CHICAGO – More than 10 years on, nearly one-fourth of patients with gastrointestinal stromal tumors treated initially with imatinib are still alive, according to results from a collaborative trial reported at the annual meeting of the American Society of Clinical Oncology.

"A significant fraction of patients can survive for more than 10 years with imatinib [Gleevec] as their initial therapy for advanced GIST; and for almost half as their only systemic therapy for advanced GIST, understanding the pathobiology of these exceptional outcomes will be important to understanding the disease better," said Dr. George Demetri, director of the Center for Sarcoma and Bone Oncology, Dana-Farber Cancer Institute, Boston.

In the 14 years that have ensued since the first patient with GIST received imatinib and had an "extraordinary" response, new drugs in the tyrosine kinase inhibitor (TKI) class have become available for patients whose disease has progressed on the TKI imatinib. The evolution in the treatment of GIST emphasizes the fact that overall survival as a trial endpoint is really "a composite endpoint of on-study and poststudy interventions," Dr. Demetri said at meeting.

In the phase III Southwest Oncology Group (SWOG) Intergroup S0033 trial, initiated in 2000, 746 patients with metastatic or unresectable GIST were randomly assigned to receive daily imatinib at a dose of either 400 mg or 800 mg (400 mg twice daily). Patients in the 400-mg qd group had the option of crossing over to the 800-mg dose at the time of disease progression, and 130 patients chose to do so.

The trial was sparked by the discovery by Japanese investigators in 1998 of gain-of-function mutations in the gene encoding for KIT kinase.

As the SWOG S0033 investigators reported in 2008, median progression-free survival at a median follow-up of 4.5 years was 18 months for patients on the 400-mg dose and 20 months for those receiving 800 mg. The median overall survival was 55 months for patients in the 400-mg arm and 51 months for those in the 800-mg arm.

"A question we ask ourselves is, what accounts for this 33-month survival median difference after objective disease progression? It seems like a long time, which is why we wanted to know what happened to these patients after progression," Dr. Demetri said.

The investigators looked at survival by mutational status. Data on the GIST genotype were available on 395 patients, 282 of whom (71%) had KIT exon 11 mutations, 32 of whom (8%) had KIT exon 9 mutations, and 14 (4%) had other KIT or PDGFRA (platelet-derived growth factor receptor–alpha) mutations. Another 67 patients (17%) had no detectable KIT or PDGFRA mutations.

An analysis of data on these patients at 4.5 months’ median follow-up showed that patients with KIT exon 11 mutations had significantly better overall survival than patients with either wild-type (no mutation) KIT (P = .0011) or exon 9 mutations (P = .049).

Updated data with follow-up out to 10 years shows that patients with the KIT exon 9 mutation had significantly worse overall survival than patients with either exon 11 mutations (P = .0001) or no mutations (P = .047). There was no significant difference between patients with exon 11 mutations and no KIT or PDGFRA mutations.

Other factors significantly associated with overall survival in multivariate analysis included age by decade, male sex, performance status, maximum tumor diameter, and serum albumin (3.5 g/dL or less vs. more than 3.5 g/dL).

An analysis of on-study and postprogression therapies among 137 of 180 long-term survivors (8 years and longer) showed that 67 of the 137 (49%) had taken imatinib continuously as the only long-term therapy.

The remaining 70 patients (51%) had some additional therapy, including systemic therapies such as sunitinib (Sutent; 30% of the 137 patients), sorafenib (Nexavar; 12%), and other agents (31%).

In addition, 41 patients (30%) had metastasectomy or other type of surgery, 10 (7%) had radiofrequency ablation of tumors, and 6 (4%) had radiation therapy.

"We know that the landscape of therapeutic options for GIST has evolved greatly since this early large-scale study. We have new TKI therapies like sunitinib, sorafenib, and regorafenib [Stivarga], which has been approved for patients following progression of first-line imatinib, and we now accept the fact that multidisciplinary management of GIST, with resection of limited sites of oligoclonal resistant disease, is a standard option, with continuation of TKI therapy to control residual, unresectable disease," he said.

"Nonetheless , what the survival curves show us is that new options for management of KIT exon 9 mutant and other resistant genotypes are still needed," he concluded.

Dr. Jon Trent, director of the bone and soft-tissue program at the University of Miami Sylvester Cancer Center, the invited discussant, commented that "molecular subtyping should be required for all GIST patients."

"Most of all, I think we really need a tool other than the current version of RECIST [Response Evaluation Criteria in Solid Tumors], in order to really identify early makers of response and early markers of progression in our GIST patients," he said.

RECIST criteria often fail to provide useful information about early responses to therapy in GIST, he said.

The study was supported by the National Cancer Institute. Dr. Demetri disclosed serving as a consultant or adviser to ARIAD, Bayer, Novartis, and Pfizer; receiving research funding from Bayer, Novartis, and Pfizer; and receiving other remuneration from Novartis. Dr. Trent disclosed consulting/advising for Ariad, Bayer/Onyx, Novartis, and Pfizer, and receiving honoraria from Pfizer.

CHICAGO – More than 10 years on, nearly one-fourth of patients with gastrointestinal stromal tumors treated initially with imatinib are still alive, according to results from a collaborative trial reported at the annual meeting of the American Society of Clinical Oncology.

"A significant fraction of patients can survive for more than 10 years with imatinib [Gleevec] as their initial therapy for advanced GIST; and for almost half as their only systemic therapy for advanced GIST, understanding the pathobiology of these exceptional outcomes will be important to understanding the disease better," said Dr. George Demetri, director of the Center for Sarcoma and Bone Oncology, Dana-Farber Cancer Institute, Boston.

In the 14 years that have ensued since the first patient with GIST received imatinib and had an "extraordinary" response, new drugs in the tyrosine kinase inhibitor (TKI) class have become available for patients whose disease has progressed on the TKI imatinib. The evolution in the treatment of GIST emphasizes the fact that overall survival as a trial endpoint is really "a composite endpoint of on-study and poststudy interventions," Dr. Demetri said at meeting.

In the phase III Southwest Oncology Group (SWOG) Intergroup S0033 trial, initiated in 2000, 746 patients with metastatic or unresectable GIST were randomly assigned to receive daily imatinib at a dose of either 400 mg or 800 mg (400 mg twice daily). Patients in the 400-mg qd group had the option of crossing over to the 800-mg dose at the time of disease progression, and 130 patients chose to do so.

The trial was sparked by the discovery by Japanese investigators in 1998 of gain-of-function mutations in the gene encoding for KIT kinase.

As the SWOG S0033 investigators reported in 2008, median progression-free survival at a median follow-up of 4.5 years was 18 months for patients on the 400-mg dose and 20 months for those receiving 800 mg. The median overall survival was 55 months for patients in the 400-mg arm and 51 months for those in the 800-mg arm.

"A question we ask ourselves is, what accounts for this 33-month survival median difference after objective disease progression? It seems like a long time, which is why we wanted to know what happened to these patients after progression," Dr. Demetri said.

The investigators looked at survival by mutational status. Data on the GIST genotype were available on 395 patients, 282 of whom (71%) had KIT exon 11 mutations, 32 of whom (8%) had KIT exon 9 mutations, and 14 (4%) had other KIT or PDGFRA (platelet-derived growth factor receptor–alpha) mutations. Another 67 patients (17%) had no detectable KIT or PDGFRA mutations.

An analysis of data on these patients at 4.5 months’ median follow-up showed that patients with KIT exon 11 mutations had significantly better overall survival than patients with either wild-type (no mutation) KIT (P = .0011) or exon 9 mutations (P = .049).

Updated data with follow-up out to 10 years shows that patients with the KIT exon 9 mutation had significantly worse overall survival than patients with either exon 11 mutations (P = .0001) or no mutations (P = .047). There was no significant difference between patients with exon 11 mutations and no KIT or PDGFRA mutations.

Other factors significantly associated with overall survival in multivariate analysis included age by decade, male sex, performance status, maximum tumor diameter, and serum albumin (3.5 g/dL or less vs. more than 3.5 g/dL).

An analysis of on-study and postprogression therapies among 137 of 180 long-term survivors (8 years and longer) showed that 67 of the 137 (49%) had taken imatinib continuously as the only long-term therapy.

The remaining 70 patients (51%) had some additional therapy, including systemic therapies such as sunitinib (Sutent; 30% of the 137 patients), sorafenib (Nexavar; 12%), and other agents (31%).

In addition, 41 patients (30%) had metastasectomy or other type of surgery, 10 (7%) had radiofrequency ablation of tumors, and 6 (4%) had radiation therapy.

"We know that the landscape of therapeutic options for GIST has evolved greatly since this early large-scale study. We have new TKI therapies like sunitinib, sorafenib, and regorafenib [Stivarga], which has been approved for patients following progression of first-line imatinib, and we now accept the fact that multidisciplinary management of GIST, with resection of limited sites of oligoclonal resistant disease, is a standard option, with continuation of TKI therapy to control residual, unresectable disease," he said.

"Nonetheless , what the survival curves show us is that new options for management of KIT exon 9 mutant and other resistant genotypes are still needed," he concluded.

Dr. Jon Trent, director of the bone and soft-tissue program at the University of Miami Sylvester Cancer Center, the invited discussant, commented that "molecular subtyping should be required for all GIST patients."

"Most of all, I think we really need a tool other than the current version of RECIST [Response Evaluation Criteria in Solid Tumors], in order to really identify early makers of response and early markers of progression in our GIST patients," he said.

RECIST criteria often fail to provide useful information about early responses to therapy in GIST, he said.

The study was supported by the National Cancer Institute. Dr. Demetri disclosed serving as a consultant or adviser to ARIAD, Bayer, Novartis, and Pfizer; receiving research funding from Bayer, Novartis, and Pfizer; and receiving other remuneration from Novartis. Dr. Trent disclosed consulting/advising for Ariad, Bayer/Onyx, Novartis, and Pfizer, and receiving honoraria from Pfizer.

CHICAGO – More than 10 years on, nearly one-fourth of patients with gastrointestinal stromal tumors treated initially with imatinib are still alive, according to results from a collaborative trial reported at the annual meeting of the American Society of Clinical Oncology.

"A significant fraction of patients can survive for more than 10 years with imatinib [Gleevec] as their initial therapy for advanced GIST; and for almost half as their only systemic therapy for advanced GIST, understanding the pathobiology of these exceptional outcomes will be important to understanding the disease better," said Dr. George Demetri, director of the Center for Sarcoma and Bone Oncology, Dana-Farber Cancer Institute, Boston.

In the 14 years that have ensued since the first patient with GIST received imatinib and had an "extraordinary" response, new drugs in the tyrosine kinase inhibitor (TKI) class have become available for patients whose disease has progressed on the TKI imatinib. The evolution in the treatment of GIST emphasizes the fact that overall survival as a trial endpoint is really "a composite endpoint of on-study and poststudy interventions," Dr. Demetri said at meeting.

In the phase III Southwest Oncology Group (SWOG) Intergroup S0033 trial, initiated in 2000, 746 patients with metastatic or unresectable GIST were randomly assigned to receive daily imatinib at a dose of either 400 mg or 800 mg (400 mg twice daily). Patients in the 400-mg qd group had the option of crossing over to the 800-mg dose at the time of disease progression, and 130 patients chose to do so.

The trial was sparked by the discovery by Japanese investigators in 1998 of gain-of-function mutations in the gene encoding for KIT kinase.

As the SWOG S0033 investigators reported in 2008, median progression-free survival at a median follow-up of 4.5 years was 18 months for patients on the 400-mg dose and 20 months for those receiving 800 mg. The median overall survival was 55 months for patients in the 400-mg arm and 51 months for those in the 800-mg arm.

"A question we ask ourselves is, what accounts for this 33-month survival median difference after objective disease progression? It seems like a long time, which is why we wanted to know what happened to these patients after progression," Dr. Demetri said.

The investigators looked at survival by mutational status. Data on the GIST genotype were available on 395 patients, 282 of whom (71%) had KIT exon 11 mutations, 32 of whom (8%) had KIT exon 9 mutations, and 14 (4%) had other KIT or PDGFRA (platelet-derived growth factor receptor–alpha) mutations. Another 67 patients (17%) had no detectable KIT or PDGFRA mutations.

An analysis of data on these patients at 4.5 months’ median follow-up showed that patients with KIT exon 11 mutations had significantly better overall survival than patients with either wild-type (no mutation) KIT (P = .0011) or exon 9 mutations (P = .049).

Updated data with follow-up out to 10 years shows that patients with the KIT exon 9 mutation had significantly worse overall survival than patients with either exon 11 mutations (P = .0001) or no mutations (P = .047). There was no significant difference between patients with exon 11 mutations and no KIT or PDGFRA mutations.

Other factors significantly associated with overall survival in multivariate analysis included age by decade, male sex, performance status, maximum tumor diameter, and serum albumin (3.5 g/dL or less vs. more than 3.5 g/dL).

An analysis of on-study and postprogression therapies among 137 of 180 long-term survivors (8 years and longer) showed that 67 of the 137 (49%) had taken imatinib continuously as the only long-term therapy.

The remaining 70 patients (51%) had some additional therapy, including systemic therapies such as sunitinib (Sutent; 30% of the 137 patients), sorafenib (Nexavar; 12%), and other agents (31%).

In addition, 41 patients (30%) had metastasectomy or other type of surgery, 10 (7%) had radiofrequency ablation of tumors, and 6 (4%) had radiation therapy.

"We know that the landscape of therapeutic options for GIST has evolved greatly since this early large-scale study. We have new TKI therapies like sunitinib, sorafenib, and regorafenib [Stivarga], which has been approved for patients following progression of first-line imatinib, and we now accept the fact that multidisciplinary management of GIST, with resection of limited sites of oligoclonal resistant disease, is a standard option, with continuation of TKI therapy to control residual, unresectable disease," he said.

"Nonetheless , what the survival curves show us is that new options for management of KIT exon 9 mutant and other resistant genotypes are still needed," he concluded.

Dr. Jon Trent, director of the bone and soft-tissue program at the University of Miami Sylvester Cancer Center, the invited discussant, commented that "molecular subtyping should be required for all GIST patients."

"Most of all, I think we really need a tool other than the current version of RECIST [Response Evaluation Criteria in Solid Tumors], in order to really identify early makers of response and early markers of progression in our GIST patients," he said.

RECIST criteria often fail to provide useful information about early responses to therapy in GIST, he said.

The study was supported by the National Cancer Institute. Dr. Demetri disclosed serving as a consultant or adviser to ARIAD, Bayer, Novartis, and Pfizer; receiving research funding from Bayer, Novartis, and Pfizer; and receiving other remuneration from Novartis. Dr. Trent disclosed consulting/advising for Ariad, Bayer/Onyx, Novartis, and Pfizer, and receiving honoraria from Pfizer.

Nonforensic psychiatrists in private practice rarely expect to be dealing with patients involved in the correctional system, but unexpected things happen even with the most carefully chosen patients. I’m writing this column to offer guidance to clinicians facing this situation for the first time, based upon the most common questions I get asked.

The most common situation I hear about is that a patient has missed an appointment, and the clinician hears from a family member that the patient has been arrested. The conscientious doctor wants to make sure that his seriously mentally ill client doesn’t experience an interruption in treatment, and that an appointment will be ready after release. The first challenge is to locate the patient.

In small communities, or when a family member was present at the time of arrest, it’s relatively easy to figure out which detention center or jail the patient was taken to. If the patient was arrested in a large urban area, or even out of state, this can be more of a challenge. Fortunately, many states and even now some local county or city jurisdictions have inmate locator web pages. The website will provide search capabilities to identify anyone currently in custody, and will generally provide a unique booking or inmate number that should be used in any facility communication, along with a date of birth and the address of the facility. Be aware that a large jail with high turnover may not have real-time data capability, meaning that new arrests may not show up on the website for 24 hours.

For psychiatrists who spend a lot of time tracking down their patients in custody, there is even an iPhone- and Android-compatible app called MobilePatrol, which provides a convenient interface to many inmate locator databases nationwide. MobilePatrol does not provide information about charges or date of birth, so it’s mainly useful if the patient can be identified by age and has a unique name.

The next step is to ensure that the patient has been identified as needing psychiatric care within the facility. Almost all jails and prisons now have routine multilevel screens to identify arrestees with chronic medical or mental health needs, and to assess suicide risk at intake. This is required by any jail or prison accredited by the National Commission on Correctional Health Care. Nevertheless, some patients are reluctant to self-identify out of fear they might be inappropriately or precipitously thrown into a suicide observation cell.

When it comes to transmitting information to a correctional facility, don’t rely on custody staff. They aren’t clinicians, they change with every shift, and they won’t know what questions to ask about the patient. This includes the warden’s office. The best thing to do is call the psychology department to transmit the patient’s name, date of birth, jail or prison number, and any pertinent clinical information. Don’t rely on an administrative assistant or nonmedical therapist to do this for you – I can’t tell you the number of times I’ve gotten a message that "...John Doe is in your jail and he needs to be seen..." with absolutely no information about medication names, dosage, and frequency, or even a diagnosis! An initial phone call will ensure that the patient is found within the facility and scheduled to see the institutional psychiatrist.

Follow the phone call up with a letter. This will ensure that the clinical information is still available on the day the psychiatrist comes in, and for the next institutional physician if the patient is transferred to another facility. The letter should summarize pertinent symptoms, violence or suicide risk factors, and previous medication trials. The past med trial information is particularly important for correctional psychiatrists, given that many jails and prisons require "fail-first" prescribing policies. Outside documentation that supports a current nonformulary medication regimen can be crucial to ensuring a smooth transition of care. But please, resist the temptation to reprimand the correctional psychiatrist in advance for making a medication change – there are many valid clinical reasons for a correctional psychiatrist to alter a treatment regimen upon arrest that have nothing to do with formulary issues.

Finally, encourage the patient’s family members to maintain contact with their incarcerated loved one if that relationship is healthy and supportive. No one knows a patient better than those in his own household, and a family member can be particularly sensitive to early signs of relapse sometimes through nothing more than a patient’s tone of voice during a phone call. Give the primary caregivers contact information for the institutional psychology department and encourage them to call if they observe anything concerning during a visit or court appearance. Court dates are particularly stressful times and may serve as a crisis point for a suicidal inmate. Having an extra pair of eyes on the scene could be lifesaving.

Once the patient has been identified and referred, and treatment started, your job is done until release. For misdemeanor offenders in local detention, this could take place within days or a few weeks, or even the day of arrest if the patient is able to make bail. Following the steps I’ve recommended to ensure continuity of care will help your patient return to you in at least as good a condition as when he came in.

Dr. Hanson is a forensic psychiatrist and coauthor of "Shrink Rap: Three Psychiatrists Explain Their Work" (Baltimore: The Johns Hopkins University Press, 2011). The opinions expressed are those of the author only, and do not represent those of any of Dr. Hanson’s employers or consultees, including the Maryland Department of Health and Mental Hygiene or the Maryland Division of Correction.

Nonforensic psychiatrists in private practice rarely expect to be dealing with patients involved in the correctional system, but unexpected things happen even with the most carefully chosen patients. I’m writing this column to offer guidance to clinicians facing this situation for the first time, based upon the most common questions I get asked.

The most common situation I hear about is that a patient has missed an appointment, and the clinician hears from a family member that the patient has been arrested. The conscientious doctor wants to make sure that his seriously mentally ill client doesn’t experience an interruption in treatment, and that an appointment will be ready after release. The first challenge is to locate the patient.

In small communities, or when a family member was present at the time of arrest, it’s relatively easy to figure out which detention center or jail the patient was taken to. If the patient was arrested in a large urban area, or even out of state, this can be more of a challenge. Fortunately, many states and even now some local county or city jurisdictions have inmate locator web pages. The website will provide search capabilities to identify anyone currently in custody, and will generally provide a unique booking or inmate number that should be used in any facility communication, along with a date of birth and the address of the facility. Be aware that a large jail with high turnover may not have real-time data capability, meaning that new arrests may not show up on the website for 24 hours.

For psychiatrists who spend a lot of time tracking down their patients in custody, there is even an iPhone- and Android-compatible app called MobilePatrol, which provides a convenient interface to many inmate locator databases nationwide. MobilePatrol does not provide information about charges or date of birth, so it’s mainly useful if the patient can be identified by age and has a unique name.

The next step is to ensure that the patient has been identified as needing psychiatric care within the facility. Almost all jails and prisons now have routine multilevel screens to identify arrestees with chronic medical or mental health needs, and to assess suicide risk at intake. This is required by any jail or prison accredited by the National Commission on Correctional Health Care. Nevertheless, some patients are reluctant to self-identify out of fear they might be inappropriately or precipitously thrown into a suicide observation cell.

When it comes to transmitting information to a correctional facility, don’t rely on custody staff. They aren’t clinicians, they change with every shift, and they won’t know what questions to ask about the patient. This includes the warden’s office. The best thing to do is call the psychology department to transmit the patient’s name, date of birth, jail or prison number, and any pertinent clinical information. Don’t rely on an administrative assistant or nonmedical therapist to do this for you – I can’t tell you the number of times I’ve gotten a message that "...John Doe is in your jail and he needs to be seen..." with absolutely no information about medication names, dosage, and frequency, or even a diagnosis! An initial phone call will ensure that the patient is found within the facility and scheduled to see the institutional psychiatrist.

Follow the phone call up with a letter. This will ensure that the clinical information is still available on the day the psychiatrist comes in, and for the next institutional physician if the patient is transferred to another facility. The letter should summarize pertinent symptoms, violence or suicide risk factors, and previous medication trials. The past med trial information is particularly important for correctional psychiatrists, given that many jails and prisons require "fail-first" prescribing policies. Outside documentation that supports a current nonformulary medication regimen can be crucial to ensuring a smooth transition of care. But please, resist the temptation to reprimand the correctional psychiatrist in advance for making a medication change – there are many valid clinical reasons for a correctional psychiatrist to alter a treatment regimen upon arrest that have nothing to do with formulary issues.

Finally, encourage the patient’s family members to maintain contact with their incarcerated loved one if that relationship is healthy and supportive. No one knows a patient better than those in his own household, and a family member can be particularly sensitive to early signs of relapse sometimes through nothing more than a patient’s tone of voice during a phone call. Give the primary caregivers contact information for the institutional psychology department and encourage them to call if they observe anything concerning during a visit or court appearance. Court dates are particularly stressful times and may serve as a crisis point for a suicidal inmate. Having an extra pair of eyes on the scene could be lifesaving.

Once the patient has been identified and referred, and treatment started, your job is done until release. For misdemeanor offenders in local detention, this could take place within days or a few weeks, or even the day of arrest if the patient is able to make bail. Following the steps I’ve recommended to ensure continuity of care will help your patient return to you in at least as good a condition as when he came in.

Dr. Hanson is a forensic psychiatrist and coauthor of "Shrink Rap: Three Psychiatrists Explain Their Work" (Baltimore: The Johns Hopkins University Press, 2011). The opinions expressed are those of the author only, and do not represent those of any of Dr. Hanson’s employers or consultees, including the Maryland Department of Health and Mental Hygiene or the Maryland Division of Correction.

Nonforensic psychiatrists in private practice rarely expect to be dealing with patients involved in the correctional system, but unexpected things happen even with the most carefully chosen patients. I’m writing this column to offer guidance to clinicians facing this situation for the first time, based upon the most common questions I get asked.

The most common situation I hear about is that a patient has missed an appointment, and the clinician hears from a family member that the patient has been arrested. The conscientious doctor wants to make sure that his seriously mentally ill client doesn’t experience an interruption in treatment, and that an appointment will be ready after release. The first challenge is to locate the patient.

In small communities, or when a family member was present at the time of arrest, it’s relatively easy to figure out which detention center or jail the patient was taken to. If the patient was arrested in a large urban area, or even out of state, this can be more of a challenge. Fortunately, many states and even now some local county or city jurisdictions have inmate locator web pages. The website will provide search capabilities to identify anyone currently in custody, and will generally provide a unique booking or inmate number that should be used in any facility communication, along with a date of birth and the address of the facility. Be aware that a large jail with high turnover may not have real-time data capability, meaning that new arrests may not show up on the website for 24 hours.

For psychiatrists who spend a lot of time tracking down their patients in custody, there is even an iPhone- and Android-compatible app called MobilePatrol, which provides a convenient interface to many inmate locator databases nationwide. MobilePatrol does not provide information about charges or date of birth, so it’s mainly useful if the patient can be identified by age and has a unique name.

The next step is to ensure that the patient has been identified as needing psychiatric care within the facility. Almost all jails and prisons now have routine multilevel screens to identify arrestees with chronic medical or mental health needs, and to assess suicide risk at intake. This is required by any jail or prison accredited by the National Commission on Correctional Health Care. Nevertheless, some patients are reluctant to self-identify out of fear they might be inappropriately or precipitously thrown into a suicide observation cell.

When it comes to transmitting information to a correctional facility, don’t rely on custody staff. They aren’t clinicians, they change with every shift, and they won’t know what questions to ask about the patient. This includes the warden’s office. The best thing to do is call the psychology department to transmit the patient’s name, date of birth, jail or prison number, and any pertinent clinical information. Don’t rely on an administrative assistant or nonmedical therapist to do this for you – I can’t tell you the number of times I’ve gotten a message that "...John Doe is in your jail and he needs to be seen..." with absolutely no information about medication names, dosage, and frequency, or even a diagnosis! An initial phone call will ensure that the patient is found within the facility and scheduled to see the institutional psychiatrist.

Follow the phone call up with a letter. This will ensure that the clinical information is still available on the day the psychiatrist comes in, and for the next institutional physician if the patient is transferred to another facility. The letter should summarize pertinent symptoms, violence or suicide risk factors, and previous medication trials. The past med trial information is particularly important for correctional psychiatrists, given that many jails and prisons require "fail-first" prescribing policies. Outside documentation that supports a current nonformulary medication regimen can be crucial to ensuring a smooth transition of care. But please, resist the temptation to reprimand the correctional psychiatrist in advance for making a medication change – there are many valid clinical reasons for a correctional psychiatrist to alter a treatment regimen upon arrest that have nothing to do with formulary issues.

Finally, encourage the patient’s family members to maintain contact with their incarcerated loved one if that relationship is healthy and supportive. No one knows a patient better than those in his own household, and a family member can be particularly sensitive to early signs of relapse sometimes through nothing more than a patient’s tone of voice during a phone call. Give the primary caregivers contact information for the institutional psychology department and encourage them to call if they observe anything concerning during a visit or court appearance. Court dates are particularly stressful times and may serve as a crisis point for a suicidal inmate. Having an extra pair of eyes on the scene could be lifesaving.

Once the patient has been identified and referred, and treatment started, your job is done until release. For misdemeanor offenders in local detention, this could take place within days or a few weeks, or even the day of arrest if the patient is able to make bail. Following the steps I’ve recommended to ensure continuity of care will help your patient return to you in at least as good a condition as when he came in.

Dr. Hanson is a forensic psychiatrist and coauthor of "Shrink Rap: Three Psychiatrists Explain Their Work" (Baltimore: The Johns Hopkins University Press, 2011). The opinions expressed are those of the author only, and do not represent those of any of Dr. Hanson’s employers or consultees, including the Maryland Department of Health and Mental Hygiene or the Maryland Division of Correction.

MRI scanner

Results of a new study indicate that MRI and mammography can detect invasive breast tumors at very early stages in female survivors of Hodgkin lymphoma (HL).

Researchers said the findings underscore the need for at-risk childhood HL survivors and their physicians to be aware of screening guidelines.

The guidelines recommend survivors undergo breast MRI screening beginning at age 25 or 8 years after they received chest radiation, whichever is later.

“Female survivors of childhood HL who had chest radiation should speak with their family doctor about after-care assessment and breast cancer screening,” said David Hodgson, MD, of Princess Margaret Cancer Centre in Toronto, Canada.

“We estimate that 75% of women who are at high risk because of prior radiotherapy to the chest are not being screened. So my hope is that this new evidence will encourage these survivors to discuss early screening with their doctors.”

Dr Hodgson and his colleagues reported this evidence in Cancer.

The researchers evaluated the results of breast MRI and mammography screening among 96 female survivors of childhood HL who had been treated with chest radiotherapy.

The median patient age at first screening was 30 years, and the median number of MRI screening rounds was 3. Ten breast cancers—half of them invasive tumors—were diagnosed in 9 women during 363 person-years follow up.

The median age at breast cancer diagnosis was 39 years (range, 24 to 43 years), and the median latency period between HL diagnosis and age at breast cancer diagnoses was 21 years (range, 12 to 27 years).

“This illustrates the young age at which these cancers can occur,” Dr Hodgson said. “For some of these women, if they had been screened starting at age 40 or 50, like average-risk women, it would have been too late.”

MRI alone detected tumors with 80% sensitivity and 93.5% specificity. Mammography alone detected tumors with 70% sensitivity and 95% specificity. And both modalities combined detected tumors with 100% sensitivity and 88.6% specificity. All invasive tumors were detected by MRI.

In other words, of the 10 breast tumors, 5 were visible on both MRI and mammogram, 3 were visible only on MRI, and 2 were detected via mammogram alone (but were non-invasive). The median size of invasive tumors size was 8 mm (range, 3-15 mm), and none had spread to the lymph nodes.

The researchers noted that these results are substantially better than prior studies using only mammographic screening in young patients.

Dr Hodgson also pointed out that, because MRI screening is so much more sensitive to small changes in the appearance of the breast tissue than mammography, up to a third of patients may be called back for further testing of suspicious findings. But many of these are benign or not clinically significant and, therefore, require no treatment.

MRI scanner

Results of a new study indicate that MRI and mammography can detect invasive breast tumors at very early stages in female survivors of Hodgkin lymphoma (HL).

Researchers said the findings underscore the need for at-risk childhood HL survivors and their physicians to be aware of screening guidelines.

The guidelines recommend survivors undergo breast MRI screening beginning at age 25 or 8 years after they received chest radiation, whichever is later.

“Female survivors of childhood HL who had chest radiation should speak with their family doctor about after-care assessment and breast cancer screening,” said David Hodgson, MD, of Princess Margaret Cancer Centre in Toronto, Canada.

“We estimate that 75% of women who are at high risk because of prior radiotherapy to the chest are not being screened. So my hope is that this new evidence will encourage these survivors to discuss early screening with their doctors.”

Dr Hodgson and his colleagues reported this evidence in Cancer.

The researchers evaluated the results of breast MRI and mammography screening among 96 female survivors of childhood HL who had been treated with chest radiotherapy.

The median patient age at first screening was 30 years, and the median number of MRI screening rounds was 3. Ten breast cancers—half of them invasive tumors—were diagnosed in 9 women during 363 person-years follow up.

The median age at breast cancer diagnosis was 39 years (range, 24 to 43 years), and the median latency period between HL diagnosis and age at breast cancer diagnoses was 21 years (range, 12 to 27 years).

“This illustrates the young age at which these cancers can occur,” Dr Hodgson said. “For some of these women, if they had been screened starting at age 40 or 50, like average-risk women, it would have been too late.”

MRI alone detected tumors with 80% sensitivity and 93.5% specificity. Mammography alone detected tumors with 70% sensitivity and 95% specificity. And both modalities combined detected tumors with 100% sensitivity and 88.6% specificity. All invasive tumors were detected by MRI.

In other words, of the 10 breast tumors, 5 were visible on both MRI and mammogram, 3 were visible only on MRI, and 2 were detected via mammogram alone (but were non-invasive). The median size of invasive tumors size was 8 mm (range, 3-15 mm), and none had spread to the lymph nodes.

The researchers noted that these results are substantially better than prior studies using only mammographic screening in young patients.

Dr Hodgson also pointed out that, because MRI screening is so much more sensitive to small changes in the appearance of the breast tissue than mammography, up to a third of patients may be called back for further testing of suspicious findings. But many of these are benign or not clinically significant and, therefore, require no treatment.

MRI scanner

Results of a new study indicate that MRI and mammography can detect invasive breast tumors at very early stages in female survivors of Hodgkin lymphoma (HL).

Researchers said the findings underscore the need for at-risk childhood HL survivors and their physicians to be aware of screening guidelines.

The guidelines recommend survivors undergo breast MRI screening beginning at age 25 or 8 years after they received chest radiation, whichever is later.

“Female survivors of childhood HL who had chest radiation should speak with their family doctor about after-care assessment and breast cancer screening,” said David Hodgson, MD, of Princess Margaret Cancer Centre in Toronto, Canada.

“We estimate that 75% of women who are at high risk because of prior radiotherapy to the chest are not being screened. So my hope is that this new evidence will encourage these survivors to discuss early screening with their doctors.”

Dr Hodgson and his colleagues reported this evidence in Cancer.

The researchers evaluated the results of breast MRI and mammography screening among 96 female survivors of childhood HL who had been treated with chest radiotherapy.

The median patient age at first screening was 30 years, and the median number of MRI screening rounds was 3. Ten breast cancers—half of them invasive tumors—were diagnosed in 9 women during 363 person-years follow up.

The median age at breast cancer diagnosis was 39 years (range, 24 to 43 years), and the median latency period between HL diagnosis and age at breast cancer diagnoses was 21 years (range, 12 to 27 years).

“This illustrates the young age at which these cancers can occur,” Dr Hodgson said. “For some of these women, if they had been screened starting at age 40 or 50, like average-risk women, it would have been too late.”

MRI alone detected tumors with 80% sensitivity and 93.5% specificity. Mammography alone detected tumors with 70% sensitivity and 95% specificity. And both modalities combined detected tumors with 100% sensitivity and 88.6% specificity. All invasive tumors were detected by MRI.

In other words, of the 10 breast tumors, 5 were visible on both MRI and mammogram, 3 were visible only on MRI, and 2 were detected via mammogram alone (but were non-invasive). The median size of invasive tumors size was 8 mm (range, 3-15 mm), and none had spread to the lymph nodes.

The researchers noted that these results are substantially better than prior studies using only mammographic screening in young patients.

Dr Hodgson also pointed out that, because MRI screening is so much more sensitive to small changes in the appearance of the breast tissue than mammography, up to a third of patients may be called back for further testing of suspicious findings. But many of these are benign or not clinically significant and, therefore, require no treatment.

Hospitalist Ateev Mehrotra, MD, MPH, garnered an audience in Congress last month with his speech on telemedicine that called on lawmakers to take a deliberate approach to the healthcare strategy.

Dr. Mehrotra, a staff physician at Beth Israel Deaconess Medical Center in Boston and a policy analyst for RAND Corporation in Santa Monica, Calif., testified before a health subcommittee of the Energy & Commerce Committee[PDF]. He urged politicians to understand that telemedicine has immense potential but needs to be implemented deliberately to ensure that it provides quality care, improves access to those who need it most, and is used in the most cost-efficient manner.

He spoke with The Hospitalist after testifying:

Question: What do you hope the committee took away from your speech?

Answer: Go in with [your] eyes wide open. Experience tells us this is going to work in some ways and is not going to work in some ways. I think some people are naive and think telemedicine is perfect.

Q: Overutilization is a fear of yours. Tell me why.

A: For every great and remarkable intervention we have introduced in medicine, there has been this potential concern. I gave the example of cardiac catheterization, [which] has saved tens of thousands of lives probably. I can cite many other examples from MRIs to CTs [computed tomography] to robot-assisted surgery, etc., where that overuse issue is very significant. Economists believe [new technologies] are one of the greatest drivers of increased healthcare spending in the United States. With that as background, one shouldn’t be surprised that telemedicine would face the same issues.

Q: With a national push for telemedicine, is that overall a good thing?

A: Maybe I’m just too much of a doctor, but I think about this very much like I think about a drug. You have positive benefits, and you’ve got side effects. You need to be aware of the side effects … it doesn’t mean in many cases you don’t prescribe the drug because the drug is helping overall. If you take that same framework to telemedicine, I would say I’m overall very enthusiastic about the multitude of benefits … but not all telemedicine is the same. TH

Visit our website for more information on telemedicine and hospitalists.

Hospitalist Ateev Mehrotra, MD, MPH, garnered an audience in Congress last month with his speech on telemedicine that called on lawmakers to take a deliberate approach to the healthcare strategy.

Dr. Mehrotra, a staff physician at Beth Israel Deaconess Medical Center in Boston and a policy analyst for RAND Corporation in Santa Monica, Calif., testified before a health subcommittee of the Energy & Commerce Committee[PDF]. He urged politicians to understand that telemedicine has immense potential but needs to be implemented deliberately to ensure that it provides quality care, improves access to those who need it most, and is used in the most cost-efficient manner.

He spoke with The Hospitalist after testifying:

Question: What do you hope the committee took away from your speech?

Answer: Go in with [your] eyes wide open. Experience tells us this is going to work in some ways and is not going to work in some ways. I think some people are naive and think telemedicine is perfect.

Q: Overutilization is a fear of yours. Tell me why.

A: For every great and remarkable intervention we have introduced in medicine, there has been this potential concern. I gave the example of cardiac catheterization, [which] has saved tens of thousands of lives probably. I can cite many other examples from MRIs to CTs [computed tomography] to robot-assisted surgery, etc., where that overuse issue is very significant. Economists believe [new technologies] are one of the greatest drivers of increased healthcare spending in the United States. With that as background, one shouldn’t be surprised that telemedicine would face the same issues.

Q: With a national push for telemedicine, is that overall a good thing?

A: Maybe I’m just too much of a doctor, but I think about this very much like I think about a drug. You have positive benefits, and you’ve got side effects. You need to be aware of the side effects … it doesn’t mean in many cases you don’t prescribe the drug because the drug is helping overall. If you take that same framework to telemedicine, I would say I’m overall very enthusiastic about the multitude of benefits … but not all telemedicine is the same. TH

Visit our website for more information on telemedicine and hospitalists.

Hospitalist Ateev Mehrotra, MD, MPH, garnered an audience in Congress last month with his speech on telemedicine that called on lawmakers to take a deliberate approach to the healthcare strategy.

Dr. Mehrotra, a staff physician at Beth Israel Deaconess Medical Center in Boston and a policy analyst for RAND Corporation in Santa Monica, Calif., testified before a health subcommittee of the Energy & Commerce Committee[PDF]. He urged politicians to understand that telemedicine has immense potential but needs to be implemented deliberately to ensure that it provides quality care, improves access to those who need it most, and is used in the most cost-efficient manner.

He spoke with The Hospitalist after testifying:

Question: What do you hope the committee took away from your speech?

Answer: Go in with [your] eyes wide open. Experience tells us this is going to work in some ways and is not going to work in some ways. I think some people are naive and think telemedicine is perfect.

Q: Overutilization is a fear of yours. Tell me why.

A: For every great and remarkable intervention we have introduced in medicine, there has been this potential concern. I gave the example of cardiac catheterization, [which] has saved tens of thousands of lives probably. I can cite many other examples from MRIs to CTs [computed tomography] to robot-assisted surgery, etc., where that overuse issue is very significant. Economists believe [new technologies] are one of the greatest drivers of increased healthcare spending in the United States. With that as background, one shouldn’t be surprised that telemedicine would face the same issues.

Q: With a national push for telemedicine, is that overall a good thing?

A: Maybe I’m just too much of a doctor, but I think about this very much like I think about a drug. You have positive benefits, and you’ve got side effects. You need to be aware of the side effects … it doesn’t mean in many cases you don’t prescribe the drug because the drug is helping overall. If you take that same framework to telemedicine, I would say I’m overall very enthusiastic about the multitude of benefits … but not all telemedicine is the same. TH

Visit our website for more information on telemedicine and hospitalists.

As hospitalist workloads increase, so do hospital costs and patients' lengths of stay (LOS), according to findings in a recent study.

Those results, says SHM President Burke T. Kealey, MD, SFHM, provide a good starting point to determine an ideal patient census for hospitalists.

"Pushing hospitalist workloads ever higher to meet the demands of patient-care needs or flawed payment models has costs associated with it," says Dr. Kealey, associate medical director of hospital specialties at HealthPartners Medical Group in St. Paul, Minn. "The costs may be borne by the system or by patients, but there are costs."

For the study published in JAMA Internal Medicine, researchers analyzed data from 20,241 hospitalizations involving 13,916 patients seen by hospitalists at the Christiana Care Health System in Newark, Del., between February 2008 and January 2011.

For hospital occupancies less than 75%, they found that LOS increased from 5.5 to 7.5 days as workload increased. For occupancies of 75% to 85%, LOS increased to about 8 days with higher workloads. For occupancies greater than 85%, the LOS decreased slightly and then increased significantly with higher workloads, with this change occurring at about 15 patients or more per hospitalist.

Costs were also significantly associated with an increase in workload. As the study notes, benchmark recommendations for an individual hospitalist’s workload range from 10 to 15 patient encounters per day.

Dr. Kealey says the findings seem to support the conventional wisdom that hospitalists should ideally see no more than 15 patients a day. He notes, however, that deciding the optimal number of cases for a given practice depends on several factors, including duration of shift, the availability of physician extenders, and the addition of surgical or cardiology cases.

"We won't be able as a specialty to fully realize our potential until we understand and apply the learnings about workload into our practices to ensure hospitalist career sustainability, system health, and best patient care," Dr. Kealey says. "This paper really gets the discussion going."

For more from Dr. Kealey on hospitalist workloads, read his recent blog post on "The Hospital Leader." TH

Visit our website for more information about hospitalist workloads.

As hospitalist workloads increase, so do hospital costs and patients' lengths of stay (LOS), according to findings in a recent study.

Those results, says SHM President Burke T. Kealey, MD, SFHM, provide a good starting point to determine an ideal patient census for hospitalists.

"Pushing hospitalist workloads ever higher to meet the demands of patient-care needs or flawed payment models has costs associated with it," says Dr. Kealey, associate medical director of hospital specialties at HealthPartners Medical Group in St. Paul, Minn. "The costs may be borne by the system or by patients, but there are costs."

For the study published in JAMA Internal Medicine, researchers analyzed data from 20,241 hospitalizations involving 13,916 patients seen by hospitalists at the Christiana Care Health System in Newark, Del., between February 2008 and January 2011.

For hospital occupancies less than 75%, they found that LOS increased from 5.5 to 7.5 days as workload increased. For occupancies of 75% to 85%, LOS increased to about 8 days with higher workloads. For occupancies greater than 85%, the LOS decreased slightly and then increased significantly with higher workloads, with this change occurring at about 15 patients or more per hospitalist.

Costs were also significantly associated with an increase in workload. As the study notes, benchmark recommendations for an individual hospitalist’s workload range from 10 to 15 patient encounters per day.

Dr. Kealey says the findings seem to support the conventional wisdom that hospitalists should ideally see no more than 15 patients a day. He notes, however, that deciding the optimal number of cases for a given practice depends on several factors, including duration of shift, the availability of physician extenders, and the addition of surgical or cardiology cases.

"We won't be able as a specialty to fully realize our potential until we understand and apply the learnings about workload into our practices to ensure hospitalist career sustainability, system health, and best patient care," Dr. Kealey says. "This paper really gets the discussion going."

For more from Dr. Kealey on hospitalist workloads, read his recent blog post on "The Hospital Leader." TH

Visit our website for more information about hospitalist workloads.

As hospitalist workloads increase, so do hospital costs and patients' lengths of stay (LOS), according to findings in a recent study.

Those results, says SHM President Burke T. Kealey, MD, SFHM, provide a good starting point to determine an ideal patient census for hospitalists.

"Pushing hospitalist workloads ever higher to meet the demands of patient-care needs or flawed payment models has costs associated with it," says Dr. Kealey, associate medical director of hospital specialties at HealthPartners Medical Group in St. Paul, Minn. "The costs may be borne by the system or by patients, but there are costs."

For the study published in JAMA Internal Medicine, researchers analyzed data from 20,241 hospitalizations involving 13,916 patients seen by hospitalists at the Christiana Care Health System in Newark, Del., between February 2008 and January 2011.

For hospital occupancies less than 75%, they found that LOS increased from 5.5 to 7.5 days as workload increased. For occupancies of 75% to 85%, LOS increased to about 8 days with higher workloads. For occupancies greater than 85%, the LOS decreased slightly and then increased significantly with higher workloads, with this change occurring at about 15 patients or more per hospitalist.

Costs were also significantly associated with an increase in workload. As the study notes, benchmark recommendations for an individual hospitalist’s workload range from 10 to 15 patient encounters per day.

Dr. Kealey says the findings seem to support the conventional wisdom that hospitalists should ideally see no more than 15 patients a day. He notes, however, that deciding the optimal number of cases for a given practice depends on several factors, including duration of shift, the availability of physician extenders, and the addition of surgical or cardiology cases.

"We won't be able as a specialty to fully realize our potential until we understand and apply the learnings about workload into our practices to ensure hospitalist career sustainability, system health, and best patient care," Dr. Kealey says. "This paper really gets the discussion going."

For more from Dr. Kealey on hospitalist workloads, read his recent blog post on "The Hospital Leader." TH

Visit our website for more information about hospitalist workloads.

Nephrolithiasis affects 1 in 11 people in the United States resulting in several million emergency department visits annually. The prevalence of nephrolithiasis is higher among men, obese individuals, and white non-Hispanics. The prevalence of kidney stones also appears to be increasing.

Our patients tell us that few things hurt worse than kidney stones. We may feel especially compelled to make a diagnosis given pain severity in otherwise healthy adults who have "never experienced this kind of pain before." Perhaps because of this, lots of patients are undergoing CT imaging for kidney stones ... in the United States. Interestingly, the European Urology Association recommends ultrasonography as the first-line test for urolithiasis.

Can we predict who has a kidney stone?

Moore and colleagues derived and validated a clinical prediction rule for uncomplicated ureteral stone. The derivation cohort was 1,040 patients undergoing noncontrast CT for suspected uncomplicated kidney stone. The validation cohort was 491 consecutively enrolled patients.

Data analysis revealed five factors that were significantly associated with the presence of a ureteral stone: male sex (2 points), duration of pain to presentation (greater than 24 hours: 0 points; 6-24 hours: 1 point; less than 6 hours: 3 points), nonblack race (3 points), presence of nausea or vomiting (nausea alone: 1 point; vomiting alone: 2 points), and microscopic hematuria (3 points). The points add up to low probability (0-5 points = 10% chance of stone), moderate probability (6-9 points = about 50% chance of stone), and high probability (10-13 points = about 90% chance of stone). Acutely important alternative causes were found in 1.6% of the high-probability group in the validation set. These causes were diverticulitis, appendicitis, mass, pyelonephritis, cholecystitis, pneumonia, bowel obstruction, colitis, aortic aneurysm, and pancreatitis.

This algorithm was derived and validated in the emergency setting so it will have different performance characteristics in the outpatient, ambulatory, phone-triage world. However, as the authors discuss, this algorithm could be used to help institutions make decisions about lowering radiation doses for "stone protocol" scans. Scales such as these should be incorporated into electronic medical record systems to improve care delivery.

Dr. Ebbert is professor of medicine, a general internist at the Mayo Clinic in Rochester, Minn., and a diplomate of the American Board of Addiction Medicine. The opinions expressed are those of the author. He reports no disclosures.

Nephrolithiasis affects 1 in 11 people in the United States resulting in several million emergency department visits annually. The prevalence of nephrolithiasis is higher among men, obese individuals, and white non-Hispanics. The prevalence of kidney stones also appears to be increasing.

Our patients tell us that few things hurt worse than kidney stones. We may feel especially compelled to make a diagnosis given pain severity in otherwise healthy adults who have "never experienced this kind of pain before." Perhaps because of this, lots of patients are undergoing CT imaging for kidney stones ... in the United States. Interestingly, the European Urology Association recommends ultrasonography as the first-line test for urolithiasis.

Can we predict who has a kidney stone?

Moore and colleagues derived and validated a clinical prediction rule for uncomplicated ureteral stone. The derivation cohort was 1,040 patients undergoing noncontrast CT for suspected uncomplicated kidney stone. The validation cohort was 491 consecutively enrolled patients.

Data analysis revealed five factors that were significantly associated with the presence of a ureteral stone: male sex (2 points), duration of pain to presentation (greater than 24 hours: 0 points; 6-24 hours: 1 point; less than 6 hours: 3 points), nonblack race (3 points), presence of nausea or vomiting (nausea alone: 1 point; vomiting alone: 2 points), and microscopic hematuria (3 points). The points add up to low probability (0-5 points = 10% chance of stone), moderate probability (6-9 points = about 50% chance of stone), and high probability (10-13 points = about 90% chance of stone). Acutely important alternative causes were found in 1.6% of the high-probability group in the validation set. These causes were diverticulitis, appendicitis, mass, pyelonephritis, cholecystitis, pneumonia, bowel obstruction, colitis, aortic aneurysm, and pancreatitis.

This algorithm was derived and validated in the emergency setting so it will have different performance characteristics in the outpatient, ambulatory, phone-triage world. However, as the authors discuss, this algorithm could be used to help institutions make decisions about lowering radiation doses for "stone protocol" scans. Scales such as these should be incorporated into electronic medical record systems to improve care delivery.

Dr. Ebbert is professor of medicine, a general internist at the Mayo Clinic in Rochester, Minn., and a diplomate of the American Board of Addiction Medicine. The opinions expressed are those of the author. He reports no disclosures.

Nephrolithiasis affects 1 in 11 people in the United States resulting in several million emergency department visits annually. The prevalence of nephrolithiasis is higher among men, obese individuals, and white non-Hispanics. The prevalence of kidney stones also appears to be increasing.

Our patients tell us that few things hurt worse than kidney stones. We may feel especially compelled to make a diagnosis given pain severity in otherwise healthy adults who have "never experienced this kind of pain before." Perhaps because of this, lots of patients are undergoing CT imaging for kidney stones ... in the United States. Interestingly, the European Urology Association recommends ultrasonography as the first-line test for urolithiasis.

Can we predict who has a kidney stone?

Moore and colleagues derived and validated a clinical prediction rule for uncomplicated ureteral stone. The derivation cohort was 1,040 patients undergoing noncontrast CT for suspected uncomplicated kidney stone. The validation cohort was 491 consecutively enrolled patients.

Data analysis revealed five factors that were significantly associated with the presence of a ureteral stone: male sex (2 points), duration of pain to presentation (greater than 24 hours: 0 points; 6-24 hours: 1 point; less than 6 hours: 3 points), nonblack race (3 points), presence of nausea or vomiting (nausea alone: 1 point; vomiting alone: 2 points), and microscopic hematuria (3 points). The points add up to low probability (0-5 points = 10% chance of stone), moderate probability (6-9 points = about 50% chance of stone), and high probability (10-13 points = about 90% chance of stone). Acutely important alternative causes were found in 1.6% of the high-probability group in the validation set. These causes were diverticulitis, appendicitis, mass, pyelonephritis, cholecystitis, pneumonia, bowel obstruction, colitis, aortic aneurysm, and pancreatitis.

This algorithm was derived and validated in the emergency setting so it will have different performance characteristics in the outpatient, ambulatory, phone-triage world. However, as the authors discuss, this algorithm could be used to help institutions make decisions about lowering radiation doses for "stone protocol" scans. Scales such as these should be incorporated into electronic medical record systems to improve care delivery.

Dr. Ebbert is professor of medicine, a general internist at the Mayo Clinic in Rochester, Minn., and a diplomate of the American Board of Addiction Medicine. The opinions expressed are those of the author. He reports no disclosures.

For a problem that has been on the back burner for decades, the treatment of atrial fibrillation has suddenly become a "marquis" diagnosis.

Age and technology have led to an explosion of interest in this arcane cardiac problem. Advertisements for new anticoagulants and thrombin inhibitors for "A Fib" have become almost as common as those for male impotency. The aging of the world population certainly has been a major factor in its increased incidence. New technology and pharmacology has driven the increase in clinical interest and has advanced our knowledge about the disease. Epidemiology data have provided important information about the natural history of paroxysmal atrial fibrillation (AF), and its relationship to chronic AF and its adverse effects on long-term mortality.

The importance of anticoagulant therapy for the prevention of systemic emboli and stroke has been the mainstay of therapy for almost 50 years. Although we have struggled with a variety of antiarrhythmic drugs, their shortcomings have been more than apparent. Most of us now use a rate-control strategy to control the tachycardia inherent in AF. The development of new factor Xa and direct thrombin inhibitor drugs have made the logistics of providing adequate thrombus prevention much simpler, if somewhat more expensive.

The elephant in the room is the increasing use of radiofrequency catheter ablation technology that has had some success in the prevention of AF arising from the tissue in the pulmonary vein–atrial interface. Numerous small studies have reported that this technology surpasses rhythm control with antiarrhythmic agents, a hurdle not too difficult to beat. The best results have been observed in patients with recurrent paroxysmal AF where maintenance of regular sinus rhythm has been the primary outcome measurement (JAMA 2014;311:692-700). Even here, recurrence after ablation has been common. The benefit of ablation therapy in patients with initial paroxysmal AF (N. Engl. J. Med. 2012;367:1587-95) or chronic persistent AF has been uncertain at best. As a result, the AHA/ACC/HRS (American Heart Association/American College of Cardiology/Heart Rhythm Society) guidelines have given a class I (evidence level A) recommendation for ablation therapy for symptomatic paroxysmal AF and class IIa (evidence level A) and IIb (evidence level B) for symptomatic recurrent paroxysmal and longstanding persistent AF when balanced against drug tolerability, respectively (J. Am. Coll. Cardiol. 2014 [doi:10.1016/j.jacc.2014.03.021]).

All of these clinical data are exciting and have led to enthusiasm for ablation technology despite the potential for nonfatal and rare fatal complication, based almost entirely on its ability to improve upon the dismal benefits of antiarrhythmic rhythm control. Even as we consider the benefit of ablation therapy, new techniques are being developed. The lack of mortality and morbidity data is a result of the short follow-up, usually limited to a year or two, and small sample size. This lack of long-term outcome data for ablation therapy should be of some concern to clinicians who have lived through the last few years. Many of my readers had not been born when we embarked on the ineffective and dangerous pharmacologic prevention of sudden death by pharmacologic suppression of ambient ventricular premature beats. Numerous surrogate measures of clinical benefit of a variety of therapeutic interventions have been disproven and disposed of in the subsequent years. The use of surrogate measures like the partial suppression of AF rather than morbidity and mortality outcomes to establish clinical benefit, have been largely discarded as a dead end.

The Catheter Ablation Versus Anti-arrhythmic Drug Therapy for Atrial Fibrillation Trial (CABANA), which is beginning to recruit more than 2,000 patients with new-onset or undertreated paroxysmal, persistent, or longstanding AF to be followed for over 4 years may answer the question of whether radiofrequency ablation therapy, rate control, or rhythm control provides the best clinical treatment of atrial fibrillation. The primary outcome will be the composite endpoint of total mortality, disabling stroke or serious bleeding, or cardiac arrest. An important secondary endpoint will be total mortality. Until its conclusion, we should proceed cautiously with expanding radiofrequency ablation therapy for the treatment of AF.

Dr. Goldstein, medical editor of Cardiology News, is professor of medicine at Wayne State University and division head emeritus of cardiovascular medicine at Henry Ford Hospital, both in Detroit. He is on data safety monitoring committees for the National Institutes of Health and several pharmaceutical companies.

For a problem that has been on the back burner for decades, the treatment of atrial fibrillation has suddenly become a "marquis" diagnosis.

Age and technology have led to an explosion of interest in this arcane cardiac problem. Advertisements for new anticoagulants and thrombin inhibitors for "A Fib" have become almost as common as those for male impotency. The aging of the world population certainly has been a major factor in its increased incidence. New technology and pharmacology has driven the increase in clinical interest and has advanced our knowledge about the disease. Epidemiology data have provided important information about the natural history of paroxysmal atrial fibrillation (AF), and its relationship to chronic AF and its adverse effects on long-term mortality.

The importance of anticoagulant therapy for the prevention of systemic emboli and stroke has been the mainstay of therapy for almost 50 years. Although we have struggled with a variety of antiarrhythmic drugs, their shortcomings have been more than apparent. Most of us now use a rate-control strategy to control the tachycardia inherent in AF. The development of new factor Xa and direct thrombin inhibitor drugs have made the logistics of providing adequate thrombus prevention much simpler, if somewhat more expensive.

The elephant in the room is the increasing use of radiofrequency catheter ablation technology that has had some success in the prevention of AF arising from the tissue in the pulmonary vein–atrial interface. Numerous small studies have reported that this technology surpasses rhythm control with antiarrhythmic agents, a hurdle not too difficult to beat. The best results have been observed in patients with recurrent paroxysmal AF where maintenance of regular sinus rhythm has been the primary outcome measurement (JAMA 2014;311:692-700). Even here, recurrence after ablation has been common. The benefit of ablation therapy in patients with initial paroxysmal AF (N. Engl. J. Med. 2012;367:1587-95) or chronic persistent AF has been uncertain at best. As a result, the AHA/ACC/HRS (American Heart Association/American College of Cardiology/Heart Rhythm Society) guidelines have given a class I (evidence level A) recommendation for ablation therapy for symptomatic paroxysmal AF and class IIa (evidence level A) and IIb (evidence level B) for symptomatic recurrent paroxysmal and longstanding persistent AF when balanced against drug tolerability, respectively (J. Am. Coll. Cardiol. 2014 [doi:10.1016/j.jacc.2014.03.021]).

All of these clinical data are exciting and have led to enthusiasm for ablation technology despite the potential for nonfatal and rare fatal complication, based almost entirely on its ability to improve upon the dismal benefits of antiarrhythmic rhythm control. Even as we consider the benefit of ablation therapy, new techniques are being developed. The lack of mortality and morbidity data is a result of the short follow-up, usually limited to a year or two, and small sample size. This lack of long-term outcome data for ablation therapy should be of some concern to clinicians who have lived through the last few years. Many of my readers had not been born when we embarked on the ineffective and dangerous pharmacologic prevention of sudden death by pharmacologic suppression of ambient ventricular premature beats. Numerous surrogate measures of clinical benefit of a variety of therapeutic interventions have been disproven and disposed of in the subsequent years. The use of surrogate measures like the partial suppression of AF rather than morbidity and mortality outcomes to establish clinical benefit, have been largely discarded as a dead end.

The Catheter Ablation Versus Anti-arrhythmic Drug Therapy for Atrial Fibrillation Trial (CABANA), which is beginning to recruit more than 2,000 patients with new-onset or undertreated paroxysmal, persistent, or longstanding AF to be followed for over 4 years may answer the question of whether radiofrequency ablation therapy, rate control, or rhythm control provides the best clinical treatment of atrial fibrillation. The primary outcome will be the composite endpoint of total mortality, disabling stroke or serious bleeding, or cardiac arrest. An important secondary endpoint will be total mortality. Until its conclusion, we should proceed cautiously with expanding radiofrequency ablation therapy for the treatment of AF.

Dr. Goldstein, medical editor of Cardiology News, is professor of medicine at Wayne State University and division head emeritus of cardiovascular medicine at Henry Ford Hospital, both in Detroit. He is on data safety monitoring committees for the National Institutes of Health and several pharmaceutical companies.

For a problem that has been on the back burner for decades, the treatment of atrial fibrillation has suddenly become a "marquis" diagnosis.

Age and technology have led to an explosion of interest in this arcane cardiac problem. Advertisements for new anticoagulants and thrombin inhibitors for "A Fib" have become almost as common as those for male impotency. The aging of the world population certainly has been a major factor in its increased incidence. New technology and pharmacology has driven the increase in clinical interest and has advanced our knowledge about the disease. Epidemiology data have provided important information about the natural history of paroxysmal atrial fibrillation (AF), and its relationship to chronic AF and its adverse effects on long-term mortality.

The importance of anticoagulant therapy for the prevention of systemic emboli and stroke has been the mainstay of therapy for almost 50 years. Although we have struggled with a variety of antiarrhythmic drugs, their shortcomings have been more than apparent. Most of us now use a rate-control strategy to control the tachycardia inherent in AF. The development of new factor Xa and direct thrombin inhibitor drugs have made the logistics of providing adequate thrombus prevention much simpler, if somewhat more expensive.

The elephant in the room is the increasing use of radiofrequency catheter ablation technology that has had some success in the prevention of AF arising from the tissue in the pulmonary vein–atrial interface. Numerous small studies have reported that this technology surpasses rhythm control with antiarrhythmic agents, a hurdle not too difficult to beat. The best results have been observed in patients with recurrent paroxysmal AF where maintenance of regular sinus rhythm has been the primary outcome measurement (JAMA 2014;311:692-700). Even here, recurrence after ablation has been common. The benefit of ablation therapy in patients with initial paroxysmal AF (N. Engl. J. Med. 2012;367:1587-95) or chronic persistent AF has been uncertain at best. As a result, the AHA/ACC/HRS (American Heart Association/American College of Cardiology/Heart Rhythm Society) guidelines have given a class I (evidence level A) recommendation for ablation therapy for symptomatic paroxysmal AF and class IIa (evidence level A) and IIb (evidence level B) for symptomatic recurrent paroxysmal and longstanding persistent AF when balanced against drug tolerability, respectively (J. Am. Coll. Cardiol. 2014 [doi:10.1016/j.jacc.2014.03.021]).

All of these clinical data are exciting and have led to enthusiasm for ablation technology despite the potential for nonfatal and rare fatal complication, based almost entirely on its ability to improve upon the dismal benefits of antiarrhythmic rhythm control. Even as we consider the benefit of ablation therapy, new techniques are being developed. The lack of mortality and morbidity data is a result of the short follow-up, usually limited to a year or two, and small sample size. This lack of long-term outcome data for ablation therapy should be of some concern to clinicians who have lived through the last few years. Many of my readers had not been born when we embarked on the ineffective and dangerous pharmacologic prevention of sudden death by pharmacologic suppression of ambient ventricular premature beats. Numerous surrogate measures of clinical benefit of a variety of therapeutic interventions have been disproven and disposed of in the subsequent years. The use of surrogate measures like the partial suppression of AF rather than morbidity and mortality outcomes to establish clinical benefit, have been largely discarded as a dead end.

The Catheter Ablation Versus Anti-arrhythmic Drug Therapy for Atrial Fibrillation Trial (CABANA), which is beginning to recruit more than 2,000 patients with new-onset or undertreated paroxysmal, persistent, or longstanding AF to be followed for over 4 years may answer the question of whether radiofrequency ablation therapy, rate control, or rhythm control provides the best clinical treatment of atrial fibrillation. The primary outcome will be the composite endpoint of total mortality, disabling stroke or serious bleeding, or cardiac arrest. An important secondary endpoint will be total mortality. Until its conclusion, we should proceed cautiously with expanding radiofrequency ablation therapy for the treatment of AF.

Dr. Goldstein, medical editor of Cardiology News, is professor of medicine at Wayne State University and division head emeritus of cardiovascular medicine at Henry Ford Hospital, both in Detroit. He is on data safety monitoring committees for the National Institutes of Health and several pharmaceutical companies.

The Diagnosis: Blaschkoid Punctate Vitiligo

Based on the patient’s clinical appearance as well as the histologic findings, the diagnosis of vitiligo was made. Although vitiligo is certainly not uncommon and punctate vitiligo is a known clinical presentation,¹ punctate vitiliginous depigmentation conforming to lines of Blaschko is unique. Follicular repigmentation in a patch of vitiligo potentially could lead to this “spotty” appearance, but our patient maintained that the band was never confluently depigmented and that small macules arose within normally pigmented skin. The patient’s adult age at onset makes this case even more unusual.

Follicular repigmentation in vitiligo is fairly well understood, as the perifollicular pigment is formed by upward migration of activated melanoblasts in the outer root sheath.² Follicular depigmentation as well as selective or initial loss of melanocytes around hair follicles in early vitiligo has not been described. It is unclear if the seemingly folliculocentric nature of the patient’s vitiliginous macules was a false observation, coincidental, or actually related to selective melanocyte loss around follicles.

Blaschkoid distribution has been described in numerous skin disorders and is known to be based on genetic mosaicism.³ Most of these disorders are X-linked and/or congenital. However, many acquired skin conditions have been described exhibiting blaschkoid distribution, such as vitiligo, psoriasis, lichen planus, atopic dermatitis, and mycosis fungoides.^4,5

Confettilike depigmentation has been described as an unusual clinical variant of vitiligo.¹ It also has been reported after psoralen plus UVA therapy in patients with more classic vitiligo,⁶ numerous domestic chemicals,⁷ and in association with mycosis fungoides.⁸ In these cases, punctate lesions were disseminated, symmetric on extremities, or limited to areas exposed to chemicals.

The Diagnosis: Blaschkoid Punctate Vitiligo

Based on the patient’s clinical appearance as well as the histologic findings, the diagnosis of vitiligo was made. Although vitiligo is certainly not uncommon and punctate vitiligo is a known clinical presentation,¹ punctate vitiliginous depigmentation conforming to lines of Blaschko is unique. Follicular repigmentation in a patch of vitiligo potentially could lead to this “spotty” appearance, but our patient maintained that the band was never confluently depigmented and that small macules arose within normally pigmented skin. The patient’s adult age at onset makes this case even more unusual.

Follicular repigmentation in vitiligo is fairly well understood, as the perifollicular pigment is formed by upward migration of activated melanoblasts in the outer root sheath.² Follicular depigmentation as well as selective or initial loss of melanocytes around hair follicles in early vitiligo has not been described. It is unclear if the seemingly folliculocentric nature of the patient’s vitiliginous macules was a false observation, coincidental, or actually related to selective melanocyte loss around follicles.

Blaschkoid distribution has been described in numerous skin disorders and is known to be based on genetic mosaicism.³ Most of these disorders are X-linked and/or congenital. However, many acquired skin conditions have been described exhibiting blaschkoid distribution, such as vitiligo, psoriasis, lichen planus, atopic dermatitis, and mycosis fungoides.^4,5

Confettilike depigmentation has been described as an unusual clinical variant of vitiligo.¹ It also has been reported after psoralen plus UVA therapy in patients with more classic vitiligo,⁶ numerous domestic chemicals,⁷ and in association with mycosis fungoides.⁸ In these cases, punctate lesions were disseminated, symmetric on extremities, or limited to areas exposed to chemicals.

The Diagnosis: Blaschkoid Punctate Vitiligo

Based on the patient’s clinical appearance as well as the histologic findings, the diagnosis of vitiligo was made. Although vitiligo is certainly not uncommon and punctate vitiligo is a known clinical presentation,¹ punctate vitiliginous depigmentation conforming to lines of Blaschko is unique. Follicular repigmentation in a patch of vitiligo potentially could lead to this “spotty” appearance, but our patient maintained that the band was never confluently depigmented and that small macules arose within normally pigmented skin. The patient’s adult age at onset makes this case even more unusual.

Follicular repigmentation in vitiligo is fairly well understood, as the perifollicular pigment is formed by upward migration of activated melanoblasts in the outer root sheath.² Follicular depigmentation as well as selective or initial loss of melanocytes around hair follicles in early vitiligo has not been described. It is unclear if the seemingly folliculocentric nature of the patient’s vitiliginous macules was a false observation, coincidental, or actually related to selective melanocyte loss around follicles.

Blaschkoid distribution has been described in numerous skin disorders and is known to be based on genetic mosaicism.³ Most of these disorders are X-linked and/or congenital. However, many acquired skin conditions have been described exhibiting blaschkoid distribution, such as vitiligo, psoriasis, lichen planus, atopic dermatitis, and mycosis fungoides.^4,5

Confettilike depigmentation has been described as an unusual clinical variant of vitiligo.¹ It also has been reported after psoralen plus UVA therapy in patients with more classic vitiligo,⁶ numerous domestic chemicals,⁷ and in association with mycosis fungoides.⁸ In these cases, punctate lesions were disseminated, symmetric on extremities, or limited to areas exposed to chemicals.

Micrograph showing AML cells

Credit: Lance Liotta

New research has revealed a mechanism of drug resistance in acute myeloid leukemia (AML) that may also occur in other cancers.

Investigators found evidence suggesting that glioma-associated protein 1 (GLI1) and the UDP glucuronosyltransferase (UGT1A) family of enzymes drive resistance to 2 drugs—ribavirin and cytarabine—in AML.

But the researchers were able to overcome this resistance by genetic or pharmacologic inhibition of GLI1.

They described this research in a letter to Nature.

“By studying drug-resistant cancer cells from AML patients and head and neck tumors, we found that a gene called GLI1 is dramatically overactive in these cells,” said study author Hiba Zahreddine, a doctoral student at the University of Montreal in Canada.

“[W[e were then able to show that this results in a specific chemical change to the drugs that prevents their toxicity toward the cancer cells,” said author Kathy Borden, PhD, of the University of Montreal’s Institute for Research in Immunology and Cancer.

Specifically, the investigators found that UGT1A enzymes add glucuronic acid to the drugs, thereby modifying their activity. And GLI1 alone is sufficient to drive UGT1A-dependent glucuronidation of ribavirin and cytarabine, which fuels drug resistance.

Fortunately, the researchers found that inhibiting GLI1, either genetically or with pharmacologic inhibitors, could force cancer cells to revert to a treatment-sensitive state.

The team therefore hopes that using GLI1 inhibitors in combination with ribavirin, cytarabine, or other therapies can overcome treatment resistance in patients with AML. The investigators have received approval from Health Canada to conduct a new clinical trial to test this theory.

“If this new approach is successful, it could have very broad applications, since the mode of action of ribavirin suggests that it could be effective against up to 30% of all cancers, including some types of breast, prostate, colon, stomach, and head and neck cancers, in addition to AML,” said Morris Goodman, co-founder and Chairman of the Board of Pharmascience Inc., the company that manufactured the ribavirin for this research.

Micrograph showing AML cells

Credit: Lance Liotta

New research has revealed a mechanism of drug resistance in acute myeloid leukemia (AML) that may also occur in other cancers.

Investigators found evidence suggesting that glioma-associated protein 1 (GLI1) and the UDP glucuronosyltransferase (UGT1A) family of enzymes drive resistance to 2 drugs—ribavirin and cytarabine—in AML.

But the researchers were able to overcome this resistance by genetic or pharmacologic inhibition of GLI1.

They described this research in a letter to Nature.

“By studying drug-resistant cancer cells from AML patients and head and neck tumors, we found that a gene called GLI1 is dramatically overactive in these cells,” said study author Hiba Zahreddine, a doctoral student at the University of Montreal in Canada.

“[W[e were then able to show that this results in a specific chemical change to the drugs that prevents their toxicity toward the cancer cells,” said author Kathy Borden, PhD, of the University of Montreal’s Institute for Research in Immunology and Cancer.

Specifically, the investigators found that UGT1A enzymes add glucuronic acid to the drugs, thereby modifying their activity. And GLI1 alone is sufficient to drive UGT1A-dependent glucuronidation of ribavirin and cytarabine, which fuels drug resistance.

Fortunately, the researchers found that inhibiting GLI1, either genetically or with pharmacologic inhibitors, could force cancer cells to revert to a treatment-sensitive state.

The team therefore hopes that using GLI1 inhibitors in combination with ribavirin, cytarabine, or other therapies can overcome treatment resistance in patients with AML. The investigators have received approval from Health Canada to conduct a new clinical trial to test this theory.

“If this new approach is successful, it could have very broad applications, since the mode of action of ribavirin suggests that it could be effective against up to 30% of all cancers, including some types of breast, prostate, colon, stomach, and head and neck cancers, in addition to AML,” said Morris Goodman, co-founder and Chairman of the Board of Pharmascience Inc., the company that manufactured the ribavirin for this research.

Micrograph showing AML cells

Credit: Lance Liotta

New research has revealed a mechanism of drug resistance in acute myeloid leukemia (AML) that may also occur in other cancers.

Investigators found evidence suggesting that glioma-associated protein 1 (GLI1) and the UDP glucuronosyltransferase (UGT1A) family of enzymes drive resistance to 2 drugs—ribavirin and cytarabine—in AML.

But the researchers were able to overcome this resistance by genetic or pharmacologic inhibition of GLI1.

They described this research in a letter to Nature.

“By studying drug-resistant cancer cells from AML patients and head and neck tumors, we found that a gene called GLI1 is dramatically overactive in these cells,” said study author Hiba Zahreddine, a doctoral student at the University of Montreal in Canada.

“[W[e were then able to show that this results in a specific chemical change to the drugs that prevents their toxicity toward the cancer cells,” said author Kathy Borden, PhD, of the University of Montreal’s Institute for Research in Immunology and Cancer.

Specifically, the investigators found that UGT1A enzymes add glucuronic acid to the drugs, thereby modifying their activity. And GLI1 alone is sufficient to drive UGT1A-dependent glucuronidation of ribavirin and cytarabine, which fuels drug resistance.

Fortunately, the researchers found that inhibiting GLI1, either genetically or with pharmacologic inhibitors, could force cancer cells to revert to a treatment-sensitive state.

The team therefore hopes that using GLI1 inhibitors in combination with ribavirin, cytarabine, or other therapies can overcome treatment resistance in patients with AML. The investigators have received approval from Health Canada to conduct a new clinical trial to test this theory.

“If this new approach is successful, it could have very broad applications, since the mode of action of ribavirin suggests that it could be effective against up to 30% of all cancers, including some types of breast, prostate, colon, stomach, and head and neck cancers, in addition to AML,” said Morris Goodman, co-founder and Chairman of the Board of Pharmascience Inc., the company that manufactured the ribavirin for this research.