LONDON – The European League Against Rheumatism and the European Federation of National Associations of Orthopaedics and Traumatology have joined forces to develop recommendations for the prevention and management of fragility fractures.

Such fractures are common in men and women over the age of 50 years and can lead to repeat fracture in some patients. The recommendations are unique as they are the first to consider both acute orthopedic and postfracture rheumatologic care, said Willem F. Lems, MD, PhD, of the Amsterdam Rheumatology and Immunology Centre.

At the European Congress of Rheumatology, Dr. Lems provided an overview of the draft recommendations, noting that there would be several overarching principles, one of which recognized the multidisciplinary nature of caring for someone with a fragility fracture. An important point is not who is taking care of the patient, but that the patient is given the best possible care within the multidisciplinary framework.

Wikimedia Commons/Sjoehest/ CC BY-llSA 3.0

What constitutes optimal care of course depends on the clinical situation, notably the type of fracture and the age of the patient, and optimal care in all phases of presentation (pre-, peri- and postoperative) can have an important effect on a patient’s outcome. The prevention of subsequent fractures is a key focus, with the recommendation that all patients should be investigated systematically and those deemed at high risk for another fracture should be prescribed both pharmacologic and nonpharmacologic interventions as appropriate. Patient education is also considered important.

As for all EULAR-developed recommendations, standard procedures were followed that involved convening an expert scientific advisory committee and using the Delphi technique to come up with the most important research questions that would be used to formulate the final 10 recommendations. Four of the recommendations cover the acute care setting and six provide advice on postfracture care.

The first of the acute care recommendations looks at pre- and perioperative management of a fragility fracture and highlights that, within 24-48 hours of admission, patients should receive adequate pain and fluid management and treatment, including early surgery if appropriate. This is based on evidence that better outcomes can be achieved in terms of both morbidity and mortality if patients can be seen and managed quickly.

Another of the acute care recommendations focuses on orthogeriatric care, noting that the orthopedic surgeon and a dedicated orthogeriatric team should work together, particularly for elderly patients who have suffered a hip fracture. Key elements here are the management of and prevention of delirium, deep vein thrombosis, pressure sores, and malnutrition.

As for actual fracture treatment, a balanced approach is advised when deciding upon a surgical or nonsurgical approach, especially because this is likely to be an older population with other comorbidities. Only one in three vertebral fractures are symptomatic and only about 10% of patients will be hospitalized for pain. Analgesics, modifying activities, and bracing can be options here. Surgical options for distal radial fracture, hip fracture, and trochanteric and femoral neck fractures are included.

The fourth recommendation looks at the organization of postfracture care and the need for a systematic approach to identify those who may be at risk for subsequent fractures, starting with the suggestion that any patient older than 50 years with a recent fracture should be assessed. The fifth recommendation addresses ways to evaluate this risk, such as looking at the clinical risk factors, performing bone scans and imaging, and screening for underlying osteoporosis or metabolic disorders.

Implementation is the next step, and the sixth recommendation suggests ways these recommendations could be integrated into routine practice. Often one of the biggest barriers to effective postfracture care is the lack of patient, and sometimes clinician, awareness of the risk for a subsequent fracture. This recommendation looks at the role of a possible local fracture liaison service or facilitator to coordinate between the various members of the multidisciplinary team from secondary (orthopedic surgeons, rheumatologists, endocrinologists, and geriatricians) to primary care.

The seventh recommendation addresses rehabilitation and the need to initiate physical training and muscle strengthening as early as possible after the initial fracture, with long-term continuation of balance training and fall prevention.

The final three recommendations focus on how to educate patients about their risk factors, need for follow-up, and the duration of any pharmacologic or nonpharmacologic therapy that they may need. Nonpharmacologic options might include stopping smoking, limiting alcohol intake, as well as taking supplements such as calcium or vitamin D. There will be specific guidance on the use of calcium and vitamin D, which have both pros and cons, but the optimal dosage appears to be 1,000–1,200 mg/day for calcium and 800 IU/day for vitamin D.

Pharmacologic options to prevent subsequent fragility fractures include the bisphosphonates alendronate, risedronate, and zoledronic acid (Reclast), and also the monoclonal antibody denosumab (Prolia). These are the only drugs that have been shown to reduced the risk for vertebral, nonvertebral, and hip fractures in primary analyses. Adherence, tolerance, and regular monitoring are key, and a five-step plan is suggested to aid clinical decision making that covers case finding, risk evaluation, differential diagnosis, treatment, and follow-up.

The recommendations are being finalized and should be available for publication later this year. The recommendations task force also plans to propose a research agenda.

Dr. Lems had no relevant disclosures.

LONDON – The European League Against Rheumatism and the European Federation of National Associations of Orthopaedics and Traumatology have joined forces to develop recommendations for the prevention and management of fragility fractures.

Such fractures are common in men and women over the age of 50 years and can lead to repeat fracture in some patients. The recommendations are unique as they are the first to consider both acute orthopedic and postfracture rheumatologic care, said Willem F. Lems, MD, PhD, of the Amsterdam Rheumatology and Immunology Centre.

At the European Congress of Rheumatology, Dr. Lems provided an overview of the draft recommendations, noting that there would be several overarching principles, one of which recognized the multidisciplinary nature of caring for someone with a fragility fracture. An important point is not who is taking care of the patient, but that the patient is given the best possible care within the multidisciplinary framework.

Wikimedia Commons/Sjoehest/ CC BY-llSA 3.0

What constitutes optimal care of course depends on the clinical situation, notably the type of fracture and the age of the patient, and optimal care in all phases of presentation (pre-, peri- and postoperative) can have an important effect on a patient’s outcome. The prevention of subsequent fractures is a key focus, with the recommendation that all patients should be investigated systematically and those deemed at high risk for another fracture should be prescribed both pharmacologic and nonpharmacologic interventions as appropriate. Patient education is also considered important.

As for all EULAR-developed recommendations, standard procedures were followed that involved convening an expert scientific advisory committee and using the Delphi technique to come up with the most important research questions that would be used to formulate the final 10 recommendations. Four of the recommendations cover the acute care setting and six provide advice on postfracture care.

The first of the acute care recommendations looks at pre- and perioperative management of a fragility fracture and highlights that, within 24-48 hours of admission, patients should receive adequate pain and fluid management and treatment, including early surgery if appropriate. This is based on evidence that better outcomes can be achieved in terms of both morbidity and mortality if patients can be seen and managed quickly.

Another of the acute care recommendations focuses on orthogeriatric care, noting that the orthopedic surgeon and a dedicated orthogeriatric team should work together, particularly for elderly patients who have suffered a hip fracture. Key elements here are the management of and prevention of delirium, deep vein thrombosis, pressure sores, and malnutrition.

As for actual fracture treatment, a balanced approach is advised when deciding upon a surgical or nonsurgical approach, especially because this is likely to be an older population with other comorbidities. Only one in three vertebral fractures are symptomatic and only about 10% of patients will be hospitalized for pain. Analgesics, modifying activities, and bracing can be options here. Surgical options for distal radial fracture, hip fracture, and trochanteric and femoral neck fractures are included.

The fourth recommendation looks at the organization of postfracture care and the need for a systematic approach to identify those who may be at risk for subsequent fractures, starting with the suggestion that any patient older than 50 years with a recent fracture should be assessed. The fifth recommendation addresses ways to evaluate this risk, such as looking at the clinical risk factors, performing bone scans and imaging, and screening for underlying osteoporosis or metabolic disorders.

Implementation is the next step, and the sixth recommendation suggests ways these recommendations could be integrated into routine practice. Often one of the biggest barriers to effective postfracture care is the lack of patient, and sometimes clinician, awareness of the risk for a subsequent fracture. This recommendation looks at the role of a possible local fracture liaison service or facilitator to coordinate between the various members of the multidisciplinary team from secondary (orthopedic surgeons, rheumatologists, endocrinologists, and geriatricians) to primary care.

The seventh recommendation addresses rehabilitation and the need to initiate physical training and muscle strengthening as early as possible after the initial fracture, with long-term continuation of balance training and fall prevention.

The final three recommendations focus on how to educate patients about their risk factors, need for follow-up, and the duration of any pharmacologic or nonpharmacologic therapy that they may need. Nonpharmacologic options might include stopping smoking, limiting alcohol intake, as well as taking supplements such as calcium or vitamin D. There will be specific guidance on the use of calcium and vitamin D, which have both pros and cons, but the optimal dosage appears to be 1,000–1,200 mg/day for calcium and 800 IU/day for vitamin D.

Pharmacologic options to prevent subsequent fragility fractures include the bisphosphonates alendronate, risedronate, and zoledronic acid (Reclast), and also the monoclonal antibody denosumab (Prolia). These are the only drugs that have been shown to reduced the risk for vertebral, nonvertebral, and hip fractures in primary analyses. Adherence, tolerance, and regular monitoring are key, and a five-step plan is suggested to aid clinical decision making that covers case finding, risk evaluation, differential diagnosis, treatment, and follow-up.

The recommendations are being finalized and should be available for publication later this year. The recommendations task force also plans to propose a research agenda.

Dr. Lems had no relevant disclosures.

LONDON – The European League Against Rheumatism and the European Federation of National Associations of Orthopaedics and Traumatology have joined forces to develop recommendations for the prevention and management of fragility fractures.

Such fractures are common in men and women over the age of 50 years and can lead to repeat fracture in some patients. The recommendations are unique as they are the first to consider both acute orthopedic and postfracture rheumatologic care, said Willem F. Lems, MD, PhD, of the Amsterdam Rheumatology and Immunology Centre.

At the European Congress of Rheumatology, Dr. Lems provided an overview of the draft recommendations, noting that there would be several overarching principles, one of which recognized the multidisciplinary nature of caring for someone with a fragility fracture. An important point is not who is taking care of the patient, but that the patient is given the best possible care within the multidisciplinary framework.

Wikimedia Commons/Sjoehest/ CC BY-llSA 3.0

What constitutes optimal care of course depends on the clinical situation, notably the type of fracture and the age of the patient, and optimal care in all phases of presentation (pre-, peri- and postoperative) can have an important effect on a patient’s outcome. The prevention of subsequent fractures is a key focus, with the recommendation that all patients should be investigated systematically and those deemed at high risk for another fracture should be prescribed both pharmacologic and nonpharmacologic interventions as appropriate. Patient education is also considered important.

As for all EULAR-developed recommendations, standard procedures were followed that involved convening an expert scientific advisory committee and using the Delphi technique to come up with the most important research questions that would be used to formulate the final 10 recommendations. Four of the recommendations cover the acute care setting and six provide advice on postfracture care.

The first of the acute care recommendations looks at pre- and perioperative management of a fragility fracture and highlights that, within 24-48 hours of admission, patients should receive adequate pain and fluid management and treatment, including early surgery if appropriate. This is based on evidence that better outcomes can be achieved in terms of both morbidity and mortality if patients can be seen and managed quickly.

Another of the acute care recommendations focuses on orthogeriatric care, noting that the orthopedic surgeon and a dedicated orthogeriatric team should work together, particularly for elderly patients who have suffered a hip fracture. Key elements here are the management of and prevention of delirium, deep vein thrombosis, pressure sores, and malnutrition.

As for actual fracture treatment, a balanced approach is advised when deciding upon a surgical or nonsurgical approach, especially because this is likely to be an older population with other comorbidities. Only one in three vertebral fractures are symptomatic and only about 10% of patients will be hospitalized for pain. Analgesics, modifying activities, and bracing can be options here. Surgical options for distal radial fracture, hip fracture, and trochanteric and femoral neck fractures are included.

The fourth recommendation looks at the organization of postfracture care and the need for a systematic approach to identify those who may be at risk for subsequent fractures, starting with the suggestion that any patient older than 50 years with a recent fracture should be assessed. The fifth recommendation addresses ways to evaluate this risk, such as looking at the clinical risk factors, performing bone scans and imaging, and screening for underlying osteoporosis or metabolic disorders.

Implementation is the next step, and the sixth recommendation suggests ways these recommendations could be integrated into routine practice. Often one of the biggest barriers to effective postfracture care is the lack of patient, and sometimes clinician, awareness of the risk for a subsequent fracture. This recommendation looks at the role of a possible local fracture liaison service or facilitator to coordinate between the various members of the multidisciplinary team from secondary (orthopedic surgeons, rheumatologists, endocrinologists, and geriatricians) to primary care.

The seventh recommendation addresses rehabilitation and the need to initiate physical training and muscle strengthening as early as possible after the initial fracture, with long-term continuation of balance training and fall prevention.

The final three recommendations focus on how to educate patients about their risk factors, need for follow-up, and the duration of any pharmacologic or nonpharmacologic therapy that they may need. Nonpharmacologic options might include stopping smoking, limiting alcohol intake, as well as taking supplements such as calcium or vitamin D. There will be specific guidance on the use of calcium and vitamin D, which have both pros and cons, but the optimal dosage appears to be 1,000–1,200 mg/day for calcium and 800 IU/day for vitamin D.

Pharmacologic options to prevent subsequent fragility fractures include the bisphosphonates alendronate, risedronate, and zoledronic acid (Reclast), and also the monoclonal antibody denosumab (Prolia). These are the only drugs that have been shown to reduced the risk for vertebral, nonvertebral, and hip fractures in primary analyses. Adherence, tolerance, and regular monitoring are key, and a five-step plan is suggested to aid clinical decision making that covers case finding, risk evaluation, differential diagnosis, treatment, and follow-up.

The recommendations are being finalized and should be available for publication later this year. The recommendations task force also plans to propose a research agenda.

Dr. Lems had no relevant disclosures.

To the Editor:

Mycosis fungoides (MF) is the most common form of a heterogeneous group of non-Hodgkin lymphomas known as cutaneous T-cell lymphomas. Celiac disease (CD) is associated with increased risk for development of enteropathy-associated T-cell lymphoma and other intraintestinal and extraintestinal non-Hodgkin lymphomas, but a firm association between CD and MF has not been established.¹ The first and second cases of concomitant MF and CD were reported in 1985 and 2009 by Coulson and Sanderson² and Moreira et al,³ respectively. Two other reports of celiac-associated dermatitis herpetiformis and MF exist.^4,5 We report a patient with a unique constellation of MF, CD, and Sjögren syndrome (SS).

A 54-year-old woman presented with a worsening nonpruritic, slightly tender, eczematous patch on the back of 19 years’ duration. She had a history of SS diagnosed by salivary gland biopsy. She also had a diagnosis of CD confirmed with positive antigliadin IgA antibodies, with a dramatic improvement in symptoms on a gluten-free diet (GFD) after having abdominal pain and diarrhea for many years. She had no evidence of dermatitis herpetiformis. Recently, more red-brown areas of confluent light pink erythema without clear-cut borders had appeared on the axillae, trunk, and thigh (Figure). The patient also noted new lesions and more erythema of the patches when not adhering to a GFD. A biopsy specimen from the left side of the lateral trunk revealed a bandlike lymphocytic infiltrate with irregular nuclear contours displaying epidermotropism with a few Pautrier microabscesses. Immunohistochemistry showed strong CD3 and CD4 positivity with loss of CD7 and scattered CD8 staining. Peripheral blood flow cytometry showed no aberrant cell populations. The patient was diagnosed with MF stage IB and treated with topical corticosteroids and natural light with improvement.

It has been hypothesized that early MF is an autoimmune process caused by dysregulation of a lymphocytic reaction against chronic exogenous or endogenous antigens.^4,5 The association of MF with CD supports the possibility of lymphocytic stimulation by a persistent antigen (ie, gluten) in the gastrointestinal tract. Porter et al⁴ suggested that in susceptible individuals, the resulting clonal T cells may migrate into the epidermis, causing MF. This theory also is supported by the finding that adherence to a GFD leads to decreased risk for malignancy and morbidity.⁶ In our patient, the chronic autoimmune stimulation in SS could be a factor in the pathogenesis of MF. Additionally, SS, CD, and MF are all strongly associated with increased incidence of specific but different HLA class II antigens. Mycosis fungoides is associated with HLA-DR5 and DQB1*03 alleles, CD with HLA-DQ2 and DQ8, and SS with HLA-DR15 and DR3. We do not know the HLA type of our patient, but she likely possessed multiple alleles, leading to the unique aggregation of diseases.

Furthermore, studies have shown that lymphocytes in CD patients display impaired regulatory T-cell function, causing increased incidence of autoimmune diseases and malignancy.^7,8 By this theory, the occurrence of MF in patients is facilitated by the inability of CD lymphocytes to control the abnormal T-cell proliferation in the skin. Interestingly, the finding of SS in our patient supports the possibility of impaired regulatory T-cell function.

Although the occurrence of both MF and CD in our patient could be coincidental, the possibility of correlation must be considered as more cases are documented.

To the Editor:

Mycosis fungoides (MF) is the most common form of a heterogeneous group of non-Hodgkin lymphomas known as cutaneous T-cell lymphomas. Celiac disease (CD) is associated with increased risk for development of enteropathy-associated T-cell lymphoma and other intraintestinal and extraintestinal non-Hodgkin lymphomas, but a firm association between CD and MF has not been established.¹ The first and second cases of concomitant MF and CD were reported in 1985 and 2009 by Coulson and Sanderson² and Moreira et al,³ respectively. Two other reports of celiac-associated dermatitis herpetiformis and MF exist.^4,5 We report a patient with a unique constellation of MF, CD, and Sjögren syndrome (SS).

A 54-year-old woman presented with a worsening nonpruritic, slightly tender, eczematous patch on the back of 19 years’ duration. She had a history of SS diagnosed by salivary gland biopsy. She also had a diagnosis of CD confirmed with positive antigliadin IgA antibodies, with a dramatic improvement in symptoms on a gluten-free diet (GFD) after having abdominal pain and diarrhea for many years. She had no evidence of dermatitis herpetiformis. Recently, more red-brown areas of confluent light pink erythema without clear-cut borders had appeared on the axillae, trunk, and thigh (Figure). The patient also noted new lesions and more erythema of the patches when not adhering to a GFD. A biopsy specimen from the left side of the lateral trunk revealed a bandlike lymphocytic infiltrate with irregular nuclear contours displaying epidermotropism with a few Pautrier microabscesses. Immunohistochemistry showed strong CD3 and CD4 positivity with loss of CD7 and scattered CD8 staining. Peripheral blood flow cytometry showed no aberrant cell populations. The patient was diagnosed with MF stage IB and treated with topical corticosteroids and natural light with improvement.

It has been hypothesized that early MF is an autoimmune process caused by dysregulation of a lymphocytic reaction against chronic exogenous or endogenous antigens.^4,5 The association of MF with CD supports the possibility of lymphocytic stimulation by a persistent antigen (ie, gluten) in the gastrointestinal tract. Porter et al⁴ suggested that in susceptible individuals, the resulting clonal T cells may migrate into the epidermis, causing MF. This theory also is supported by the finding that adherence to a GFD leads to decreased risk for malignancy and morbidity.⁶ In our patient, the chronic autoimmune stimulation in SS could be a factor in the pathogenesis of MF. Additionally, SS, CD, and MF are all strongly associated with increased incidence of specific but different HLA class II antigens. Mycosis fungoides is associated with HLA-DR5 and DQB1*03 alleles, CD with HLA-DQ2 and DQ8, and SS with HLA-DR15 and DR3. We do not know the HLA type of our patient, but she likely possessed multiple alleles, leading to the unique aggregation of diseases.

Furthermore, studies have shown that lymphocytes in CD patients display impaired regulatory T-cell function, causing increased incidence of autoimmune diseases and malignancy.^7,8 By this theory, the occurrence of MF in patients is facilitated by the inability of CD lymphocytes to control the abnormal T-cell proliferation in the skin. Interestingly, the finding of SS in our patient supports the possibility of impaired regulatory T-cell function.

Although the occurrence of both MF and CD in our patient could be coincidental, the possibility of correlation must be considered as more cases are documented.

To the Editor:

Mycosis fungoides (MF) is the most common form of a heterogeneous group of non-Hodgkin lymphomas known as cutaneous T-cell lymphomas. Celiac disease (CD) is associated with increased risk for development of enteropathy-associated T-cell lymphoma and other intraintestinal and extraintestinal non-Hodgkin lymphomas, but a firm association between CD and MF has not been established.¹ The first and second cases of concomitant MF and CD were reported in 1985 and 2009 by Coulson and Sanderson² and Moreira et al,³ respectively. Two other reports of celiac-associated dermatitis herpetiformis and MF exist.^4,5 We report a patient with a unique constellation of MF, CD, and Sjögren syndrome (SS).

A 54-year-old woman presented with a worsening nonpruritic, slightly tender, eczematous patch on the back of 19 years’ duration. She had a history of SS diagnosed by salivary gland biopsy. She also had a diagnosis of CD confirmed with positive antigliadin IgA antibodies, with a dramatic improvement in symptoms on a gluten-free diet (GFD) after having abdominal pain and diarrhea for many years. She had no evidence of dermatitis herpetiformis. Recently, more red-brown areas of confluent light pink erythema without clear-cut borders had appeared on the axillae, trunk, and thigh (Figure). The patient also noted new lesions and more erythema of the patches when not adhering to a GFD. A biopsy specimen from the left side of the lateral trunk revealed a bandlike lymphocytic infiltrate with irregular nuclear contours displaying epidermotropism with a few Pautrier microabscesses. Immunohistochemistry showed strong CD3 and CD4 positivity with loss of CD7 and scattered CD8 staining. Peripheral blood flow cytometry showed no aberrant cell populations. The patient was diagnosed with MF stage IB and treated with topical corticosteroids and natural light with improvement.

It has been hypothesized that early MF is an autoimmune process caused by dysregulation of a lymphocytic reaction against chronic exogenous or endogenous antigens.^4,5 The association of MF with CD supports the possibility of lymphocytic stimulation by a persistent antigen (ie, gluten) in the gastrointestinal tract. Porter et al⁴ suggested that in susceptible individuals, the resulting clonal T cells may migrate into the epidermis, causing MF. This theory also is supported by the finding that adherence to a GFD leads to decreased risk for malignancy and morbidity.⁶ In our patient, the chronic autoimmune stimulation in SS could be a factor in the pathogenesis of MF. Additionally, SS, CD, and MF are all strongly associated with increased incidence of specific but different HLA class II antigens. Mycosis fungoides is associated with HLA-DR5 and DQB1*03 alleles, CD with HLA-DQ2 and DQ8, and SS with HLA-DR15 and DR3. We do not know the HLA type of our patient, but she likely possessed multiple alleles, leading to the unique aggregation of diseases.

Furthermore, studies have shown that lymphocytes in CD patients display impaired regulatory T-cell function, causing increased incidence of autoimmune diseases and malignancy.^7,8 By this theory, the occurrence of MF in patients is facilitated by the inability of CD lymphocytes to control the abnormal T-cell proliferation in the skin. Interestingly, the finding of SS in our patient supports the possibility of impaired regulatory T-cell function.

Although the occurrence of both MF and CD in our patient could be coincidental, the possibility of correlation must be considered as more cases are documented.

The Diagnosis: Trigeminal Trophic Syndrome

Trigeminal trophic syndrome (TTS) is a rare condition occurring after injury to the sensory roots of the trigeminal nerve. Trigeminal trophic syndrome was first described in 1933 by Loveman¹ as a complication of ablative treatment of trigeminal neuralgia; however, it has been observed with lesions to the central or peripheral nervous system that damage sensory components of the trigeminal nerve. In our patient, the cause was likely an infarction of the posterior inferior cerebellar artery, which supplies both the cerebellum and the trigeminal nuclei in the brain stem.

Other possible causes of TTS include injury from herpes zoster ophthalmicus; vertebrobasilar insufficiency; trauma; Mycobacterium leprae neuritis; spinal cord degeneration; syringobulbia; or tumors such as astrocytomas, meningiomas, and acoustic neuromas.² The most typical presenting manifestation is a unilateral, crescent-shaped ulceration of the nasal ala, specifically where cartilage is lacking.³ Less frequently, it affects the upper lip, cheeks, forehead, scalp, and ear. It characteristically spares the nasal tip, which derives sensory innervation from the medial branch of the anterior ethmoidal nerve.⁴ The affected dermatomal distribution can show anesthesia or paresthesia, promoting the urge to touch, pick, or rub the area.

Histology of the TTS lesion is nondiagnostic, usually showing a mixed dermal inflammation without evidence of infection, vasculitis, or malignancy. In our patient, Gram stain, Grocott-Gomori methenamine-silver stain, and immunohistochemical stains to rule out leukemia or lymphoma were all negative. In addition, flow cytometry of the forehead tissue also was normal. Tests for human immunodeficiency virus, herpes simplex virus types 1 and 2, hepatitis, syphilis, histoplasmosis, blastomycosis, coccidioides, and tuberculosis were negative.During the biopsy, the patient was noted to have anesthesia of the skin. He also admitted to facial manipulation and was noted to have blood and tissue under the fingernails on mornings when the lesion was left uncovered overnight.

Treatment of TTS often can be difficult, especially if patients do not admit to wound manipulation or if manipulation occurs during sleep. Prevention of further ulceration can sometimes be achieved by occlusive dressing alone with mupirocin. Physical barriers can be supplemented with medications such as amitriptyline, carbamazepine, diazepam, chlorpromazine, and gabapentin to attempt to reduce paresthesia.² Psychiatric consultation can sometimes be necessary and helpful.³ Additionally, negative pressure wound therapy has been used with success in the pediatric setting when digital manipulation is difficult to control.⁵ More aggressive treatments include transcutaneous electrical stimulation, stellate ganglionectomy, radiotherapy, and innervated rotation flaps.^6,7

In summary, recognition of this relatively rare cause of unilateral facial erosions is critical, both to prevent counterproductive treatments such as steroids and to initiate measures to prevent further trauma to the lesion.

The Diagnosis: Trigeminal Trophic Syndrome

Trigeminal trophic syndrome (TTS) is a rare condition occurring after injury to the sensory roots of the trigeminal nerve. Trigeminal trophic syndrome was first described in 1933 by Loveman¹ as a complication of ablative treatment of trigeminal neuralgia; however, it has been observed with lesions to the central or peripheral nervous system that damage sensory components of the trigeminal nerve. In our patient, the cause was likely an infarction of the posterior inferior cerebellar artery, which supplies both the cerebellum and the trigeminal nuclei in the brain stem.

Other possible causes of TTS include injury from herpes zoster ophthalmicus; vertebrobasilar insufficiency; trauma; Mycobacterium leprae neuritis; spinal cord degeneration; syringobulbia; or tumors such as astrocytomas, meningiomas, and acoustic neuromas.² The most typical presenting manifestation is a unilateral, crescent-shaped ulceration of the nasal ala, specifically where cartilage is lacking.³ Less frequently, it affects the upper lip, cheeks, forehead, scalp, and ear. It characteristically spares the nasal tip, which derives sensory innervation from the medial branch of the anterior ethmoidal nerve.⁴ The affected dermatomal distribution can show anesthesia or paresthesia, promoting the urge to touch, pick, or rub the area.

Histology of the TTS lesion is nondiagnostic, usually showing a mixed dermal inflammation without evidence of infection, vasculitis, or malignancy. In our patient, Gram stain, Grocott-Gomori methenamine-silver stain, and immunohistochemical stains to rule out leukemia or lymphoma were all negative. In addition, flow cytometry of the forehead tissue also was normal. Tests for human immunodeficiency virus, herpes simplex virus types 1 and 2, hepatitis, syphilis, histoplasmosis, blastomycosis, coccidioides, and tuberculosis were negative.During the biopsy, the patient was noted to have anesthesia of the skin. He also admitted to facial manipulation and was noted to have blood and tissue under the fingernails on mornings when the lesion was left uncovered overnight.

Treatment of TTS often can be difficult, especially if patients do not admit to wound manipulation or if manipulation occurs during sleep. Prevention of further ulceration can sometimes be achieved by occlusive dressing alone with mupirocin. Physical barriers can be supplemented with medications such as amitriptyline, carbamazepine, diazepam, chlorpromazine, and gabapentin to attempt to reduce paresthesia.² Psychiatric consultation can sometimes be necessary and helpful.³ Additionally, negative pressure wound therapy has been used with success in the pediatric setting when digital manipulation is difficult to control.⁵ More aggressive treatments include transcutaneous electrical stimulation, stellate ganglionectomy, radiotherapy, and innervated rotation flaps.^6,7

In summary, recognition of this relatively rare cause of unilateral facial erosions is critical, both to prevent counterproductive treatments such as steroids and to initiate measures to prevent further trauma to the lesion.

The Diagnosis: Trigeminal Trophic Syndrome

Trigeminal trophic syndrome (TTS) is a rare condition occurring after injury to the sensory roots of the trigeminal nerve. Trigeminal trophic syndrome was first described in 1933 by Loveman¹ as a complication of ablative treatment of trigeminal neuralgia; however, it has been observed with lesions to the central or peripheral nervous system that damage sensory components of the trigeminal nerve. In our patient, the cause was likely an infarction of the posterior inferior cerebellar artery, which supplies both the cerebellum and the trigeminal nuclei in the brain stem.

Other possible causes of TTS include injury from herpes zoster ophthalmicus; vertebrobasilar insufficiency; trauma; Mycobacterium leprae neuritis; spinal cord degeneration; syringobulbia; or tumors such as astrocytomas, meningiomas, and acoustic neuromas.² The most typical presenting manifestation is a unilateral, crescent-shaped ulceration of the nasal ala, specifically where cartilage is lacking.³ Less frequently, it affects the upper lip, cheeks, forehead, scalp, and ear. It characteristically spares the nasal tip, which derives sensory innervation from the medial branch of the anterior ethmoidal nerve.⁴ The affected dermatomal distribution can show anesthesia or paresthesia, promoting the urge to touch, pick, or rub the area.

Histology of the TTS lesion is nondiagnostic, usually showing a mixed dermal inflammation without evidence of infection, vasculitis, or malignancy. In our patient, Gram stain, Grocott-Gomori methenamine-silver stain, and immunohistochemical stains to rule out leukemia or lymphoma were all negative. In addition, flow cytometry of the forehead tissue also was normal. Tests for human immunodeficiency virus, herpes simplex virus types 1 and 2, hepatitis, syphilis, histoplasmosis, blastomycosis, coccidioides, and tuberculosis were negative.During the biopsy, the patient was noted to have anesthesia of the skin. He also admitted to facial manipulation and was noted to have blood and tissue under the fingernails on mornings when the lesion was left uncovered overnight.

Treatment of TTS often can be difficult, especially if patients do not admit to wound manipulation or if manipulation occurs during sleep. Prevention of further ulceration can sometimes be achieved by occlusive dressing alone with mupirocin. Physical barriers can be supplemented with medications such as amitriptyline, carbamazepine, diazepam, chlorpromazine, and gabapentin to attempt to reduce paresthesia.² Psychiatric consultation can sometimes be necessary and helpful.³ Additionally, negative pressure wound therapy has been used with success in the pediatric setting when digital manipulation is difficult to control.⁵ More aggressive treatments include transcutaneous electrical stimulation, stellate ganglionectomy, radiotherapy, and innervated rotation flaps.^6,7

In summary, recognition of this relatively rare cause of unilateral facial erosions is critical, both to prevent counterproductive treatments such as steroids and to initiate measures to prevent further trauma to the lesion.

The U.S. Food and Drug Administration has approved adalimumab for treatment of noninfectious intermediate, posterior, and panuveitis in adults, making it the only approved drug for the condition that is not a corticosteroid.

The approval marks the 10th approved indication for adalimumab (Humira) in the United States. It was recently approved for this indication in the European Union as well.

Patients on adalimumab had about half the risk of those on placebo to experience treatment failure (a combination of uveitis flare and decrease in visual acuity) in two pivotal phase III studies, VISUAL-I (hazard ratio, 0.5 for VISUAL-I; P less than .001) and VISUAL-II (HR, 0.57; P = .004). In the trials, patients were treated with an 80-mg loading dose of adalimumab at baseline, followed by a 40-mg subcutaneous injection at week 1 and then 40 mg every other week for up to 80 weeks.

“These approvals provide a valuable option for patients experiencing flare and vision impairment associated with this group of inflammatory diseases of the eye,” Glenn J. Jaffe, MD, of Duke University, Durham, N.C., said in an announcement from the manufacturer of adalimumab, AbbVie. “Data from the robust VISUAL clinical trial program demonstrate the value of Humira as a treatment option for patients with these serious diseases.”

[email protected]

The U.S. Food and Drug Administration has approved adalimumab for treatment of noninfectious intermediate, posterior, and panuveitis in adults, making it the only approved drug for the condition that is not a corticosteroid.

The approval marks the 10th approved indication for adalimumab (Humira) in the United States. It was recently approved for this indication in the European Union as well.

Patients on adalimumab had about half the risk of those on placebo to experience treatment failure (a combination of uveitis flare and decrease in visual acuity) in two pivotal phase III studies, VISUAL-I (hazard ratio, 0.5 for VISUAL-I; P less than .001) and VISUAL-II (HR, 0.57; P = .004). In the trials, patients were treated with an 80-mg loading dose of adalimumab at baseline, followed by a 40-mg subcutaneous injection at week 1 and then 40 mg every other week for up to 80 weeks.

“These approvals provide a valuable option for patients experiencing flare and vision impairment associated with this group of inflammatory diseases of the eye,” Glenn J. Jaffe, MD, of Duke University, Durham, N.C., said in an announcement from the manufacturer of adalimumab, AbbVie. “Data from the robust VISUAL clinical trial program demonstrate the value of Humira as a treatment option for patients with these serious diseases.”

[email protected]

The U.S. Food and Drug Administration has approved adalimumab for treatment of noninfectious intermediate, posterior, and panuveitis in adults, making it the only approved drug for the condition that is not a corticosteroid.

The approval marks the 10th approved indication for adalimumab (Humira) in the United States. It was recently approved for this indication in the European Union as well.

Patients on adalimumab had about half the risk of those on placebo to experience treatment failure (a combination of uveitis flare and decrease in visual acuity) in two pivotal phase III studies, VISUAL-I (hazard ratio, 0.5 for VISUAL-I; P less than .001) and VISUAL-II (HR, 0.57; P = .004). In the trials, patients were treated with an 80-mg loading dose of adalimumab at baseline, followed by a 40-mg subcutaneous injection at week 1 and then 40 mg every other week for up to 80 weeks.

“These approvals provide a valuable option for patients experiencing flare and vision impairment associated with this group of inflammatory diseases of the eye,” Glenn J. Jaffe, MD, of Duke University, Durham, N.C., said in an announcement from the manufacturer of adalimumab, AbbVie. “Data from the robust VISUAL clinical trial program demonstrate the value of Humira as a treatment option for patients with these serious diseases.”

[email protected]

From the OpenLab, University Health Network, Toronto, Canada (Dr. Hahn-Goldberg, Dr. Okrainec, Dr. Abrams, Mr. Huynh); School of Health Policy and Management, York University, Toronto (Dr. Hahn-Goldberg); Toronto Central Local Health Integration Network (Ms. Damba); Centre for Addiction and Mental Health, Toronto (Ms. Solomon); and the Department of Medicine, University Health Network, Toronto (Dr. Okrainec, Dr. Abrams).

Abstract

• Objective: To describe the co-design process we under-took to create a patient-oriented discharge summary (PODS) with patients, caregivers, and providers.
• Method: Descriptive report.
• Results: We designed and produced a prototype PODS, based on best practices in information design, graphic design, and patient education. Through a co-design process, patients, health care providers, designers and system planners worked together to establish what content needed to be included, as well as how it would be organized and presented. From an initial prototype, we then refined the PODS through an iterative participatory design process involving patients, including those from hard-to-reach groups such as patients with language barriers and/or low health literacy and patients with a primary psychiatric diagnosis.
• Conclusion: Co-design events and targeted focus groups are very useful for engaging patients and caregivers in the design and development of solutions aimed at improving their experience of care. It is important to include all users, especially those who are harder to reach, such as patients with language barriers and mental health conditions. Engaging health care providers is essential to ensure feasibility of those solutions.

Traditional discharge summaries are written primarily for the patient’s primary care provider and are not designed as tools to support communication between the clinician and patient regarding instructions for patients to follow at home post discharge. A more patient-centered version of the discharge summary is needed to complement the traditional format.

To enhance our patients’ care experience in the post-discharge period, we set out to co-design a patient-oriented discharge summary (PODS) with patients, caregivers, and providers. The main objective of this project was to develop a prototype PODS that not only addressed critical information that patients felt was the most important to know following discharge, but also provided this information in the most comprehensible format at hospitals within the Toronto area. The project focused on reformatting patient-care instructions for patients discharged from inpatient medical wards as these instructions presented the best opportunity for improvement.

This project drew on work done in countries such as India, South Africa, and Pakistan, where challenges with general and health literacy have led to the introduction of simplified discharge forms and medication instructions that place a greater emphasis on visual communication to improve information comprehension. For example, the use of pictograms in patient materials has been shown to increase patient understanding of and compliance with care instructions in these countries [1–3].

We have provided an overview of the PODS project elsewhere [4]. In this article, we describe the co-design process we undertook with patients, health care providers, and designers in creating a PODS.

Design Methods

We used several methods to design and develop the PODS and to engage multiple stakeholders in the design process. Among these methods were innovative techniques for understanding the patient experience of discharge, such as cultural probes [5], where patients were given journals and cameras to document their time at home after discharge, as described by Hahn-Goldberg et al [4]. Other key methods for determining the design of the PODS included:

Patient education consultation. A patient education representative with training and expertise in designing materials for patients with low health literacy was added to the team advisory committee to act as a consultant at all stages of the study. This helped to ensure that we would be following best practices in design for our target population.

Review of literature. We reviewed the literature pertaining to design for patients with low health literacy and language barriers, including the resources available through the patient education department at the University Health Network.

Review of Toronto Central Local Health Integration Network (TCLHIN) hospitals’ tools: current discharge summaries, components they included and how they were formatted.

Co-design event. We held an interprofessional design event where teams of patients, health care providers, and designers worked together to create draft PODS for 4 hypothetical patient cases.

Focus groups and surveys. We used feedback from focus groups and surveys to revise and improve the first PODS prototype.

Insights from the Literature

Studies have shown that multiple interventions tend to increase adherence, that self-management should be encouraged, and that modes of communication other than verbal must be used [6]. Visual cues, such as pictures or symbols, are useful to help with recall of medications and instructions for people with language barriers or limited health literacy [7]. Simplified written instructions and larger fonts have been found to be effective in patients with language barriers or limited health literacy, as have use of illustrated medication schedules [8]. Other guidelines include using short words and sentences, writing directly to the reader, listing important points in list format, and using left justification so there is even spacing between words.

The literature is consistent with our findings from speaking with patient education representatives and patients. Patients and caregivers noted that the PODS should be written in plain language, use large fonts, include illustrations of care and medication schedules, and include headings that are meaningful to the patient. Patients also expressed the desire for charts and lists that they could use while completing their follow-up care plan.

“My mom made me a chart of when to drink water and how much (patient).”

“We were given a sheet to record all feedings (caregiver).”

“We can provide a list of patient meds in a grid format with days of the week and times of day. We use our judgement to give this to patients. It is not standard practice (pharmacist).”

“A discharge form in ‘plain English’ should be standardized (patient).”

The Co-design Event

Solutions resulting from the design event ranged from more traditional discharge summaries that were enhanced with multiple languages and images to make things clear for patients, to solutions including interactive patient portals. There were solutions that came with stickers to color-code your medications, areas for patients to write notes, and checklists for them to keep track of all their follow-up plans. 

Refining the Design Using Focus Groups and Surveys

The ideas and concepts generated during the design event were analyzed by the interdisciplinary advisory team at OpenLab. In addition, several team sessions were held with health care 

This is a great piece. You guys are doing an awesome job. This would have saved me so much anxiety and fear of doing something wrong when I was discharged. I didn’t want to bother my doctors and went on a hope and prayer. Even my home care people weren’t always sure of what to do. Again this would be a great step forward in easing patients’ fears, especially senior citizens. GREAT WORK. THANKS FOR CARING.

Discussion

Innovative methods such as co-design events and targeted focus groups are very useful for 

Future Plans

The PODS template has now been adapted and implemented in several hospitals in Toronto, Canada, using a supported early adopter process [10]. Future plans are to test the impact of the PODS on patient experience and health outcomes using a randomized controlled trial. Also, for now, we have focused on a paper version of PODS, but with the increasing prevalence of electronic health records and consumer-oriented health care apps, future consideration for a digital and mobile version of PODS is warranted.

Conclusion

Patients need to be prepared for discharge so that they can engage in supported self-management once they return home. 

Corresponding author: Shoshana Hahn-Goldberg, PhD, 294 Mullen Dr., Thornhill, ON L4J 2P2.

Funding/support: The PODS project has been funded by the Toronto Central Local Health Integration Network.

Financial disclosures: None.

From the OpenLab, University Health Network, Toronto, Canada (Dr. Hahn-Goldberg, Dr. Okrainec, Dr. Abrams, Mr. Huynh); School of Health Policy and Management, York University, Toronto (Dr. Hahn-Goldberg); Toronto Central Local Health Integration Network (Ms. Damba); Centre for Addiction and Mental Health, Toronto (Ms. Solomon); and the Department of Medicine, University Health Network, Toronto (Dr. Okrainec, Dr. Abrams).

Abstract

• Objective: To describe the co-design process we under-took to create a patient-oriented discharge summary (PODS) with patients, caregivers, and providers.
• Method: Descriptive report.
• Results: We designed and produced a prototype PODS, based on best practices in information design, graphic design, and patient education. Through a co-design process, patients, health care providers, designers and system planners worked together to establish what content needed to be included, as well as how it would be organized and presented. From an initial prototype, we then refined the PODS through an iterative participatory design process involving patients, including those from hard-to-reach groups such as patients with language barriers and/or low health literacy and patients with a primary psychiatric diagnosis.
• Conclusion: Co-design events and targeted focus groups are very useful for engaging patients and caregivers in the design and development of solutions aimed at improving their experience of care. It is important to include all users, especially those who are harder to reach, such as patients with language barriers and mental health conditions. Engaging health care providers is essential to ensure feasibility of those solutions.

Traditional discharge summaries are written primarily for the patient’s primary care provider and are not designed as tools to support communication between the clinician and patient regarding instructions for patients to follow at home post discharge. A more patient-centered version of the discharge summary is needed to complement the traditional format.

To enhance our patients’ care experience in the post-discharge period, we set out to co-design a patient-oriented discharge summary (PODS) with patients, caregivers, and providers. The main objective of this project was to develop a prototype PODS that not only addressed critical information that patients felt was the most important to know following discharge, but also provided this information in the most comprehensible format at hospitals within the Toronto area. The project focused on reformatting patient-care instructions for patients discharged from inpatient medical wards as these instructions presented the best opportunity for improvement.

This project drew on work done in countries such as India, South Africa, and Pakistan, where challenges with general and health literacy have led to the introduction of simplified discharge forms and medication instructions that place a greater emphasis on visual communication to improve information comprehension. For example, the use of pictograms in patient materials has been shown to increase patient understanding of and compliance with care instructions in these countries [1–3].

We have provided an overview of the PODS project elsewhere [4]. In this article, we describe the co-design process we undertook with patients, health care providers, and designers in creating a PODS.

Design Methods

We used several methods to design and develop the PODS and to engage multiple stakeholders in the design process. Among these methods were innovative techniques for understanding the patient experience of discharge, such as cultural probes [5], where patients were given journals and cameras to document their time at home after discharge, as described by Hahn-Goldberg et al [4]. Other key methods for determining the design of the PODS included:

Patient education consultation. A patient education representative with training and expertise in designing materials for patients with low health literacy was added to the team advisory committee to act as a consultant at all stages of the study. This helped to ensure that we would be following best practices in design for our target population.

Review of literature. We reviewed the literature pertaining to design for patients with low health literacy and language barriers, including the resources available through the patient education department at the University Health Network.

Review of Toronto Central Local Health Integration Network (TCLHIN) hospitals’ tools: current discharge summaries, components they included and how they were formatted.

Co-design event. We held an interprofessional design event where teams of patients, health care providers, and designers worked together to create draft PODS for 4 hypothetical patient cases.

Focus groups and surveys. We used feedback from focus groups and surveys to revise and improve the first PODS prototype.

Insights from the Literature

Studies have shown that multiple interventions tend to increase adherence, that self-management should be encouraged, and that modes of communication other than verbal must be used [6]. Visual cues, such as pictures or symbols, are useful to help with recall of medications and instructions for people with language barriers or limited health literacy [7]. Simplified written instructions and larger fonts have been found to be effective in patients with language barriers or limited health literacy, as have use of illustrated medication schedules [8]. Other guidelines include using short words and sentences, writing directly to the reader, listing important points in list format, and using left justification so there is even spacing between words.

The literature is consistent with our findings from speaking with patient education representatives and patients. Patients and caregivers noted that the PODS should be written in plain language, use large fonts, include illustrations of care and medication schedules, and include headings that are meaningful to the patient. Patients also expressed the desire for charts and lists that they could use while completing their follow-up care plan.

“My mom made me a chart of when to drink water and how much (patient).”

“We were given a sheet to record all feedings (caregiver).”

“We can provide a list of patient meds in a grid format with days of the week and times of day. We use our judgement to give this to patients. It is not standard practice (pharmacist).”

“A discharge form in ‘plain English’ should be standardized (patient).”

The Co-design Event

Solutions resulting from the design event ranged from more traditional discharge summaries that were enhanced with multiple languages and images to make things clear for patients, to solutions including interactive patient portals. There were solutions that came with stickers to color-code your medications, areas for patients to write notes, and checklists for them to keep track of all their follow-up plans. 

Refining the Design Using Focus Groups and Surveys

The ideas and concepts generated during the design event were analyzed by the interdisciplinary advisory team at OpenLab. In addition, several team sessions were held with health care 

This is a great piece. You guys are doing an awesome job. This would have saved me so much anxiety and fear of doing something wrong when I was discharged. I didn’t want to bother my doctors and went on a hope and prayer. Even my home care people weren’t always sure of what to do. Again this would be a great step forward in easing patients’ fears, especially senior citizens. GREAT WORK. THANKS FOR CARING.

Discussion

Innovative methods such as co-design events and targeted focus groups are very useful for 

Future Plans

The PODS template has now been adapted and implemented in several hospitals in Toronto, Canada, using a supported early adopter process [10]. Future plans are to test the impact of the PODS on patient experience and health outcomes using a randomized controlled trial. Also, for now, we have focused on a paper version of PODS, but with the increasing prevalence of electronic health records and consumer-oriented health care apps, future consideration for a digital and mobile version of PODS is warranted.

Conclusion

Patients need to be prepared for discharge so that they can engage in supported self-management once they return home. 

Corresponding author: Shoshana Hahn-Goldberg, PhD, 294 Mullen Dr., Thornhill, ON L4J 2P2.

Funding/support: The PODS project has been funded by the Toronto Central Local Health Integration Network.

Financial disclosures: None.

From the OpenLab, University Health Network, Toronto, Canada (Dr. Hahn-Goldberg, Dr. Okrainec, Dr. Abrams, Mr. Huynh); School of Health Policy and Management, York University, Toronto (Dr. Hahn-Goldberg); Toronto Central Local Health Integration Network (Ms. Damba); Centre for Addiction and Mental Health, Toronto (Ms. Solomon); and the Department of Medicine, University Health Network, Toronto (Dr. Okrainec, Dr. Abrams).

Abstract

• Objective: To describe the co-design process we under-took to create a patient-oriented discharge summary (PODS) with patients, caregivers, and providers.
• Method: Descriptive report.
• Results: We designed and produced a prototype PODS, based on best practices in information design, graphic design, and patient education. Through a co-design process, patients, health care providers, designers and system planners worked together to establish what content needed to be included, as well as how it would be organized and presented. From an initial prototype, we then refined the PODS through an iterative participatory design process involving patients, including those from hard-to-reach groups such as patients with language barriers and/or low health literacy and patients with a primary psychiatric diagnosis.
• Conclusion: Co-design events and targeted focus groups are very useful for engaging patients and caregivers in the design and development of solutions aimed at improving their experience of care. It is important to include all users, especially those who are harder to reach, such as patients with language barriers and mental health conditions. Engaging health care providers is essential to ensure feasibility of those solutions.

Traditional discharge summaries are written primarily for the patient’s primary care provider and are not designed as tools to support communication between the clinician and patient regarding instructions for patients to follow at home post discharge. A more patient-centered version of the discharge summary is needed to complement the traditional format.

To enhance our patients’ care experience in the post-discharge period, we set out to co-design a patient-oriented discharge summary (PODS) with patients, caregivers, and providers. The main objective of this project was to develop a prototype PODS that not only addressed critical information that patients felt was the most important to know following discharge, but also provided this information in the most comprehensible format at hospitals within the Toronto area. The project focused on reformatting patient-care instructions for patients discharged from inpatient medical wards as these instructions presented the best opportunity for improvement.

This project drew on work done in countries such as India, South Africa, and Pakistan, where challenges with general and health literacy have led to the introduction of simplified discharge forms and medication instructions that place a greater emphasis on visual communication to improve information comprehension. For example, the use of pictograms in patient materials has been shown to increase patient understanding of and compliance with care instructions in these countries [1–3].

We have provided an overview of the PODS project elsewhere [4]. In this article, we describe the co-design process we undertook with patients, health care providers, and designers in creating a PODS.

Design Methods

We used several methods to design and develop the PODS and to engage multiple stakeholders in the design process. Among these methods were innovative techniques for understanding the patient experience of discharge, such as cultural probes [5], where patients were given journals and cameras to document their time at home after discharge, as described by Hahn-Goldberg et al [4]. Other key methods for determining the design of the PODS included:

Patient education consultation. A patient education representative with training and expertise in designing materials for patients with low health literacy was added to the team advisory committee to act as a consultant at all stages of the study. This helped to ensure that we would be following best practices in design for our target population.

Review of literature. We reviewed the literature pertaining to design for patients with low health literacy and language barriers, including the resources available through the patient education department at the University Health Network.

Review of Toronto Central Local Health Integration Network (TCLHIN) hospitals’ tools: current discharge summaries, components they included and how they were formatted.

Co-design event. We held an interprofessional design event where teams of patients, health care providers, and designers worked together to create draft PODS for 4 hypothetical patient cases.

Focus groups and surveys. We used feedback from focus groups and surveys to revise and improve the first PODS prototype.

Insights from the Literature

Studies have shown that multiple interventions tend to increase adherence, that self-management should be encouraged, and that modes of communication other than verbal must be used [6]. Visual cues, such as pictures or symbols, are useful to help with recall of medications and instructions for people with language barriers or limited health literacy [7]. Simplified written instructions and larger fonts have been found to be effective in patients with language barriers or limited health literacy, as have use of illustrated medication schedules [8]. Other guidelines include using short words and sentences, writing directly to the reader, listing important points in list format, and using left justification so there is even spacing between words.

The literature is consistent with our findings from speaking with patient education representatives and patients. Patients and caregivers noted that the PODS should be written in plain language, use large fonts, include illustrations of care and medication schedules, and include headings that are meaningful to the patient. Patients also expressed the desire for charts and lists that they could use while completing their follow-up care plan.

“My mom made me a chart of when to drink water and how much (patient).”

“We were given a sheet to record all feedings (caregiver).”

“We can provide a list of patient meds in a grid format with days of the week and times of day. We use our judgement to give this to patients. It is not standard practice (pharmacist).”

“A discharge form in ‘plain English’ should be standardized (patient).”

The Co-design Event

Solutions resulting from the design event ranged from more traditional discharge summaries that were enhanced with multiple languages and images to make things clear for patients, to solutions including interactive patient portals. There were solutions that came with stickers to color-code your medications, areas for patients to write notes, and checklists for them to keep track of all their follow-up plans. 

Refining the Design Using Focus Groups and Surveys

The ideas and concepts generated during the design event were analyzed by the interdisciplinary advisory team at OpenLab. In addition, several team sessions were held with health care 

This is a great piece. You guys are doing an awesome job. This would have saved me so much anxiety and fear of doing something wrong when I was discharged. I didn’t want to bother my doctors and went on a hope and prayer. Even my home care people weren’t always sure of what to do. Again this would be a great step forward in easing patients’ fears, especially senior citizens. GREAT WORK. THANKS FOR CARING.

Discussion

Innovative methods such as co-design events and targeted focus groups are very useful for 

Future Plans

The PODS template has now been adapted and implemented in several hospitals in Toronto, Canada, using a supported early adopter process [10]. Future plans are to test the impact of the PODS on patient experience and health outcomes using a randomized controlled trial. Also, for now, we have focused on a paper version of PODS, but with the increasing prevalence of electronic health records and consumer-oriented health care apps, future consideration for a digital and mobile version of PODS is warranted.

Conclusion

Patients need to be prepared for discharge so that they can engage in supported self-management once they return home. 

Corresponding author: Shoshana Hahn-Goldberg, PhD, 294 Mullen Dr., Thornhill, ON L4J 2P2.

Funding/support: The PODS project has been funded by the Toronto Central Local Health Integration Network.

Financial disclosures: None.

Qualified physicians soon will be allowed to provide medication-assisted treatment (MAT) with buprenorphine to nearly triple the number of patients under a new rule by the Substance Abuse and Mental Health Services Administration (SAMHSA).

The rule, announced by the Health & Human Services department on July 6, allows qualified practitioners to prescribe buprenorphine to up to 275 patients, up from the previous limit of 100. Raising the cap will mean treatment of 10,000-70,000 more patients within the first year, according to HHS. The rule takes effect Aug. 5.

Courtesy HHS

In addition, HHS plans to eliminate pain management questions from the payment scoring calculation of the Hospital Consumer Assessment of Healthcare Providers and Systems (HCAHPS) survey. The removal aims to relieve pressure on clinicians to overprescribe opioids since scores on the HCAHPS survey are tied to Medicare payments to hospitals. Hospitals would continue to use the questions to survey patients about their inpatient pain management experience, but the questions would not affect the level of payment that hospitals receive, HHS Secretary Sylvia M. Burwell said during a press conference. The changes are part of a number of steps announced by HHS to build on the agency’s Opioid Initiative.

“Together, these announcements will help us take additional steps forward,” Ms. Burwell said. “They increase access to help more people receive the evidence-based treatment they need. They help providers safely prescribe while helping their patients manage chronic pain, and they fill in the gaps of our understanding of this epidemic and how best to fight it.”

The agency also released a report on ongoing, federally funded opioid misuse and pain treatment research. The report is designed to help stakeholders and external funders of research in avoiding unnecessary duplication of research currently underway, according to HHS. The agency plans to launch more than a dozen new scientific studies on opioid misuse and pain treatment in the near future, Ms. Burwell said.

Another new rule mandates that Indian Health Service (IHS) clinicians and pharmacists check their state Prescription Drug Monitoring Program database prior to prescribing or dispensing any opioid for more than 7 days. The new policy is effective immediately for IHS clinicians authorized to prescribe opioids.

Amid the new steps, Secretary Burwell and others called on Congress to approve the President Obama’s proposed $1.1 billion in new funding to further address prescription opioid abuse and heroin use. Legislators are meeting July 6 to weigh final legislation aimed at the opioid epidemic, but have thus far, not fully supported the president’s proposed funding. In a July 5 letter, Democrats vowed to oppose the bill unless it included more money to treat addicted patients.

“If you want treatment for an opioid use disorder, you should be able to access it when you need it,” Michael Botticelli, director of National Drug Control Policy said during the press conference. “There is still time for Congress to do what’s right.”

Qualified physicians soon will be allowed to provide medication-assisted treatment (MAT) with buprenorphine to nearly triple the number of patients under a new rule by the Substance Abuse and Mental Health Services Administration (SAMHSA).

The rule, announced by the Health & Human Services department on July 6, allows qualified practitioners to prescribe buprenorphine to up to 275 patients, up from the previous limit of 100. Raising the cap will mean treatment of 10,000-70,000 more patients within the first year, according to HHS. The rule takes effect Aug. 5.

Courtesy HHS

In addition, HHS plans to eliminate pain management questions from the payment scoring calculation of the Hospital Consumer Assessment of Healthcare Providers and Systems (HCAHPS) survey. The removal aims to relieve pressure on clinicians to overprescribe opioids since scores on the HCAHPS survey are tied to Medicare payments to hospitals. Hospitals would continue to use the questions to survey patients about their inpatient pain management experience, but the questions would not affect the level of payment that hospitals receive, HHS Secretary Sylvia M. Burwell said during a press conference. The changes are part of a number of steps announced by HHS to build on the agency’s Opioid Initiative.

“Together, these announcements will help us take additional steps forward,” Ms. Burwell said. “They increase access to help more people receive the evidence-based treatment they need. They help providers safely prescribe while helping their patients manage chronic pain, and they fill in the gaps of our understanding of this epidemic and how best to fight it.”

The agency also released a report on ongoing, federally funded opioid misuse and pain treatment research. The report is designed to help stakeholders and external funders of research in avoiding unnecessary duplication of research currently underway, according to HHS. The agency plans to launch more than a dozen new scientific studies on opioid misuse and pain treatment in the near future, Ms. Burwell said.

Another new rule mandates that Indian Health Service (IHS) clinicians and pharmacists check their state Prescription Drug Monitoring Program database prior to prescribing or dispensing any opioid for more than 7 days. The new policy is effective immediately for IHS clinicians authorized to prescribe opioids.

Amid the new steps, Secretary Burwell and others called on Congress to approve the President Obama’s proposed $1.1 billion in new funding to further address prescription opioid abuse and heroin use. Legislators are meeting July 6 to weigh final legislation aimed at the opioid epidemic, but have thus far, not fully supported the president’s proposed funding. In a July 5 letter, Democrats vowed to oppose the bill unless it included more money to treat addicted patients.

“If you want treatment for an opioid use disorder, you should be able to access it when you need it,” Michael Botticelli, director of National Drug Control Policy said during the press conference. “There is still time for Congress to do what’s right.”

Qualified physicians soon will be allowed to provide medication-assisted treatment (MAT) with buprenorphine to nearly triple the number of patients under a new rule by the Substance Abuse and Mental Health Services Administration (SAMHSA).

The rule, announced by the Health & Human Services department on July 6, allows qualified practitioners to prescribe buprenorphine to up to 275 patients, up from the previous limit of 100. Raising the cap will mean treatment of 10,000-70,000 more patients within the first year, according to HHS. The rule takes effect Aug. 5.

Courtesy HHS

In addition, HHS plans to eliminate pain management questions from the payment scoring calculation of the Hospital Consumer Assessment of Healthcare Providers and Systems (HCAHPS) survey. The removal aims to relieve pressure on clinicians to overprescribe opioids since scores on the HCAHPS survey are tied to Medicare payments to hospitals. Hospitals would continue to use the questions to survey patients about their inpatient pain management experience, but the questions would not affect the level of payment that hospitals receive, HHS Secretary Sylvia M. Burwell said during a press conference. The changes are part of a number of steps announced by HHS to build on the agency’s Opioid Initiative.

“Together, these announcements will help us take additional steps forward,” Ms. Burwell said. “They increase access to help more people receive the evidence-based treatment they need. They help providers safely prescribe while helping their patients manage chronic pain, and they fill in the gaps of our understanding of this epidemic and how best to fight it.”

The agency also released a report on ongoing, federally funded opioid misuse and pain treatment research. The report is designed to help stakeholders and external funders of research in avoiding unnecessary duplication of research currently underway, according to HHS. The agency plans to launch more than a dozen new scientific studies on opioid misuse and pain treatment in the near future, Ms. Burwell said.

Another new rule mandates that Indian Health Service (IHS) clinicians and pharmacists check their state Prescription Drug Monitoring Program database prior to prescribing or dispensing any opioid for more than 7 days. The new policy is effective immediately for IHS clinicians authorized to prescribe opioids.

Amid the new steps, Secretary Burwell and others called on Congress to approve the President Obama’s proposed $1.1 billion in new funding to further address prescription opioid abuse and heroin use. Legislators are meeting July 6 to weigh final legislation aimed at the opioid epidemic, but have thus far, not fully supported the president’s proposed funding. In a July 5 letter, Democrats vowed to oppose the bill unless it included more money to treat addicted patients.

“If you want treatment for an opioid use disorder, you should be able to access it when you need it,” Michael Botticelli, director of National Drug Control Policy said during the press conference. “There is still time for Congress to do what’s right.”

Qualified physicians soon will be allowed to provide medication-assisted treatment (MAT) with buprenorphine to nearly triple the number of patients under a new rule by the Substance Abuse and Mental Health Services Administration (SAMHSA).

The rule, announced by the Health & Human Services department on July 6, allows qualified practitioners to prescribe buprenorphine to up to 275 patients, up from the previous limit of 100. Raising the cap will mean treatment of 10,000-70,000 more patients within the first year, according to HHS. The rule takes effect Aug. 5.

Courtesy HHS

In addition, HHS plans to eliminate pain management questions from the payment scoring calculation of the Hospital Consumer Assessment of Healthcare Providers and Systems (HCAHPS) survey. The removal aims to relieve pressure on clinicians to overprescribe opioids since scores on the HCAHPS survey are tied to Medicare payments to hospitals. Hospitals would continue to use the questions to survey patients about their inpatient pain management experience, but the questions would not affect the level of payment that hospitals receive, HHS Secretary Sylvia M. Burwell said during a press conference. The changes are part of a number of steps announced by HHS to build on the agency’s Opioid Initiative.

“Together, these announcements will help us take additional steps forward,” Ms. Burwell said. “They increase access to help more people receive the evidence-based treatment they need. They help providers safely prescribe while helping their patients manage chronic pain, and they fill in the gaps of our understanding of this epidemic and how best to fight it.”

The agency also released a report on ongoing, federally funded opioid misuse and pain treatment research. The report is designed to help stakeholders and external funders of research in avoiding unnecessary duplication of research currently underway, according to HHS. The agency plans to launch more than a dozen new scientific studies on opioid misuse and pain treatment in the near future, Ms. Burwell said.

Another new rule mandates that Indian Health Service (IHS) clinicians and pharmacists check their state Prescription Drug Monitoring Program database prior to prescribing or dispensing any opioid for more than 7 days. The new policy is effective immediately for IHS clinicians authorized to prescribe opioids.

Amid the new steps, Secretary Burwell and others called on Congress to approve the President Obama’s proposed $1.1 billion in new funding to further address prescription opioid abuse and heroin use. Legislators are meeting July 6 to weigh final legislation aimed at the opioid epidemic, but have thus far, not fully supported the president’s proposed funding. In a July 5 letter, Democrats vowed to oppose the bill unless it included more money to treat addicted patients.

“If you want treatment for an opioid use disorder, you should be able to access it when you need it,” Michael Botticelli, director of National Drug Control Policy said during the press conference. “There is still time for Congress to do what’s right.”

[email protected]

On Twitter @legal_med

Qualified physicians soon will be allowed to provide medication-assisted treatment (MAT) with buprenorphine to nearly triple the number of patients under a new rule by the Substance Abuse and Mental Health Services Administration (SAMHSA).

The rule, announced by the Health & Human Services department on July 6, allows qualified practitioners to prescribe buprenorphine to up to 275 patients, up from the previous limit of 100. Raising the cap will mean treatment of 10,000-70,000 more patients within the first year, according to HHS. The rule takes effect Aug. 5.

Courtesy HHS

In addition, HHS plans to eliminate pain management questions from the payment scoring calculation of the Hospital Consumer Assessment of Healthcare Providers and Systems (HCAHPS) survey. The removal aims to relieve pressure on clinicians to overprescribe opioids since scores on the HCAHPS survey are tied to Medicare payments to hospitals. Hospitals would continue to use the questions to survey patients about their inpatient pain management experience, but the questions would not affect the level of payment that hospitals receive, HHS Secretary Sylvia M. Burwell said during a press conference. The changes are part of a number of steps announced by HHS to build on the agency’s Opioid Initiative.

“Together, these announcements will help us take additional steps forward,” Ms. Burwell said. “They increase access to help more people receive the evidence-based treatment they need. They help providers safely prescribe while helping their patients manage chronic pain, and they fill in the gaps of our understanding of this epidemic and how best to fight it.”

The agency also released a report on ongoing, federally funded opioid misuse and pain treatment research. The report is designed to help stakeholders and external funders of research in avoiding unnecessary duplication of research currently underway, according to HHS. The agency plans to launch more than a dozen new scientific studies on opioid misuse and pain treatment in the near future, Ms. Burwell said.

Another new rule mandates that Indian Health Service (IHS) clinicians and pharmacists check their state Prescription Drug Monitoring Program database prior to prescribing or dispensing any opioid for more than 7 days. The new policy is effective immediately for IHS clinicians authorized to prescribe opioids.

Amid the new steps, Secretary Burwell and others called on Congress to approve the President Obama’s proposed $1.1 billion in new funding to further address prescription opioid abuse and heroin use. Legislators are meeting July 6 to weigh final legislation aimed at the opioid epidemic, but have thus far, not fully supported the president’s proposed funding. In a July 5 letter, Democrats vowed to oppose the bill unless it included more money to treat addicted patients.

“If you want treatment for an opioid use disorder, you should be able to access it when you need it,” Michael Botticelli, director of National Drug Control Policy said during the press conference. “There is still time for Congress to do what’s right.”

[email protected]

On Twitter @legal_med

Qualified physicians soon will be allowed to provide medication-assisted treatment (MAT) with buprenorphine to nearly triple the number of patients under a new rule by the Substance Abuse and Mental Health Services Administration (SAMHSA).

The rule, announced by the Health & Human Services department on July 6, allows qualified practitioners to prescribe buprenorphine to up to 275 patients, up from the previous limit of 100. Raising the cap will mean treatment of 10,000-70,000 more patients within the first year, according to HHS. The rule takes effect Aug. 5.

Courtesy HHS

In addition, HHS plans to eliminate pain management questions from the payment scoring calculation of the Hospital Consumer Assessment of Healthcare Providers and Systems (HCAHPS) survey. The removal aims to relieve pressure on clinicians to overprescribe opioids since scores on the HCAHPS survey are tied to Medicare payments to hospitals. Hospitals would continue to use the questions to survey patients about their inpatient pain management experience, but the questions would not affect the level of payment that hospitals receive, HHS Secretary Sylvia M. Burwell said during a press conference. The changes are part of a number of steps announced by HHS to build on the agency’s Opioid Initiative.

“Together, these announcements will help us take additional steps forward,” Ms. Burwell said. “They increase access to help more people receive the evidence-based treatment they need. They help providers safely prescribe while helping their patients manage chronic pain, and they fill in the gaps of our understanding of this epidemic and how best to fight it.”

The agency also released a report on ongoing, federally funded opioid misuse and pain treatment research. The report is designed to help stakeholders and external funders of research in avoiding unnecessary duplication of research currently underway, according to HHS. The agency plans to launch more than a dozen new scientific studies on opioid misuse and pain treatment in the near future, Ms. Burwell said.

Another new rule mandates that Indian Health Service (IHS) clinicians and pharmacists check their state Prescription Drug Monitoring Program database prior to prescribing or dispensing any opioid for more than 7 days. The new policy is effective immediately for IHS clinicians authorized to prescribe opioids.

Amid the new steps, Secretary Burwell and others called on Congress to approve the President Obama’s proposed $1.1 billion in new funding to further address prescription opioid abuse and heroin use. Legislators are meeting July 6 to weigh final legislation aimed at the opioid epidemic, but have thus far, not fully supported the president’s proposed funding. In a July 5 letter, Democrats vowed to oppose the bill unless it included more money to treat addicted patients.

“If you want treatment for an opioid use disorder, you should be able to access it when you need it,” Michael Botticelli, director of National Drug Control Policy said during the press conference. “There is still time for Congress to do what’s right.”

[email protected]

On Twitter @legal_med

From the Division of Endocrinology, Diabetes, and Metabolism, University of Alabama at Birmingham, Birmingham, Alabama.

Abstract

• Objective: To review the treatment of osteoporosis, challenges to treatment adherence, and factors associated with improved adherence.
• Methods: Review of the literature.
• Results: With the growing aging population, there is an increased number of people at risk of osteoporosis and fracture. Several medications are available that reduce the risk of fracture. However, adherence to osteoporosis medications is suboptimal. Factors related to nonadherence include dosing frequency, real side effects, and concern about potential side effects. Interventions that may improve adherence include clinician and patient education, less frequent and less complex dosing regimens, medication reminders, and adherence counseling.
• Conclusions: Improving adherence to osteoporosis medications is a complex and challenging issue. Considering and implementing strategies to improve adherence tailored to patient preferences may enhance long-term outcomes for patients with osteoporosis.

Osteoporosis is a chronic but asymptomatic disease that is characterized by an increased fragility of bones and increased risk of fractures. Hip and vertebral fractures are associated with the greatest morbidity and mortality. The prevalence of osteoporosis is estimated to be 10.3% in the US, with approximately 10.2 million adults over the age of 50 having osteoporosis based on 2010 census data and results from the National Health and Nutrition Examination Survey (NHANES) [1].

Several drugs are currently available for the treatment of osteoporosis, but adherence to treatment is low. Understanding the factors associated with low adherence and actions that can be taken to improve adherence to treatment is important given the large number of individuals with osteoporosis and the need to reduce the burden caused by fragility fracture. In this article, we review the treatment of osteoporosis, challenges to treatment adherence, and factors associated with improved adherence.

Nonprescription Medications

Calcium

There have been several published studies over the last decade evaluating calcium supplementation and its efficacy in reducing fractures. Although these studies showed that calcium reduces bone turnover by 20% and slowed postmenopausal bone loss by one third [2,3], none of these studies or a recent systematic review [4] showed any degree of fracture risk reduction with calcium supplements alone.

Although some calcium intake may be good, too much calcium has the potential to cause harm, including an increased risk of nephrolithiasis and constipation/bloating. An analysis of the Women’s Health Initiative (WHI) study reported a 17% increase in renal calculi in women who received calcium and vitamin D supplements [5]. Another recently published meta-analysis showed a 43% increase in gastrointestinal complaints in patients who were taking calcium supplements [6]. The potential for increased cardiovascular risk with calcium supplements is controversial [7]. The WHI study did not show an increased occurrence of cardiovascular events among those taking calcium supplements [8]. In a different population, men who consumed more than 1000 mg per day of supplemental calcium had higher all-cause and cardiovascular disease-specific mortality [9]. Large, well-conducted randomized controlled trials will be needed to further elucidate the question of calcium supplementation and risk of cardiovascular disease.

Vitamin D

Deficiency of vitamin D is common with one study finding more than 90% of older adults deficient in vitamin D [10]. Vitamin D is essential for proper calcium metabolism and deficiency is known to induce secondary hyperparathyroidism. Studies in mouse models have also shown that normal vitamin D receptors in enterocytes are essential for normal bone mineralization [11,12]. A systematic Cochrane database review showed that vitamin D3 supplementation decreased mortality in elderly people living independently or in institutional care [13]. Vitamin D was administered for a weighted mean of 4.4 years. Vitamin D2, alfacalcidol, and calcitriol had no statistically significant beneficial effects on mortality. Vitamin D3 combined with calcium was associated with an increased risk of nephrolithiasis during a follow-up period of 1.25 to 7 years (relative risk [RR] 1.17, 95% confidence interval (CI) 1.02–1.34) [13]. The inconsistencies of published reports looking at benefits of vitamin D supplementation may be due in part to variability in compliance with taking the supplements and baseline vitamin D levels.

Two randomized controlled trials have shown that low vitamin D appears to be an independent predictor of fall risk, and vitamin D supplementation has been found to reduce this risk of falls, through improved musculo-skeletal function [14–16]. Thus, vitamin D may play a role in fracture risk reduction beyond direct bone effects.

Prescription Osteoporosis Treatments

Bisphosphonates

Bisphosphonates are the most commonly prescribed medication for osteoporosis. The efficacy of bisphosphonates to reduce fractures is well established. There are oral bisphosphonates, which can be dosed daily, weekly, or monthly, and intravenous bisphosphonates, which can be given every 3 months or annually. Side effects with this class of medications include gastrointestinal effects with the oral options in up to 20% to 30% of users [17]. With intravenous bisphosphonates, the greatest risk is an acute phase response, which can occur in up to 42% of patients [18]. The risk of an acute phase reaction is much lower with doses beyond the first dose and lower if patients have ever previously taken an oral bisphosphonate and/or receive acetaminophen prior to the infusion. Other potential side effects with all bisphosphonates include osteonecrosis of jaw (ONJ) and atypical subtrochanteric fractures. Post marketing studies have indicated that the incidence of ONJ is less than 2 per 100,000 patient-years among those taking bisphosphonates [19,20]. A number of database analyses have shown that ONJ-like lesions can also occur in older individuals with osteoporosis who have never been exposed to bisphosphonates [21]. A case series of an osteoporotic population showed that ONJ-like lesions are lower grade than those typically seen in cancer patients who usually are exposed to higher doses of bisphosphonates [22]. A study of Swedish older men and women reported that long-term use of bisphosphonates (4 years or more) was associated with an increased incidence of atypical fractures. The RR for women was 126.0 (95% CI, 55.1–288.1) after 4 years of bisphosphonates [23]. A U.S. health care database analysis reported that 90% of those with atypical fractures were bisphosphonate users, almost half were Asian (49%), and use beyond 6 years showed the greatest risk [24].

Non-Bisphosphonate Medications

Other osteoporosis medications include denosumab, raloxifene, estrogen, and teriparatide (calcitonin will not be discussed here). Newer options currently under study, including cathepsin K inhibitors and anti-sclerostin therapies, are not available in the United States.

Denosumab is a monoclonal antibody that interferes with the receptor activator of nuclear kappa B ligand (RANK-L), which is the principal stimulus for osteoclastogenesis. Denosumab is administered once every 6 months subcutaneously. Phase III trials of denosumab demonstrated a 68% reduction in vertebral fractures and 40% and 20% reduction in fractures at hip and non-vertebral sites, respectively [25]. Similar to bisphosphonates, other risks include atypical femoral fractures and ONJ. In addition, hypocalcemia, including severe, symptomatic hypocalcemia, has been reported at rates higher than initially reported in the original clinical trials [26]. Hypocalcemia can be severe, especially in patients who are deficient in vitamin D [10,27].

Estrogen is effective in reducing the risk of vertebral fractures. Selective estrogen receptor modulators (SERMs) have both estrogen agonist and antagonist effects. The SERM, raloxifene, has been used in osteoporosis for its antiresorptive effects through the estrogen receptor [28,29]. A newer SERM, bazedoxifene, has been studied in combination with conjugated estrogen and has been reported to improve bone mineral density and other symptoms of menopause, like vasomotor symptoms and vulvo-vaginal atrophy, but its efficacy in reducing fracture risk has not been demonstrated [30,31].

Teriparatide is an anabolic agent that works by stimulating osteoblastic bone formation which results in an increase in bone density and reduction in both vertebral and non-vertebral fracture risk. In women with postmenopausal osteoporosis, it is typically reserved for those with very low bone mineral density (BMD) or those who continue to have fractures despite a bisphosphonate [32]. Barriers to use of teriparatide include high cost, the need for daily injections, and approved use for a total of two years in a lifetime. There is also a theoretical risk of osteosarcoma shown in animal studies but human cases have not been reported when used for postmenopausal osteoporosis. Published studies have shown that combination zolendronate and teriparatide have additive benefits to spine and hip BMD [33]. Another study reported that the combination of denosumab and teriparatide resulted in additive effects, ie, an increase in lumbar, hip, and femoral neck BMD [34]. These combinations have not been studied in populations large enough or for long enough duration to evaluate fracture risk reduction.

Adherence to Osteoporosis Medications

Treatment of osteoporosis reduces risk of fracture, but the benefit of osteoporosis medications is dependent on adherence. Adherence is associated with improved clinical outcomes [35,36] as well as reduced costs and utilization [37,38]; however, adherence to osteoporosis medications is poor. In a meta-analysis of 24 observational studies conducted in large populations, overall adherence for all osteoporosis therapies ranged from approximately 40% to 70% [39]. A recent retrospective claims database analysis in the U.S. reported a 60% noncompliance rate among the 57,913 postmenopausal women prescribed bisphosphonates over 1 year [40]. Another administrative database analysis from a managed care population compared the 3 oral bisphosphonates (risedronate, ibandronate, and alendronate) and found a mean medication possession ratio (MPR) between 0.57–0.58 at 12 months, which dropped to 0.47–0.50 after 24 months and 0.44–0.47 after 36 months [41]. In an observational study of 3200 older women in the U.K. low adherence was self-reported in 8.5%, and 21.6% self-discontinued treatment within 2 years [42]. In a study of Medicare Advantage prescription drug plan members, a small but significant increase in adherence was seen after osteo-porosis treatment change but overall adherence remained low (51% MPR in the change cohort and vs. 44% in the no-change cohort at 24 months, P < 0.01) [43].

Some patients restart osteoporosis therapy after a prolonged lapse in medication use. In one study, re-initiation rates for bisphosphonate therapy among persons who discontinued were as high as 30% within 6 months and 50% within 2 years [44]. Predictors of treatment re-initiation included younger age, female sex, history of fracture, recent hip fracture, nursing home discharge, and BMD testing [44].

Factors that Impact Adherence

Understanding which patients are most likely to be compliant with medications can aid physicians when monitoring osteoporosis treatment responses. In a retro-spective claims analysis, older age was found to be a predictor of compliance: women 65 years and older were more likely to be compliant than younger patients (P = 0.012) [45]. Among women receiving denosumab, improved adherence was found among women with a family history of a parent with a hip fracture, and lower adherence was seen in those with higher age, decreased mobility, and further distance from the clinic where the medication was provided [46].

Major reasons for nonadherence include a fear of potential side effects, occurrence of real side effects, the complicated dosing regimens, and perceived lack of benefit from the medications due to the asymptomatic nature of osteoporosis. In the above noted observational study from the U.K., more than half of the nonadherent patients attributed their nonadherence to side effects (53.9%), with a smaller proportion reporting fear of potential side effects (20.5%) or trouble with the dosing regimen (8.0%)[42].

Patients may also be unwilling to continue to take an osteoporosis medication if a fracture develops while on it and if they are not otherwise provided evidence that the medication is working. In a study by Costa Paiva et al, an understanding and knowledge to osteoporosis was a prerequisite to adherence and the strongest predictor of knowledge was higher education level [47]. Factors that impaired adherence were lower socioeconomic status and presence of comorbidities [47]. In a phenomenological qualitative study, trust in a health care provider was the most common reason for patients’ decision to accept an osteoporosis medication, emphasizing the importance of physician-patient communication [48].

Interventions to Enhance Adherence

Current methods of improving adherence for chronic health problems are mostly complex and not very effective [49]. In a systematic review of interventions to improve medication adherence, only 37 out of 81 studies reported improved adherence in the treatment of chronic diseases, and multifaceted treatments were more likely to succeed [49]. Improving adherence to osteoporosis medications is a complex issue, and a number of interventions evaluated in systematic reviews have shown limited efficacy [50,51]. Simplification of dosing regimens have been found to have a significant impact in chronic disease management [52,53] as well as in some studies of osteoporosis medications.

Simplification of Dosing

Among women prescribed daily vs. weekly bisphosphonates, those on the weekly regimen had significantly higher compliance [54]. However, rates were suboptimal in both groups and more than 50% of women discontinued at 1 year [54]. In addition, in a meta-analysis of osteoporosis medication adherence, a nearly two-fold higher odds of discontinuation with daily vs. weekly bisphosphonates was seen (odds ratio 1.90, 95% CI 1.81–2.00) [55]. Likewise, in a retrospective study in Spain, nearly 85% of those started on a daily bisphosphonate stopped within a year [56], while discontinuation was significantly lower in those prescribed a weekly or monthly bisphosphonate or daily teriparatide; however, discontinuation was still nearly 50% in these groups [56].

Once monthly dosing may be preferred by some patients as there is less time involved in thinking about the disease being treated and a perception of lower likelihood of side effects. In one study, postmenopausal women who had previously stopped oral bisphosphonates due to GI side effects had high adherence rates after self-selecting either monthly oral or quarterly intravenous ibandronate therapy [57]. However, not all studies show significant differences in adherence between weekly and monthly preparations [58–60].

The newer parenteral treatment options that can be given every 6 months or once yearly have the potential to significantly improve adherence. Once a year parenteral administration of a bisphosphonate was preferred over once-weekly oral administration, according to a 1-year study in patients with low bone density previously treated with alendronate [61]. A recent study that looked at persistence with an infusion of zolendronic acid in Taiwanese patients for 48 months found that 85% of patients received at least 2 infusions [62]. In patients treated with denosumab in 4 European countries, adherence and persistence at 12 months were consistently > 80% [46]. Persistence in this study was defined as receiving the subsequent injection within 6 months ± 8 weeks of the previous injection; adherence was defined as receiving 2 consecutive injections within 6 months ± 4 weeks of each other [46].

In a study by Cramer et al, increased adherence and persistence was seen with weekly alendronate compared daily alendronate at the end of 12 months [54]. Similar results were seen in a large longitudinal cohort study of weekly vs. daily bisphosphonates but less than 50% of patients were adherent with the weekly regimen [63]. When once monthly preparations of bisphosphonates became available, studies continued to support a patient preference for less frequently dosed bisphosphonates, with the majority of patients preferring monthly over weekly dosed medications [64–66].

The availability of quarterly ibandronate and yearly zoledronic acid infusions have further simplified dosing. In large, randomized, multicenter studies, patients consistently expressed a preference for yearly infusions over a weekly oral medication [61,67]. Adherence and persistence to osteoporosis medications was also greater in women receiving intravenous ibandronate compared to those receiving oral alendronate [68,69]. However, a study by Curtis et al showed low persistence with intravenous bisphosphonates in a Medicare population [70]. A possible reason for the lower adherence in this population was postulated to include the provision of the infusions at an outpatient center rather than a physician office. Automated nursing reminders with either phone calls or emails have the potential to mitigate the problem of persistence with this less frequent regimen [71,72]. In a review of patient preferences, less frequent dosing of medications was a common desire, but further generalizability were limited, emphasizing the need to individualize treatment [73].

Patient-Provider Communication

Individualizing treatment with better patient-provider communication and identification of potential barriers may increase compliance [74]. In one study, increasing patient participation in determining the treatment option was associated with improved patient adherence [57]. A systematic review of literature on interventions to improve adherence found that periodic follow-up interaction between patients and their health professionals also improved adherence [50]. Positive reinforcement via physician-patient discussion of either bone turnover markers or bone mineral density test results has also been found to improve long-term adherence with osteoporosis medications [71,75].

Better perceived physician knowledge may help with patient adherence. A study by Pickney et al reported that the patient confidence in their health care providers has influence on improved adherence, and patients were more likely to comply when the medications were prescribed by a specialist rather than a general practitioner [76].

Education, Reminders, Phone-Based

Improving patient knowledge of osteoporosis, especially with education using visual aids, may help with improving adherence [47]. In a randomized controlled trial at a single health management organization, an interactive voice response phone call plus a letter 1 week later increased the rate of obtaining a prescribed oral bisphosphonate in the intervention group (48.8% vs. 30.5% control; OR 2.3, 95% CI 1.34–3.94) when adjusted for age, sex, prior BMD, and fracture [77]. Use of an encounter decision aid also improved knowledge of osteoporosis medication options and led to a doubling of medication prescription attainment. However, adherence at 6 months was not improved [78].

Pill reminders in the form of text messages, paging systems on medication devices, and alarm beeps have been studied in patients with chronic diseases, and these technologies could be utilized for osteoporosis treatment [79–81]. A study of smart phone applications showed that many apps help with adherence, especially in noncompliant patients [82]. The researchers reported that of apps studied, MyMedSchedule, MyMeds, and RxmindMe were among the most highly rated due to their ease of use and enhanced functions. Solomon et all studied the effectiveness of a telephone-based counseling program using motivational interviewing in a large randomized study. They found no significant improvement in adherence to an osteoporosis regimen with the telephonic motivational interview compared to mailed educational materials (control group) (P = 0.07) [83]. In a 12-month multicenter, prospective randomized study, Bianchi et al examined the effectiveness of an intervention of reminders or reminders plus phone calls and meetings at the referral center in postmenopausal women initiating an oral osteoporosis prescription. No significant difference was seen in adherence at 12 months compared to standard care [84]. Adherence among the entire cohort, however, was very high [84]

Pharmacist-Based

The role of pharmacists in the treatment of chronic diseases, including osteoporosis, has been studied and shown to be cost-effective. In a study by van Boven et al, an algorithm was designed to detect patients with nonadherence and then tailor an intervention that consisted of structured counseling and active monitoring by pharmacists in initial and continuous phases [85]. This effort-intensive intervention resulted in reduced discontinuation of bisphosphonates after 12 months (reduction from 31.7% to 16.2% at 12 months) [85]. Despite the effort required, findings from the study support overall cost-effectiveness of this intervention [85]. A randomized controlled study by Lai et al showed that pharmacists can play a role in improving medication adherence through counseling patients on the importance of adherence, side effects, and goals of therapy [86]. The same authors also showed that involvement of a clinical pharmacist in the care of patients helped to further improve patient knowledge of medications and osteoporosis treatments, resolve medication-related concerns, and improve overall quality of life [87]. Such pharmacist-led interventions would require pharmacists to understand their role and the potential for drug holidays in the course of osteoporosis treatments and not mislabel patients as nonadherent when in fact purposefully holding osteoporosis medications [88].

Conclusion

Osteoporosis is a growing problem with increasing numbers of patients at risk for osteoporosis and related fractures. Currently available osteoporosis medications have shown clear benefit in reducing fracture risk; however, adherence to these therapies is required to obtain benefit. Unfortunately, osteoporosis medications have several limitations to full compliance, particularly the oral treatment options, including known possible side effects acutely and chronically, potential/feared side effects, irregular dosing intervals, complicated dosing instructions, and absence of an immediate recognizable benefit/effect. Improving adherence is complex [89] and tailoring to individual patients is of importance. Successful techniques for improving adherence may include a focus on physician-patient communication, use of the less frequently dosed medications, various medication reminders, use of available technology, and use of pharmacists for patient counseling and monitoring. Recognition of this common problem by clinicians is of utmost importance.

Corresponding author: Amy H. Warriner, MD, The University of Alabama at Birmingham, Division of Endocrinology, Diabetes and Metabolism, 702 Faculty Office Tower, 510 20th Street South, Birmingham, AL 35294, [email protected].

Financial disclosures: None.

From the Division of Endocrinology, Diabetes, and Metabolism, University of Alabama at Birmingham, Birmingham, Alabama.

Abstract

• Objective: To review the treatment of osteoporosis, challenges to treatment adherence, and factors associated with improved adherence.
• Methods: Review of the literature.
• Results: With the growing aging population, there is an increased number of people at risk of osteoporosis and fracture. Several medications are available that reduce the risk of fracture. However, adherence to osteoporosis medications is suboptimal. Factors related to nonadherence include dosing frequency, real side effects, and concern about potential side effects. Interventions that may improve adherence include clinician and patient education, less frequent and less complex dosing regimens, medication reminders, and adherence counseling.
• Conclusions: Improving adherence to osteoporosis medications is a complex and challenging issue. Considering and implementing strategies to improve adherence tailored to patient preferences may enhance long-term outcomes for patients with osteoporosis.

Osteoporosis is a chronic but asymptomatic disease that is characterized by an increased fragility of bones and increased risk of fractures. Hip and vertebral fractures are associated with the greatest morbidity and mortality. The prevalence of osteoporosis is estimated to be 10.3% in the US, with approximately 10.2 million adults over the age of 50 having osteoporosis based on 2010 census data and results from the National Health and Nutrition Examination Survey (NHANES) [1].

Several drugs are currently available for the treatment of osteoporosis, but adherence to treatment is low. Understanding the factors associated with low adherence and actions that can be taken to improve adherence to treatment is important given the large number of individuals with osteoporosis and the need to reduce the burden caused by fragility fracture. In this article, we review the treatment of osteoporosis, challenges to treatment adherence, and factors associated with improved adherence.

Nonprescription Medications

Calcium

There have been several published studies over the last decade evaluating calcium supplementation and its efficacy in reducing fractures. Although these studies showed that calcium reduces bone turnover by 20% and slowed postmenopausal bone loss by one third [2,3], none of these studies or a recent systematic review [4] showed any degree of fracture risk reduction with calcium supplements alone.

Although some calcium intake may be good, too much calcium has the potential to cause harm, including an increased risk of nephrolithiasis and constipation/bloating. An analysis of the Women’s Health Initiative (WHI) study reported a 17% increase in renal calculi in women who received calcium and vitamin D supplements [5]. Another recently published meta-analysis showed a 43% increase in gastrointestinal complaints in patients who were taking calcium supplements [6]. The potential for increased cardiovascular risk with calcium supplements is controversial [7]. The WHI study did not show an increased occurrence of cardiovascular events among those taking calcium supplements [8]. In a different population, men who consumed more than 1000 mg per day of supplemental calcium had higher all-cause and cardiovascular disease-specific mortality [9]. Large, well-conducted randomized controlled trials will be needed to further elucidate the question of calcium supplementation and risk of cardiovascular disease.

Vitamin D

Deficiency of vitamin D is common with one study finding more than 90% of older adults deficient in vitamin D [10]. Vitamin D is essential for proper calcium metabolism and deficiency is known to induce secondary hyperparathyroidism. Studies in mouse models have also shown that normal vitamin D receptors in enterocytes are essential for normal bone mineralization [11,12]. A systematic Cochrane database review showed that vitamin D3 supplementation decreased mortality in elderly people living independently or in institutional care [13]. Vitamin D was administered for a weighted mean of 4.4 years. Vitamin D2, alfacalcidol, and calcitriol had no statistically significant beneficial effects on mortality. Vitamin D3 combined with calcium was associated with an increased risk of nephrolithiasis during a follow-up period of 1.25 to 7 years (relative risk [RR] 1.17, 95% confidence interval (CI) 1.02–1.34) [13]. The inconsistencies of published reports looking at benefits of vitamin D supplementation may be due in part to variability in compliance with taking the supplements and baseline vitamin D levels.

Two randomized controlled trials have shown that low vitamin D appears to be an independent predictor of fall risk, and vitamin D supplementation has been found to reduce this risk of falls, through improved musculo-skeletal function [14–16]. Thus, vitamin D may play a role in fracture risk reduction beyond direct bone effects.

Prescription Osteoporosis Treatments

Bisphosphonates

Bisphosphonates are the most commonly prescribed medication for osteoporosis. The efficacy of bisphosphonates to reduce fractures is well established. There are oral bisphosphonates, which can be dosed daily, weekly, or monthly, and intravenous bisphosphonates, which can be given every 3 months or annually. Side effects with this class of medications include gastrointestinal effects with the oral options in up to 20% to 30% of users [17]. With intravenous bisphosphonates, the greatest risk is an acute phase response, which can occur in up to 42% of patients [18]. The risk of an acute phase reaction is much lower with doses beyond the first dose and lower if patients have ever previously taken an oral bisphosphonate and/or receive acetaminophen prior to the infusion. Other potential side effects with all bisphosphonates include osteonecrosis of jaw (ONJ) and atypical subtrochanteric fractures. Post marketing studies have indicated that the incidence of ONJ is less than 2 per 100,000 patient-years among those taking bisphosphonates [19,20]. A number of database analyses have shown that ONJ-like lesions can also occur in older individuals with osteoporosis who have never been exposed to bisphosphonates [21]. A case series of an osteoporotic population showed that ONJ-like lesions are lower grade than those typically seen in cancer patients who usually are exposed to higher doses of bisphosphonates [22]. A study of Swedish older men and women reported that long-term use of bisphosphonates (4 years or more) was associated with an increased incidence of atypical fractures. The RR for women was 126.0 (95% CI, 55.1–288.1) after 4 years of bisphosphonates [23]. A U.S. health care database analysis reported that 90% of those with atypical fractures were bisphosphonate users, almost half were Asian (49%), and use beyond 6 years showed the greatest risk [24].

Non-Bisphosphonate Medications

Other osteoporosis medications include denosumab, raloxifene, estrogen, and teriparatide (calcitonin will not be discussed here). Newer options currently under study, including cathepsin K inhibitors and anti-sclerostin therapies, are not available in the United States.

Denosumab is a monoclonal antibody that interferes with the receptor activator of nuclear kappa B ligand (RANK-L), which is the principal stimulus for osteoclastogenesis. Denosumab is administered once every 6 months subcutaneously. Phase III trials of denosumab demonstrated a 68% reduction in vertebral fractures and 40% and 20% reduction in fractures at hip and non-vertebral sites, respectively [25]. Similar to bisphosphonates, other risks include atypical femoral fractures and ONJ. In addition, hypocalcemia, including severe, symptomatic hypocalcemia, has been reported at rates higher than initially reported in the original clinical trials [26]. Hypocalcemia can be severe, especially in patients who are deficient in vitamin D [10,27].

Estrogen is effective in reducing the risk of vertebral fractures. Selective estrogen receptor modulators (SERMs) have both estrogen agonist and antagonist effects. The SERM, raloxifene, has been used in osteoporosis for its antiresorptive effects through the estrogen receptor [28,29]. A newer SERM, bazedoxifene, has been studied in combination with conjugated estrogen and has been reported to improve bone mineral density and other symptoms of menopause, like vasomotor symptoms and vulvo-vaginal atrophy, but its efficacy in reducing fracture risk has not been demonstrated [30,31].

Teriparatide is an anabolic agent that works by stimulating osteoblastic bone formation which results in an increase in bone density and reduction in both vertebral and non-vertebral fracture risk. In women with postmenopausal osteoporosis, it is typically reserved for those with very low bone mineral density (BMD) or those who continue to have fractures despite a bisphosphonate [32]. Barriers to use of teriparatide include high cost, the need for daily injections, and approved use for a total of two years in a lifetime. There is also a theoretical risk of osteosarcoma shown in animal studies but human cases have not been reported when used for postmenopausal osteoporosis. Published studies have shown that combination zolendronate and teriparatide have additive benefits to spine and hip BMD [33]. Another study reported that the combination of denosumab and teriparatide resulted in additive effects, ie, an increase in lumbar, hip, and femoral neck BMD [34]. These combinations have not been studied in populations large enough or for long enough duration to evaluate fracture risk reduction.

Adherence to Osteoporosis Medications

Treatment of osteoporosis reduces risk of fracture, but the benefit of osteoporosis medications is dependent on adherence. Adherence is associated with improved clinical outcomes [35,36] as well as reduced costs and utilization [37,38]; however, adherence to osteoporosis medications is poor. In a meta-analysis of 24 observational studies conducted in large populations, overall adherence for all osteoporosis therapies ranged from approximately 40% to 70% [39]. A recent retrospective claims database analysis in the U.S. reported a 60% noncompliance rate among the 57,913 postmenopausal women prescribed bisphosphonates over 1 year [40]. Another administrative database analysis from a managed care population compared the 3 oral bisphosphonates (risedronate, ibandronate, and alendronate) and found a mean medication possession ratio (MPR) between 0.57–0.58 at 12 months, which dropped to 0.47–0.50 after 24 months and 0.44–0.47 after 36 months [41]. In an observational study of 3200 older women in the U.K. low adherence was self-reported in 8.5%, and 21.6% self-discontinued treatment within 2 years [42]. In a study of Medicare Advantage prescription drug plan members, a small but significant increase in adherence was seen after osteo-porosis treatment change but overall adherence remained low (51% MPR in the change cohort and vs. 44% in the no-change cohort at 24 months, P < 0.01) [43].

Some patients restart osteoporosis therapy after a prolonged lapse in medication use. In one study, re-initiation rates for bisphosphonate therapy among persons who discontinued were as high as 30% within 6 months and 50% within 2 years [44]. Predictors of treatment re-initiation included younger age, female sex, history of fracture, recent hip fracture, nursing home discharge, and BMD testing [44].

Factors that Impact Adherence

Understanding which patients are most likely to be compliant with medications can aid physicians when monitoring osteoporosis treatment responses. In a retro-spective claims analysis, older age was found to be a predictor of compliance: women 65 years and older were more likely to be compliant than younger patients (P = 0.012) [45]. Among women receiving denosumab, improved adherence was found among women with a family history of a parent with a hip fracture, and lower adherence was seen in those with higher age, decreased mobility, and further distance from the clinic where the medication was provided [46].

Major reasons for nonadherence include a fear of potential side effects, occurrence of real side effects, the complicated dosing regimens, and perceived lack of benefit from the medications due to the asymptomatic nature of osteoporosis. In the above noted observational study from the U.K., more than half of the nonadherent patients attributed their nonadherence to side effects (53.9%), with a smaller proportion reporting fear of potential side effects (20.5%) or trouble with the dosing regimen (8.0%)[42].

Patients may also be unwilling to continue to take an osteoporosis medication if a fracture develops while on it and if they are not otherwise provided evidence that the medication is working. In a study by Costa Paiva et al, an understanding and knowledge to osteoporosis was a prerequisite to adherence and the strongest predictor of knowledge was higher education level [47]. Factors that impaired adherence were lower socioeconomic status and presence of comorbidities [47]. In a phenomenological qualitative study, trust in a health care provider was the most common reason for patients’ decision to accept an osteoporosis medication, emphasizing the importance of physician-patient communication [48].

Interventions to Enhance Adherence

Current methods of improving adherence for chronic health problems are mostly complex and not very effective [49]. In a systematic review of interventions to improve medication adherence, only 37 out of 81 studies reported improved adherence in the treatment of chronic diseases, and multifaceted treatments were more likely to succeed [49]. Improving adherence to osteoporosis medications is a complex issue, and a number of interventions evaluated in systematic reviews have shown limited efficacy [50,51]. Simplification of dosing regimens have been found to have a significant impact in chronic disease management [52,53] as well as in some studies of osteoporosis medications.

Simplification of Dosing

Among women prescribed daily vs. weekly bisphosphonates, those on the weekly regimen had significantly higher compliance [54]. However, rates were suboptimal in both groups and more than 50% of women discontinued at 1 year [54]. In addition, in a meta-analysis of osteoporosis medication adherence, a nearly two-fold higher odds of discontinuation with daily vs. weekly bisphosphonates was seen (odds ratio 1.90, 95% CI 1.81–2.00) [55]. Likewise, in a retrospective study in Spain, nearly 85% of those started on a daily bisphosphonate stopped within a year [56], while discontinuation was significantly lower in those prescribed a weekly or monthly bisphosphonate or daily teriparatide; however, discontinuation was still nearly 50% in these groups [56].

Once monthly dosing may be preferred by some patients as there is less time involved in thinking about the disease being treated and a perception of lower likelihood of side effects. In one study, postmenopausal women who had previously stopped oral bisphosphonates due to GI side effects had high adherence rates after self-selecting either monthly oral or quarterly intravenous ibandronate therapy [57]. However, not all studies show significant differences in adherence between weekly and monthly preparations [58–60].

The newer parenteral treatment options that can be given every 6 months or once yearly have the potential to significantly improve adherence. Once a year parenteral administration of a bisphosphonate was preferred over once-weekly oral administration, according to a 1-year study in patients with low bone density previously treated with alendronate [61]. A recent study that looked at persistence with an infusion of zolendronic acid in Taiwanese patients for 48 months found that 85% of patients received at least 2 infusions [62]. In patients treated with denosumab in 4 European countries, adherence and persistence at 12 months were consistently > 80% [46]. Persistence in this study was defined as receiving the subsequent injection within 6 months ± 8 weeks of the previous injection; adherence was defined as receiving 2 consecutive injections within 6 months ± 4 weeks of each other [46].

In a study by Cramer et al, increased adherence and persistence was seen with weekly alendronate compared daily alendronate at the end of 12 months [54]. Similar results were seen in a large longitudinal cohort study of weekly vs. daily bisphosphonates but less than 50% of patients were adherent with the weekly regimen [63]. When once monthly preparations of bisphosphonates became available, studies continued to support a patient preference for less frequently dosed bisphosphonates, with the majority of patients preferring monthly over weekly dosed medications [64–66].

The availability of quarterly ibandronate and yearly zoledronic acid infusions have further simplified dosing. In large, randomized, multicenter studies, patients consistently expressed a preference for yearly infusions over a weekly oral medication [61,67]. Adherence and persistence to osteoporosis medications was also greater in women receiving intravenous ibandronate compared to those receiving oral alendronate [68,69]. However, a study by Curtis et al showed low persistence with intravenous bisphosphonates in a Medicare population [70]. A possible reason for the lower adherence in this population was postulated to include the provision of the infusions at an outpatient center rather than a physician office. Automated nursing reminders with either phone calls or emails have the potential to mitigate the problem of persistence with this less frequent regimen [71,72]. In a review of patient preferences, less frequent dosing of medications was a common desire, but further generalizability were limited, emphasizing the need to individualize treatment [73].

Patient-Provider Communication

Individualizing treatment with better patient-provider communication and identification of potential barriers may increase compliance [74]. In one study, increasing patient participation in determining the treatment option was associated with improved patient adherence [57]. A systematic review of literature on interventions to improve adherence found that periodic follow-up interaction between patients and their health professionals also improved adherence [50]. Positive reinforcement via physician-patient discussion of either bone turnover markers or bone mineral density test results has also been found to improve long-term adherence with osteoporosis medications [71,75].

Better perceived physician knowledge may help with patient adherence. A study by Pickney et al reported that the patient confidence in their health care providers has influence on improved adherence, and patients were more likely to comply when the medications were prescribed by a specialist rather than a general practitioner [76].

Education, Reminders, Phone-Based

Improving patient knowledge of osteoporosis, especially with education using visual aids, may help with improving adherence [47]. In a randomized controlled trial at a single health management organization, an interactive voice response phone call plus a letter 1 week later increased the rate of obtaining a prescribed oral bisphosphonate in the intervention group (48.8% vs. 30.5% control; OR 2.3, 95% CI 1.34–3.94) when adjusted for age, sex, prior BMD, and fracture [77]. Use of an encounter decision aid also improved knowledge of osteoporosis medication options and led to a doubling of medication prescription attainment. However, adherence at 6 months was not improved [78].

Pill reminders in the form of text messages, paging systems on medication devices, and alarm beeps have been studied in patients with chronic diseases, and these technologies could be utilized for osteoporosis treatment [79–81]. A study of smart phone applications showed that many apps help with adherence, especially in noncompliant patients [82]. The researchers reported that of apps studied, MyMedSchedule, MyMeds, and RxmindMe were among the most highly rated due to their ease of use and enhanced functions. Solomon et all studied the effectiveness of a telephone-based counseling program using motivational interviewing in a large randomized study. They found no significant improvement in adherence to an osteoporosis regimen with the telephonic motivational interview compared to mailed educational materials (control group) (P = 0.07) [83]. In a 12-month multicenter, prospective randomized study, Bianchi et al examined the effectiveness of an intervention of reminders or reminders plus phone calls and meetings at the referral center in postmenopausal women initiating an oral osteoporosis prescription. No significant difference was seen in adherence at 12 months compared to standard care [84]. Adherence among the entire cohort, however, was very high [84]

Pharmacist-Based

The role of pharmacists in the treatment of chronic diseases, including osteoporosis, has been studied and shown to be cost-effective. In a study by van Boven et al, an algorithm was designed to detect patients with nonadherence and then tailor an intervention that consisted of structured counseling and active monitoring by pharmacists in initial and continuous phases [85]. This effort-intensive intervention resulted in reduced discontinuation of bisphosphonates after 12 months (reduction from 31.7% to 16.2% at 12 months) [85]. Despite the effort required, findings from the study support overall cost-effectiveness of this intervention [85]. A randomized controlled study by Lai et al showed that pharmacists can play a role in improving medication adherence through counseling patients on the importance of adherence, side effects, and goals of therapy [86]. The same authors also showed that involvement of a clinical pharmacist in the care of patients helped to further improve patient knowledge of medications and osteoporosis treatments, resolve medication-related concerns, and improve overall quality of life [87]. Such pharmacist-led interventions would require pharmacists to understand their role and the potential for drug holidays in the course of osteoporosis treatments and not mislabel patients as nonadherent when in fact purposefully holding osteoporosis medications [88].

Conclusion

Osteoporosis is a growing problem with increasing numbers of patients at risk for osteoporosis and related fractures. Currently available osteoporosis medications have shown clear benefit in reducing fracture risk; however, adherence to these therapies is required to obtain benefit. Unfortunately, osteoporosis medications have several limitations to full compliance, particularly the oral treatment options, including known possible side effects acutely and chronically, potential/feared side effects, irregular dosing intervals, complicated dosing instructions, and absence of an immediate recognizable benefit/effect. Improving adherence is complex [89] and tailoring to individual patients is of importance. Successful techniques for improving adherence may include a focus on physician-patient communication, use of the less frequently dosed medications, various medication reminders, use of available technology, and use of pharmacists for patient counseling and monitoring. Recognition of this common problem by clinicians is of utmost importance.

Corresponding author: Amy H. Warriner, MD, The University of Alabama at Birmingham, Division of Endocrinology, Diabetes and Metabolism, 702 Faculty Office Tower, 510 20th Street South, Birmingham, AL 35294, [email protected].

Financial disclosures: None.

From the Division of Endocrinology, Diabetes, and Metabolism, University of Alabama at Birmingham, Birmingham, Alabama.

Abstract

• Objective: To review the treatment of osteoporosis, challenges to treatment adherence, and factors associated with improved adherence.
• Methods: Review of the literature.
• Results: With the growing aging population, there is an increased number of people at risk of osteoporosis and fracture. Several medications are available that reduce the risk of fracture. However, adherence to osteoporosis medications is suboptimal. Factors related to nonadherence include dosing frequency, real side effects, and concern about potential side effects. Interventions that may improve adherence include clinician and patient education, less frequent and less complex dosing regimens, medication reminders, and adherence counseling.
• Conclusions: Improving adherence to osteoporosis medications is a complex and challenging issue. Considering and implementing strategies to improve adherence tailored to patient preferences may enhance long-term outcomes for patients with osteoporosis.

Osteoporosis is a chronic but asymptomatic disease that is characterized by an increased fragility of bones and increased risk of fractures. Hip and vertebral fractures are associated with the greatest morbidity and mortality. The prevalence of osteoporosis is estimated to be 10.3% in the US, with approximately 10.2 million adults over the age of 50 having osteoporosis based on 2010 census data and results from the National Health and Nutrition Examination Survey (NHANES) [1].

Several drugs are currently available for the treatment of osteoporosis, but adherence to treatment is low. Understanding the factors associated with low adherence and actions that can be taken to improve adherence to treatment is important given the large number of individuals with osteoporosis and the need to reduce the burden caused by fragility fracture. In this article, we review the treatment of osteoporosis, challenges to treatment adherence, and factors associated with improved adherence.

Nonprescription Medications

Calcium

There have been several published studies over the last decade evaluating calcium supplementation and its efficacy in reducing fractures. Although these studies showed that calcium reduces bone turnover by 20% and slowed postmenopausal bone loss by one third [2,3], none of these studies or a recent systematic review [4] showed any degree of fracture risk reduction with calcium supplements alone.

Although some calcium intake may be good, too much calcium has the potential to cause harm, including an increased risk of nephrolithiasis and constipation/bloating. An analysis of the Women’s Health Initiative (WHI) study reported a 17% increase in renal calculi in women who received calcium and vitamin D supplements [5]. Another recently published meta-analysis showed a 43% increase in gastrointestinal complaints in patients who were taking calcium supplements [6]. The potential for increased cardiovascular risk with calcium supplements is controversial [7]. The WHI study did not show an increased occurrence of cardiovascular events among those taking calcium supplements [8]. In a different population, men who consumed more than 1000 mg per day of supplemental calcium had higher all-cause and cardiovascular disease-specific mortality [9]. Large, well-conducted randomized controlled trials will be needed to further elucidate the question of calcium supplementation and risk of cardiovascular disease.

Vitamin D

Deficiency of vitamin D is common with one study finding more than 90% of older adults deficient in vitamin D [10]. Vitamin D is essential for proper calcium metabolism and deficiency is known to induce secondary hyperparathyroidism. Studies in mouse models have also shown that normal vitamin D receptors in enterocytes are essential for normal bone mineralization [11,12]. A systematic Cochrane database review showed that vitamin D3 supplementation decreased mortality in elderly people living independently or in institutional care [13]. Vitamin D was administered for a weighted mean of 4.4 years. Vitamin D2, alfacalcidol, and calcitriol had no statistically significant beneficial effects on mortality. Vitamin D3 combined with calcium was associated with an increased risk of nephrolithiasis during a follow-up period of 1.25 to 7 years (relative risk [RR] 1.17, 95% confidence interval (CI) 1.02–1.34) [13]. The inconsistencies of published reports looking at benefits of vitamin D supplementation may be due in part to variability in compliance with taking the supplements and baseline vitamin D levels.

Two randomized controlled trials have shown that low vitamin D appears to be an independent predictor of fall risk, and vitamin D supplementation has been found to reduce this risk of falls, through improved musculo-skeletal function [14–16]. Thus, vitamin D may play a role in fracture risk reduction beyond direct bone effects.

Prescription Osteoporosis Treatments

Bisphosphonates

Bisphosphonates are the most commonly prescribed medication for osteoporosis. The efficacy of bisphosphonates to reduce fractures is well established. There are oral bisphosphonates, which can be dosed daily, weekly, or monthly, and intravenous bisphosphonates, which can be given every 3 months or annually. Side effects with this class of medications include gastrointestinal effects with the oral options in up to 20% to 30% of users [17]. With intravenous bisphosphonates, the greatest risk is an acute phase response, which can occur in up to 42% of patients [18]. The risk of an acute phase reaction is much lower with doses beyond the first dose and lower if patients have ever previously taken an oral bisphosphonate and/or receive acetaminophen prior to the infusion. Other potential side effects with all bisphosphonates include osteonecrosis of jaw (ONJ) and atypical subtrochanteric fractures. Post marketing studies have indicated that the incidence of ONJ is less than 2 per 100,000 patient-years among those taking bisphosphonates [19,20]. A number of database analyses have shown that ONJ-like lesions can also occur in older individuals with osteoporosis who have never been exposed to bisphosphonates [21]. A case series of an osteoporotic population showed that ONJ-like lesions are lower grade than those typically seen in cancer patients who usually are exposed to higher doses of bisphosphonates [22]. A study of Swedish older men and women reported that long-term use of bisphosphonates (4 years or more) was associated with an increased incidence of atypical fractures. The RR for women was 126.0 (95% CI, 55.1–288.1) after 4 years of bisphosphonates [23]. A U.S. health care database analysis reported that 90% of those with atypical fractures were bisphosphonate users, almost half were Asian (49%), and use beyond 6 years showed the greatest risk [24].

Non-Bisphosphonate Medications

Other osteoporosis medications include denosumab, raloxifene, estrogen, and teriparatide (calcitonin will not be discussed here). Newer options currently under study, including cathepsin K inhibitors and anti-sclerostin therapies, are not available in the United States.

Denosumab is a monoclonal antibody that interferes with the receptor activator of nuclear kappa B ligand (RANK-L), which is the principal stimulus for osteoclastogenesis. Denosumab is administered once every 6 months subcutaneously. Phase III trials of denosumab demonstrated a 68% reduction in vertebral fractures and 40% and 20% reduction in fractures at hip and non-vertebral sites, respectively [25]. Similar to bisphosphonates, other risks include atypical femoral fractures and ONJ. In addition, hypocalcemia, including severe, symptomatic hypocalcemia, has been reported at rates higher than initially reported in the original clinical trials [26]. Hypocalcemia can be severe, especially in patients who are deficient in vitamin D [10,27].

Estrogen is effective in reducing the risk of vertebral fractures. Selective estrogen receptor modulators (SERMs) have both estrogen agonist and antagonist effects. The SERM, raloxifene, has been used in osteoporosis for its antiresorptive effects through the estrogen receptor [28,29]. A newer SERM, bazedoxifene, has been studied in combination with conjugated estrogen and has been reported to improve bone mineral density and other symptoms of menopause, like vasomotor symptoms and vulvo-vaginal atrophy, but its efficacy in reducing fracture risk has not been demonstrated [30,31].

Teriparatide is an anabolic agent that works by stimulating osteoblastic bone formation which results in an increase in bone density and reduction in both vertebral and non-vertebral fracture risk. In women with postmenopausal osteoporosis, it is typically reserved for those with very low bone mineral density (BMD) or those who continue to have fractures despite a bisphosphonate [32]. Barriers to use of teriparatide include high cost, the need for daily injections, and approved use for a total of two years in a lifetime. There is also a theoretical risk of osteosarcoma shown in animal studies but human cases have not been reported when used for postmenopausal osteoporosis. Published studies have shown that combination zolendronate and teriparatide have additive benefits to spine and hip BMD [33]. Another study reported that the combination of denosumab and teriparatide resulted in additive effects, ie, an increase in lumbar, hip, and femoral neck BMD [34]. These combinations have not been studied in populations large enough or for long enough duration to evaluate fracture risk reduction.

Adherence to Osteoporosis Medications

Treatment of osteoporosis reduces risk of fracture, but the benefit of osteoporosis medications is dependent on adherence. Adherence is associated with improved clinical outcomes [35,36] as well as reduced costs and utilization [37,38]; however, adherence to osteoporosis medications is poor. In a meta-analysis of 24 observational studies conducted in large populations, overall adherence for all osteoporosis therapies ranged from approximately 40% to 70% [39]. A recent retrospective claims database analysis in the U.S. reported a 60% noncompliance rate among the 57,913 postmenopausal women prescribed bisphosphonates over 1 year [40]. Another administrative database analysis from a managed care population compared the 3 oral bisphosphonates (risedronate, ibandronate, and alendronate) and found a mean medication possession ratio (MPR) between 0.57–0.58 at 12 months, which dropped to 0.47–0.50 after 24 months and 0.44–0.47 after 36 months [41]. In an observational study of 3200 older women in the U.K. low adherence was self-reported in 8.5%, and 21.6% self-discontinued treatment within 2 years [42]. In a study of Medicare Advantage prescription drug plan members, a small but significant increase in adherence was seen after osteo-porosis treatment change but overall adherence remained low (51% MPR in the change cohort and vs. 44% in the no-change cohort at 24 months, P < 0.01) [43].

Some patients restart osteoporosis therapy after a prolonged lapse in medication use. In one study, re-initiation rates for bisphosphonate therapy among persons who discontinued were as high as 30% within 6 months and 50% within 2 years [44]. Predictors of treatment re-initiation included younger age, female sex, history of fracture, recent hip fracture, nursing home discharge, and BMD testing [44].

Factors that Impact Adherence

Understanding which patients are most likely to be compliant with medications can aid physicians when monitoring osteoporosis treatment responses. In a retro-spective claims analysis, older age was found to be a predictor of compliance: women 65 years and older were more likely to be compliant than younger patients (P = 0.012) [45]. Among women receiving denosumab, improved adherence was found among women with a family history of a parent with a hip fracture, and lower adherence was seen in those with higher age, decreased mobility, and further distance from the clinic where the medication was provided [46].

Major reasons for nonadherence include a fear of potential side effects, occurrence of real side effects, the complicated dosing regimens, and perceived lack of benefit from the medications due to the asymptomatic nature of osteoporosis. In the above noted observational study from the U.K., more than half of the nonadherent patients attributed their nonadherence to side effects (53.9%), with a smaller proportion reporting fear of potential side effects (20.5%) or trouble with the dosing regimen (8.0%)[42].

Patients may also be unwilling to continue to take an osteoporosis medication if a fracture develops while on it and if they are not otherwise provided evidence that the medication is working. In a study by Costa Paiva et al, an understanding and knowledge to osteoporosis was a prerequisite to adherence and the strongest predictor of knowledge was higher education level [47]. Factors that impaired adherence were lower socioeconomic status and presence of comorbidities [47]. In a phenomenological qualitative study, trust in a health care provider was the most common reason for patients’ decision to accept an osteoporosis medication, emphasizing the importance of physician-patient communication [48].

Interventions to Enhance Adherence

Current methods of improving adherence for chronic health problems are mostly complex and not very effective [49]. In a systematic review of interventions to improve medication adherence, only 37 out of 81 studies reported improved adherence in the treatment of chronic diseases, and multifaceted treatments were more likely to succeed [49]. Improving adherence to osteoporosis medications is a complex issue, and a number of interventions evaluated in systematic reviews have shown limited efficacy [50,51]. Simplification of dosing regimens have been found to have a significant impact in chronic disease management [52,53] as well as in some studies of osteoporosis medications.

Simplification of Dosing

Among women prescribed daily vs. weekly bisphosphonates, those on the weekly regimen had significantly higher compliance [54]. However, rates were suboptimal in both groups and more than 50% of women discontinued at 1 year [54]. In addition, in a meta-analysis of osteoporosis medication adherence, a nearly two-fold higher odds of discontinuation with daily vs. weekly bisphosphonates was seen (odds ratio 1.90, 95% CI 1.81–2.00) [55]. Likewise, in a retrospective study in Spain, nearly 85% of those started on a daily bisphosphonate stopped within a year [56], while discontinuation was significantly lower in those prescribed a weekly or monthly bisphosphonate or daily teriparatide; however, discontinuation was still nearly 50% in these groups [56].

Once monthly dosing may be preferred by some patients as there is less time involved in thinking about the disease being treated and a perception of lower likelihood of side effects. In one study, postmenopausal women who had previously stopped oral bisphosphonates due to GI side effects had high adherence rates after self-selecting either monthly oral or quarterly intravenous ibandronate therapy [57]. However, not all studies show significant differences in adherence between weekly and monthly preparations [58–60].

The newer parenteral treatment options that can be given every 6 months or once yearly have the potential to significantly improve adherence. Once a year parenteral administration of a bisphosphonate was preferred over once-weekly oral administration, according to a 1-year study in patients with low bone density previously treated with alendronate [61]. A recent study that looked at persistence with an infusion of zolendronic acid in Taiwanese patients for 48 months found that 85% of patients received at least 2 infusions [62]. In patients treated with denosumab in 4 European countries, adherence and persistence at 12 months were consistently > 80% [46]. Persistence in this study was defined as receiving the subsequent injection within 6 months ± 8 weeks of the previous injection; adherence was defined as receiving 2 consecutive injections within 6 months ± 4 weeks of each other [46].

In a study by Cramer et al, increased adherence and persistence was seen with weekly alendronate compared daily alendronate at the end of 12 months [54]. Similar results were seen in a large longitudinal cohort study of weekly vs. daily bisphosphonates but less than 50% of patients were adherent with the weekly regimen [63]. When once monthly preparations of bisphosphonates became available, studies continued to support a patient preference for less frequently dosed bisphosphonates, with the majority of patients preferring monthly over weekly dosed medications [64–66].

The availability of quarterly ibandronate and yearly zoledronic acid infusions have further simplified dosing. In large, randomized, multicenter studies, patients consistently expressed a preference for yearly infusions over a weekly oral medication [61,67]. Adherence and persistence to osteoporosis medications was also greater in women receiving intravenous ibandronate compared to those receiving oral alendronate [68,69]. However, a study by Curtis et al showed low persistence with intravenous bisphosphonates in a Medicare population [70]. A possible reason for the lower adherence in this population was postulated to include the provision of the infusions at an outpatient center rather than a physician office. Automated nursing reminders with either phone calls or emails have the potential to mitigate the problem of persistence with this less frequent regimen [71,72]. In a review of patient preferences, less frequent dosing of medications was a common desire, but further generalizability were limited, emphasizing the need to individualize treatment [73].

Patient-Provider Communication

Individualizing treatment with better patient-provider communication and identification of potential barriers may increase compliance [74]. In one study, increasing patient participation in determining the treatment option was associated with improved patient adherence [57]. A systematic review of literature on interventions to improve adherence found that periodic follow-up interaction between patients and their health professionals also improved adherence [50]. Positive reinforcement via physician-patient discussion of either bone turnover markers or bone mineral density test results has also been found to improve long-term adherence with osteoporosis medications [71,75].

Better perceived physician knowledge may help with patient adherence. A study by Pickney et al reported that the patient confidence in their health care providers has influence on improved adherence, and patients were more likely to comply when the medications were prescribed by a specialist rather than a general practitioner [76].

Education, Reminders, Phone-Based

Improving patient knowledge of osteoporosis, especially with education using visual aids, may help with improving adherence [47]. In a randomized controlled trial at a single health management organization, an interactive voice response phone call plus a letter 1 week later increased the rate of obtaining a prescribed oral bisphosphonate in the intervention group (48.8% vs. 30.5% control; OR 2.3, 95% CI 1.34–3.94) when adjusted for age, sex, prior BMD, and fracture [77]. Use of an encounter decision aid also improved knowledge of osteoporosis medication options and led to a doubling of medication prescription attainment. However, adherence at 6 months was not improved [78].

Pill reminders in the form of text messages, paging systems on medication devices, and alarm beeps have been studied in patients with chronic diseases, and these technologies could be utilized for osteoporosis treatment [79–81]. A study of smart phone applications showed that many apps help with adherence, especially in noncompliant patients [82]. The researchers reported that of apps studied, MyMedSchedule, MyMeds, and RxmindMe were among the most highly rated due to their ease of use and enhanced functions. Solomon et all studied the effectiveness of a telephone-based counseling program using motivational interviewing in a large randomized study. They found no significant improvement in adherence to an osteoporosis regimen with the telephonic motivational interview compared to mailed educational materials (control group) (P = 0.07) [83]. In a 12-month multicenter, prospective randomized study, Bianchi et al examined the effectiveness of an intervention of reminders or reminders plus phone calls and meetings at the referral center in postmenopausal women initiating an oral osteoporosis prescription. No significant difference was seen in adherence at 12 months compared to standard care [84]. Adherence among the entire cohort, however, was very high [84]

Pharmacist-Based

The role of pharmacists in the treatment of chronic diseases, including osteoporosis, has been studied and shown to be cost-effective. In a study by van Boven et al, an algorithm was designed to detect patients with nonadherence and then tailor an intervention that consisted of structured counseling and active monitoring by pharmacists in initial and continuous phases [85]. This effort-intensive intervention resulted in reduced discontinuation of bisphosphonates after 12 months (reduction from 31.7% to 16.2% at 12 months) [85]. Despite the effort required, findings from the study support overall cost-effectiveness of this intervention [85]. A randomized controlled study by Lai et al showed that pharmacists can play a role in improving medication adherence through counseling patients on the importance of adherence, side effects, and goals of therapy [86]. The same authors also showed that involvement of a clinical pharmacist in the care of patients helped to further improve patient knowledge of medications and osteoporosis treatments, resolve medication-related concerns, and improve overall quality of life [87]. Such pharmacist-led interventions would require pharmacists to understand their role and the potential for drug holidays in the course of osteoporosis treatments and not mislabel patients as nonadherent when in fact purposefully holding osteoporosis medications [88].

Conclusion

Osteoporosis is a growing problem with increasing numbers of patients at risk for osteoporosis and related fractures. Currently available osteoporosis medications have shown clear benefit in reducing fracture risk; however, adherence to these therapies is required to obtain benefit. Unfortunately, osteoporosis medications have several limitations to full compliance, particularly the oral treatment options, including known possible side effects acutely and chronically, potential/feared side effects, irregular dosing intervals, complicated dosing instructions, and absence of an immediate recognizable benefit/effect. Improving adherence is complex [89] and tailoring to individual patients is of importance. Successful techniques for improving adherence may include a focus on physician-patient communication, use of the less frequently dosed medications, various medication reminders, use of available technology, and use of pharmacists for patient counseling and monitoring. Recognition of this common problem by clinicians is of utmost importance.

Corresponding author: Amy H. Warriner, MD, The University of Alabama at Birmingham, Division of Endocrinology, Diabetes and Metabolism, 702 Faculty Office Tower, 510 20th Street South, Birmingham, AL 35294, [email protected].

Financial disclosures: None.

Insomnia is a more pronounced problem than expected among Hispanics over age 50, according to results of a study by Christopher N. Kaufmann, PhD, and his coauthors.

Dr. Kaufmann and his colleagues studied 22,252 participants of white, Non-Hispanic black, Hispanic, or other race/ethnicity. Participant data came from a nationally representative survey from 2002 to 2010, in which patients rated the severity of four insomnia symptoms. All participants were adults older than 50 years.

Insomnia severity scores increased 0.19 points over time after the investigators controlled for sex, race/ethnicity, education, and baseline age (95% CI, 0.14-0.24; t = 7.52; design df = 56; P less than .001). After adjustment for accumulated health conditions and body mass index, this trend decreased, Dr. Kaufmann and his colleagues added. However, the increasing trajectory of insomnia severity was “significantly more pronounced” among Hispanics, compared with non-Hispanic whites, after adjustment for accumulated health conditions, body mass index, and number of depressive symptoms, the investigators said in the report.

Although health conditions can result in greater insomnia severity with age, “further research is needed to determine the reasons for a different insomnia trajectory among Hispanics,” the authors concluded.

Read the full article in the American Journal of Geriatric Psychiatry.

Insomnia is a more pronounced problem than expected among Hispanics over age 50, according to results of a study by Christopher N. Kaufmann, PhD, and his coauthors.

Dr. Kaufmann and his colleagues studied 22,252 participants of white, Non-Hispanic black, Hispanic, or other race/ethnicity. Participant data came from a nationally representative survey from 2002 to 2010, in which patients rated the severity of four insomnia symptoms. All participants were adults older than 50 years.

Insomnia severity scores increased 0.19 points over time after the investigators controlled for sex, race/ethnicity, education, and baseline age (95% CI, 0.14-0.24; t = 7.52; design df = 56; P less than .001). After adjustment for accumulated health conditions and body mass index, this trend decreased, Dr. Kaufmann and his colleagues added. However, the increasing trajectory of insomnia severity was “significantly more pronounced” among Hispanics, compared with non-Hispanic whites, after adjustment for accumulated health conditions, body mass index, and number of depressive symptoms, the investigators said in the report.

Although health conditions can result in greater insomnia severity with age, “further research is needed to determine the reasons for a different insomnia trajectory among Hispanics,” the authors concluded.

Read the full article in the American Journal of Geriatric Psychiatry.

Insomnia is a more pronounced problem than expected among Hispanics over age 50, according to results of a study by Christopher N. Kaufmann, PhD, and his coauthors.

Dr. Kaufmann and his colleagues studied 22,252 participants of white, Non-Hispanic black, Hispanic, or other race/ethnicity. Participant data came from a nationally representative survey from 2002 to 2010, in which patients rated the severity of four insomnia symptoms. All participants were adults older than 50 years.

Insomnia severity scores increased 0.19 points over time after the investigators controlled for sex, race/ethnicity, education, and baseline age (95% CI, 0.14-0.24; t = 7.52; design df = 56; P less than .001). After adjustment for accumulated health conditions and body mass index, this trend decreased, Dr. Kaufmann and his colleagues added. However, the increasing trajectory of insomnia severity was “significantly more pronounced” among Hispanics, compared with non-Hispanic whites, after adjustment for accumulated health conditions, body mass index, and number of depressive symptoms, the investigators said in the report.

Although health conditions can result in greater insomnia severity with age, “further research is needed to determine the reasons for a different insomnia trajectory among Hispanics,” the authors concluded.

Read the full article in the American Journal of Geriatric Psychiatry.

HELSINKI, FINLAND – Scratching the endometrium to create a “favorable inflammation” may improve the likelihood of embryo implantation in subfertile women trying to conceive either naturally or by intrauterine insemination, according to a Cochrane review.

The “injury” caused by the process, which is known as endometrial scratching, has been reported to increase the probability of pregnancy in women undergoing in vitro fertilization, especially those with recurrent implantation failure. The inflammatory response to the injury, which is performed by pipelle biopsy or a similar device, is thought to make the endometrium more receptive to implantation.

In the current meta-analysis and systematic review of eight trials comprising 1,180 women, endometrial scratching appeared to approximately double the chance of clinical pregnancy and live birth/ongoing pregnancy (relative risk, 1.92 and 2.26, respectively), compared with either no procedure or a placebo procedure, lead author Sarah Lensen reported in a poster at the annual meeting of the European Society of Human Reproduction and Embryology.

The difference between the groups was statistically significant.

The evidence suggests that endometrial scratching would increase the normal chance of a live birth or ongoing pregnancy over a set period of time from 9% to between 14% and 28%, explained Ms. Lensen, a PhD candidate at the University of Auckland, New Zealand.

No evidence was seen that endometrial scratching has any effect on miscarriage, ectopic pregnancy, or multiple pregnancy.

Pain during the procedure was reported in one of the eight studies, in which the average pain score was 6 out of 10.

Endometrial scratching is a simple and inexpensive procedure that can be conducted without analgesia during a short clinic visit, although the internal examination that is required can be associated with pain and discomfort, Ms. Lensen said.

For the review, she and her colleagues looked at randomized controlled trials evaluating endometrial scratching in women planning to have intrauterine insemination or attempting to conceive spontaneously (with or without ovulation induction), compared with either no intervention, mock intervention, or endometrial scratching performed at a different time or to a greater or lesser degree.

The researchers acknowledged that the quality of the evidence is quite low, with a risk of bias associated with most of the included trials. For this reason, the results should be viewed with caution, they said.

“High quality randomized controlled trials which recruit sufficient numbers of women are needed to confirm to refute these findings,” they wrote.

Ms. Lensen reported having no financial disclosures.

[email protected]

HELSINKI, FINLAND – Scratching the endometrium to create a “favorable inflammation” may improve the likelihood of embryo implantation in subfertile women trying to conceive either naturally or by intrauterine insemination, according to a Cochrane review.

The “injury” caused by the process, which is known as endometrial scratching, has been reported to increase the probability of pregnancy in women undergoing in vitro fertilization, especially those with recurrent implantation failure. The inflammatory response to the injury, which is performed by pipelle biopsy or a similar device, is thought to make the endometrium more receptive to implantation.

In the current meta-analysis and systematic review of eight trials comprising 1,180 women, endometrial scratching appeared to approximately double the chance of clinical pregnancy and live birth/ongoing pregnancy (relative risk, 1.92 and 2.26, respectively), compared with either no procedure or a placebo procedure, lead author Sarah Lensen reported in a poster at the annual meeting of the European Society of Human Reproduction and Embryology.

The difference between the groups was statistically significant.

The evidence suggests that endometrial scratching would increase the normal chance of a live birth or ongoing pregnancy over a set period of time from 9% to between 14% and 28%, explained Ms. Lensen, a PhD candidate at the University of Auckland, New Zealand.

No evidence was seen that endometrial scratching has any effect on miscarriage, ectopic pregnancy, or multiple pregnancy.

Pain during the procedure was reported in one of the eight studies, in which the average pain score was 6 out of 10.

Endometrial scratching is a simple and inexpensive procedure that can be conducted without analgesia during a short clinic visit, although the internal examination that is required can be associated with pain and discomfort, Ms. Lensen said.

For the review, she and her colleagues looked at randomized controlled trials evaluating endometrial scratching in women planning to have intrauterine insemination or attempting to conceive spontaneously (with or without ovulation induction), compared with either no intervention, mock intervention, or endometrial scratching performed at a different time or to a greater or lesser degree.

The researchers acknowledged that the quality of the evidence is quite low, with a risk of bias associated with most of the included trials. For this reason, the results should be viewed with caution, they said.

“High quality randomized controlled trials which recruit sufficient numbers of women are needed to confirm to refute these findings,” they wrote.

Ms. Lensen reported having no financial disclosures.

[email protected]

HELSINKI, FINLAND – Scratching the endometrium to create a “favorable inflammation” may improve the likelihood of embryo implantation in subfertile women trying to conceive either naturally or by intrauterine insemination, according to a Cochrane review.

The “injury” caused by the process, which is known as endometrial scratching, has been reported to increase the probability of pregnancy in women undergoing in vitro fertilization, especially those with recurrent implantation failure. The inflammatory response to the injury, which is performed by pipelle biopsy or a similar device, is thought to make the endometrium more receptive to implantation.

In the current meta-analysis and systematic review of eight trials comprising 1,180 women, endometrial scratching appeared to approximately double the chance of clinical pregnancy and live birth/ongoing pregnancy (relative risk, 1.92 and 2.26, respectively), compared with either no procedure or a placebo procedure, lead author Sarah Lensen reported in a poster at the annual meeting of the European Society of Human Reproduction and Embryology.

The difference between the groups was statistically significant.

The evidence suggests that endometrial scratching would increase the normal chance of a live birth or ongoing pregnancy over a set period of time from 9% to between 14% and 28%, explained Ms. Lensen, a PhD candidate at the University of Auckland, New Zealand.

No evidence was seen that endometrial scratching has any effect on miscarriage, ectopic pregnancy, or multiple pregnancy.

Pain during the procedure was reported in one of the eight studies, in which the average pain score was 6 out of 10.

Endometrial scratching is a simple and inexpensive procedure that can be conducted without analgesia during a short clinic visit, although the internal examination that is required can be associated with pain and discomfort, Ms. Lensen said.

For the review, she and her colleagues looked at randomized controlled trials evaluating endometrial scratching in women planning to have intrauterine insemination or attempting to conceive spontaneously (with or without ovulation induction), compared with either no intervention, mock intervention, or endometrial scratching performed at a different time or to a greater or lesser degree.

The researchers acknowledged that the quality of the evidence is quite low, with a risk of bias associated with most of the included trials. For this reason, the results should be viewed with caution, they said.

“High quality randomized controlled trials which recruit sufficient numbers of women are needed to confirm to refute these findings,” they wrote.

Ms. Lensen reported having no financial disclosures.

[email protected]