 complimentary systems: a short‐term system that regulates K+ variation by modifying translocation across the cellular membrane and a long‐term system that adjusts overall K+ balance. The translocation system is regulated primarily by insulin and ‐2 stimulation. Overall K+ balance is mainly controlled by the kidney (90‐95%) although the gastrointestinal (GI) tract can have a more preponderant role in anephric patients.

Hyperkalemia can ensue by either a dysregulation of the translocation system (as in diabetic Ketoacidosis secondary to insulin deficiency) or impairment of K+ elimination.

Acid‐base status was previously thought to have a prominent influence on K+ concentration, based on studies that demonstrated that. However, studies looking at metabolic acidosis revealed that contrary to the effect of mineral acidosis (excess of nonmetabolizable anions)11 where there is an inverse correlation between potassium concentration and pH; organic acidosis (excess of metabolizable anions)11 was not associated with hyperkalemia.1214 However, organic acidosis can be seen simultaneously and induced by a same underlying disease (such as organ ischemia with lactic acidosis or insulin deficiency complicated by ketoacidosis). Also, when changes in pH are induced by respiratory variations or with alkalosis, the impact on serum K+ concentration is less remarkable.15 Hence, it seems that it is the nature of the acid‐base disturbance that impacts K+ concentration more than the change in pH itself.

In the kidney, the main site for regulation of K+ balance is the collecting duct. Factors that affect elimination include urinary sodium delivery, urine flow, and aldosterone.16 In order to adequately eliminate K+ these factors must be optimized in conjunction.

Treatment of hyperkalemia includes the sequential administration of agents that stabilize the cardiac membrane (calcium gluconate), shift the potassium intracellularly (insulin, ‐2 agonists), and remove the potassium (diuretics, sodium polystyrene, or dialysis).

The use of sodium bicarbonate for treatment of hyperkalemia has been long advocated.17 It was thought to act by translocation of potassium hence could be used to quickly lower K+ concentration. However, this dogma has been challenged recently.

To assess the true impact of sodium bicarbonate on potassium translocation, studies have been conducted on anephric patients with hyperkalemia. Bicarbonate infusion failed to elicit a significant rapid change in serum K+ concentration despite increase in bicarbonate concentration, arguing against a translocation mechanism.1821 After 60 minutes of treatment, neither isotonic nor hypertonic bicarbonate infusion affected Serum K+ levels in end‐stage renal disease (ESRD) patients.19, 20 On the contrary, hypertonic sodium bicarbonate increased the K+ concentration after 180 minutes of treatment,20 and it took a prolonged infusion of 4 hours to see a significant decrease in K+ concentration (0.6 mmol/L); half of which could be accounted for solely by volume administration. Moreover, this reduction was highly variable.

Rather, sodium bicarbonate seems to enhance potassium elimination by increasing sodium delivery to the distal tubule, increasing urinary pH and negative luminal charge and potentiating the action of diuretics.23 In an elegant study on normovolemic patients, the induction of bicarbonaturia practically doubled potassium excretion.23 However, such an effect is heterogeneous and usually takes place over 4 hours to 6 hours.17

At the cellular level, 2 ion exchange pumps cooperate to handle Na/K/H movement across the cellular membrane: an Na⁺/H⁺ exchanger (NHE) and the Na⁺/K⁺ ATP‐ase pump (Figure 1). The NHE is normally inactive and is only upregulated in cases of severe intracellular acidosis.24 The infusion of sodium bicarbonate to patients with severe metabolic acidosis could possibly decrease the serum potassium concentration by translocation if the NHE was significantly upregulated. However, this treatment can be associated with a drop in the ionized calcium level, a worsening of the intracellular acidosis, and a decreased peripheral oxygen delivery.25 Thus, the benefits should be balanced with the potential adverse effects and, even in cases of severe metabolic acidosis with hyperkalemia, we would advise the clinician to restrictively administer sodium bicarbonate.

Figure 1

In addition, in ESRD patients, the administration of sodium bicarbonate can be problematic owing to the osmotic and volume burden it carries. It should also be avoided in patients who are volume overload or in those with decreased ability to eliminate potassium.

When treating hyperkalemic patients, hospitalists should use sodium bicarbonate to potentiate urinary elimination of potassium and should consider administering it either with acetazolamide or a loop diuretic, anticipating a lowering effect after a few hours.26 It should be avoided in patients with volume overload and anuria. Immediate translocation of potassium into cells is best achieved by insulin and ‐2 agonists.

5‐Oxoprolinuria: A Newly Recognized Cause of High Anion Gap Metabolic Acidosis

There are several causes of metabolic high anion gap acidosis in hospitalized patients. However, despite careful investigations, the cause of that disorder is not always apparent.27 Recently, 5‐oxoprolinuria (also called pyroglutamic acidosis) has become increasingly recognized as a potential etiology.2832

The metabolism of glutamate (though the ‐Glutamyl cycle) generates glutathione which provides negative feedback to the ‐Glutamyl‐cysteine synthetase enzyme. The depletion of glutathione increases 5‐oxoproline production owing to the loss of that inhibition (Figures 2 and 3). Low glutathione levels can be seen with liver disease,33 chronic alcohol intake,34 acetaminophen use,35 malnutrition,36 renal dysfunction,29 use of vigabatrim (an antiepileptic that received Food and Drug Administration [FDA] approval for use in April 2009)37 and sepsis.38 Most of the reported cases were female and had more than one risk factor.39

Figure 2

Figure 3

Typically, patients present with high anion gap acidosis (often more than 20)28 with normal acetaminophen levels and all usual tests being negative. A history of chronic acetaminophen use with or without other risk factors can frequently be found. The true independent impact of this type of acidosis on outcomes is difficult to determine as all of the reported cases had many confounding factors.

A urinary organic acid level is diagnostic and will reveal increased levels of pyroglutamic acid. Alternatively, the finding of a positive urinary anion gap (U_Na +U_K U_Cl) with a positive urinary osmolar gap (Uosm_measured‐Uosm_calculated) in the appropriate clinical setting (unexplained high anion gap acidosis with negative workup and presence of risk factors for 5‐oxoproliniuria) can point towards the diagnosis.40

A study of patients with unexplained metabolic acidosis did not find any cases of 5‐oxoprolinuria.41 Although this might suggest that the incidence of this disease is low, very few of those patients were actually taking acetaminophen (therefore had a reduced propensity for developing pyroglutamic acidosis).41 Thus, the actual incidence of 5‐oxoprolinuria is hard to determine.

Once recognized, acetaminophen should be withheld and N‐acetylcysteine (NAC) can be used to replete glutathione levels although there is no convincing evidence for this use.42 It is important for hospitalists to be aware of this disorder as it can pose a diagnostic challenge (negative usual work‐up), is easy to treat by stopping acetaminophen, and can (possibly) negatively affect outcomes.

Furosemide and Patients With Sulfa Allergy

Allergic reactions are a common occurrence with sulfa‐containing antibiotics (SCA) and reports estimates the incidence to be approximately 3% to 5%.43, 44

One misbelief is that patients who are allergic to SCAs should not receive sulfa containing diuretics or other sulfa‐containing medications.45 This leads some physicians to substitute commonly used diuretics (such as furosemide or thiazides) for ethacrynic acid. The use of ethacrynic acid has several challenges: the limited supply of the intravenous form, the discontinuation of the oral form, the increased cost, and the risk of permanent ototoxicity.

The evidence for potential allergic cross‐reactivity among medications containing the sulfa moiety has been primarily derived from Case Reports.4649

The molecular structures of sulfamethoxazole and furosemide are shown below. The allergic antigen is most often the N1 component,45 and sometimes N4 but not the sulfa moiety. Both of the incriminated antigens are not present in the furosemide structure (as well as all other sulfa containing diuretics) (Figures 4 and 5).

Figure 4

Figure 5

Experimental data showed that serum from patients allergic to SCAs did not bind to diuretics.50 In addition, clinical reports failed to demonstrate cross‐reactivity.5153 In a large clinical trial, Strom et al.53 showed that although there was a higher risk for allergic reaction to sulfa containing medications (SCM) in patients allergic to SCA (compared to those who were not), it was lower among patients with an allergy to sulfa antibiotic than among patients with a history of hypersensitivity to penicillins, suggesting this was due to a predisposition to allergic reactions in general rather than true cross‐reactivity. In another report, patients who were receiving ethacrynic acid for many years were successfully and uneventfully switched to furosemide.54

Taken together, these findings suggest that there is no evidence for withholding sulfa nonantibiotics in patients allergic to sulfa containing antibiotics.

Conclusion

Hypothyroidism, unlike myxedema, is not a cause of hyponatremia (although it can be sometimes seen in conjunction with the latter) and additional investigations should be done to determine its etiology. Sodium bicarbonate is effective for treatment of hyperkalemia by enhancing renal potassium elimination, rather than from shifting potassium into cells. The 5‐oxoprolinuria is a newly recognized cause of high anion‐gap metabolic acidosis and should be considered in patients who have taken acetaminophen. Furosemide (and sulfa containing diuretics) can be used safely in patients with an allergy to SCA.

The United States spends more money per capita on healthcare than any other industrialized nation,1 yet patients are the least satisfied with their care.2 Patient satisfaction is associated in both cross‐sectional3 and longitudinal studies4 with improved physical and mental health outcomes. Conversely, dissatisfaction with care hampers future medical interactions, prevents sharing of information, and impairs the building of trust.5 The increasing recognition that a patient's experience of care affects patient outcomes has furthered efforts to evaluate satisfaction with care.6, 7

However, patient satisfaction is challenging to define and understand. Even the definition of satisfaction is ambiguous, for to satisfy can mean both to make happy and the lesser, to be adequate. To dissatisfy is to displease or disappoint, but dissatisfaction is not the opposite of satisfaction: qualitative studies give little if any indication that patients evaluate satisfaction on a continuum ranging from dissatisfied at one end to very satisfied at the other.8 Instead, it appears that satisfaction and dissatisfaction are different constructs, such that patients may simultaneously be both satisfied and dissatisfied.9, 10 Patients often express overall satisfaction with a service or encounter while also reporting specific criticisms about its shortcomings.11, 12 Alternatively, consumers may be generally satisfied unless something unpleasant or improper happens.13 Thus, dissatisfaction and satisfaction may require different methods of measurement.

The most common model for measuring patient satisfaction is a quantitative survey of patients' experiences in specific predetermined domains. Of 54 hospital satisfaction surveys in common use, only 11 included patient input in their development,14 casting doubt on the relevance of these attributes to patients' priorities of care. Since it is well recognized that patient expectations influence satisfaction,8, 13, 15 it is important to identify patient expectations and priorities up front. However, these have not been clearly established. Furthermore, focusing purely on satisfaction with particular domains of care may miss the separate but illuminating construct of patient dissatisfaction.

In this study we therefore aim to understand patient dissatisfaction with hospitalization more fully as a means of elucidating implicit expectations for hospital care. Using qualitative techniques, we analyzed a large volume of patient responses to a single open‐ended study question to identify determinants and patterns of patient dissatisfaction.

Methods

Results

A total of 976 surveys was randomly selected from 9,764 postdischarge phone interviews completed between July 1, 2007 and June 30, 2008. A total of 56.3% of patients was female. Nearly half the patients were discharged from medical units (Table 1). Of the 976 patients, 439 (45.0%) gave at least one suggestion for improvement, yielding a total of 579 suggestions. Patients also offered numerous positive comments about their care, but these comments were not included in the analysis.

Through qualitative analysis, we assigned suggestions for improvement to six major categories of dissatisfaction: 1) ineptitude, 2) disrespect, 3) prolonged waits, 4) ineffective communication, 5) lack of environmental control, and 6) substandard amenities. We considered the inverse of these problems to represent six implicit expectations of good hospital care: 1) safety, 2) treatment with respect and dignity, 3) prompt and efficient care, 4) successful exchange of information, 5) environmental autonomy and control, and 6) high‐quality amenities (Table 2). The number of patient suggestions related to each domain is detailed in Table 3.

Discussion

We analyzed 439 patient suggestions for improving hospital care and found that dissatisfaction resulted from six categories of negative experiences: 1) ineptitude, 2) disrespect, 3) prolonged wait times, 4) ineffective communication, 5) lack of environmental control, and 6) substandard amenities. These domains represented a corresponding set of implicit patient expectations for: 1) safety, 2) treatment with respect and dignity, 3) prompt and efficient care, 4) successful exchange of information, 5) environmental autonomy and control, and 6) high‐quality amenities. Each of these categories suggests avenues by which both the assessment and provision of hospital care can be made more patient‐centered.

The most widely used patient satisfaction survey in use in the United States today is the Hospital Consumer Assessment of Healthcare Providers & Systems (HCAHPS), which includes eight domains: communication with doctors, communication with nurses, responsiveness of hospital staff, pain management, communication about medicines, discharge information, cleanliness of the hospital environment, and quietness of the hospital environment.17 The dissatisfaction domains found in this study closely overlap the HCAHPS satisfaction domains, but with a few key differences.

First, dissatisfaction with ineptitude in our study encompassed concerns over adverse events and near misses, in addition to the cleanliness of the environment. Other research has shown that dissatisfaction with hospitalization can be predicted by the number of reported problems18 and the perception of receiving incorrect treatment.19 While elaborate methods have been devised to assess and compare the hospital quality and safety, patient satisfaction surveys including the HCAHPS survey often fail to ask patients directly about their perceptions of safety. In fact, this study and others20, 21 show that patients are able to recognize adverse events during hospitalization. Patient report may be a useful adjunct to other methods of adverse event case finding and outcomes reporting.

Second, while HCAHPS and others identify warmth, courtesy, concern, and respect as dimensions of patient‐centered care,14, 17, 22, 23 the ability of quantitative satisfaction surveys to capture the experience of disrespectful treatment may be limited, especially during hospitalization. Most respondents who commented on feeling disrespected identified only a single encounter, which can be masked by otherwise satisfying interactions with numerous care providers. Directly asking patients whether any experience during hospitalization caused them to feel disrespected, and allowing room for explanation, might more efficiently identify problem areas. This is particularly important because even one episode of disrespectful treatment, particularly when perceived to be racially motivated, increases the likelihood of not following a doctor's advice or putting off care.24

Third, HCAHPS emphasizes two aspects of communication: that between patients and doctors, and that between patients and nurses. Our patients confirmed that these are important, but they also noted a third dimension of communication contributing to dissatisfaction: provider‐provider communication. Communication and coordination failures among providers are key contributors to adverse events or near misses,2528 but their influence on patient satisfaction has not been widely assessed. Furthermore, patient input is rarely utilized to identify poor interprovider communication. Our study suggests that, just as patients can identify adverse events, they are also able to recognize poor provider‐provider communication.

Patients' reports of dissatisfying events also highlight areas in which small changes in hospital practice might greatly improve the patient experience. For instance, concerns over environment, food, sleep, hygiene, and pain appeared to be representative of a broader dissatisfaction with loss of autonomy and control. Hospitalized patients are often obliged to room with strangers, are subject to noise and interruptions, and cede control of their medication management at a time when they are feeling particularly vulnerable. The importance of this lack of autonomy to patients suggests a variety of small interventions that could improve satisfaction, such as individual control of noise and temperature, a visible commitment to a quiet hospital environment, and minimized interruptions and sleep disturbance.2932 Single‐occupancy hospital rooms have been associated with lower rates of nosocomial infection, medication errors, and patient stress, as well as increased privacy, rest, visitor involvement, and doctor‐patient communication.33, 34 The most sophisticated intervention, acuity‐adaptable private hospital rooms, allows hospitals to maintain patients in the same private hospital room during an entire admission, regardless of changes to level of acuity.35

In‐depth analysis of suggestions for improvement, as gathered by telephone surveys of recently discharged patients, was a particularly well‐suited approach to identifying explicit expectations for care that were violated by dissatisfying incidents. When allowed to express dissatisfaction in terms of suggestions for improvement, patients talked freely about specific dissatisfying experiences. Using telephone interviews allowed a large volume of patient responses to be included, unlike smaller focus groups. Our study was oral and did not rely on the literacy level of patients. Additionally, the open‐ended nature of questioning avoided some of the usual pitfalls of satisfaction surveys. We did not rely on predetermined satisfaction categories or presume the inherent value of particular attributes of care. Nonetheless, our study does have important limitations.

Patient perceptions were not compared with chart data or clinician report. Caregivers were allowed to participate in lieu of patients, which may have reduced identification of some dissatisfying events. Likewise, patients discharged to nursing homes or who were not English or Spanish speaking were excluded and may have had different dissatisfying experiences. Interviews were brief and dissatisfying events were not explored in detail. Although nearly half of respondents reported dissatisfying events, some patients may have been reluctant to criticize their care directly to a hospital representative. Finally, patients generally confined their comments to one or two dissatisfying events, even though there may have been others. We therefore cannot draw any conclusions about the relative frequency of dissatisfying events by domain.

Conclusions

All hospitalized patients bring expectations for their hospital experience. While specific expectations vary between patients, expectations for: 1) safety, 2) treatment with respect and dignity, 3) prompt and efficient care, 4) successful exchange of information, 5) environmental autonomy and control, and 6) high‐quality amenities were found in this study to encompass core expectations for hospitalization. It may be useful to ensure that postdischarge surveys explicitly address these expectations. Efforts to address and manage these core expectations of hospital care may help to reduce patient dissatisfaction with hospitalization and improve the delivery and quality of hospital care.

The United States spends more money per capita on healthcare than any other industrialized nation,1 yet patients are the least satisfied with their care.2 Patient satisfaction is associated in both cross‐sectional3 and longitudinal studies4 with improved physical and mental health outcomes. Conversely, dissatisfaction with care hampers future medical interactions, prevents sharing of information, and impairs the building of trust.5 The increasing recognition that a patient's experience of care affects patient outcomes has furthered efforts to evaluate satisfaction with care.6, 7

However, patient satisfaction is challenging to define and understand. Even the definition of satisfaction is ambiguous, for to satisfy can mean both to make happy and the lesser, to be adequate. To dissatisfy is to displease or disappoint, but dissatisfaction is not the opposite of satisfaction: qualitative studies give little if any indication that patients evaluate satisfaction on a continuum ranging from dissatisfied at one end to very satisfied at the other.8 Instead, it appears that satisfaction and dissatisfaction are different constructs, such that patients may simultaneously be both satisfied and dissatisfied.9, 10 Patients often express overall satisfaction with a service or encounter while also reporting specific criticisms about its shortcomings.11, 12 Alternatively, consumers may be generally satisfied unless something unpleasant or improper happens.13 Thus, dissatisfaction and satisfaction may require different methods of measurement.

The most common model for measuring patient satisfaction is a quantitative survey of patients' experiences in specific predetermined domains. Of 54 hospital satisfaction surveys in common use, only 11 included patient input in their development,14 casting doubt on the relevance of these attributes to patients' priorities of care. Since it is well recognized that patient expectations influence satisfaction,8, 13, 15 it is important to identify patient expectations and priorities up front. However, these have not been clearly established. Furthermore, focusing purely on satisfaction with particular domains of care may miss the separate but illuminating construct of patient dissatisfaction.

In this study we therefore aim to understand patient dissatisfaction with hospitalization more fully as a means of elucidating implicit expectations for hospital care. Using qualitative techniques, we analyzed a large volume of patient responses to a single open‐ended study question to identify determinants and patterns of patient dissatisfaction.

Methods

Results

A total of 976 surveys was randomly selected from 9,764 postdischarge phone interviews completed between July 1, 2007 and June 30, 2008. A total of 56.3% of patients was female. Nearly half the patients were discharged from medical units (Table 1). Of the 976 patients, 439 (45.0%) gave at least one suggestion for improvement, yielding a total of 579 suggestions. Patients also offered numerous positive comments about their care, but these comments were not included in the analysis.

Through qualitative analysis, we assigned suggestions for improvement to six major categories of dissatisfaction: 1) ineptitude, 2) disrespect, 3) prolonged waits, 4) ineffective communication, 5) lack of environmental control, and 6) substandard amenities. We considered the inverse of these problems to represent six implicit expectations of good hospital care: 1) safety, 2) treatment with respect and dignity, 3) prompt and efficient care, 4) successful exchange of information, 5) environmental autonomy and control, and 6) high‐quality amenities (Table 2). The number of patient suggestions related to each domain is detailed in Table 3.

Discussion

We analyzed 439 patient suggestions for improving hospital care and found that dissatisfaction resulted from six categories of negative experiences: 1) ineptitude, 2) disrespect, 3) prolonged wait times, 4) ineffective communication, 5) lack of environmental control, and 6) substandard amenities. These domains represented a corresponding set of implicit patient expectations for: 1) safety, 2) treatment with respect and dignity, 3) prompt and efficient care, 4) successful exchange of information, 5) environmental autonomy and control, and 6) high‐quality amenities. Each of these categories suggests avenues by which both the assessment and provision of hospital care can be made more patient‐centered.

The most widely used patient satisfaction survey in use in the United States today is the Hospital Consumer Assessment of Healthcare Providers & Systems (HCAHPS), which includes eight domains: communication with doctors, communication with nurses, responsiveness of hospital staff, pain management, communication about medicines, discharge information, cleanliness of the hospital environment, and quietness of the hospital environment.17 The dissatisfaction domains found in this study closely overlap the HCAHPS satisfaction domains, but with a few key differences.

First, dissatisfaction with ineptitude in our study encompassed concerns over adverse events and near misses, in addition to the cleanliness of the environment. Other research has shown that dissatisfaction with hospitalization can be predicted by the number of reported problems18 and the perception of receiving incorrect treatment.19 While elaborate methods have been devised to assess and compare the hospital quality and safety, patient satisfaction surveys including the HCAHPS survey often fail to ask patients directly about their perceptions of safety. In fact, this study and others20, 21 show that patients are able to recognize adverse events during hospitalization. Patient report may be a useful adjunct to other methods of adverse event case finding and outcomes reporting.

Second, while HCAHPS and others identify warmth, courtesy, concern, and respect as dimensions of patient‐centered care,14, 17, 22, 23 the ability of quantitative satisfaction surveys to capture the experience of disrespectful treatment may be limited, especially during hospitalization. Most respondents who commented on feeling disrespected identified only a single encounter, which can be masked by otherwise satisfying interactions with numerous care providers. Directly asking patients whether any experience during hospitalization caused them to feel disrespected, and allowing room for explanation, might more efficiently identify problem areas. This is particularly important because even one episode of disrespectful treatment, particularly when perceived to be racially motivated, increases the likelihood of not following a doctor's advice or putting off care.24

Third, HCAHPS emphasizes two aspects of communication: that between patients and doctors, and that between patients and nurses. Our patients confirmed that these are important, but they also noted a third dimension of communication contributing to dissatisfaction: provider‐provider communication. Communication and coordination failures among providers are key contributors to adverse events or near misses,2528 but their influence on patient satisfaction has not been widely assessed. Furthermore, patient input is rarely utilized to identify poor interprovider communication. Our study suggests that, just as patients can identify adverse events, they are also able to recognize poor provider‐provider communication.

Patients' reports of dissatisfying events also highlight areas in which small changes in hospital practice might greatly improve the patient experience. For instance, concerns over environment, food, sleep, hygiene, and pain appeared to be representative of a broader dissatisfaction with loss of autonomy and control. Hospitalized patients are often obliged to room with strangers, are subject to noise and interruptions, and cede control of their medication management at a time when they are feeling particularly vulnerable. The importance of this lack of autonomy to patients suggests a variety of small interventions that could improve satisfaction, such as individual control of noise and temperature, a visible commitment to a quiet hospital environment, and minimized interruptions and sleep disturbance.2932 Single‐occupancy hospital rooms have been associated with lower rates of nosocomial infection, medication errors, and patient stress, as well as increased privacy, rest, visitor involvement, and doctor‐patient communication.33, 34 The most sophisticated intervention, acuity‐adaptable private hospital rooms, allows hospitals to maintain patients in the same private hospital room during an entire admission, regardless of changes to level of acuity.35

In‐depth analysis of suggestions for improvement, as gathered by telephone surveys of recently discharged patients, was a particularly well‐suited approach to identifying explicit expectations for care that were violated by dissatisfying incidents. When allowed to express dissatisfaction in terms of suggestions for improvement, patients talked freely about specific dissatisfying experiences. Using telephone interviews allowed a large volume of patient responses to be included, unlike smaller focus groups. Our study was oral and did not rely on the literacy level of patients. Additionally, the open‐ended nature of questioning avoided some of the usual pitfalls of satisfaction surveys. We did not rely on predetermined satisfaction categories or presume the inherent value of particular attributes of care. Nonetheless, our study does have important limitations.

Patient perceptions were not compared with chart data or clinician report. Caregivers were allowed to participate in lieu of patients, which may have reduced identification of some dissatisfying events. Likewise, patients discharged to nursing homes or who were not English or Spanish speaking were excluded and may have had different dissatisfying experiences. Interviews were brief and dissatisfying events were not explored in detail. Although nearly half of respondents reported dissatisfying events, some patients may have been reluctant to criticize their care directly to a hospital representative. Finally, patients generally confined their comments to one or two dissatisfying events, even though there may have been others. We therefore cannot draw any conclusions about the relative frequency of dissatisfying events by domain.

Conclusions

All hospitalized patients bring expectations for their hospital experience. While specific expectations vary between patients, expectations for: 1) safety, 2) treatment with respect and dignity, 3) prompt and efficient care, 4) successful exchange of information, 5) environmental autonomy and control, and 6) high‐quality amenities were found in this study to encompass core expectations for hospitalization. It may be useful to ensure that postdischarge surveys explicitly address these expectations. Efforts to address and manage these core expectations of hospital care may help to reduce patient dissatisfaction with hospitalization and improve the delivery and quality of hospital care.

The United States spends more money per capita on healthcare than any other industrialized nation,1 yet patients are the least satisfied with their care.2 Patient satisfaction is associated in both cross‐sectional3 and longitudinal studies4 with improved physical and mental health outcomes. Conversely, dissatisfaction with care hampers future medical interactions, prevents sharing of information, and impairs the building of trust.5 The increasing recognition that a patient's experience of care affects patient outcomes has furthered efforts to evaluate satisfaction with care.6, 7

However, patient satisfaction is challenging to define and understand. Even the definition of satisfaction is ambiguous, for to satisfy can mean both to make happy and the lesser, to be adequate. To dissatisfy is to displease or disappoint, but dissatisfaction is not the opposite of satisfaction: qualitative studies give little if any indication that patients evaluate satisfaction on a continuum ranging from dissatisfied at one end to very satisfied at the other.8 Instead, it appears that satisfaction and dissatisfaction are different constructs, such that patients may simultaneously be both satisfied and dissatisfied.9, 10 Patients often express overall satisfaction with a service or encounter while also reporting specific criticisms about its shortcomings.11, 12 Alternatively, consumers may be generally satisfied unless something unpleasant or improper happens.13 Thus, dissatisfaction and satisfaction may require different methods of measurement.

The most common model for measuring patient satisfaction is a quantitative survey of patients' experiences in specific predetermined domains. Of 54 hospital satisfaction surveys in common use, only 11 included patient input in their development,14 casting doubt on the relevance of these attributes to patients' priorities of care. Since it is well recognized that patient expectations influence satisfaction,8, 13, 15 it is important to identify patient expectations and priorities up front. However, these have not been clearly established. Furthermore, focusing purely on satisfaction with particular domains of care may miss the separate but illuminating construct of patient dissatisfaction.

In this study we therefore aim to understand patient dissatisfaction with hospitalization more fully as a means of elucidating implicit expectations for hospital care. Using qualitative techniques, we analyzed a large volume of patient responses to a single open‐ended study question to identify determinants and patterns of patient dissatisfaction.

Methods

Results

A total of 976 surveys was randomly selected from 9,764 postdischarge phone interviews completed between July 1, 2007 and June 30, 2008. A total of 56.3% of patients was female. Nearly half the patients were discharged from medical units (Table 1). Of the 976 patients, 439 (45.0%) gave at least one suggestion for improvement, yielding a total of 579 suggestions. Patients also offered numerous positive comments about their care, but these comments were not included in the analysis.

Through qualitative analysis, we assigned suggestions for improvement to six major categories of dissatisfaction: 1) ineptitude, 2) disrespect, 3) prolonged waits, 4) ineffective communication, 5) lack of environmental control, and 6) substandard amenities. We considered the inverse of these problems to represent six implicit expectations of good hospital care: 1) safety, 2) treatment with respect and dignity, 3) prompt and efficient care, 4) successful exchange of information, 5) environmental autonomy and control, and 6) high‐quality amenities (Table 2). The number of patient suggestions related to each domain is detailed in Table 3.

Discussion

We analyzed 439 patient suggestions for improving hospital care and found that dissatisfaction resulted from six categories of negative experiences: 1) ineptitude, 2) disrespect, 3) prolonged wait times, 4) ineffective communication, 5) lack of environmental control, and 6) substandard amenities. These domains represented a corresponding set of implicit patient expectations for: 1) safety, 2) treatment with respect and dignity, 3) prompt and efficient care, 4) successful exchange of information, 5) environmental autonomy and control, and 6) high‐quality amenities. Each of these categories suggests avenues by which both the assessment and provision of hospital care can be made more patient‐centered.

The most widely used patient satisfaction survey in use in the United States today is the Hospital Consumer Assessment of Healthcare Providers & Systems (HCAHPS), which includes eight domains: communication with doctors, communication with nurses, responsiveness of hospital staff, pain management, communication about medicines, discharge information, cleanliness of the hospital environment, and quietness of the hospital environment.17 The dissatisfaction domains found in this study closely overlap the HCAHPS satisfaction domains, but with a few key differences.

First, dissatisfaction with ineptitude in our study encompassed concerns over adverse events and near misses, in addition to the cleanliness of the environment. Other research has shown that dissatisfaction with hospitalization can be predicted by the number of reported problems18 and the perception of receiving incorrect treatment.19 While elaborate methods have been devised to assess and compare the hospital quality and safety, patient satisfaction surveys including the HCAHPS survey often fail to ask patients directly about their perceptions of safety. In fact, this study and others20, 21 show that patients are able to recognize adverse events during hospitalization. Patient report may be a useful adjunct to other methods of adverse event case finding and outcomes reporting.

Second, while HCAHPS and others identify warmth, courtesy, concern, and respect as dimensions of patient‐centered care,14, 17, 22, 23 the ability of quantitative satisfaction surveys to capture the experience of disrespectful treatment may be limited, especially during hospitalization. Most respondents who commented on feeling disrespected identified only a single encounter, which can be masked by otherwise satisfying interactions with numerous care providers. Directly asking patients whether any experience during hospitalization caused them to feel disrespected, and allowing room for explanation, might more efficiently identify problem areas. This is particularly important because even one episode of disrespectful treatment, particularly when perceived to be racially motivated, increases the likelihood of not following a doctor's advice or putting off care.24

Third, HCAHPS emphasizes two aspects of communication: that between patients and doctors, and that between patients and nurses. Our patients confirmed that these are important, but they also noted a third dimension of communication contributing to dissatisfaction: provider‐provider communication. Communication and coordination failures among providers are key contributors to adverse events or near misses,2528 but their influence on patient satisfaction has not been widely assessed. Furthermore, patient input is rarely utilized to identify poor interprovider communication. Our study suggests that, just as patients can identify adverse events, they are also able to recognize poor provider‐provider communication.

Patients' reports of dissatisfying events also highlight areas in which small changes in hospital practice might greatly improve the patient experience. For instance, concerns over environment, food, sleep, hygiene, and pain appeared to be representative of a broader dissatisfaction with loss of autonomy and control. Hospitalized patients are often obliged to room with strangers, are subject to noise and interruptions, and cede control of their medication management at a time when they are feeling particularly vulnerable. The importance of this lack of autonomy to patients suggests a variety of small interventions that could improve satisfaction, such as individual control of noise and temperature, a visible commitment to a quiet hospital environment, and minimized interruptions and sleep disturbance.2932 Single‐occupancy hospital rooms have been associated with lower rates of nosocomial infection, medication errors, and patient stress, as well as increased privacy, rest, visitor involvement, and doctor‐patient communication.33, 34 The most sophisticated intervention, acuity‐adaptable private hospital rooms, allows hospitals to maintain patients in the same private hospital room during an entire admission, regardless of changes to level of acuity.35

In‐depth analysis of suggestions for improvement, as gathered by telephone surveys of recently discharged patients, was a particularly well‐suited approach to identifying explicit expectations for care that were violated by dissatisfying incidents. When allowed to express dissatisfaction in terms of suggestions for improvement, patients talked freely about specific dissatisfying experiences. Using telephone interviews allowed a large volume of patient responses to be included, unlike smaller focus groups. Our study was oral and did not rely on the literacy level of patients. Additionally, the open‐ended nature of questioning avoided some of the usual pitfalls of satisfaction surveys. We did not rely on predetermined satisfaction categories or presume the inherent value of particular attributes of care. Nonetheless, our study does have important limitations.

Patient perceptions were not compared with chart data or clinician report. Caregivers were allowed to participate in lieu of patients, which may have reduced identification of some dissatisfying events. Likewise, patients discharged to nursing homes or who were not English or Spanish speaking were excluded and may have had different dissatisfying experiences. Interviews were brief and dissatisfying events were not explored in detail. Although nearly half of respondents reported dissatisfying events, some patients may have been reluctant to criticize their care directly to a hospital representative. Finally, patients generally confined their comments to one or two dissatisfying events, even though there may have been others. We therefore cannot draw any conclusions about the relative frequency of dissatisfying events by domain.

Conclusions

All hospitalized patients bring expectations for their hospital experience. While specific expectations vary between patients, expectations for: 1) safety, 2) treatment with respect and dignity, 3) prompt and efficient care, 4) successful exchange of information, 5) environmental autonomy and control, and 6) high‐quality amenities were found in this study to encompass core expectations for hospitalization. It may be useful to ensure that postdischarge surveys explicitly address these expectations. Efforts to address and manage these core expectations of hospital care may help to reduce patient dissatisfaction with hospitalization and improve the delivery and quality of hospital care.

Effective communication between patients and physicians improves a number of important outcomes including patient adherence to treatment,1‐3 quality of the medical history4 and clinical outcomes.1, 5, 6 Recognizing the importance of physician communication skills, the American Board of Medical Specialties, American Council for Graduate Medical Education and The Joint Commission all identify communication as a core competency for physicians.7‐9 For hospitalists and their patients, building a therapeutic partnership is challenged by the lack of a preexisting relationship and potential lack of patient history information, particularly psychosocial history.10 Other factors that complicate the relationships between hospitalists and their patients include acuity of illness, limited time course, and absence of or lack of input from patients' primary physicians.11

As a rapidly increasing percentage of hospitalized patients are cared for by hospitalists,12, 13 communication skills need to be directly assessed and addressed. As of 2006, at least 37% of all Medicare claims for inpatient evaluation and management services by general internists were attributed to hospitalists, and more than half of hospitalized Medicare patients are seen by hospitalists.14 Yet, a search of the MEDLINE database for articles published between 1965 and September 2009, querying hospitalist AND patient AND communication within the article title and abstract, yielded only 2 studies assessing hospitalist‐patient communication. A 1998 study15 compared patient‐reported communication problems with hospitalists versus continuity physicians involved with hospital care, and found that patients whose continuity physicians remained involved with care during the hospitalization were less likely to report communication problems than those patients who were cared for by a hospitalist alone. A 2004 study16 utilized chart documentation to compare the end‐of‐life care and communication provided by continuity physicians and hospitalists. Hospitalists were found to document end‐of‐life care discussions more often than continuity physicians, and were more likely to be present for these meetings, which may suggest improved end‐of‐life care. Neither of these hospitalist‐patient communication studies directly assessed patient perceptions of communication with hospitalists.

We undertook this study to explore patient perceptions of communication with hospitalists using the Communication Assessment Tool (CAT), a psychometrically validated instrument for patient assessment of physician communication skills.17 The CAT was initially field tested in outpatient offices, omitting the inpatient experience. A 2008 study18 successfully adapted the CAT tool for use in assessing emergency department (ED) teams. Given the importance of physician‐patient communication when patients are sickest and most vulnerable in the hospital setting, we sought to establish a baseline assessment of patient perceptions of communication with hospitalists in our group. Second, we compared results of our CAT implementation with published results examining communication in other physician groups.

Methods

Between September 2008 and August 2009 we performed a cross‐sectional study of patients admitted to the hospital medicine service at an urban, academic medical center with 873 beds. This busy service was responsible for 10,225 admissions in 2008. Patients of age 18 years or older and cared for by a hospitalist or teaching team led by a hospitalist were eligible to participate. Exclusion criteria included patient confusion, physiological instability, non‐English speaking, patient unable to communicate, or patient in isolation status. Interviews were conducted in the patient's private room with no other staff present.

Patient perception of communication with hospitalists was measured with the CAT.17 This 15‐item survey is written at a fourth grade reading level, and measures responses along a 5‐point scale (1 = poor, 2 = fair, 3 = good, 4 = very good, 5 = excellent). The CAT was originally field tested with a convenience sample of 38 physicians from various regions within the US, across 6 specialties (Dermatology, Family Medicine, Neurosurgery, Ophthalmology, Orthopedic Surgery, and Physical Medicine & Rehabilitation). Each physician's office recruited 25 patients to complete the CAT through a phone or Internet‐based system.

The 14 core items of the CAT, which focus on communication with the individual physician, were used in this study. The 15th item, The doctor's staff treated me with respect, was dropped as it does not reflect the inpatient setting. Results for each physician are reported as the percentage of excellent responses. This dichotomized scoring is consistent with the development study, where analysis with Andrich's rating scale model19, 20 indicated that excellent scores correspond to a yes response while poor through very good scores correspond to a no response. This method of reporting scores as a percentage of excellent responses was found to be more useful for summarizing physician scores than reporting mean scores, which are highly skewed towards positive performance.17

Interviews were conducted by trained research assistants during hospitalists' weekday shifts. Hospitalists were not told which patients would be recruited, but were aware that patients on the service were being interviewed to assess communication. A list of patient names, room numbers, dates of admission, and assigned hospitalists was obtained daily from the electronic medical record system. Patients were approached on the second or third day of the hospital admission, and only if they had been assigned to the same hospitalist for at least 2 consecutive days. After explaining the study to patients and receiving verbal consent, researchers verified that the patient recognized the hospitalist, providing a photo if necessary. Patients who were not confident of their hospitalist's identity were excluded.

The 14 core items of the CAT survey were read aloud to the patient, who was provided with a copy of the instrument's scale and asked to respond with a number or word description (1 = poor to 5 = excellent). Patients were allowed to skip any questions they did not wish to answer. At the conclusion of the survey, patients were asked if they had any further comments to add. Patient demographics as well as hospitalist service (general or teaching) and unit were recorded. Most interviews were completed in less than 5 minutes. Based on the recommendations of the original development and validation of the CAT,17 we collected 20 patient surveys for each hospitalist. For CAT items that the patients skipped, we did not impute values; rather the percentage of excellent responses was calculated based on the number of questions the patient answered. To examine basic psychometric characteristics, we assessed scale reliability and performed a factor analysis using the principal components method of extraction with Varimax rotation.

This project was determined exempt by the Northwestern University Institutional Review Board.

Results

We identified 1,137 patients as potentially eligible for the study. Figure 1 shows a flowchart of patient exclusion. Of note, 107 patients consenting to participate (13% overall) were unable to identify their hospitalist by name or photo. More specifically, 70 teaching service patients (25% of 275 eligible patients) were unable to identify their hospitalist, compared to 37 patients on general service (7% of 553 eligible patients); (z = 7.58, P < 0.001). Another 21 (3%) declined to participate because they had not talked enough with their doctor to render an assessment.

Figure 1

We analyzed 700 patient surveys (20 patients for each of 35 hospitalists; 62% of patients identified). Patient and hospitalist characteristics are presented in Table 1. The proportion of excellent ratings for each hospitalist ranged from 38.5% to 73.5% with an average of 59.1% excellent (standard deviation [SD] = 9.5). See Figure 2 for the distribution of hospitalist scores. For the group as a whole, highest ratings on individual CAT items were for treating the patient with respect (66% excellent), letting the patient talk without interruptions (66%), and talking in terms the patient can understand (64%). Lowest ratings were for involving the patient in decisions as much as he or she wanted (53%), encouraging the patient to ask questions (53%), and greeting the patient in a way that made him or her feel comfortable (55%). Table 2 contains a full ranking of individual item scores.

Figure 2

Overall scale reliability proved to be high (Cronbach's alpha = 0.97) in this sample. The factor analysis showed that scores for each of the 14 items load onto 1 factor. These results are consistent with the high reliability and single‐factor loading found in Makoul's original scale reliability and validity testing.17

The ad hoc comments made by patients at the conclusion of the CAT survey were categorized as positive or negative. Although many positive comments were made, they tended to be general in nature (eg, She is a great doctor). Negative comments were more explicit. A total of 110 patients (16%) made specific negative comments, which fell into 7 general domains: lack of information (35 comments), not enough time spent with the patient (27 comments), poor listening to the patient (24 comments), ineffective care delivery (7 comments), issues of care, concern, and respect (6 comments), ineffective communication with other staff (5 comments), and unclear role of physician (3 comments). Three patient comments were not related to these domains.

Patient age, race or gender did not correlate with CAT results. Hospitalist factors of age, race, gender, years of experience also were not associated with differences in ratings. However, race concordance between the patient and hospitalist was associated with improved CAT ratings. Patients of the same race as their hospitalist rated the hospitalist's communication significantly higher (M = 64.9%, SD = 39.1) than did patients who were of a different race than their hospitalist (M = 57.3%, SD = 40.3), P < 0.05. Gender concordance was not associated with improved CAT ratings. No score differences were found between patients cared for by a hospitalist on teaching service and direct care, and there were no differences between nursing units.

Discussion

To the best of our knowledge, this is the first study to explicitly measure patient perceptions of communication with hospitalists. The results yielded a wide distribution of scores for physicians within a single, large hospital medicine group. Comparing their own scores to those of peers may allow low‐scoring hospitalists to grasp the potential for improving their communication with patients. Our reliability testing matched the results of the original development study,17 indicating very high overall scale reliability. This suggests that the CAT could be streamlined by dropping some of the survey items. However we agree with Makoul et al.17 that it is best to keep the full set as it provides specific information for physicians without placing undue burden on patients (ie, the CAT takes only 1‐2 min to complete). Individual item scores for each of the 14 CAT items highlight specific communication tasks where intervention may be targeted for individual hospitalists and the group as a whole. It may be feasible to utilize CAT results as an individual report card for physicians. While program leaders should be aware that implementation of the CAT requires standardized data collection, it may be possible to build this into existing structures such as the discharge process.

Interestingly, many patients could not recognize the hospitalist caring for them by name or photo. More than 1 in 10 patients (107 of 828; 13%) were unable to identify their hospitalist. This was more than 3 times as common on the teaching service, where the hospitalist is accompanied by house staff and the intern or resident is the primary physician for patient contact, compared to the service on which hospitalists directly take care of patients without residents. It is also troubling that another 3% of patients (21 of 828) stated they hadn't talked enough with their hospitalist to answer basic communication questions, when approached 2 or 3 days into the relationship. It may be telling that Greeted me in a way that made me feel comfortable was one of the lowest‐rated survey items. Hospitalists should recognize that patients, in addition to facing their own physical and emotional stressors, see many hospital staff members throughout the day; all of whom may be strangers to them. Thus it becomes vital for hospitalists to not only establish an initial rapport with the patient, but to reintroduce themselves each time they enter the room.

An examination of the ad hoc negative comments made by survey respondents reinforces and extends findings related to the CAT items, particularly about those areas of communication valued by patients. The majority of comments fell into categories of failing to give enough information (eg, Sometimes I was left confused when the doctor was ready to leave), not spending enough time with the patient (eg, He was just in and out), and not listening to the patient's own ideas (eg, When giving my history, she cut me off at some points when I had more to say). The information and time categories may directly relate to scores on the CAT items Gave me as much information as I wanted and Spent the right amount of time with me, which are among the lowest‐scoring items. Listening to the patient may reflect broader issues of considering the patient's own experience, questions, concerns and goals.

In this study, patient‐physician race concordance was associated with CAT ratings. Patients who were of the same race as their hospitalist rated the hospitalist higher compared to patients who were of a different race than their hospitalist. This effect is consistent with previous research describing higher patient ratings of communication and care when the patient and physician are of the same race or ethnicity.21

A number of factors limit interpretation of the results of this study. The data were collected at a single site, thus limiting generalizability to other hospitalist practice environments. We used a retrospective, patient assessment of hospitalist communication which may have inherent biases different from a study using direct researcher observation or recording of patient‐hospitalist interactions to assess communication. This methodology allowed us to examine the patient's own perceptions and expectations of communication, but certainly leaves room for selection bias in recruitment and recall bias. Patients were interviewed on the second or third day of their admission. This controlled the length of exposure to the hospitalist, but the course of treatment might vary considerably; at the time of interview, some patients may not yet have had a clear diagnosis and plan while others may have been ready for discharge. Future work should examine how stage of evaluation and management might affect patients' perception of communication with hospitalists. Severity of condition is another factor that may affect patients' ratings, and was not examined in this study.

When compared to physicians from the CAT development study's field test, this study sample of hospitalists scored much lower, 59.1% excellent vs. 76.3% (P < 0.001). A number of factors may account for some of these differences. The majority of patients in the original field test had multiple interactions with their physician, and rated their health status as good or very good. In contrast, hospitalized patients usually lack previous exposure to the hospitalist, and likely have poorer health status. Also, physicians in the original field test volunteered to participate, and patients completed the CAT survey through the Internet or phone response system, rather than through a face‐to‐face interview by trained research assistants. Another key difference is that field‐test patients answered the CAT within 1 day of their outpatient visit, while in this study patients were interviewed in the midst of their hospital admission and prior to completion of their hospital course. Finally, patients commonly choose their outpatient physician and can select someone else if dissatisfied with their communication skills, while hospitalized patients are assigned hospitalists based on availability. Thus, given this potential selection bias, outpatients could be expected to rate their personal physician higher.

Another possibility is that hospitalists are on average less skilled in patient communication than outpatient physicians. Given the transient nature of the inpatient relationship, hospitalists may not value developing rapport with patients, and may not make this a goal of patient care or seek extensive training in communication skills. In future research, evaluating hospitalists' training in and attitudes towards patient communication could be paired with communication assessment results.

Although it is beyond the scope of this study to assess precisely how these environmental and survey implementation factors may affect CAT summary scores, their importance is evident. Another hospital‐based implementation of the CAT tool, an evaluation of ED teams,18 utilized face‐to‐face interviews with trained research assistants. The study yielded results similar to our findings: the average percent excellent score for ED teams was 62.3%, vs. 58.2% percent excellent for our hospitalist group. Taken together, these study comparisons between the original field‐test, our hospitalist implementation, and the ED team implementation support the argument that factors of setting (inpatient vs. outpatient), mode of survey administration (face‐to‐face interview vs. self‐administration through phone or Internet), and shorter duration or course of patient‐physician interaction may be important considerations when implementing the CAT tool to assess physician communication skills, or attempting to set standards of minimally acceptable or desired scoring.

More work must be done to establish norms and/or minimally acceptable scores for hospitalists. Numerous factors of specialty, practice setting, survey implementation, patient variables, and even the expertise of who is setting the communication standards22 may strongly influence comparisons between physician groups, even within a single institution. Organizations seeking to establish norms or minimally acceptable scores for physician‐patient communication should be aware of these factors. As the original development study points out, standard‐setting studies could establish specialty‐specific and country‐specific norms as well as norms or standards for level‐of‐training (eg, medical students versus attending physicians).17

Conclusion

The previously validated CAT instrument appears to have reliable test characteristics and can be used to gauge patient perceptions of hospitalist communication skills. Comparative scores between physicians of different specialties and settings should be interpreted cautiously as there may be confounding variables. Within our single institution, comparative scores between hospitalists, along with an examination of the hospitalist's individual item scores, may offer useful feedback for efforts aimed at enhancing communication. Many hospitalists in this study may benefit from targeted training to improve patient communication skills, particularly in the areas of encouraging questions and involving patients in decision making. Future qualitative research in the context of hospital medicine could identify specific communication techniques used by highly‐rated physicians, with the goal of developing tools for targeted improvement and determining impact on outcomes.

Effective communication between patients and physicians improves a number of important outcomes including patient adherence to treatment,1‐3 quality of the medical history4 and clinical outcomes.1, 5, 6 Recognizing the importance of physician communication skills, the American Board of Medical Specialties, American Council for Graduate Medical Education and The Joint Commission all identify communication as a core competency for physicians.7‐9 For hospitalists and their patients, building a therapeutic partnership is challenged by the lack of a preexisting relationship and potential lack of patient history information, particularly psychosocial history.10 Other factors that complicate the relationships between hospitalists and their patients include acuity of illness, limited time course, and absence of or lack of input from patients' primary physicians.11

As a rapidly increasing percentage of hospitalized patients are cared for by hospitalists,12, 13 communication skills need to be directly assessed and addressed. As of 2006, at least 37% of all Medicare claims for inpatient evaluation and management services by general internists were attributed to hospitalists, and more than half of hospitalized Medicare patients are seen by hospitalists.14 Yet, a search of the MEDLINE database for articles published between 1965 and September 2009, querying hospitalist AND patient AND communication within the article title and abstract, yielded only 2 studies assessing hospitalist‐patient communication. A 1998 study15 compared patient‐reported communication problems with hospitalists versus continuity physicians involved with hospital care, and found that patients whose continuity physicians remained involved with care during the hospitalization were less likely to report communication problems than those patients who were cared for by a hospitalist alone. A 2004 study16 utilized chart documentation to compare the end‐of‐life care and communication provided by continuity physicians and hospitalists. Hospitalists were found to document end‐of‐life care discussions more often than continuity physicians, and were more likely to be present for these meetings, which may suggest improved end‐of‐life care. Neither of these hospitalist‐patient communication studies directly assessed patient perceptions of communication with hospitalists.

We undertook this study to explore patient perceptions of communication with hospitalists using the Communication Assessment Tool (CAT), a psychometrically validated instrument for patient assessment of physician communication skills.17 The CAT was initially field tested in outpatient offices, omitting the inpatient experience. A 2008 study18 successfully adapted the CAT tool for use in assessing emergency department (ED) teams. Given the importance of physician‐patient communication when patients are sickest and most vulnerable in the hospital setting, we sought to establish a baseline assessment of patient perceptions of communication with hospitalists in our group. Second, we compared results of our CAT implementation with published results examining communication in other physician groups.

Methods

Between September 2008 and August 2009 we performed a cross‐sectional study of patients admitted to the hospital medicine service at an urban, academic medical center with 873 beds. This busy service was responsible for 10,225 admissions in 2008. Patients of age 18 years or older and cared for by a hospitalist or teaching team led by a hospitalist were eligible to participate. Exclusion criteria included patient confusion, physiological instability, non‐English speaking, patient unable to communicate, or patient in isolation status. Interviews were conducted in the patient's private room with no other staff present.

Patient perception of communication with hospitalists was measured with the CAT.17 This 15‐item survey is written at a fourth grade reading level, and measures responses along a 5‐point scale (1 = poor, 2 = fair, 3 = good, 4 = very good, 5 = excellent). The CAT was originally field tested with a convenience sample of 38 physicians from various regions within the US, across 6 specialties (Dermatology, Family Medicine, Neurosurgery, Ophthalmology, Orthopedic Surgery, and Physical Medicine & Rehabilitation). Each physician's office recruited 25 patients to complete the CAT through a phone or Internet‐based system.

The 14 core items of the CAT, which focus on communication with the individual physician, were used in this study. The 15th item, The doctor's staff treated me with respect, was dropped as it does not reflect the inpatient setting. Results for each physician are reported as the percentage of excellent responses. This dichotomized scoring is consistent with the development study, where analysis with Andrich's rating scale model19, 20 indicated that excellent scores correspond to a yes response while poor through very good scores correspond to a no response. This method of reporting scores as a percentage of excellent responses was found to be more useful for summarizing physician scores than reporting mean scores, which are highly skewed towards positive performance.17

Interviews were conducted by trained research assistants during hospitalists' weekday shifts. Hospitalists were not told which patients would be recruited, but were aware that patients on the service were being interviewed to assess communication. A list of patient names, room numbers, dates of admission, and assigned hospitalists was obtained daily from the electronic medical record system. Patients were approached on the second or third day of the hospital admission, and only if they had been assigned to the same hospitalist for at least 2 consecutive days. After explaining the study to patients and receiving verbal consent, researchers verified that the patient recognized the hospitalist, providing a photo if necessary. Patients who were not confident of their hospitalist's identity were excluded.

The 14 core items of the CAT survey were read aloud to the patient, who was provided with a copy of the instrument's scale and asked to respond with a number or word description (1 = poor to 5 = excellent). Patients were allowed to skip any questions they did not wish to answer. At the conclusion of the survey, patients were asked if they had any further comments to add. Patient demographics as well as hospitalist service (general or teaching) and unit were recorded. Most interviews were completed in less than 5 minutes. Based on the recommendations of the original development and validation of the CAT,17 we collected 20 patient surveys for each hospitalist. For CAT items that the patients skipped, we did not impute values; rather the percentage of excellent responses was calculated based on the number of questions the patient answered. To examine basic psychometric characteristics, we assessed scale reliability and performed a factor analysis using the principal components method of extraction with Varimax rotation.

This project was determined exempt by the Northwestern University Institutional Review Board.

Results

We identified 1,137 patients as potentially eligible for the study. Figure 1 shows a flowchart of patient exclusion. Of note, 107 patients consenting to participate (13% overall) were unable to identify their hospitalist by name or photo. More specifically, 70 teaching service patients (25% of 275 eligible patients) were unable to identify their hospitalist, compared to 37 patients on general service (7% of 553 eligible patients); (z = 7.58, P < 0.001). Another 21 (3%) declined to participate because they had not talked enough with their doctor to render an assessment.

Figure 1

We analyzed 700 patient surveys (20 patients for each of 35 hospitalists; 62% of patients identified). Patient and hospitalist characteristics are presented in Table 1. The proportion of excellent ratings for each hospitalist ranged from 38.5% to 73.5% with an average of 59.1% excellent (standard deviation [SD] = 9.5). See Figure 2 for the distribution of hospitalist scores. For the group as a whole, highest ratings on individual CAT items were for treating the patient with respect (66% excellent), letting the patient talk without interruptions (66%), and talking in terms the patient can understand (64%). Lowest ratings were for involving the patient in decisions as much as he or she wanted (53%), encouraging the patient to ask questions (53%), and greeting the patient in a way that made him or her feel comfortable (55%). Table 2 contains a full ranking of individual item scores.

Figure 2

Overall scale reliability proved to be high (Cronbach's alpha = 0.97) in this sample. The factor analysis showed that scores for each of the 14 items load onto 1 factor. These results are consistent with the high reliability and single‐factor loading found in Makoul's original scale reliability and validity testing.17

The ad hoc comments made by patients at the conclusion of the CAT survey were categorized as positive or negative. Although many positive comments were made, they tended to be general in nature (eg, She is a great doctor). Negative comments were more explicit. A total of 110 patients (16%) made specific negative comments, which fell into 7 general domains: lack of information (35 comments), not enough time spent with the patient (27 comments), poor listening to the patient (24 comments), ineffective care delivery (7 comments), issues of care, concern, and respect (6 comments), ineffective communication with other staff (5 comments), and unclear role of physician (3 comments). Three patient comments were not related to these domains.

Patient age, race or gender did not correlate with CAT results. Hospitalist factors of age, race, gender, years of experience also were not associated with differences in ratings. However, race concordance between the patient and hospitalist was associated with improved CAT ratings. Patients of the same race as their hospitalist rated the hospitalist's communication significantly higher (M = 64.9%, SD = 39.1) than did patients who were of a different race than their hospitalist (M = 57.3%, SD = 40.3), P < 0.05. Gender concordance was not associated with improved CAT ratings. No score differences were found between patients cared for by a hospitalist on teaching service and direct care, and there were no differences between nursing units.

Discussion

To the best of our knowledge, this is the first study to explicitly measure patient perceptions of communication with hospitalists. The results yielded a wide distribution of scores for physicians within a single, large hospital medicine group. Comparing their own scores to those of peers may allow low‐scoring hospitalists to grasp the potential for improving their communication with patients. Our reliability testing matched the results of the original development study,17 indicating very high overall scale reliability. This suggests that the CAT could be streamlined by dropping some of the survey items. However we agree with Makoul et al.17 that it is best to keep the full set as it provides specific information for physicians without placing undue burden on patients (ie, the CAT takes only 1‐2 min to complete). Individual item scores for each of the 14 CAT items highlight specific communication tasks where intervention may be targeted for individual hospitalists and the group as a whole. It may be feasible to utilize CAT results as an individual report card for physicians. While program leaders should be aware that implementation of the CAT requires standardized data collection, it may be possible to build this into existing structures such as the discharge process.

Interestingly, many patients could not recognize the hospitalist caring for them by name or photo. More than 1 in 10 patients (107 of 828; 13%) were unable to identify their hospitalist. This was more than 3 times as common on the teaching service, where the hospitalist is accompanied by house staff and the intern or resident is the primary physician for patient contact, compared to the service on which hospitalists directly take care of patients without residents. It is also troubling that another 3% of patients (21 of 828) stated they hadn't talked enough with their hospitalist to answer basic communication questions, when approached 2 or 3 days into the relationship. It may be telling that Greeted me in a way that made me feel comfortable was one of the lowest‐rated survey items. Hospitalists should recognize that patients, in addition to facing their own physical and emotional stressors, see many hospital staff members throughout the day; all of whom may be strangers to them. Thus it becomes vital for hospitalists to not only establish an initial rapport with the patient, but to reintroduce themselves each time they enter the room.

An examination of the ad hoc negative comments made by survey respondents reinforces and extends findings related to the CAT items, particularly about those areas of communication valued by patients. The majority of comments fell into categories of failing to give enough information (eg, Sometimes I was left confused when the doctor was ready to leave), not spending enough time with the patient (eg, He was just in and out), and not listening to the patient's own ideas (eg, When giving my history, she cut me off at some points when I had more to say). The information and time categories may directly relate to scores on the CAT items Gave me as much information as I wanted and Spent the right amount of time with me, which are among the lowest‐scoring items. Listening to the patient may reflect broader issues of considering the patient's own experience, questions, concerns and goals.

In this study, patient‐physician race concordance was associated with CAT ratings. Patients who were of the same race as their hospitalist rated the hospitalist higher compared to patients who were of a different race than their hospitalist. This effect is consistent with previous research describing higher patient ratings of communication and care when the patient and physician are of the same race or ethnicity.21

A number of factors limit interpretation of the results of this study. The data were collected at a single site, thus limiting generalizability to other hospitalist practice environments. We used a retrospective, patient assessment of hospitalist communication which may have inherent biases different from a study using direct researcher observation or recording of patient‐hospitalist interactions to assess communication. This methodology allowed us to examine the patient's own perceptions and expectations of communication, but certainly leaves room for selection bias in recruitment and recall bias. Patients were interviewed on the second or third day of their admission. This controlled the length of exposure to the hospitalist, but the course of treatment might vary considerably; at the time of interview, some patients may not yet have had a clear diagnosis and plan while others may have been ready for discharge. Future work should examine how stage of evaluation and management might affect patients' perception of communication with hospitalists. Severity of condition is another factor that may affect patients' ratings, and was not examined in this study.

When compared to physicians from the CAT development study's field test, this study sample of hospitalists scored much lower, 59.1% excellent vs. 76.3% (P < 0.001). A number of factors may account for some of these differences. The majority of patients in the original field test had multiple interactions with their physician, and rated their health status as good or very good. In contrast, hospitalized patients usually lack previous exposure to the hospitalist, and likely have poorer health status. Also, physicians in the original field test volunteered to participate, and patients completed the CAT survey through the Internet or phone response system, rather than through a face‐to‐face interview by trained research assistants. Another key difference is that field‐test patients answered the CAT within 1 day of their outpatient visit, while in this study patients were interviewed in the midst of their hospital admission and prior to completion of their hospital course. Finally, patients commonly choose their outpatient physician and can select someone else if dissatisfied with their communication skills, while hospitalized patients are assigned hospitalists based on availability. Thus, given this potential selection bias, outpatients could be expected to rate their personal physician higher.

Another possibility is that hospitalists are on average less skilled in patient communication than outpatient physicians. Given the transient nature of the inpatient relationship, hospitalists may not value developing rapport with patients, and may not make this a goal of patient care or seek extensive training in communication skills. In future research, evaluating hospitalists' training in and attitudes towards patient communication could be paired with communication assessment results.

Although it is beyond the scope of this study to assess precisely how these environmental and survey implementation factors may affect CAT summary scores, their importance is evident. Another hospital‐based implementation of the CAT tool, an evaluation of ED teams,18 utilized face‐to‐face interviews with trained research assistants. The study yielded results similar to our findings: the average percent excellent score for ED teams was 62.3%, vs. 58.2% percent excellent for our hospitalist group. Taken together, these study comparisons between the original field‐test, our hospitalist implementation, and the ED team implementation support the argument that factors of setting (inpatient vs. outpatient), mode of survey administration (face‐to‐face interview vs. self‐administration through phone or Internet), and shorter duration or course of patient‐physician interaction may be important considerations when implementing the CAT tool to assess physician communication skills, or attempting to set standards of minimally acceptable or desired scoring.

More work must be done to establish norms and/or minimally acceptable scores for hospitalists. Numerous factors of specialty, practice setting, survey implementation, patient variables, and even the expertise of who is setting the communication standards22 may strongly influence comparisons between physician groups, even within a single institution. Organizations seeking to establish norms or minimally acceptable scores for physician‐patient communication should be aware of these factors. As the original development study points out, standard‐setting studies could establish specialty‐specific and country‐specific norms as well as norms or standards for level‐of‐training (eg, medical students versus attending physicians).17

Conclusion

The previously validated CAT instrument appears to have reliable test characteristics and can be used to gauge patient perceptions of hospitalist communication skills. Comparative scores between physicians of different specialties and settings should be interpreted cautiously as there may be confounding variables. Within our single institution, comparative scores between hospitalists, along with an examination of the hospitalist's individual item scores, may offer useful feedback for efforts aimed at enhancing communication. Many hospitalists in this study may benefit from targeted training to improve patient communication skills, particularly in the areas of encouraging questions and involving patients in decision making. Future qualitative research in the context of hospital medicine could identify specific communication techniques used by highly‐rated physicians, with the goal of developing tools for targeted improvement and determining impact on outcomes.

Effective communication between patients and physicians improves a number of important outcomes including patient adherence to treatment,1‐3 quality of the medical history4 and clinical outcomes.1, 5, 6 Recognizing the importance of physician communication skills, the American Board of Medical Specialties, American Council for Graduate Medical Education and The Joint Commission all identify communication as a core competency for physicians.7‐9 For hospitalists and their patients, building a therapeutic partnership is challenged by the lack of a preexisting relationship and potential lack of patient history information, particularly psychosocial history.10 Other factors that complicate the relationships between hospitalists and their patients include acuity of illness, limited time course, and absence of or lack of input from patients' primary physicians.11

As a rapidly increasing percentage of hospitalized patients are cared for by hospitalists,12, 13 communication skills need to be directly assessed and addressed. As of 2006, at least 37% of all Medicare claims for inpatient evaluation and management services by general internists were attributed to hospitalists, and more than half of hospitalized Medicare patients are seen by hospitalists.14 Yet, a search of the MEDLINE database for articles published between 1965 and September 2009, querying hospitalist AND patient AND communication within the article title and abstract, yielded only 2 studies assessing hospitalist‐patient communication. A 1998 study15 compared patient‐reported communication problems with hospitalists versus continuity physicians involved with hospital care, and found that patients whose continuity physicians remained involved with care during the hospitalization were less likely to report communication problems than those patients who were cared for by a hospitalist alone. A 2004 study16 utilized chart documentation to compare the end‐of‐life care and communication provided by continuity physicians and hospitalists. Hospitalists were found to document end‐of‐life care discussions more often than continuity physicians, and were more likely to be present for these meetings, which may suggest improved end‐of‐life care. Neither of these hospitalist‐patient communication studies directly assessed patient perceptions of communication with hospitalists.

We undertook this study to explore patient perceptions of communication with hospitalists using the Communication Assessment Tool (CAT), a psychometrically validated instrument for patient assessment of physician communication skills.17 The CAT was initially field tested in outpatient offices, omitting the inpatient experience. A 2008 study18 successfully adapted the CAT tool for use in assessing emergency department (ED) teams. Given the importance of physician‐patient communication when patients are sickest and most vulnerable in the hospital setting, we sought to establish a baseline assessment of patient perceptions of communication with hospitalists in our group. Second, we compared results of our CAT implementation with published results examining communication in other physician groups.

Methods

Between September 2008 and August 2009 we performed a cross‐sectional study of patients admitted to the hospital medicine service at an urban, academic medical center with 873 beds. This busy service was responsible for 10,225 admissions in 2008. Patients of age 18 years or older and cared for by a hospitalist or teaching team led by a hospitalist were eligible to participate. Exclusion criteria included patient confusion, physiological instability, non‐English speaking, patient unable to communicate, or patient in isolation status. Interviews were conducted in the patient's private room with no other staff present.

Patient perception of communication with hospitalists was measured with the CAT.17 This 15‐item survey is written at a fourth grade reading level, and measures responses along a 5‐point scale (1 = poor, 2 = fair, 3 = good, 4 = very good, 5 = excellent). The CAT was originally field tested with a convenience sample of 38 physicians from various regions within the US, across 6 specialties (Dermatology, Family Medicine, Neurosurgery, Ophthalmology, Orthopedic Surgery, and Physical Medicine & Rehabilitation). Each physician's office recruited 25 patients to complete the CAT through a phone or Internet‐based system.

The 14 core items of the CAT, which focus on communication with the individual physician, were used in this study. The 15th item, The doctor's staff treated me with respect, was dropped as it does not reflect the inpatient setting. Results for each physician are reported as the percentage of excellent responses. This dichotomized scoring is consistent with the development study, where analysis with Andrich's rating scale model19, 20 indicated that excellent scores correspond to a yes response while poor through very good scores correspond to a no response. This method of reporting scores as a percentage of excellent responses was found to be more useful for summarizing physician scores than reporting mean scores, which are highly skewed towards positive performance.17

Interviews were conducted by trained research assistants during hospitalists' weekday shifts. Hospitalists were not told which patients would be recruited, but were aware that patients on the service were being interviewed to assess communication. A list of patient names, room numbers, dates of admission, and assigned hospitalists was obtained daily from the electronic medical record system. Patients were approached on the second or third day of the hospital admission, and only if they had been assigned to the same hospitalist for at least 2 consecutive days. After explaining the study to patients and receiving verbal consent, researchers verified that the patient recognized the hospitalist, providing a photo if necessary. Patients who were not confident of their hospitalist's identity were excluded.

The 14 core items of the CAT survey were read aloud to the patient, who was provided with a copy of the instrument's scale and asked to respond with a number or word description (1 = poor to 5 = excellent). Patients were allowed to skip any questions they did not wish to answer. At the conclusion of the survey, patients were asked if they had any further comments to add. Patient demographics as well as hospitalist service (general or teaching) and unit were recorded. Most interviews were completed in less than 5 minutes. Based on the recommendations of the original development and validation of the CAT,17 we collected 20 patient surveys for each hospitalist. For CAT items that the patients skipped, we did not impute values; rather the percentage of excellent responses was calculated based on the number of questions the patient answered. To examine basic psychometric characteristics, we assessed scale reliability and performed a factor analysis using the principal components method of extraction with Varimax rotation.

This project was determined exempt by the Northwestern University Institutional Review Board.

Results

We identified 1,137 patients as potentially eligible for the study. Figure 1 shows a flowchart of patient exclusion. Of note, 107 patients consenting to participate (13% overall) were unable to identify their hospitalist by name or photo. More specifically, 70 teaching service patients (25% of 275 eligible patients) were unable to identify their hospitalist, compared to 37 patients on general service (7% of 553 eligible patients); (z = 7.58, P < 0.001). Another 21 (3%) declined to participate because they had not talked enough with their doctor to render an assessment.

Figure 1

We analyzed 700 patient surveys (20 patients for each of 35 hospitalists; 62% of patients identified). Patient and hospitalist characteristics are presented in Table 1. The proportion of excellent ratings for each hospitalist ranged from 38.5% to 73.5% with an average of 59.1% excellent (standard deviation [SD] = 9.5). See Figure 2 for the distribution of hospitalist scores. For the group as a whole, highest ratings on individual CAT items were for treating the patient with respect (66% excellent), letting the patient talk without interruptions (66%), and talking in terms the patient can understand (64%). Lowest ratings were for involving the patient in decisions as much as he or she wanted (53%), encouraging the patient to ask questions (53%), and greeting the patient in a way that made him or her feel comfortable (55%). Table 2 contains a full ranking of individual item scores.

Figure 2

Overall scale reliability proved to be high (Cronbach's alpha = 0.97) in this sample. The factor analysis showed that scores for each of the 14 items load onto 1 factor. These results are consistent with the high reliability and single‐factor loading found in Makoul's original scale reliability and validity testing.17

The ad hoc comments made by patients at the conclusion of the CAT survey were categorized as positive or negative. Although many positive comments were made, they tended to be general in nature (eg, She is a great doctor). Negative comments were more explicit. A total of 110 patients (16%) made specific negative comments, which fell into 7 general domains: lack of information (35 comments), not enough time spent with the patient (27 comments), poor listening to the patient (24 comments), ineffective care delivery (7 comments), issues of care, concern, and respect (6 comments), ineffective communication with other staff (5 comments), and unclear role of physician (3 comments). Three patient comments were not related to these domains.

Patient age, race or gender did not correlate with CAT results. Hospitalist factors of age, race, gender, years of experience also were not associated with differences in ratings. However, race concordance between the patient and hospitalist was associated with improved CAT ratings. Patients of the same race as their hospitalist rated the hospitalist's communication significantly higher (M = 64.9%, SD = 39.1) than did patients who were of a different race than their hospitalist (M = 57.3%, SD = 40.3), P < 0.05. Gender concordance was not associated with improved CAT ratings. No score differences were found between patients cared for by a hospitalist on teaching service and direct care, and there were no differences between nursing units.

Discussion

To the best of our knowledge, this is the first study to explicitly measure patient perceptions of communication with hospitalists. The results yielded a wide distribution of scores for physicians within a single, large hospital medicine group. Comparing their own scores to those of peers may allow low‐scoring hospitalists to grasp the potential for improving their communication with patients. Our reliability testing matched the results of the original development study,17 indicating very high overall scale reliability. This suggests that the CAT could be streamlined by dropping some of the survey items. However we agree with Makoul et al.17 that it is best to keep the full set as it provides specific information for physicians without placing undue burden on patients (ie, the CAT takes only 1‐2 min to complete). Individual item scores for each of the 14 CAT items highlight specific communication tasks where intervention may be targeted for individual hospitalists and the group as a whole. It may be feasible to utilize CAT results as an individual report card for physicians. While program leaders should be aware that implementation of the CAT requires standardized data collection, it may be possible to build this into existing structures such as the discharge process.

Interestingly, many patients could not recognize the hospitalist caring for them by name or photo. More than 1 in 10 patients (107 of 828; 13%) were unable to identify their hospitalist. This was more than 3 times as common on the teaching service, where the hospitalist is accompanied by house staff and the intern or resident is the primary physician for patient contact, compared to the service on which hospitalists directly take care of patients without residents. It is also troubling that another 3% of patients (21 of 828) stated they hadn't talked enough with their hospitalist to answer basic communication questions, when approached 2 or 3 days into the relationship. It may be telling that Greeted me in a way that made me feel comfortable was one of the lowest‐rated survey items. Hospitalists should recognize that patients, in addition to facing their own physical and emotional stressors, see many hospital staff members throughout the day; all of whom may be strangers to them. Thus it becomes vital for hospitalists to not only establish an initial rapport with the patient, but to reintroduce themselves each time they enter the room.

An examination of the ad hoc negative comments made by survey respondents reinforces and extends findings related to the CAT items, particularly about those areas of communication valued by patients. The majority of comments fell into categories of failing to give enough information (eg, Sometimes I was left confused when the doctor was ready to leave), not spending enough time with the patient (eg, He was just in and out), and not listening to the patient's own ideas (eg, When giving my history, she cut me off at some points when I had more to say). The information and time categories may directly relate to scores on the CAT items Gave me as much information as I wanted and Spent the right amount of time with me, which are among the lowest‐scoring items. Listening to the patient may reflect broader issues of considering the patient's own experience, questions, concerns and goals.

In this study, patient‐physician race concordance was associated with CAT ratings. Patients who were of the same race as their hospitalist rated the hospitalist higher compared to patients who were of a different race than their hospitalist. This effect is consistent with previous research describing higher patient ratings of communication and care when the patient and physician are of the same race or ethnicity.21

A number of factors limit interpretation of the results of this study. The data were collected at a single site, thus limiting generalizability to other hospitalist practice environments. We used a retrospective, patient assessment of hospitalist communication which may have inherent biases different from a study using direct researcher observation or recording of patient‐hospitalist interactions to assess communication. This methodology allowed us to examine the patient's own perceptions and expectations of communication, but certainly leaves room for selection bias in recruitment and recall bias. Patients were interviewed on the second or third day of their admission. This controlled the length of exposure to the hospitalist, but the course of treatment might vary considerably; at the time of interview, some patients may not yet have had a clear diagnosis and plan while others may have been ready for discharge. Future work should examine how stage of evaluation and management might affect patients' perception of communication with hospitalists. Severity of condition is another factor that may affect patients' ratings, and was not examined in this study.

When compared to physicians from the CAT development study's field test, this study sample of hospitalists scored much lower, 59.1% excellent vs. 76.3% (P < 0.001). A number of factors may account for some of these differences. The majority of patients in the original field test had multiple interactions with their physician, and rated their health status as good or very good. In contrast, hospitalized patients usually lack previous exposure to the hospitalist, and likely have poorer health status. Also, physicians in the original field test volunteered to participate, and patients completed the CAT survey through the Internet or phone response system, rather than through a face‐to‐face interview by trained research assistants. Another key difference is that field‐test patients answered the CAT within 1 day of their outpatient visit, while in this study patients were interviewed in the midst of their hospital admission and prior to completion of their hospital course. Finally, patients commonly choose their outpatient physician and can select someone else if dissatisfied with their communication skills, while hospitalized patients are assigned hospitalists based on availability. Thus, given this potential selection bias, outpatients could be expected to rate their personal physician higher.

Another possibility is that hospitalists are on average less skilled in patient communication than outpatient physicians. Given the transient nature of the inpatient relationship, hospitalists may not value developing rapport with patients, and may not make this a goal of patient care or seek extensive training in communication skills. In future research, evaluating hospitalists' training in and attitudes towards patient communication could be paired with communication assessment results.

Although it is beyond the scope of this study to assess precisely how these environmental and survey implementation factors may affect CAT summary scores, their importance is evident. Another hospital‐based implementation of the CAT tool, an evaluation of ED teams,18 utilized face‐to‐face interviews with trained research assistants. The study yielded results similar to our findings: the average percent excellent score for ED teams was 62.3%, vs. 58.2% percent excellent for our hospitalist group. Taken together, these study comparisons between the original field‐test, our hospitalist implementation, and the ED team implementation support the argument that factors of setting (inpatient vs. outpatient), mode of survey administration (face‐to‐face interview vs. self‐administration through phone or Internet), and shorter duration or course of patient‐physician interaction may be important considerations when implementing the CAT tool to assess physician communication skills, or attempting to set standards of minimally acceptable or desired scoring.

More work must be done to establish norms and/or minimally acceptable scores for hospitalists. Numerous factors of specialty, practice setting, survey implementation, patient variables, and even the expertise of who is setting the communication standards22 may strongly influence comparisons between physician groups, even within a single institution. Organizations seeking to establish norms or minimally acceptable scores for physician‐patient communication should be aware of these factors. As the original development study points out, standard‐setting studies could establish specialty‐specific and country‐specific norms as well as norms or standards for level‐of‐training (eg, medical students versus attending physicians).17

Conclusion

The previously validated CAT instrument appears to have reliable test characteristics and can be used to gauge patient perceptions of hospitalist communication skills. Comparative scores between physicians of different specialties and settings should be interpreted cautiously as there may be confounding variables. Within our single institution, comparative scores between hospitalists, along with an examination of the hospitalist's individual item scores, may offer useful feedback for efforts aimed at enhancing communication. Many hospitalists in this study may benefit from targeted training to improve patient communication skills, particularly in the areas of encouraging questions and involving patients in decision making. Future qualitative research in the context of hospital medicine could identify specific communication techniques used by highly‐rated physicians, with the goal of developing tools for targeted improvement and determining impact on outcomes.

A 23‐year‐old man presented to his family physician's office with a 2‐week history of fever, chills, night sweats, anorexia, and fatigue. This was associated with a 4‐month history of a nonproductive cough and a 20‐pound involuntary weight loss. He denied shortness of breath, chest pain, headaches, abdominal pain, vomiting, diarrhea, dysuria, and rash. There was no recent travel, sick contacts, or animal exposures.

This patient's symptoms could represent an underlying infectious, neoplastic, or inflammatory process. I would ascertain any relevant personal or family history and explore whether the patient has risk factors for human immunodeficiency virus (HIV) infection or tuberculosis (TB). On physical examination, I would listen for a heart murmur and look for lymphadenopathy, hepatosplenomegaly, and arthritis. Investigations including cultures, urinalysis, and a chest radiograph would be indicated at this time.

During the 2 weeks after his initial presentation, he experienced persistent fever, and further weight loss. He was admitted to the hospital to determine the etiology of his symptoms. The patient had no previous medical problems. On initial examination, his temperature was 102 degrees Fahrenheit, blood pressure was 100/65 mmHg, heart rate was 105 per minute, respiratory rate was 22 breaths per minute and oxygen saturation was normal on ambient air. He appeared cachectic. He was oriented to person, place, and time. Head and neck examination revealed no intraoral pathology, lymphadenopathy or scleral icterus, but did reveal conjunctival pallor. The chest was clear to auscultation, and the cardiovascular examination revealed a normal apical impulse and heart sounds with no murmurs. There was peripheral edema to the level of the mid‐shins bilaterally. The abdomen was soft and non‐tender with no appreciable hepatosplenomegaly. There were no stigmata of chronic liver disease. There was no axillary or inguinal lymphadenopathy. The remainder of the examination was normal. A complete blood count showed a hemoglobin concentration of 5.2 g/dL with a mean corpuscular volume (MCV) of 89fL, white blood cells were 1,400 cells/mm³ with an absolute neutrophil count (ANC) of 800 cells/mm³ and a platelet count of 90,000 cells/mm³ The serum sodium was 124 mmol/L, potassium 3.0 mmol/L, chloride 91 mmol/L, bicarbonate 26 mmol/L, and the creatinine 1.36 mg/dL His liver enzyme profile showed aspartate aminotransferase (AST) 68 U/L (normal <35), alanine aminotransferase (ALT) 25 U/L (normal <40), alkaline phosphatase (ALP) 210 U/L (normal <110) and a total bilirubin of 1.64 mg/dL.

The patient is clearly very unwell and requires admission to the hospital for treatment and further investigation. Emergent management includes administration of intravenous fluids to correct his electrolyte abnormalities, empiric broad spectrum antibiotics (given his relative neutropenia and fever), and a transfusion for his profound anemia. I would be very concerned that he has an underlying malignancy such as lymphoma or leukemia. Pancytopenia related to decreased cell production may be secondary to infiltration (malignant or granulomatous), infection (HIV, TB, fungal, viral), or aplasia (primary or drug‐related). Less likely etiologies include B12 or folate deficiency (unlikely given the normal MCV), systemic lupus erythematosus, paroxysmal nocturnal hemoglobinuria or cell sequestration due to hypersplenism. A history of recent exposure to drugs or toxins should be elicited. The patient's pulmonary symptoms may relate to the primary disorder or may represent an infection secondary to myelosuppression. I would want an immediate review of the peripheral blood smear, a hemolysis work‐up (drawn prior to transfusion including lactate dehydrogenase [LDH], haptoglobin, fractionated bilirubin, reticulocyte count and direct antiglobulin testing), antinuclear antibody (ANA), B12 and folate levels, imaging of the chest and blood cultures.

With evidence of fever and pancytopenia, acute leukemia was suspected and the patient was admitted to a hematology service. Over the next two weeks an extensive investigation including blood and urine cultures, and computed tomograms (CT) of the chest and abdomen were performed. A bone marrow aspirate and biopsy were also were done and were submitted for histopathologic examination and culture. The CT scan of the chest revealed left axillary and supraclavicular lymphadenopathy (Figure 1), and the abdominal imaging revealed splenomegaly. The blood, urine and bone marrow cultures were all negative. A peripheral blood smear showed pancytopenia with a hematologist interpretation suggesting that an intrinsic bone marrow process may be resulting in impaired cell production. The corresponding bone marrow biopsy and aspirate showed no evidence of malignancy, but there were numerous granulomata, and the periodic acid‐Schiff (PAS) and silver staining showed cells that resembled fungal elements (Figure 2).

Figure 1

Figure 2

The absence of malignant cells in the bone marrow leaves us to consider infectious and inflammatory causes of this patient's presentation. Infectious etiologies associated with bone marrow granulomata include fungal, mycobacterial, bacterial (brucellosis, typhoid and Q fever) and viral pathogens including HIV, Epstein‐Barr virus (EBV), and cytomegalovirus (CMV). Noninfectious causes include sarcoidosis, drug effects, and autoimmune conditions. The PAS and silver staining suggests this patient has a disseminated fungal infection. Disseminated Histoplasma capsulatum is the most likely organism but blastomycosis and coccidioidomycosis should be considered. HIV and occult lymphoma are considerations as is a primary immune disorder such as common variable immunodeficiency (CVID) which can present in this age group. While there is no recent travel history, it will be critical to determine where the patient currently lives and previously resided, review the medical record for prior infections and HIV risk factors, and take a thorough occupational history.

At this point, the following investigations should be undertaken: blood, sputum, and bone marrow culture; fungal and acid‐fast bacilli (AFB) stains on sputum and bone marrow; Histoplasma urine antigen; tuberculin skin test; serology for HIV and histoplasmosis; and serum protein electrophoresis with immunofixation and quantitation of immunoglobulins.

Acid fast staining of the bone marrow as well as mycobacterial and fungal cultures were negative. He lived in eastern Ontario and worked in construction. He reported helping tear down an old cabin in a wooded area, but denied any insect bites. This project coincided with the onset of his cough. He had no history of high risk sexual activity, intravenous drug use, tattoos or blood transfusions previous to his presentation. The HIV test was negative. His clinicians at this point considered a disseminated fungal infection as a cause for his symptoms and started him empirically on itraconazole He was discharged from the hospital with a plan for close outpatient followup. Within three days of discharge on the itraconazole, the patient's fever began to diminish, but did not completely resolve.

The clinical picture including cough, geography, and recent occupational exposure is entirely consistent with disseminated histoplasmosis. However, we are still lacking microbiologic confirmation of the diagnosis. Sarcoidosis and occult malignancy must still be considered. In the absence of a definitive diagnosis, I would consider bronchoscopy with bronchoalveolar lavage (BAL) and obtaining a lymph node or liver biopsy for microbiologic and pathologic examination. With the patient now receiving antifungal therapy, a diagnosis of histoplasmosis would be supported by a response to therapy, declining Histoplasma antigen levels and clinical improvement including recovery of his bone marrow.

The urine specimen was negative for Histoplasma antigen. Seven days after initiating itraconazole, he developed jaundice and confusion and was taken back to the hospital. On presentation, he was disoriented but awake. His temperature was 103.1 degrees Fahrenheit, blood pressure was 90/60 mm Hg, heart rate was 115 per minute, and oxygen saturation was normal on room air. He was obviously jaundiced, and more cachectic than previous. The neurologic examination demonstrated disorientation with no localizing findings. The chest and cardiovascular examinations were normal. His abdomen was soft and non‐tender with no evidence of hepatomegaly, but the spleen tip was palpable. There was no ascites or any other signs of portal hypertension, but his peripheral edema was worse than before and asterixis was present. The remainder of the examination was unchanged from previous. His laboratory investigations at this point showed a bilirubin of 18.5 mg/dL, AST 269 U/L, ALT 76 U/L, ALP 165 U/L, albumin 18 g/L, fibrinogen 1.53 g/L (normal 1.5‐3.5), triglycerides 2.4 mmol/L (normal <2), ferritin 59415 ug/L (normal 22‐275) an international normalized ratio (INR) of 2.65. His complete blood count still showed pancytopenia.

The patient has now developed fulminant hepatic failure. He requires volume resuscitation, drawing of repeat cultures, initiation of empiric broad spectrum antibiotics, urgent hepatology consultation and intensive care unit (ICU) support. The most common causes of acute liver failure are drug toxicity (including acetaminophen), viral hepatitis, Wilson's disease, Budd‐Chiari syndrome, cryptogenic liver disease and fatty infiltration. The critical diagnostic issue at this point is to determine if the liver failure is a secondary process (in which case drug toxicity due to itraconazole would be the most likely cause) or if this represents evolution of his primary disease with extensive hepatic involvement. Liver failure due to itraconazole has been reported and given the lack of microbiologic confirmation of a fungal infection, this agent should clearly be discontinued. Returning to our initial differential diagnosis of this man's granulomatous bone marrow infiltration and pancytopenia, etiologies which may progress to hepatic failure include viral infections (EBV or CMV) and malignancy. This patient's presentation could be an unusual manifestation of a common illness such as EBV or a rapidly progressive lymphoma. An abdominal Doppler ultrasound is required to rule out Budd‐Chiari syndrome. Given his abrupt change in clinical status, I would repeat a CT scan of his chest and abdomen to evaluate for evidence of infection, infiltration, or malignancy. Owing to the uncertainty regarding this patient's diagnosis and the rapidly progressive nature of his disease, serious consideration must be given to a transjugular liver biopsy.

Soon after admission, he developed hematemesis. He was given multiple blood transfusions, and then intravenous fluids, broad spectrum antibiotics and lactulose. Upper gastrointestinal endoscopy showed no varices, but did reveal multiple esophageal and gastric ulcerations. He was then transferred to a liver transplant center where repeat bone marrow biopsy and a liver biopsy were done. Both revealed extensive granulomatosis and the bone marrow biopsy showed evidence of hemophagocytosis (Figure 3).

Figure 3

The finding of hemophagocytosis in the setting of fever, hepatosplenomegaly, and pancytopenia is consistent with a diagnosis of hemophagocytic lymphohistiocytosis (HLH). The cornerstone of therapy for patients with HLH is suppression of the severe inflammatory response with corticosteroids, etoposide and cyclosporin. Patients who respond to this are candidates for allogeneic stem cell transplant with curative intent. This patient's hepatic dysfunction precludes the use of etoposide and initial therapy should therefore include dexamethasone and cyclosporin.

All bacterial, fungal, and mycobacterial cultures again demonstrated no growth. Broad spectrum antibiotics were continued, and empiric intravenous amphotericin B was added. He became hemodynamically unstable, was intubated, put on mechanical ventilation and required vasoactive medications to maintain his blood pressure. An empiric course of pulse corticosteroids was given for the possibility of sarcoidosis. His blood pressure stabilized, though he continued to require vasopressors.

While HLH has been very rarely reported in association with sarcoidosis, the underlying pathogenesis of his clinical presentation (infectious, neoplastic, or inflammatory) has not yet been confirmed. In the meantime, I would continue with supportive care and intravenous corticosteroids.

Immunohistochemical studies of the liver biopsy returned showing CD15/30+ cells with weak‐to‐negative CD45 expression cells typical of Hodgkin lymphoma (HL) (Figure 4). He was started on chemotherapy, but over 48 hours became progressively more hypotensive. The patient died of Klebsiella and Pseudomonas sepsis on the 7th hospital day. Post‐mortem immunohistochemical examination revealed evidence of Hodgkin disease in the axillary lymph nodes, bone marrow and liver. The bone marrow showed evidence of hemophagocytosis and was also positive for Epstein‐Barr encoded RNA (EBER). Serologic studies were subsequently available and revealed positive EBV IgM against the viral capsid antigen (VCA) as well as EBV IgG VCA, which in conjunction with the marrow findings, was highly suggestive of reactivation EBV disease.

Figure 4

Discussion

This patient's diagnostic course led both the clinical team and discussant down a winding path, which ultimately ended in the finding of Hodgkin lymphoma, a relatively common diagnosis that had been clouded by seemingly contradictory clinical and laboratory data. The provisional diagnosis of disseminated histoplasmosis was reasonable given that H. capsulatum is endemic in Ontario and that the patient's occupation placed him at risk of infection. Given the acuity of his illness, empiric antifungal therapy based on the report of fungal elements on bone marrow examination seemed reasonable. However, Histoplasma urinary antigen testing has been shown in the literature to be 98% sensitive in immunosuppressed populations, and the negative result prompted a re‐examination of the marrow specimen. The previously described fungal elements were felt to be most likely artifact, and the underlying diagnosis was reconsidered.¹ This is when the repeat bone marrow examination pointed towards the diagnosis of HLH.

Hemophagocytic lymphohistiocytosis (HLH) is a severe, systemic hyperinflammatory disorder characterized by histiocytic proliferation that may be primary or can be triggered by infection, connective tissue diseases or malignancy.25 The central pathogenesis involves dysregulated Th1 cytokine secretion. This results in an uncontrolled accumulation of activated T‐lymphocytes and histiocytes in various organs including the liver, spleen and bone marrow. The infiltration of histiocytes into major organs can lead to disruption of function and multiorgan failure.6 Viruses are the most common infectious triggers of HLH, particularly EBV, and lymphoma is the most common associated malignancy.25 It is hypothesized that EBV can interfere with normal lymphocyte signaling pathways leading to the aforementioned over‐expression of Th1 cytokines, which can then trigger HLH.7 The diagnosis of HLH is based on a combination of clinical and laboratory parameters as outlined in Table 1.8 Our patient met all five of the major criteria.

The recommended treatment of HLH involves the administration of the HLH‐94 protocol consisting of corticosteroids, cyclosporine and etoposide.9, 10 Those who survive this initial phase are recommended for hematopoetic stem cell transplantation producing an overall 3‐year survival rate of 64%. However, those who do not receive early etoposide therapy fare much worse, with a mortality rate of 92%.10 This patient was not able to receive etoposide because of his decompensated liver disease.

In this case, the development of Hodgkin lymphoma involving the bone marrow and liver may have resulted in a state of immune suppression. The loss of immune function likely allowed the reactivation of Epstein‐Barr virus which triggered HLH and his fulminant presentation.^35,9 Indeed, both the liver and bone marrow samples showed evidence of EBV reactivation as evidenced by the presence of EBER. The diagnosis of Hodgkin lymphoma was made from a liver biopsy specimen rather than bone marrow examination. The diagnosis of Hodgkin lymphoma is based on the presence of Reed‐Sternberg cells surrounded by an inflammatory milieu of cells including variable numbers of small lymphocytes, neutrophils eosinophils and fibroblasts. The HLH‐induced pancytopenia depleted the aforementioned inflammatory milieu in the bone marrow, which obscured the diagnosis of Hodgkin lymphoma. Unfortunately, lymphoma‐associated HLH has a very poor prognosis with a mortality rate of up to 60%.⁴ At the outset of this case, the reported fungal elements proved to be a source of confusion which delayed the diagnosis of Hodgkin lymphoma. Given the poor prognosis of lymphoma‐associated HLH, it is unlikely this would have had any effect on the ultimate outcome.

A 23‐year‐old man presented to his family physician's office with a 2‐week history of fever, chills, night sweats, anorexia, and fatigue. This was associated with a 4‐month history of a nonproductive cough and a 20‐pound involuntary weight loss. He denied shortness of breath, chest pain, headaches, abdominal pain, vomiting, diarrhea, dysuria, and rash. There was no recent travel, sick contacts, or animal exposures.

This patient's symptoms could represent an underlying infectious, neoplastic, or inflammatory process. I would ascertain any relevant personal or family history and explore whether the patient has risk factors for human immunodeficiency virus (HIV) infection or tuberculosis (TB). On physical examination, I would listen for a heart murmur and look for lymphadenopathy, hepatosplenomegaly, and arthritis. Investigations including cultures, urinalysis, and a chest radiograph would be indicated at this time.

During the 2 weeks after his initial presentation, he experienced persistent fever, and further weight loss. He was admitted to the hospital to determine the etiology of his symptoms. The patient had no previous medical problems. On initial examination, his temperature was 102 degrees Fahrenheit, blood pressure was 100/65 mmHg, heart rate was 105 per minute, respiratory rate was 22 breaths per minute and oxygen saturation was normal on ambient air. He appeared cachectic. He was oriented to person, place, and time. Head and neck examination revealed no intraoral pathology, lymphadenopathy or scleral icterus, but did reveal conjunctival pallor. The chest was clear to auscultation, and the cardiovascular examination revealed a normal apical impulse and heart sounds with no murmurs. There was peripheral edema to the level of the mid‐shins bilaterally. The abdomen was soft and non‐tender with no appreciable hepatosplenomegaly. There were no stigmata of chronic liver disease. There was no axillary or inguinal lymphadenopathy. The remainder of the examination was normal. A complete blood count showed a hemoglobin concentration of 5.2 g/dL with a mean corpuscular volume (MCV) of 89fL, white blood cells were 1,400 cells/mm³ with an absolute neutrophil count (ANC) of 800 cells/mm³ and a platelet count of 90,000 cells/mm³ The serum sodium was 124 mmol/L, potassium 3.0 mmol/L, chloride 91 mmol/L, bicarbonate 26 mmol/L, and the creatinine 1.36 mg/dL His liver enzyme profile showed aspartate aminotransferase (AST) 68 U/L (normal <35), alanine aminotransferase (ALT) 25 U/L (normal <40), alkaline phosphatase (ALP) 210 U/L (normal <110) and a total bilirubin of 1.64 mg/dL.

The patient is clearly very unwell and requires admission to the hospital for treatment and further investigation. Emergent management includes administration of intravenous fluids to correct his electrolyte abnormalities, empiric broad spectrum antibiotics (given his relative neutropenia and fever), and a transfusion for his profound anemia. I would be very concerned that he has an underlying malignancy such as lymphoma or leukemia. Pancytopenia related to decreased cell production may be secondary to infiltration (malignant or granulomatous), infection (HIV, TB, fungal, viral), or aplasia (primary or drug‐related). Less likely etiologies include B12 or folate deficiency (unlikely given the normal MCV), systemic lupus erythematosus, paroxysmal nocturnal hemoglobinuria or cell sequestration due to hypersplenism. A history of recent exposure to drugs or toxins should be elicited. The patient's pulmonary symptoms may relate to the primary disorder or may represent an infection secondary to myelosuppression. I would want an immediate review of the peripheral blood smear, a hemolysis work‐up (drawn prior to transfusion including lactate dehydrogenase [LDH], haptoglobin, fractionated bilirubin, reticulocyte count and direct antiglobulin testing), antinuclear antibody (ANA), B12 and folate levels, imaging of the chest and blood cultures.

With evidence of fever and pancytopenia, acute leukemia was suspected and the patient was admitted to a hematology service. Over the next two weeks an extensive investigation including blood and urine cultures, and computed tomograms (CT) of the chest and abdomen were performed. A bone marrow aspirate and biopsy were also were done and were submitted for histopathologic examination and culture. The CT scan of the chest revealed left axillary and supraclavicular lymphadenopathy (Figure 1), and the abdominal imaging revealed splenomegaly. The blood, urine and bone marrow cultures were all negative. A peripheral blood smear showed pancytopenia with a hematologist interpretation suggesting that an intrinsic bone marrow process may be resulting in impaired cell production. The corresponding bone marrow biopsy and aspirate showed no evidence of malignancy, but there were numerous granulomata, and the periodic acid‐Schiff (PAS) and silver staining showed cells that resembled fungal elements (Figure 2).

Figure 1

Figure 2

The absence of malignant cells in the bone marrow leaves us to consider infectious and inflammatory causes of this patient's presentation. Infectious etiologies associated with bone marrow granulomata include fungal, mycobacterial, bacterial (brucellosis, typhoid and Q fever) and viral pathogens including HIV, Epstein‐Barr virus (EBV), and cytomegalovirus (CMV). Noninfectious causes include sarcoidosis, drug effects, and autoimmune conditions. The PAS and silver staining suggests this patient has a disseminated fungal infection. Disseminated Histoplasma capsulatum is the most likely organism but blastomycosis and coccidioidomycosis should be considered. HIV and occult lymphoma are considerations as is a primary immune disorder such as common variable immunodeficiency (CVID) which can present in this age group. While there is no recent travel history, it will be critical to determine where the patient currently lives and previously resided, review the medical record for prior infections and HIV risk factors, and take a thorough occupational history.

At this point, the following investigations should be undertaken: blood, sputum, and bone marrow culture; fungal and acid‐fast bacilli (AFB) stains on sputum and bone marrow; Histoplasma urine antigen; tuberculin skin test; serology for HIV and histoplasmosis; and serum protein electrophoresis with immunofixation and quantitation of immunoglobulins.

Acid fast staining of the bone marrow as well as mycobacterial and fungal cultures were negative. He lived in eastern Ontario and worked in construction. He reported helping tear down an old cabin in a wooded area, but denied any insect bites. This project coincided with the onset of his cough. He had no history of high risk sexual activity, intravenous drug use, tattoos or blood transfusions previous to his presentation. The HIV test was negative. His clinicians at this point considered a disseminated fungal infection as a cause for his symptoms and started him empirically on itraconazole He was discharged from the hospital with a plan for close outpatient followup. Within three days of discharge on the itraconazole, the patient's fever began to diminish, but did not completely resolve.

The clinical picture including cough, geography, and recent occupational exposure is entirely consistent with disseminated histoplasmosis. However, we are still lacking microbiologic confirmation of the diagnosis. Sarcoidosis and occult malignancy must still be considered. In the absence of a definitive diagnosis, I would consider bronchoscopy with bronchoalveolar lavage (BAL) and obtaining a lymph node or liver biopsy for microbiologic and pathologic examination. With the patient now receiving antifungal therapy, a diagnosis of histoplasmosis would be supported by a response to therapy, declining Histoplasma antigen levels and clinical improvement including recovery of his bone marrow.

The urine specimen was negative for Histoplasma antigen. Seven days after initiating itraconazole, he developed jaundice and confusion and was taken back to the hospital. On presentation, he was disoriented but awake. His temperature was 103.1 degrees Fahrenheit, blood pressure was 90/60 mm Hg, heart rate was 115 per minute, and oxygen saturation was normal on room air. He was obviously jaundiced, and more cachectic than previous. The neurologic examination demonstrated disorientation with no localizing findings. The chest and cardiovascular examinations were normal. His abdomen was soft and non‐tender with no evidence of hepatomegaly, but the spleen tip was palpable. There was no ascites or any other signs of portal hypertension, but his peripheral edema was worse than before and asterixis was present. The remainder of the examination was unchanged from previous. His laboratory investigations at this point showed a bilirubin of 18.5 mg/dL, AST 269 U/L, ALT 76 U/L, ALP 165 U/L, albumin 18 g/L, fibrinogen 1.53 g/L (normal 1.5‐3.5), triglycerides 2.4 mmol/L (normal <2), ferritin 59415 ug/L (normal 22‐275) an international normalized ratio (INR) of 2.65. His complete blood count still showed pancytopenia.

The patient has now developed fulminant hepatic failure. He requires volume resuscitation, drawing of repeat cultures, initiation of empiric broad spectrum antibiotics, urgent hepatology consultation and intensive care unit (ICU) support. The most common causes of acute liver failure are drug toxicity (including acetaminophen), viral hepatitis, Wilson's disease, Budd‐Chiari syndrome, cryptogenic liver disease and fatty infiltration. The critical diagnostic issue at this point is to determine if the liver failure is a secondary process (in which case drug toxicity due to itraconazole would be the most likely cause) or if this represents evolution of his primary disease with extensive hepatic involvement. Liver failure due to itraconazole has been reported and given the lack of microbiologic confirmation of a fungal infection, this agent should clearly be discontinued. Returning to our initial differential diagnosis of this man's granulomatous bone marrow infiltration and pancytopenia, etiologies which may progress to hepatic failure include viral infections (EBV or CMV) and malignancy. This patient's presentation could be an unusual manifestation of a common illness such as EBV or a rapidly progressive lymphoma. An abdominal Doppler ultrasound is required to rule out Budd‐Chiari syndrome. Given his abrupt change in clinical status, I would repeat a CT scan of his chest and abdomen to evaluate for evidence of infection, infiltration, or malignancy. Owing to the uncertainty regarding this patient's diagnosis and the rapidly progressive nature of his disease, serious consideration must be given to a transjugular liver biopsy.

Soon after admission, he developed hematemesis. He was given multiple blood transfusions, and then intravenous fluids, broad spectrum antibiotics and lactulose. Upper gastrointestinal endoscopy showed no varices, but did reveal multiple esophageal and gastric ulcerations. He was then transferred to a liver transplant center where repeat bone marrow biopsy and a liver biopsy were done. Both revealed extensive granulomatosis and the bone marrow biopsy showed evidence of hemophagocytosis (Figure 3).

Figure 3

The finding of hemophagocytosis in the setting of fever, hepatosplenomegaly, and pancytopenia is consistent with a diagnosis of hemophagocytic lymphohistiocytosis (HLH). The cornerstone of therapy for patients with HLH is suppression of the severe inflammatory response with corticosteroids, etoposide and cyclosporin. Patients who respond to this are candidates for allogeneic stem cell transplant with curative intent. This patient's hepatic dysfunction precludes the use of etoposide and initial therapy should therefore include dexamethasone and cyclosporin.

All bacterial, fungal, and mycobacterial cultures again demonstrated no growth. Broad spectrum antibiotics were continued, and empiric intravenous amphotericin B was added. He became hemodynamically unstable, was intubated, put on mechanical ventilation and required vasoactive medications to maintain his blood pressure. An empiric course of pulse corticosteroids was given for the possibility of sarcoidosis. His blood pressure stabilized, though he continued to require vasopressors.

While HLH has been very rarely reported in association with sarcoidosis, the underlying pathogenesis of his clinical presentation (infectious, neoplastic, or inflammatory) has not yet been confirmed. In the meantime, I would continue with supportive care and intravenous corticosteroids.

Immunohistochemical studies of the liver biopsy returned showing CD15/30+ cells with weak‐to‐negative CD45 expression cells typical of Hodgkin lymphoma (HL) (Figure 4). He was started on chemotherapy, but over 48 hours became progressively more hypotensive. The patient died of Klebsiella and Pseudomonas sepsis on the 7th hospital day. Post‐mortem immunohistochemical examination revealed evidence of Hodgkin disease in the axillary lymph nodes, bone marrow and liver. The bone marrow showed evidence of hemophagocytosis and was also positive for Epstein‐Barr encoded RNA (EBER). Serologic studies were subsequently available and revealed positive EBV IgM against the viral capsid antigen (VCA) as well as EBV IgG VCA, which in conjunction with the marrow findings, was highly suggestive of reactivation EBV disease.

Figure 4

Discussion

This patient's diagnostic course led both the clinical team and discussant down a winding path, which ultimately ended in the finding of Hodgkin lymphoma, a relatively common diagnosis that had been clouded by seemingly contradictory clinical and laboratory data. The provisional diagnosis of disseminated histoplasmosis was reasonable given that H. capsulatum is endemic in Ontario and that the patient's occupation placed him at risk of infection. Given the acuity of his illness, empiric antifungal therapy based on the report of fungal elements on bone marrow examination seemed reasonable. However, Histoplasma urinary antigen testing has been shown in the literature to be 98% sensitive in immunosuppressed populations, and the negative result prompted a re‐examination of the marrow specimen. The previously described fungal elements were felt to be most likely artifact, and the underlying diagnosis was reconsidered.¹ This is when the repeat bone marrow examination pointed towards the diagnosis of HLH.

Hemophagocytic lymphohistiocytosis (HLH) is a severe, systemic hyperinflammatory disorder characterized by histiocytic proliferation that may be primary or can be triggered by infection, connective tissue diseases or malignancy.25 The central pathogenesis involves dysregulated Th1 cytokine secretion. This results in an uncontrolled accumulation of activated T‐lymphocytes and histiocytes in various organs including the liver, spleen and bone marrow. The infiltration of histiocytes into major organs can lead to disruption of function and multiorgan failure.6 Viruses are the most common infectious triggers of HLH, particularly EBV, and lymphoma is the most common associated malignancy.25 It is hypothesized that EBV can interfere with normal lymphocyte signaling pathways leading to the aforementioned over‐expression of Th1 cytokines, which can then trigger HLH.7 The diagnosis of HLH is based on a combination of clinical and laboratory parameters as outlined in Table 1.8 Our patient met all five of the major criteria.

The recommended treatment of HLH involves the administration of the HLH‐94 protocol consisting of corticosteroids, cyclosporine and etoposide.9, 10 Those who survive this initial phase are recommended for hematopoetic stem cell transplantation producing an overall 3‐year survival rate of 64%. However, those who do not receive early etoposide therapy fare much worse, with a mortality rate of 92%.10 This patient was not able to receive etoposide because of his decompensated liver disease.

In this case, the development of Hodgkin lymphoma involving the bone marrow and liver may have resulted in a state of immune suppression. The loss of immune function likely allowed the reactivation of Epstein‐Barr virus which triggered HLH and his fulminant presentation.^35,9 Indeed, both the liver and bone marrow samples showed evidence of EBV reactivation as evidenced by the presence of EBER. The diagnosis of Hodgkin lymphoma was made from a liver biopsy specimen rather than bone marrow examination. The diagnosis of Hodgkin lymphoma is based on the presence of Reed‐Sternberg cells surrounded by an inflammatory milieu of cells including variable numbers of small lymphocytes, neutrophils eosinophils and fibroblasts. The HLH‐induced pancytopenia depleted the aforementioned inflammatory milieu in the bone marrow, which obscured the diagnosis of Hodgkin lymphoma. Unfortunately, lymphoma‐associated HLH has a very poor prognosis with a mortality rate of up to 60%.⁴ At the outset of this case, the reported fungal elements proved to be a source of confusion which delayed the diagnosis of Hodgkin lymphoma. Given the poor prognosis of lymphoma‐associated HLH, it is unlikely this would have had any effect on the ultimate outcome.

A 23‐year‐old man presented to his family physician's office with a 2‐week history of fever, chills, night sweats, anorexia, and fatigue. This was associated with a 4‐month history of a nonproductive cough and a 20‐pound involuntary weight loss. He denied shortness of breath, chest pain, headaches, abdominal pain, vomiting, diarrhea, dysuria, and rash. There was no recent travel, sick contacts, or animal exposures.

This patient's symptoms could represent an underlying infectious, neoplastic, or inflammatory process. I would ascertain any relevant personal or family history and explore whether the patient has risk factors for human immunodeficiency virus (HIV) infection or tuberculosis (TB). On physical examination, I would listen for a heart murmur and look for lymphadenopathy, hepatosplenomegaly, and arthritis. Investigations including cultures, urinalysis, and a chest radiograph would be indicated at this time.

During the 2 weeks after his initial presentation, he experienced persistent fever, and further weight loss. He was admitted to the hospital to determine the etiology of his symptoms. The patient had no previous medical problems. On initial examination, his temperature was 102 degrees Fahrenheit, blood pressure was 100/65 mmHg, heart rate was 105 per minute, respiratory rate was 22 breaths per minute and oxygen saturation was normal on ambient air. He appeared cachectic. He was oriented to person, place, and time. Head and neck examination revealed no intraoral pathology, lymphadenopathy or scleral icterus, but did reveal conjunctival pallor. The chest was clear to auscultation, and the cardiovascular examination revealed a normal apical impulse and heart sounds with no murmurs. There was peripheral edema to the level of the mid‐shins bilaterally. The abdomen was soft and non‐tender with no appreciable hepatosplenomegaly. There were no stigmata of chronic liver disease. There was no axillary or inguinal lymphadenopathy. The remainder of the examination was normal. A complete blood count showed a hemoglobin concentration of 5.2 g/dL with a mean corpuscular volume (MCV) of 89fL, white blood cells were 1,400 cells/mm³ with an absolute neutrophil count (ANC) of 800 cells/mm³ and a platelet count of 90,000 cells/mm³ The serum sodium was 124 mmol/L, potassium 3.0 mmol/L, chloride 91 mmol/L, bicarbonate 26 mmol/L, and the creatinine 1.36 mg/dL His liver enzyme profile showed aspartate aminotransferase (AST) 68 U/L (normal <35), alanine aminotransferase (ALT) 25 U/L (normal <40), alkaline phosphatase (ALP) 210 U/L (normal <110) and a total bilirubin of 1.64 mg/dL.